Fluoride-Promoted Cross-Coupling of Chloro(mono-, di-, or triphenyl)germanes with Aryl Halides in "Moist" Toluene. Multiple Transfer of the Phenyl Group from Organogermane Substrates and Comparison of the Coupling Efficiencies of Chloro(phenyl)germanes with their Corresponding Stannane and Silane Counterparts

Abstract

The trichlorophenyl-, dichlorodiphenyl-, and chlorotriphenylgermanes undergo Pd-catalyzed cross-couplings with aryl bromides and iodides in the presence of tetrabutylammonium fluoride in toluene with addition of the measured amount of water. One chloride ligand on the Ge center allows efficient activation by fluoride to promote transfer of one, two or three phenyl groups from the organogermanes. The corresponding chlorophenylstannanes were found to be more reactive than chlorophenylsilanes, which in turn were more effective than chlorophenylgermanes. One chloride ligand on Ge or Si center allows efficient activation by fluoride to promote transfer of up to three aryl groups from germane or silicon. However, no haloligand was necessary to be present on Sn center, since tetraphenyltin efficiently transferred up to four phenyl groups during fluoride-promoted couplings with aryl halides. ¹⁹F NMR studies suggested formation of the fluorophenylgermanes and the hypervalent germanate species as possible intermediates.

Introduction

Pd-catalyzed cross-coupling reactions are a powerful method for the formation of carbon-carbon bonds under conditions that are compatible with a broad range of functional groups.¹ Among these methods, couplings between organometallics derived from Group 14 metals and various electrophiles are well developed. Despite widespread application of organostannanes^2,3 and organosilanes^4,5 to coupling reactions, the Pd-catalyzed coupling of organogermanes has not been utilized,⁶ even though germanium lies between silicon and tin in the periodic table. The development of organogermanes as transmetalation reagents in Pd-catalyzed coupling reactions has been limited by the lower reactivity of tetracoordinated organogermanium species, the less developed syntheses of vinyl/aryl germanyl derivatives, and the higher cost of germanium relative to silicon.⁷

The 1-aza-5-germa-5-organobicyclo-[3,3,3]undecanes (carbagermatranes) 1 were the first examples of reactive tetracoordinated germanes utilized in Pd-catalyzed cross-coupling reactions with aryl bromides due to the activation of germanium by internal coordination to nitrogen⁸ (Figure 1). The allyl, aryl, alkenyl and alkynyl oxagermatranes 2 were found to be more efficient than carbagermatranes 1 and triethoxygermanes.⁹ The couplings were promoted by fluoride, and in fact, arylalkynyl oxagermatranes 2 underwent couplings even with less reactive aryl chlorides and triflates under milder conditions than are usually required for Sonogashira couplings with triorganosilicon reagents.¹⁰ The fluoride-promoted couplings with aryltri(2-furyl)germanes¹¹ and the NaOH-activated couplings with arylgermanium trichlorides¹² or their hydrolyzed and stable sesquioxide alternatives¹³ were also reported. Bis(2-naphthylmethyl)arylgermanes 3 were developed as the photochemically activated “safety-catch” arylgermanes for the synthesis of biaryls.^14,15 The vinyl tris(trimethylsilyl)germanes 4 were employed as transmetalation reagents in "ligand-free" and "fluoride-free" cross-coupling reactions with aryl and alkenyl halides under oxidative conditions (H₂O₂) in either aqueous or anhydrous basic conditions.^16,17 Interestingly, the (α-fluoro)vinyl germanes 5 provided a synthetic route to fluoroalkenes and fluorodienes.¹⁸ In contrast, the use of (α-fluoro)vinyl stannanes and silanes as transmetalation reagents in Pd-catalyzed couplings proved to be of very limited value.^19,20 Maleczka et al. reported that the Pd-mediated coupling of vinyltributylgermanes with aryl halides occurred more efficiently under Heck than Stille conditions to give preferentially Z-alkenes, especially when oxygen was present at the allylic position.²¹

Figure 1.

Examples of organogermanes employed in Pd-catalyzed cross-couplings.

Couplings with organogermanes appear to be promoted either by intramolecular chelation of a pendant Lewis basic heteroatom which renders the Ge centre "permanently" pentavalent^8,9,21 or by the presence of at least one heteroatom bound to the Ge centre that renders the Ge centre more susceptible to coordination by an external Lewis basic ligand (e.g. fluoride, hydroxide etc.) thereby also rendering the Ge centre pentavalent.^{11–13,17,22} Although the effects of the fluoride or base activation and Pd-catalyst/ligand combination on the coupling of organogermanes are still ambiguous, all but one⁸ of the successful examples of organogermane couplings with aryl/alkenyl halides involved activation with either base or fluoride. Proposed reactive species were Na_n[ArGe(OH)_3+n] (n = 1, 2),¹² [ArGe(OH)₃F]⁻,¹¹ or RGe(OH)_n(SiMe₃)_3-n/NaOH (n =1, 2, 3).¹⁷

We have recently communicated that (phenyl)_n(chloro)_4-ngermanes (n = 1, 2, or 3) undergo Pd-catalyzed cross-couplings with aryl halides in the presence of TBAF in “moist” toluene, with transfer of up to three phenyl groups from germane.²² Interestingly, organotin halides were initially considered to be inactive in Pd-catalyzed couplings due to the deactivating nature of the halogen.^3,23 However, coupling between halostannanes (e.g., ArBu₂SnCl) and organic halides were later found to be facilitated by TBAF.^3,24 Hypervalent organotin species³ were suggested as the active species in the Pd-catalyzed coupling reactions of organotin trichlorides with aryl halides in aqueous base.^25,26 Moreover, alkenylsilyl chlorides and fluorides were among the first alkenyl silanes to act as effective and general substrates in the coupling reactions.⁴ Hatanaka and Hiyama found that introduction of fluorine atom(s) into the silicon substituent accelerates the cross-coupling reactions.²⁷ Thus, reaction of the alkenyl/aryl substituted fluoro(alkyl)silanes and difluoro(alkyl)silanes with organic halides or triflates in the presence of fluoride promoters (TASF) provided cross-coupling products in a stereo- and regioselective manner and in good yields.^27,28 Interestingly, trifluorosilanes were ineffective in the cross-coupling with 1-iodonapthalene²⁷ but coupled with alkenyl triflates.²⁸ The (aryl)halosilanes were also employed successfully in the coupling with aryl halides promoted by KF in DMF.²⁹ Yet again, aryl(trifluoro)- and aryl(trichloro)silanes failed to generate cross-coupling products.²⁹ Couplings of organochlorosilanes with aryl chlorides promoted by KF³⁰ or NaOH³¹ and aryl iodides in aqueous KOH media³² have been also reported.

Although systems which will allow direct comparison of the cross-coupling reactions between the organometallic reagents derived from Group 14 metals and electrophiles are lacking,^33–35 organochlorogermanes can render a coupling efficiency comparable to the usually more reactive stannane and silane counterparts.^12,22 Therefore, herein, we report a comparative study on the reactivity of chlorophenylgermanes and their corresponding silanes and stannanes counterparts towards TBAF-promoted Pd-catalyzed cross-couplings with aryl halides in wet toluene, as well as some mechanistic considerations.

Results and Discussion

We first explored the effect of the Pd-catalysts, solvent, time, temperature and the amount and type of fluoride promoter on the coupling between dichlorodiphenylgermane 6 and the corresponding silane 7 and stannane 8 counterparts and 1-iodonaphthalene (9a; 2.2 equiv.) as electrophile. The results are summarized in Table 1. Thus, the amount of TBAF was found to be crucial for the successful coupling of 6–8 with 9a in the presence of Pd₂(dba)₃ in toluene (entries 1–4). At least 7 equiv. of TBAF were required to produce the maximum yield of the cross-coupling product 10a from germane 6 and silane 7, whereas 5 equiv. were sufficient for stannane 8. Reactions required 15 h for germane 6, 5 h for silane 7, and only 2 h for stannane 8 for the best results at 100 °C. Dichlorodiphenyl organometallic reagents 6–8 allowed us to test for multiple phenyl group transfer from Ge, Si, and Sn atoms, a concept which has been sparsely developed (vide infra). Thus, two phenyl groups can be efficiently transferred from all three reagents 6–8 but coupling with germane 6 and silane 7 produced also varying amount of binaphthyl homocoupling byproduct 11a (5–10%) while stannane 8 produced 10a almost quantitatively.

Table 1.

Effect of Various Reaction Parameters on the Efficiency of Cross-coupling of Dichlorodiphenylgermane 6, Silane 7, and Stannane 8 with 1-Iodonaphthalene^a

entry	Pd	TBAFb or base (equiv.)	solvent	from germane 6 (15 h)		from silane 7 (5 h)		from stannane 8 (2 h)
				yield (%)c,d 10a	ratiod,e 10a:11a	yield (%)c,d 10a	ratiod,e 10a:11a	yield (%)c,d 10a	ratiod,e 10a:11a
1	Pd2(dba)3	1.0	Toluene	--	--	--	--	14	99:1
2	Pd2(dba)3	3.0	Toluene	7	18:1	6	25:1	63	99:1
3	Pd2(dba)3	5.0	Toluene	34	9:1	52	15:1	93	99:1
4	Pd2(dba)3	7.0	Toluene	58f	2.2:1	83g	10:1	97h	99:1
5	Pd(OAc)2	7.0	Toluene	49	3.7:1	70	8:1	81	25:3
6	Pd(PPh3)4	7.0	Toluene	14	2.3:1	18	15:1	89	199:1
7	Pd2(dba)3	7.0i	Toluene	72	3.5:1	92	33:1	96	125:1
8	Pd2(dba)3	7.0	DMFj	64	4:1	33	3:1	97	35:1
9	Pd2(dba)3	7.0	THFk	38	6:1	56	2:1	95	199:1
10	Pd2(dba)3	7.0	Dioxanel	64	12:1	71	17:1	97	199:1
11	Pd2(dba)3	NaOHm	Dioxane/H2On	48o	2:1	54	26:1	75	125:1
12	Pd2(dba)3	KOSiMe3m	Toluene	8	3:1	52	30:1	58	53:1

^aCouplings were performed on 0.14 mmol scale of organometallics (0.04 M) with 2.2 equiv. of 1-iodonaphthalene and 0.05 equiv. of Pd catalyst.

^bCommercial 1M THF solution containing 5% H₂O, unless otherwise noted.

^cBased upon transferring two phenyl groups from 6–8.

^dDetermined by GC-MS of the crude reaction mixture.

^eMolar ratio.

^fAt 60 °C (19%, 10:1) and at 80 °C (43%, 4:1).

^gAt 60 °C (43%, 30:1) and at 80 °C (80%, 15:1).

^hAt 60 °C (87%, 199:1) and at 80 °C (94%, 199:1).

ⁱTBAF•3H₂O.

^j100 °C.

^k60 °C.

^l80 °C.

^m7 equiv.

ⁿ2:1; v/v.

^oWith Pd(OAc)₂ (21%, 8:1).

Other Pd catalysts afforded 10a in lower yields and similar ratios of 10a to 11a (entries 5–6). Replacement of 1M TBAF/THF solution with neat TBAF•3H₂O also gave the product 10a (entry 7), however coupling in the presence of Me₄NF (as well as CsF and NH₄F) failed to produce 10a most probably because of the low solubility of the salts in toluene. Coupling of stannane 8 also proceeded in high yield at 80 °C and even at 60 °C, while reactions with silane 7 and germane 6 required at least 80 °C and 100 °C, respectively to produce 10a in high yields with the transfer of two phenyl groups (Table 1, footnotes f–h). Toluene was the solvent of choice, although attempts in DMF (100 °C), THF (60 °C) and dioxane (80 °C) afforded cross-coupling product 10a in good (from germane 6 and silane 7) to excellent (from stannane 8, entries 8–10) yields. The higher yields for the coupling in dioxane than in THF may be attributable to the increased temperature of the reaction as well as the difference in dielectric constant [7.58 for THF as compared to dioxane (2.21) and toluene (2.15)].³⁶ Using bases such as NaOH (dioxane/H₂O, 2:1) or KOSiMe₃ (toluene) in place of TBAF promoted couplings less efficiently (entries 11–12).

Following our initial finding²² that couplings of organogermanes with aryl halides in toluene with addition of the measured amount of water gave optimal yields of the cross-coupling products, we investigated couplings of (phenyl)_n(chloro)_4-ngermanes, silanes and stannanes (n = 1, 2, 3 or 4) in "moist" toluene and their capability of transferring multiple phenyl groups. Results for couplings of PhGeCl₃ 12, Ph₂GeCl₂ 6, Ph₃GeCl 13, or Ph₄Ge 14 with 1.1, 2.2, 3.3, or 4.4 equiv. of 1-iodonaphthalene 9a (100 ° C, 15 h) promoted by 7 equiv. of TBAF in toluene (Method A) and in toluene with an additional amount of water added (40 equiv; 1 M TBAF/THF//H₂O, ~1:5 M/M; Method B) are presented in Table 2.³⁷ The biphasic reaction mixture (toluene//THF/H₂O or toluene//H₂O when neat TBAF was used) in the presence of high concentration of tetrabutylammonium ions might promote conversion of Pd catalyst to the active Pd-colloids which are known³⁸ to be reactive species in Pd-catalyzed coupling reactions. Thus, coupling of 12 with 1.1 equiv. of 9a afforded 10a (entries 1–2), although it was previously noted that fluoride ion did not promote the couplings of PhGeCl₃ with aryl halides.¹² Coupling of 6 with 1.1 or 2.2 equiv. of 9a resulted in total consumption of iodide to afford 10a and 11a (entries 3–6). Two phenyl groups were efficiently transferred in the presence of excess iodide (entry 6). Couplings of 13 with 1.1, 2.2 or 3.3 equiv. of 9a proceeded with efficient transfer of up to three phenyl groups to give 10a (entries 7–12).^37b The yields of 10a and 10a:11a ratios increased when wet toluene and excess of halide were used. Unlike the present work, halides are often used in couplings as limiting reagents to reduce formation of homocoupling byproducts and the yields are based on the halide components. As expected,¹¹ coupling attempts with Ph₄Ge 14 failed (entries 13–14) confirming the need for at least one labile heteroatom ligand at the Ge center. The necessity of two halogen ligands was proposed for nucleophilic activation by F⁻ or OH⁻ ions.¹⁵

Table 2.

Cross-coupling of Germanes 6, 12, 13 and 14 with 1-Iodonaphthalene Promoted by TBAF and TBAF/H₂O

entry	germane	9a (equiv.)	methoda	yield (%)b,c 10a	ratiod 10a:11a
1	12	1.1	A	88 (81)	19:1
2	12	1.1	B	99 (96)	35:1
3	6	1.1	A	32e (30)	2.7:1
4	6	2.2	A	58 (55)	2.2:1
5	6	1.1	B	45 (42)	23:1
6	6	2.2	B	91 (89)	10:1
7	13	1.1	A	13f (12)	1:1.4
8	13	2.2	A	37 (35)	2:1
9	13	3.3	A	40 (39)	1.2:1
10	13	1.1	B	18 (17)	2.5:1
11	13	2.2	B	60 (59)	9:1
12	13	3.3	B	95g (88)	13:1
13	14	4.4	A	0	--
14	14	4.4	B	0	--

^aMethod A: Couplings were performed on 0.14 mmol scale of germane (0.04 mM) with 0.05 equiv. of Pd catalyst, 7 equiv. of TBAF (1M/THF solution containing 5% of water). Method B: as in Method A with addition of H₂O (~40 equiv.).

^bBased on total transferring of one, two, or three phenyl groups from 12, 6, or 13, respectively.

^cDetermined by GC-MS of crude reaction mixture (isolated yields in parenthesis).

^dMolar ratio.

^e26% and 31% with 6 and 8 equiv. of TBAF.

^f11% and 14% with 6 and 8 equiv. of TBAF.

^g57% (3.8:1) with 50 µL H₂O; 82% (7:1) with 150 µL H₂O.

We found that outcome of the coupling reactions sometimes varied with different batches of TBAF. It became apparent that the older bottles of TBAF reagents often provided the best results. Correspondingly, the poorest performance was obtained with newly purchased bottles that were carefully stored and when no additional amount of water was added to the reactions mixtures. Therefore, to find the optimal water content for the reaction and to establish a reproducible protocol for the cross-coupling, we carried out a study in which we varied the amount of water added to the reaction mixture. Thus, coupling of Ph₃GeCl (13, 0.14 mmol) with 1-iodonaphthalene (9a, 3.3 equiv) promoted by TBAF (7 equiv.) were performed in dry toluene (0.04 M solution) with the addition of 40, 70, 100, 130, 160 and 200 µL of water (16–80 equiv). The best results both in terms of yields and ratios of coupled product 10a to homocoupled byproduct 11a were obtained by the addition of 100 µL water (40 equiv.) to the reaction mixture (Figure 2). The commercially available 1M TBAF solution in THF containing 5% of water was used for this study. Replacement of the 1M TBAF/THF solution with neat TBAF•3H₂O also produced a similar yield and ratio dependence on the addition of measured amount of water. It is noteworthy that each of these fluoride reagents introduced approximately same amount of water to the reaction mixture. Water might play multiple roles³⁹ in enhancing the efficiency of the couplings including the formation of the reactive hydroxypalladium intermediates.^6,40,41 For example, the hydration levels of Cs₂CO₃ and CsOH were found to be decisive factors during the coupling of the aryl(dimethyl)silanols with aryl halides.⁴² Also, Denmark and Sweis showed that water was a critical additive in the fluoride promoted reaction of alkenylsilanols with phenyl nonaflate.^6,43

Figure 2.

Water-dependent efficiency of TBAF-promoted coupling of Ph₃GeCl 13 with 1-iodonaphthalene 9a in toluene.

Results for the couplings of PhSiCl₃ 15, Ph₂SiCl₂ 7, Ph₃SiCl 16, or Ph₄Si 17 with 1.1, 2.2, 3.3, or 4.4 equiv. of iodonaphthalene 9a (100 °C, 5 h) promoted by TBAF in toluene (Method A) and in "moist" toluene (Method B) are presented in Table 3. Thus, coupling of 15 with 1.1 equiv. of 9a afforded 10a (entries 1–2). Attempts to couple either 15 or trifluoro(phenyl)silane with aryl bromides and halides (KF/DMF) failed to yield the products in detectable amount.²⁹ Coupling of 7 with 1.1 or 2.2 equiv. of 9a in toluene (Method A) afforded 10a in moderate yield in addition to 11a (10%). However, analogous coupling in wet toluene (Method B) gave 10a in quantitative yield with no detectable amount of homocoupling byproduct 11a (entries 5 vs 3 and 6 vs 4). Couplings of 16 with 1.1, 2.2 or 3.3 equiv. of 9a allowed the efficient transfer of up to three phenyl groups to give 10a (entries 7–12). The yields of 10a and 10a:11a ratios increased when wet toluene and excess of electrophiles were used. Our atom-efficient methodology offers advantages to the previously reported couplings utilizing 7 where excess of silanes were used to avoid formation of the reductive homocoupling byproducts.^29,44 It is worth noting that attempts to induce multiple transfer of the phenyl group during fluoride-promoted couplings of diallyl(diphenyl)- and allyl(triphenyl)silanes with aryl halides were unsuccessful.⁴⁵ However, vinylpolysiloxanes were shown to transfer each of their vinyl groups during Pd-catalyzed couplings with aryl and alkenyl iodides in the presence of TBAF.⁴⁶ Coupling attempts of Ph₄Si 17 with 9a were not successful; however extended heating (18 h) did produce the cross-coupling product 10a albeit in low yields (entries 13–16).

Table 3.

Cross-coupling of Silanes 7, 15, 16 and 17 with 1-Iodonaphthalene Promoted by TBAF and TBAF/H₂O

entry	silane	9a (equiv.)	methoda	yield (%)b,c 10a	ratiod 10a:11a
1	15	1.1	A	91	59:1
2	15	1.1	B	96	67:1
3	7	1.1	A	34	9:1
4	7	2.2	A	83 (80)	10:1
5	7	1.1	B	53	99:1
6	7	2.2	B	99 (96)	99:1
7	16	1.1	A	31	8:1
8	16	2.2	A	49	4:1
9	16	3.3	A	55	3:1
10	16	1.1	B	35	20:1
11	16	2.2	B	68	20:1
12	16	3.3	B	91(84)	8:1
13	17	1.1	A	5e	2:3
14	17	4.4	A	4e	1:3
15	17	1.1	B	4e	1:3
16	17	4.4	B	8e	1:2

^aMethod A: Couplings were performed on 0.14 mmol scale of silane (0.04 M) with 0.05 equiv. of Pd catalyst, 7 equiv. of TBAF (1M/THF solution containing 5% of water). Method B: as in Method A with addition of H₂O (~40 equiv.).

^bBased on total transferring of one, two, three, or four phenyl groups from 15, 7, 16 or 17, respectively.

^cDetermined by GC-MS of crude reaction mixture (isolated yields in parenthesis).

^dMolar ratio.

^eAfter 16 h.

Results for the couplings of PhSnCl₃ 18, Ph₂SnCl₂ 8, Ph₃SnCl 19, or Ph₄Sn 20 with 1.1, 2.2, 3.3, or 4.4 equiv. of iodonaphthalene 9a (100 °C, 2 h) promoted by 7 equiv. of TBAF in toluene (Method A) and in "moist" toluene (Method B) are presented in Table 4. All stannanes were coupled with 9a to produce almost exclusively 10a with efficient transfer of up to four phenyl groups (entries 1–20). Addition of water has little effect on the reactions outcome but 10a:11a ratio improved slightly for the couplings with 19 and 20 in wet toluene (entries 7–20). The couplings with tin substrates can be also accomplished in a shorter time and at lower temperature (entries 4 and 6). Atom-efficient Stille cross-couplings of Ar₄Sn with aryl halides, where all four substituents on tin participate in the carbon-carbon bond formation, are known.^24,47

Table 4.

Cross-coupling of Stannanes 8, 18, 19 and 20 with 1-Iodonaphthalene Promoted by TBAF and TBAF/H₂O

entry	stannane	9a (equiv.)	methoda	yield (%)b,c 10a	ratio d 10a:11a
1	18	1.1	A	96	54:1
2	18	1.1	B	96 (93)	56:1
3	8	1.1	A	52	99:1
4	8	2.2	A	97 (93)e	99:1
5	8	1.1	B	54 (50)	99:1
6	8	2.2	B	96 (94)f	99:1
7	19	1.1	A	33	30:1
8	19	2.2	A	69	30:1
9	19	3.3	A	96	30:1
10	19	1.1	B	36	99:1
11	19	2.2	B	72	99:1
12	19	3.3	B	99 (95)	99:1
13	20	1.1	A	24	20:1
14	20	2.2	A	56	20:1
15	20	3.3	A	72	20:1
16	20	4.4	A	86	15:1
17	20	1.1	B	27	99:1
18	20	2.2	B	54	99:1
19	20	3.3	B	81	99:1
20	20	4.4	B	99 (91)	99:1

^aMethod A: Couplings were performed on 0.14 mmol scale of stannane (0.04 M) with 0.05 equiv. of Pd catalyst, 7 equiv. of TBAF (1M/THF solution containing 5% of water). Method B: as in Method A with addition of H₂O (~40 equiv.).

^bBased on total transferring of one, two, three, or four phenyl groups from 18, 8, 19 or 20, respectively.

^cDetermined by GC-MS of crude reaction mixture (isolated yields in parenthesis).

^dMolar ratio.

^eAt 60 °C (87%, 199:1) and at 80 °C (94%, 199:1).

^fAfter 1 h (85%, 99:1).

In general, it appears that chlorophenylstannanes are more reactive than chlorophenylsilanes, which in turn are more reactive than chlorophenylgermanes in these fluoride-assisted Pd-catalyzed cross-couplings with 1-iodonaphthalene in toluene. For the silanes and germanes, reactivity seems to increase with the number of halogen ligands on the Si or Ge center (PhMCl₃ > Ph₂MCl₂ > Ph₃MCl > Ph₄M, where M = Si or Ge).⁴⁸ It is reasonable to assume that the silicon or germanium species with extra halogen ligands, which are formed after each transmetalation cycle, are more reactive for the efficient transfer of a second or third phenyl group from the Si or Ge atom. Addition of water to the reaction mixture has a profound effect on the efficiency of coupling of halogermanes. It also increases the effectiveness of the coupling of halosilanes while having little or no effect on coupling with halostannanes.

The results of couplings of phenylchlorogermanes 12, 6, and 13 with aryl, alkenyl, and heterocyclic iodides and bromides with 1.1, 2.2 or 3.3 equiv of halides, respectively promoted by TBAF/H₂O are presented in Table 5 (entries 1–33). Thus, couplings with 1-bromonaphthalene 9a' afforded biaryl 10a (entries 1, 12 and 23), although with lower yield and worse 10a:11a ratio than the coupling with 1-iodonaphthalene (e.g., entry 12 vs entry 6 in Table 2). Less reactive electrophiles such as 1-chloronaphthalene failed to produce 10a (entry 12). The reactivity of the phenylchlorogermanes increases with the number of halogen ligands on the Ge center (13 < 6 < 12). Hence, PhGeCl₃ 12 efficiently afforded coupling products 10 (entries 1–11). This finding is in contrast to a previous report that fluoride ion did not promote the couplings of PhGeCl₃ with aryl halides (as opposed to NaOH in dioxane/H₂O medium^12,13); however, there were no experimental details.¹² The germanes showed comparable reactivity with aryl iodides having either electron-donating (e.g., entries 2, 13, and 24) or electron-withdrawing substituents (entries 5, 16, and 27) on the phenyl ring. However less reactive germanes appear to be more efficient with aryl iodides bearing EDG (e.g., entry 24 vs 28 and 29). On the other hand, couplings of the aryl bromides bearing EWG was found to be more efficient than those having EDG (entries 8, 19, and 30 vs 3, 14, and 25, respectively). Methoxy substituents at the ortho postion lower the coupling yields, especially for less reactive germanes (series c vs b; i.e., entries 4, 15, and 26 vs 2, 13, and 24, respectively). Reaction of Ph₂GeCl₂ 6 or Ph₃GeCl 13 with 4-iodoacetophenone 9f produced 10f in low yield in addition to large quantities of the reductive homocoupling byproduct 11f. However, coupling of the less reactive 4-bromoacetophenone 9f' at elevated temperature and prolonged time resulted in higher yields and improved 10f:11f ratios (entries 19 vs 18 and 30 vs 29). In general, cross-coupling turned out to be more efficient with aryl halides than with other halides (series a–f vs g–i). Interestingly, formation of the biphenyl byproduct (5– 50%), via the oxidative self-coupling of the organogermane component 6, has been only observed in limited cases, mainly when coupling products 10 were formed in lower yields (e.g., entries 9, 10, 20, and 21).

Table 5.

Cross-coupling of Chlorogermanes 6, 12, and 13 with Halides^a

entry	germane	halide		equiv.	product	yield (%)b,c	ratio (10:11)d
1	12	1-Bromonaphthalene	9a′	1.1	10a	90e (82)	99:1
2	12	4-CH3OC6H4I	9b	1.1	10b	88e (80)	10:1
3	12	4-CH3OC6H4Br	9b′	1.1	10b	5 f	2:3
4	12	2-CH3OC6H4I	9c	1.1	10c	71	15:1
5	12	3-CF3C6H4I	9d	1.1	10d	93 (87)	9:1
6	12	4-CF3C6H4I	9e	1.1	10e	98 (87)	20: 1
7	12	4-CH3COC6H4I	9f	1.1	10f	99 (88)	99:1
8	12	4-CH3COC6H4Br	9f′	1.1	10f	91	99:1
9	12	PhCH=CHBrg	9g	1.1	10g	30e,h (28)	3:1
10	12	2-Iodo-5-Methylthiophene	9h	1.1	10h	48e,h (35)	3:2
11	12	Bromomethylenecyclohexane	9i	1.1	10i	5	3:1
12	6	1-Bromonaphthalenei	9a′	2.2	10a	54 (44)	7.2:1
13	6	4-CH3OC6H4I	9b	2.2	10b	86f (85)	9.8:1
14	6	4-CH3OC6H4Br	9b′	2.2	10b	4f	1:2
15	6	2-CH3OC6H4I	9c	2.2	10c	49	199:1
16	6	3-CF3C6H4I	9d	2.2	10d	70 (68)	3.4:1
17	6	4-CF3C6H4I	9e	2.2	10e	72 (70)	7:2
18	6	4-CH3COC6H4I	9f	2.2	10f	12 (10)	3:2
19	6	4-CH3COC6H4Br	9f′	2.2	10f	26f (21)	99:1
20	6	PhCH=CHBrg	9g	2.2	10g	8h (5)	1:3
21	6	2-Iodo-5-Methylthiophene	9h	2.2	10h	13h (6)	2:3
22	6	Bromomethylenecyclohexane	9i	2.2	10i	24	2:1
23	13	1-Bromonaphthalene	9a′	3.3	10a	24	1.4:1
24	13	4-CH3OC6H4I	9b	3.3	10b	48j (40)	4:1
25	13	4-CH3OC6H4Br	9b′	3.3	10b	14 f	4:1
26	13	2-CH3OC6H4I	9c	3.3	10c	1	1:2
27	13	3-CF3C6H4I	9d	3.3	10d	48	3:2
28	13	4-CF3C6H4I	9e	3.3	10e	12	3:4
29	13	4-CH3COC6H4I	9f	3.3	10f	3	1:20
30	13	4-CH3COC6H4Br	9f′	3.3	10f	24f	1:1
31	13	PhCH=CHBr g	9g	3.3	10g	3	1:8
32	13	2-Iodo-5-Methylthiophene	9h	3.3	10h	3	2:3
33	13	Bromomethylenecyclohexane	9i	3.3	10i	2	1:6

^aCouplings were performed on 0.14 mmol scale of germane (0.04 M) with 1.1, 2.2 or 3.3 equiv. of halides, 0.05 equiv. of Pd catalyst and TBAF (1 M/THF containing 5% of water, 7 equiv.) with additional water (~40 equiv.), unless otherwise noted.

^bBased on total transferring of one, two, or three phenyl groups from 12, 6, or 13, respectively.

^cDetermined by GC-MS of the crude reaction mixture (isolated yield in parenthesis).

^dMolar ratio.

^eWithout water.

^f115°C.

^gE/Z, 85:15.

^hVarious amount of biphenyl homocoupling byproducts (5~50%) were also observed.

ⁱCoupling with 1-chloronaphthalene failed.

^j28 h.

In order to investigate the effects of electron donating alkyl substituents at Ge atom on the fluoride-promoted couplings of chlorogermanes in toluene, we have examined cross-couplings of chlorodimethyl(phenyl)germane 21 with a variety of halides (1.1 equiv., Table 6). Once again reactions were more efficient with aryl halides than with other vinyl halides (entries 1–12). Reactivity of monochlorogermane 21 was found to be slightly higher than that of Ph₃GeCl 13 but lower than with PhGeCl₃ 12. Thus, Pd-catalyzed cross-coupling reactions of the chlorogermanes in "moist" toluene promoted by fluoride is general in character and is suitable for phenyl as well as phenyl/alkyl substituted germanes.

Table 6.

Cross-Coupling of Chlorodimethyl(phenyl)germane 21 with Halides^a

entry	halide		product	yield (%)b	ratio (10:11)c
1	1-iodonaphthalene	9a	10a	93d (81)	20:1
2	1-bromonaphthalenee	9a′	10a	44d	6:1
3	4-CH3OC6H4I	9b	10b	88d (78)	10:1
4	4-CH3OC6H4Br	9b′	10b	6	1:9
5	2-CH3OC6H4I	9c	10c	8	1:8
6	3-CF3C6H4I	9d	10d	61d (54)	2.4:1
7	4-CF3C6H4I	9e	10e	31d (27)	1.2:1
8	4-CH3COC6H4I	9f	10f	10d	1.2:1
9	4-CH3COC6H4Br	9f′	10f	8	1:1.5
10	PhCH=CHBrf	9g	10g	8d,g	1:5
11	2-Iodo-5-Methylthiophene	9h	10h	3d	1:16
12	Bromomethylenecyclohexane	9i	10i	12	1:1.5

^aCouplings were performed on 0.14 mmol scale of germane 21 (0.04 M) with 1.1 equiv. of halides, 0.05 equiv. of Pd₂(dba)₃ and TBAF (1 M/THF containing 5% of water, 7 equiv.) with additional water (~40 equiv.), unless otherwise noted.

^bDetermined by GC-MS of the crude reaction mixture (isolated yield in parenthesis).

^cMolar ratio.

^dWithout water.

^eCoupling with 1-chloronaphthalene failed.

^fE/Z, 85:15.

^gBiphenyl homocoupling byproducts (~25%) were also observed.

Couplings of chlorophenylsilanes 15, 7, and 16 with the same halides under similar conditions, which are presented in Table 7 (entries 1–33), showed that: (a) reactivity of silanes increases with the number of halogen ligands on the Si center (16 < 7 < 15), just as was observed for germanes, (b) couplings were more efficient with aryl halides than with other halides, and (c) reactions with iodides were again more efficient than with bromides. Likewise with chlorogermanes, the nature and position of the substituents on the aryl halides had a similar effect on the coupling efficiency. These results to the best of our knowledge represent the first example of the multiple transfers of phenyl groups from organosilane precursors in Pd-catalyzed couplings.^29,44,45 Our methodology which utilizes wet toluene also resulted in excellent coupling efficiency with PhSiCl₃ 15, which failed to generate the cross-coupling products under other conditions.²⁹ Comparison of the coupling efficiency of chlorosilanes with the analogous chlorogermanes indicates that: (a) chlorophenylsilanes are, in general, more reactive than the analogous chlorophenylgermanes, and (b) the largest difference of reactivity was found to be between Ph₃SiCl 16 and Ph₃GeCl 13, whereas PhSiCl₃ 15 and PhGeCl₃ 12 both showed high reactivity, although shorter reaction time (5 h vs 15 h) was necessary for silanes. Coupling with Ph₄Si 17 either failed or produced the products 10 in low yields (entry 34). These results were only a slight improvement on the unsuccessful coupling attempts with Ph₄Ge 14 (see Table 2, entries 13–14). Also, they provided further evidence that a labile heteroatom at the Si center is required for effective coupling.

Table 7.

Cross-coupling of silanes 7, 15, 16 and 17 with halides^a

entry	silane	halide		equiv.	product	yield (%)b,c	ratio (10:11)d
1	15	1-Bromonaphthalene	9a′	1.1	10a	42e	30:1
2	15	4-CH3OC6H4I	9b	1.1	10b	99	99:1
3	15	4-CH3OC6H4Br	9b′	1.1	10b	3f	1:13
4	15	2-CH3OC6H4I	9c	1.1	10c	77g	30:1
5	15	3-CF3C6H4I	9d	1.1	10d	94	29:1
6	15	4-CF3C6H4I	9e	1.1	10e	88	15:1
7	15	4-CH3COC6H4I	9f	1.1	10f	91	99:1
8	15	4-CH3COC6H4Br	9f′	1.1	10f	59h	99:1
9	15	PhCH=CHBri	9g	1.1	10g	66	4:1
10	15	2-Iodo-5-Methylthiophene	9h	1.1	10h	57	4.8:1
11	15	Bromomethylenecyclohexane	9i	1.1	10i	6	10:1
12	7	1-Bromonaphthalene j	9a′	2.2	10a	94	7.2:1
13	7	4-CH3OC6H4I	9b	2.2	10b	78	10:1
14	7	4-CH3OC6H4Br	9b′	2.2	10b	9 f, k	3:1
15	7	2-CH3OC6H4I	9c	2.2	10c	29 k	30:1
16	7	3-CF3C6H4I	9d	2.2	10d	57	3:1
17	7	4-CF3C6H4I	9e	2.2	10e	66l	5:1
18	7	4-CH3COC6H4I	9f	2.2	10f	54	3:2
19	7	4-CH3COC6H4Br	9f′	2.2	10f	79	99:1
20	7	PhCH=CHBri	9g	2.2	10g	22h	1:3
21	7	2-Iodo-5-Methylthiophene	9h	2.2	10h	30h	2:3
22	7	Bromomethylenecyclohexane	9i	2.2	10i	18k	2:1
23	16	1-Bromonaphthalene	9a′	3.3	10a	26	12:1
24	16	4-CH3OC6H4I	9b	3.3	10b	62	5:1
25	16	4-CH3OC6H4Br	9b′	3.3	10b	11 f	2:3
26	16	2-CH3OC6H4I	9c	3.3	10c	11 f	6:1
27	16	3-CF3C6H4I	9d	3.3	10d	45	1.4:1
28	16	4-CF3C6H4I	9e	3.3	10e	44	3:2
29	16	4-CH3COC6H4I	9f	3.3	10f	78	4.8:1
30	16	4-CH3COC6H4Br	9f′	3.3	10f	73	20:1
31	16	PhCH=CHBri	9g	3.3	10g	31	1:1.3
32	16	2-Iodo-5-Methylthiophene	9h	3.3	10h	14	1:1.3
33	16	Bromomethylenecyclohexane	9i	3.3	10i	12	3:1
34	17m	3-CF3C6H4I	9d	4.4	10d	13	1:3.7

^aCouplings were performed on 0.14 mmol scale of silanes (0.04 M) with 1.1, 2.2, 3.3 or 4.4 equiv. of halides, 0.05 equiv. of Pd catalyst and TBAF (1 M/THF containing 5% of water, 7 equiv.) with additional water (~40 equiv.), unless otherwise noted.

^bBased on total transferring of one, two, three or four phenyl groups from 15, 7, 16, or 17 respectively.

^cDetermined by GC-MS of the crude reaction mixture (isolated yields in parenthesis).

^dMolar ratio.

^e16 h (51%, 99:1).

^f115 °C.

^g16 h (86%, 99:1).

^hBiphenyl homocoupling byproducts (10~20%) were also observed.

ⁱE/Z, 85:15.

^jCoupling with 1-chloronaphthalene failed.

^kLonger reaction time (11 h) did not effect yield and 10:11 ratio.

^lwithout additional water (54%, 4:1).

^mCoupling of 17 with other halides 9 gave 10a–i with the overall yields less than 5%.

Couplings of chlorophenylstannanes 18, 8, or 19 and tetraphenyltin 20 with the same halides under similar conditions are presented in Table 8 (entries 1–44). Stannanes were more reactive than either silanes or germanes in fluoride-promoted couplings in wet toluene. One, two, three or four^24,47 phenyl groups were efficiently transferred from 18, 8, 19 or 20, respectively to produce biaryls 10a–f in only 2 h in excellent yields with a high 10:11 ratio. As was shown already for 1-iodonaphthalene (See Table 4), the couplings with stannanes can be accomplished in an even shorter time and at lower temperature (entry 16) as well as with less excess of TBAF (entries 13, 19 and 20). Aryl and alkenyl bromides (e.g., series a', b', i) again showed lower reactivity; however, the yields of their couplings with stannanes can be increased by using elevated temperatures and/or longer reaction times (entries 11 and 12).

Table 8.

Cross-coupling of stannanes 8, 18, 19 and 20 with halides^a

entry	stannane	halide		equiv.	product	yield (%)b,c	ratio (10:11)d
1	18	1-Bromonaphthalene	9a′	1.1	10a	41	30:1
2	18	4-CH3OC6H4I	9b	1.1	10b	98	30:1
3	18	4-CH3OC6H4Br	9b′	1.1	10b	18e	10:1
4	18	2-CH3OC6H4I	9c	1.1	10c	88	30:1
5	18	3-CF3C6H4I	9d	1.1	10d	97	35:1
6	18	4-CF3C6H4I	9e	1.1	10e	97 (89)	29:1
7	18	4-CH3COC6H4I	9f	1.1	10f	99 (88)	199:1
8	18	4-CH3COC6H4Br	9f′	1.1	10f	84f	199:1
9	18	PhCH=CHBrg	9g	1.1	10g	75h	8:1
10	18	2-Iodo-5-Methylthiophene	9h	1.1	10h	69	7:1
11	18	Bromomethylenecyclohexane	9i	1.1	10i	8i	15:1
12	8	1-Bromonaphthalenej	9a′	2.2	10a	47k	20:1
13	8	4-CH3OC6H4I	9b	2.2	10b	84l	16:1
14	8	4-CH3OC6H4Br	9b′	2.2	10b	31e	1:1
15	8	2-CH3OC6H4I	9c	2.2	10c	70	7.7:1
16	8	3-CF3C6H4I	9d	2.2	10d	94m,n	11:1
17	8	4-CF3C6H4I	9e	2.2	10e	83	11:1
18	8	4-CH3COC6H4I	9f	2.2	10f	99o (88)	199:1
19	8	4-CH3COC6H4Br	9f′	2.2	10f	92l	199:1
20	8	PhCH=CHBrg	9g	2.2	10g	76l	40:1
21	8	2-Iodo-5-Methylthiophene	9h	2.2	10h	94 (80)	20:1
22	8	Bromomethylenecyclohexane	9i	2.2	10i	7	1:1
23	19	1-Bromonaphthalene	9a′	3.3	10a	37	199:1
24	19	4-CH3OC6H4I	9b	3.3	10b	93 (92)	11:1
25	19	4-CH3OC6H4Br	9b′	3.3	10b	13e	6:1
26	19	2-CH3OC6H4I	9c	3.3	10c	79 (76)	13:1
27	19	3-CF3C6H4I	9d	3.3	10d	90	9:1
28	19	4-CF3C6H4I	9e	3.3	10e	94	11:1
29	19	4-CH3COC6H4I	9f	3.3	10f	100	199:1
30	19	4-CH3COC6H4Br	9f′	3.3	10f	96 (92)	199:1
31	19	PhCH=CHBrg	9g	3.3	10g	35	20:1
32	19	2-Iodo-5-Methylthiophene	9h	3.3	10h	70	3.2:1
33	19	Bromomethylenecyclohexane	9i	3.3	10i	9	20:1
34	20	1-Bromonaphthalene	9a′	4.4	10a	11p	20:1
35	20	4-CH3OC6H4I	9b	4.4	10b	80p	7:1
36	20	4-CH3OC6H4Br	9b′	4.4	10b	2	1:1
37	20	2-CH3OC6H4I	9c	4.4	10c	20	30:1
38	20	3-CF3C6H4I	9d	4.4	10d	75	4.5:1
39	20	4-CF3C6H4I	9e	4.4	10e	75p	8:1
40	20	4-CH3COC6H4I	9f	4.4	10f	68	27:1
41	20	4-CH3COC6H4Br	9f′	4.4	10f	97	99:1
42	20	PhCH=CHBrg	9g	4.4	10g	55	2:1
43	20	2-Iodo-5-Methylthiophene	9h	4.4	10h	50	2:1
44	20	Bromomethylenecyclohexane	9i	4.4	10i	5	3:1

^aCouplings were performed on 0.14 mmol scale of stannanes (0.04 M) with 1.1, 2.2, 3.3 or 4.4 equiv. of halides, 0.05 equiv. of Pd catalyst and TBAF (1 M/THF containing 5% of water, 7 equiv.) with additional water (~40 equiv.), unless otherwise noted.

^bBased on total transferring of one, two, three or four phenyl groups from 18, 8, 19, or 20 respectively.

^cDetermined by GC-MS of the crude reaction mixture (isolated yields in parethesis).

^dMolar ratio.

^e115 °C.

^f6 h (87%, 99:1).

^gE/Z, 85:15.

^h6 h (78%, 7:1).

ⁱ20 h at 115 °C (52%, 13:1).

^jCouplings with 1-chloronaphthalene failed.

^k5 h (64%, 18:1).

^l5 equiv. of TBAF gave similar yield and ratio.

^mAt 80 °C (89%, 13:1).

ⁿAfter 1 h (85%, 11:1).

^oWithout additional water (93%, 99:1)

^pLonger reaction time (28 h) did not effect yield and 10:11 ratio.

During the optimization of the cross-coupling reactions between chlorogermanes and 1-iodonaphthalene (see Table 2) it became obvious that the outcome of the couplings strongly depended on TBAF/organogermanes ratios.²² TBAF most likely facilitates coupling by generating the more reactive hypervalent fluorogermanium species and the reactivity of these species could be superior in toluene solvent due to weak solvation. Hypervalent fluoro tin^49–51 and silicon^52–55 species have been established as active intermediates in Pd-catalyzed coupling reactions. Thus, a stable tetrabutylammonium difluorotriphenylstannate 22⁴⁹ (Figure 3) efficiently undergoes Pd-catalyzed cross-coupling with alkenyl and aryl triflates.⁵⁰ It was also assumed that coupling of trimethylphenyltin with arylchlorides occurred via a hypervalent fluorotin intermediate such as 23.⁵¹ Similarly, a stable difluorotriphenylsilicate (TBAT) 24^52,54 has been shown to be a versatile nucleophilic reagent for the transfer of phenyl group in coupling reactions with aryl halides and allylic alcohols.^53,55 On the other hand, treatment of triphenylgermanium fluoride⁵⁶ with KF and tetrabutylammonium hydrogensulphate in DMF afforded pentavalent difluorotriphenylgermanate 25.⁵⁷ However the application of 25 to Pd-catalyzed cross-coupling reactions and the role that these hypervalent germanium species might play in couplings has not been explored.

Figure 3.

Examples of hypervalent fluoro stannates, silicates, and germanates.

In order to get insight about the role that hypervalent germanium species play in the coupling of chlorogermanes 6, 12, 13, and 21, we have studied their interaction with TBAF. Initial experiments were conducted using PhMe₂GeCl 21. Thus, mixing 21 and TBAF (1.5 equiv. 1 M/THF) in benzene-d₆ at room temperature resulted in the substitution of the chlorine ligand by the fluoride anion and formation of PhMe₂GeF. The observed septet centered at −194.3 ppm [¹⁹F NMR (CCl₃F)] formed by coupling with the six equivalent protons of the two methyl groups (³J_F–H ~ 6.0 Hz, spectrum a, Figure 4) had a chemical shift in agreement with the literature value (−196.0 ppm) for analogous fluorodimethylgermanes.¹⁵ Heating the sample at 50 °C for 3 h resulted in broadening of the signal at −194.6 ppm and appearance of a new broad singlet at −150.8 ppm suggesting equilibrium between PhMe₂GeF and its hypervalent species (spectrum b), which are most likely fluorine-bridged species analogous to 27 (vide infra, Scheme 1). The pentavalent difluorogermanate Ph(Me)₂GeF₂⁻ appears as a minor peak at −126.4 ppm (septet, ³J_F–H ~5.8 Hz) in agreement with the reported chemical shift for the analogous hypervalent difluorotriphenylgermanate 25.⁵⁷ Overnight heating resulted in the additional broadening of the peaks at −150.8 ppm and −194.3 ppm as well as in the increased intensity of the signal(s) at −126.4 ppm (spectrum c). Interestingly, extracting the sample with D₂O resulted in the reappearance of the septet at −194.3 ppm for Ph(Me)₂GeF (spectrum d).

Figure 4.

¹⁹F NMR spectra of the reaction of PhMe₂GeCl 21 with 1.5 equiv. of TBAF in benzene-d₆.

Scheme 1.

A plausible interaction of chloro(triphenyl)germane 13 with TBAF/H₂O

Treatment of Ph₃GeCl 13 with TBAF (1.5 equiv.) in toluene-d₈ led to a parallel pattern of peaks to those observed for the reaction of 21 with TBAF. Hence, the signal for Ph₃GeF (26, 201.9 ppm) and a broad singlet at −151.6 ppm (spectrum c, Figure 5) were observed. Heating at 50 °C for 3 h resulted in the increased intensity for the peak at −151.6 ppm (spectrum d), which was tentatively assigned as hypervalent fluorine-bridged species of type 27 (vide infra, Scheme 1). Such species 27 could be formed during a fluorine exchange between the five-coordinate germanate 25 (not identified on ¹⁹F NMR spectra recorded in toluene or benzene solution) and four-coordinate germane 26. Similar bridged structures containing tin and silicon centers have been documented by Janzen⁵⁸ and Tamao⁵⁹ and their coworkers as possible intermediates in a comparable ligand exchange processes. The formation of 27 is temperature dependent, since ¹⁹F NMR experiments at −20 °C and −50 °C revealed only the presence of four-coordinate Ph₃GeF 26 (spectrum b and a).

Figure 5.

¹⁹F NMR spectra of the reaction of Ph₃GeCl 13 with 1.5 equiv. of TBAF in toluene-d₈ at various temperature.

Furthermore, treatment of the independently synthesized Ph₃GeF⁵⁶ (26) with a sub-stoichiometric amount of TBAF (0.7 equiv.) in benzene-d₆ at ambient temperature resulted in the formation of the fluorine-bridged species 27 as the sole product (¹⁹F NMR). Washing the sample with D₂O resulted in the reappearance of the signal for the four-coordinate fluoride 26 (as observed with 13, see Figure 4), but with lower intensity. Most likely the bridged species 27 and/or the corresponding hypervalent germanates (e.g., 25) are hydrolyzed⁶⁰ into 26 and the more stable hexaphenyldigermoxane 28, which was isolated from the reaction mixture.

As expected, reactions of di- and trichlorogermanes 6 and 12 with TBAF led to more complex mixtures. Nevertheless, treatment of dichlorogermane 6 produced the difluorinated tetravalent germane Ph₂GeF₂, which shows a signal at −163.9 ppm in ¹⁹F NMR that is in agreement with the value reported by Spivey et al. for the analogous difluoride (−165 ppm).¹⁵

To correlate the formation, spectroscopic characteristic, and reactivity of the hypervalent germanium species with those of the corresponding silicon and tin counterparts in the fluoride-promoted couplings, reactions of chloro(triphenyl)silane 16 and chloro(triphenyl)stannane 19 with TBAF in benzene-d₆ were also explored. Thus, heating of 19 with TBAF (1.5 equiv.) resulted in the appearance of two singlets at −158.6 ppm and −159.5 ppm which were accompanied by F-Sn satellite signals (spectrum a, Figure 6). Further addition of 1.5 equiv. of TBAF resulted in the formation of difluorotriphenylstannate 22 which appeared as a sharp singlet at −160.5 ppm with satellite peaks (¹J_F−¹¹⁹_Sn= 2034.2 Hz, ¹J_F−¹¹⁷_Sn= 1940.2 Hz) in agreement with the values reported for the isolated 22⁴⁹ (spectrum b). Treatment of 16 with TBAF (1.5 equiv.) produced a broad peak of Ph₃SiF⁶¹ at −168.4 ppm which exists in equilibrium with Ph₃SiF₂⁻ 24 (−94.5 ppm) (spectrum c). The characteristic signal⁵⁴ for the pentavalent complex 24 was, however, clearly observed with 3 equiv. of TBAF [δ −94.6 ppm (¹J_F−²⁹_Si= 255.1 Hz) and −95.3 ppm (¹J_F−²⁹_Si= 255.1 Hz)] (spectrum d). In contrast, chlorogermane 13, under similar conditions, produced only small amount of the fluorine-bridged species 27 (−154.68 ppm) in addition to 26 (−201.6 ppm, spectrum e). Addition of another portion of TBAF and extra heating resulted in the broadening of the peak(s) and disappearance of the signal for 26 [spectrum f; note that the singlet at −125.9 ppm is most probably not related to germanium species since it was also observed in experiments of chlorosilane 16 with higher excess of TBAF (see also spectrum c)].

Figure 6.

¹⁹F NMR spectra of the reaction of Ph₃GeCl 13, Ph₃SiCl 16, and Ph₃SnCl 19 with TBAF in benzene-d₆ (50 °C/3 h).

It appears that Ph₃SnCl 19 is more susceptible than its silicon and germanium counterparts to form the reactive pentavalent complex 22 in benzene solution, even at low concentrations of fluoride ions. On the other hand, the silicon analogue 16, although it requires higher concentration of TBAF to afford the corresponding pentavalent complex 24 than the tin counterpart, is more prone to form hypervalent species than the analogous organogermane precursor. Since germane 13, silane 16, and stannane 19 substrates undergo fluoride-promoted coupling in toluene but require different reaction conditions (time/temperature), these results indicate that the differences in the coupling efficiencies of these substrates might reflects their ability to generate reactive hypervalent intermediates upon fluoride activation. The lower susceptibility of the organogermanes towards fluoride activation (coupling) is probably the result of Ge anomalously high electronegativity, as compared to other group 14 elements (C, 2.50; Si, 1.74; Ge, 2.02; Sn, 1.72),^7,15 which makes C-Ge bonds less polarized than C-Si and C-Sn bonds and therefore less prone to nucleophilic attacks.

To investigate the effect of water on the coupling of chlorogermanes with aryl halides, reactions of 13 (0.2 mmol) with TBAF (1.5 equiv.) in benzene-d₆ (2.0 mL) in the presence of various amounts of water (25, 50, and 100 µL) were also analyzed by ¹⁹F NMR (Figure 7, see SI). The conversion to Ph₃GeF 26 (δ −202.3 ppm) increased at higher water loading (spectrum a vs c vs e). It is known that fluorination of bulky chlorosilanes are also accelerated by the addition of water⁶¹ and hydrated TBAF showed enhanced nucleophilicity for converting alkyl halides into alkyl fluorides.⁶² Heating at 50 °C produced the same species 27 (−152.9 ppm) that was observed in the experiments without the additional water added (spectrum e, Figure 6). Washing the sample with D₂O resulted in the detection of 26 (the sole signal on ¹⁹F NMR) and digermoxane 28 (Scheme 1). When using higher concentration of TBAF (4.5 equiv; 50 °C/overnight), washing with D₂O resulted in disappearance of signal(s) on the ¹⁹F NMR spectrum.

To establish a role of the digermoxane 28 in the coupling of chlorogermanes, the reactions of 28 with aryl iodides were carried out. Thus, treatment of the commercially available 28 with 1 equiv. of 1-iodonapthalene 9a or 4-iodoanisole 9b in the presence of TBAF (7 equiv.) and Pd₂(dba)₃ in toluene afforded biaryls 10a (32%) or 10b (60%; based on the transfer of one phenyl group from 28) in addition to the homocoupling byproducts 11a (34%) and 11b (18%, Scheme 2). Analogous coupling of 28 with 3 and 6 equiv. of 9a also afforded 10a in 68% and 96% yield, respectively in addition to larger quantities of unreacted 9a and homocoupling byproduct 11a. Treatment of 28 with excess of 4-iodoanisole 9b gave similar results (e.g., coupling with 3 equiv. of 9b produced 10b in 92% yield). The fact that total yields of 10a or 10b do not exceed theoretical yields of 100% indicates that multiple transfers of phenyl groups from 28 did not occur. All attempts at changing coupling conditions (e.g. using wet toluene, THF or 1,4-dioxane at reflux as solvent as well as addition of Ag₂O/TBAF or NaOH as base) failed to increase the yield of 10a. It appears that although 28 can couple with aryl iodides, the pathway for cross-coupling between Ph₃GeCl 13 and aryl halides most likely involves other intermediates which could be responsible for the multiple transfer of the phenyl group.

Scheme 2.

Cross-coupling of hexaphenyldigermoxane 28 with aryl halides

Our data suggest that the fluoride-promoted cross-coupling of chlorogermanes (e.g., 13) in “wet” toluene involves displacement of Cl ligands from the Ge center by the nucleophilic fluoride ions to generate four-coordinate fluorogermanes (e.g., 26). This in turn leads to the hypervalent fluorogermanates (e.g. 25) and fluorine-bridged species of type 27. The germanates and/or fluorine-bridged species could be directly engaged in transmetalation with reactive aryl-Pd-X (X = halogen, OH) complex(es) to give cross-coupling products. Alternatively, hypervalent species of type 25 and/or 27 might react with water to generate the reactive fluoro(hydroxo)triphenylgermanate species or the triphenylgermanol hydrogen-bonded complexes to TBAF. The analogous hypervalent silicate species were proposed for the fluoride-promoted coupling of vinyl silanols.^6,40 Although a mechanism that will support the multiple transfer of the phenyl groups from the same metallic centre requires additional investigation, it is likely that the tin, silicon or germanium species with extra halogen ligands formed after each transmetalation cycle are rendered more reactive to efficiently transfer a second or third phenyl group from the Sn, Si or Ge atom.

In summary, we have demonstrated that (chloro)_4-n (phenyl)_ngermanes and silanes (n = 1, 2, or 3) as well as stannanes (n = 1, 2, 3, or 4) undergo Pd-catalyzed cross-couplings with aryl iodides and bromides in the presence of TBAF in "moist" toluene. The chlorophenylstannanes are more reactive than chlorophenylsilanes, which in turn are more effective than chlorophenylgermanes. One chloride ligand on either Ge or Si center allows efficient activation by fluoride to promote transfer of up to three aryl groups from germane or silicon. For the silanes and germanes reactivity increase with the number of halogen ligands on the Si or Ge center (PhMCl₃ > Ph₂MCl₂ > Ph₃MCl > Ph₄M, where M = Si or Ge). For the germanes and to some extent for the silanes, the reactions with addition of a measured amount of water showed increased overall yields and higher cross-coupling to homocoupling product ratios. Stannanes were found to be most reactive, and even tetraphenyltin, which lacks a halogen ligand, can transfer efficiently up to four phenyl groups during fluoride-promoted couplings with aryl halides. The methodology shows that organogermanes can render a coupling efficiency comparable to the more established stannane and silane counterparts. ¹⁹F NMR studies suggested formation of the fluorophenylgermanes and the hypervalent fluorogermanate species as possible intermediates.

Experimental Section

General Procedure for Coupling of Chlorophenylgermanes

Method A. Commercial TBAF (1M THF solution containing ca 5% wt of water, 7 equiv.) was added to a stirred solution of 0.14 mmol of PhGeCl₃ 12, or Ph₂GeCl₂ 6, or Ph₃GeCl 13, or PhMe₂GeCl 21, or Ph₄Ge 14 containing the appropriate halide 9a–i (1.1–4.4 equiv.; see Table 2, 5, and 6) and Pd₂(dba)₃ (0.05 equiv.) in toluene (3.0 mL) at ambient temperature under nitrogen atmosphere. The resulting brownish mixture was heated at 100 °C (oil bath) for 15 h. The volatiles were evaporated and the residue was partitioned (H₂O/CH₂Cl₂). The organic layer was dried (MgSO₄), evaporated and purified by column chromatography (hexane) to give cross-coupling products 10 followed by homocoupling byproducts 11. Yields of 10a–i and ratio of coupling products 10a–i to homocoupling byproducts 11a–i are given in Tables 2, 5, and 6. Representative typical procedures are included in supporting information.

Method B. Couplings were carried out as in Method A with the additional amount of water (~40 equiv.) added. Representative typical procedures are included in SI.

General Procedure for Coupling of Chlorophenylsilanes

Method A. Commercial TBAF (1M THF solution containing ca 5% wt of water, 7 equiv.) was added to a stirred solution of 0.14 mmol of PhSiCl₃ 15, or Ph₂SiCl₂ 7, or Ph₃SiCl 16, or Ph₄Si 14 containing the appropriate halide 9a–i (1.1–4.4 equiv.; see Table 3 and 7) and Pd₂(dba)₃ (0.05 equiv.) in toluene (3.0 mL) at ambient temperature under nitrogen atmosphere. The resulting brownish mixture was heated at 100 °C (oil bath) for 5 h. The volatiles were evaporated and the residue was partitioned (H₂O/CH₂Cl₂). The organic layer was dried (MgSO₄), evaporated and purified by column chromatography (hexane) to give cross-coupling products 10 followed by homocoupling byproducts 11. Yields of 10a–i and ratio of coupling products 10a–i to homocoupling byproducts 11a–i are given in Tables 3 and 7. Representative typical procedures are included in SI.

Method B. Couplings were carried out as in Method A with the additional amount of water (~40 equiv.) added. Representative typical procedures are included in SI.

General Procedure for Coupling of Chlorophenylstannanes and Tetraphenyltin

Method A. Commercial TBAF (1M THF solution containing ca 5% wt of water, 7 equiv.) was added to a stirred solution of 0.14 mmol of PhSnCl₃ 18, or Ph₂SnCl₂ 8, or Ph₃SiCl 19, or Ph₄Si 20 containing the appropriate halide 9a–i (1.1–4.4 equiv.; see Table 4 and 8) and Pd₂(dba)₃ (0.05 equiv.) in toluene (3.0 mL) at ambient temperature under nitrogen atmosphere. The resulting brownish mixture was heated at 100 °C (oil bath) for 2 h. The volatiles were evaporated and the residue was partitioned (H₂O/CH₂Cl₂). The organic layer was dried (MgSO₄), evaporated and purified by column chromatography (hexane) to give cross-coupling products 10 followed by homocoupling byproducts 11. Yields of 10a–i and ratio of coupling products 10a–i to homocoupling byproducts 11a–i are given in Tables 4 and 8. Representative typical procedures are included in SI.

Method B. Couplings were carried out as in Method A with the additional amount of water (~40 equiv.) added. Representative typical procedures are included in SI.

Procedure for Coupling of Hexaphenyldigermoxane

TBAF (1M/THF, 1.12 mL, 1.12 mmol) was added to a stirred solution of (Ph₃Ge)₂O (28; 100 mg, 0.16 mmol) containing 1-iodonaphthalene (9a; 23.4 µL, 40.1 mg, 0.16 mmol) and Pd₂(dba)₃ (7.3 mg, 0.008 mmol) in toluene (3.5 mL) at ambient temperature under nitrogen atmosphere. The resulting brownish mixture was heated at 100 °C (oil bath) for 15 h. The volatiles were evaporated and the residue was partitioned (H₂O/CH₂Cl₂). The organic layer was dried (MgSO₄), evaporated and purified by column chromatography (hexane) to give 10a (10.4 mg, 32%) followed by 11a (14.0 mg, 34%; 68% consumption of 9a).

Analogous treatment 28 (100 mg, 0.16 mmol) with 9a (70.2 µL, 122 mg, 0.48 mmol) gave 10a (22.2 mg, 68%) and 11a (39.5 mg, 32%).

Analogous treatment 28 (100 mg, 0.16 mmol) with 9a (140.4 µL, 244 mg, 0.96 mmol) gave 10a (31.3 mg, 96%) and 11a (98 mg, 40%).

Analogous treatment 28 (100 mg, 0.16 mmol) with 4-iodoanisole (9b; 37.4 mg, 0.16 mmol) gave 10b (17.6 mg, 60%) and 11b (6.1 mg, 18%).

Analogous treatment 28 (100 mg, 0.16 mmol) with 9b (112.3 mg, 0.48 mmol) gave 10b (27.1 mg, 92%) and 11b (27 mg, 26%).

Typical Procedure for the Reaction of Chlorotriphenylgermane with TBAF

TBAF (0.30 mL, 0.30 mmol; 1 M in THF) and H₂O (0.10 mL, 5.55 mmol) were added to a solution of Ph₃GeCl 13 (68.5 mg, 0.20 mmol) in benzene or benzene-d₆ (2 mL) and the resulting mixture was stirred at 50 °C for 3 h. After cooling the solution was extracted with H₂O and the separated organic layer was dried (Na₂SO₄), and volatiles were evaporated to give a crude mixture of 26 and 28 (~1:3; ¹⁹F and ¹³C NMR) in addition to the small amount of other byproducts (~10%). Column chromatography (EtOAc/hexane, 1:9) afforded hexaphenyldigermoxane 28⁶³ (31 mg, 51%) as white crystals with data identical to the commercial sample: m.p. 178–180 °C (Lit.⁶³ 180–182 °C). ¹H NMR δ 7.24–7.31 (m, 6H), 7.37 (tt, J = 7.5 Hz, 1.9 Hz, 3H), 7.43–7.48 (m, 6H); ¹³C NMR (CDCl₃) δ 128.2, 129.5, 134.6, 137.7; ¹³C NMR (benzene-d₆) 128.5, 129.8, 134.9, 138.1.

Analogous treatment (50 °C, overnight) of 13 (68.5 mg, 0.20 mmol) in benzene (2 mL) with TBAF (0.90 mL, 0.90 mmol; 1 M in THF) and H₂O (0.10 mL, 5.55 mmol) gave 28 (51 mg, 82%) which crystallized directly from benzene solution (after washing) with H₂O upon slow evaporation.

Fluorotriphenylgermane (26)

A suspension of commercially available hexaphenyldigermoxane 28 (120 mg, 0.19 mmol) in MeOH (2 mL) in a polyethylene (NALGENE®) screw-capped vial was chilled for 15 min at 0 °C. Aqueous HF (48 wt %; 55 µL, 1.5 mmol,) was added and the mixture was slowly warmed to ambient temperature. After stirring for 3 h, water was added and the resulting white precipitate was filtered off and washed with additional portions of water to give 26⁵⁶ (108.0 mg, 87%): m.p. 72–74 °C (Lit.⁵⁶ 77–78 °C); ¹H NMR (benzene-d₆) δ 7.00–7.10 (m, 9H), 7.53–7.58 (m, 6H); ¹³C NMR (benzene-d₆) δ 128.9, 130.8, 134.5 (³J_F-C = 1.5 Hz), 134.6 (²J_F-C = 13.9 Hz); ¹⁹F NMR (benzene-d₆) δ −202.24 (s);