Skip to main content
NCBI home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2012 Oct 24.
Published in final edited form as: Chemistry. 2011 Sep 27;17(44):12437–12443. doi: 10.1002/chem.201101554

Alkyne–Aldehyde Reductive C–C Coupling through Ruthenium-Catalyzed Transfer Hydrogenation: Direct Regio- and Stereoselective Carbonyl Vinylation to Form Trisubstituted Allylic Alcohols in the Absence of Premetallated Reagents

Joyce C Leung 1, Ryan L Patman 1, Brannon Sam 1, Michael J Krische 1,✉
PMCID: PMC3212945  NIHMSID: NIHMS332293  PMID: 21953608

Abstract

Nonsymmetric 1,2-disubstituted alkynes engage in reductive coupling to a variety of aldehydes under the conditions of ruthenium-catalyzed transfer hydrogenation by employing formic acid as the terminal reductant and delivering the products of carbonyl vinylation with good to excellent levels of regioselectivity and with complete control of olefin stereochemistry. As revealed in an assessment of the ruthenium counterion, iodide plays an essential role in directing the regioselectivity of C–C bond formation. Isotopic labeling studies corroborate reversible catalytic propargyl C–H oxidative addition in advance of the C–C coupling, and demonstrate that the C–C coupling products do not experience reversible dehydrogenation by way of enone intermediates. This transfer hydrogenation protocol enables carbonyl vinylation in the absence of stoichiometric metallic reagents.

Keywords: green chemistry, homogeneous catalysis, hydrogenation, ruthenium, transfer hydrogenation, vinylation

Introduction

Under hydrogenation and transfer-hydrogenation conditions, π-unsaturated reactants may serve as functional equivalents to organometallic reagents in diverse C–C bond-forming processes.[1] In the specific case of C=X (X=O, NR) vinylation,[1b] rhodium- or iridium-catalyzed hydrogenation of alkynes in the presence of carbonyl compounds or imines delivers allylic alcohols or allylic amines, respectively.[2,3] Notably, these transformations do not generate stoichiometric metallic by-products as they circumvent the use of discrete vinylmetal reagents.[4–6] This atom economy differentiates hydrogen-mediated C=X vinylation from the related rhodium-,[7] titanium-,[8] and nickel-catalyzed[9–11] alkyne-carbonyl reductive couplings, which employ reductants that are more mass-intensive, such as silanes, or even pyrophoric, such as borane and organozinc reagents.[7–11]

In recent studies from our laboratory, it was found that direct alkyne–carbonyl reductive coupling is possible under the conditions of ruthenium-catalyzed transfer hydrogenation, employing formic acid as the terminal reductant.[12–14] Notably, beyond alkyne–aldehyde reductive coupling mediated by formic acid, primary alcohol dehydrogenation was found to trigger alkyne hydrometallation to generate aldehyde–vinylruthenium pairs en route to products of carbonyl vinylation. In this way, carbonyl vinylation is achieved from the alcohol or aldehyde oxidation level. The ability to engage alcohols directly in C–C coupling bypasses discrete alcohol oxidation and, hence, is reminiscent of related “hydrogen auto-transfer” or “borrowing hydrogen” processes.[15]

Whereas previous studies focused primarily on the reductive coupling of 2-butyne, a symmetrical alkyne,[12a,b] it was found that the catalyst prepared from [Ru(TFA)2(CO)-(PPh3)2] (TFA = O2CCF3) and Bu4NI enables the regioselective reductive coupling of nonsymmetric alkynes and paraformaldehyde.[12c] Based on this result, a survey of higher aldehydes was undertaken. Herein, we report that ruthenium catalyzed transfer hydrogenation of nonsymmetric 1,2-disubstituted alkynes 1a–1f in the presence of aldehydes 2a–2d results in reductive coupling to furnish trisubstituted allylic alcohols 3a–3f, 4a–4f, 5a–5f, and 6a–6f with good to excellent levels of regioselectivity and with complete control of olefin geometry.

graphic file with name nihms332293u1.jpg

Results and Discussion

In an initial experiment aimed at probing the feasibility of developing a general regioselective process, phenylpropyne (1a) was exposed to aldehyde 2b in the presence of formic acid and substoichiometric quantities of [RuHCl(CO)-(PPh3)3]. However, a complex mixture of isomeric products 4a, iso-4a, and allyl-4a were isolated in low yield (Table 1, entry 1). In parallel studies on the reductive coupling of paraformaldehyde with nonsymmetric disubstituted alkynes,[12c] it was found that the use of tetrabutylammonium iodide as an additive led to improved regioselectivities. Based on this observation, the discrete ruthenium complexes [RuHX(CO)(PPh3)3] (X=Br and I) were prepared in a manner analogous to the corresponding chloride complex.[16a] These complexes were assessed in the catalytic coupling of phenylpropyne (1a) to aldehyde 2b under otherwise identical conditions to those employed by using [RuHCl(CO)(PPh3)3]. Although no improvement in regioselectivity was observed by using the bromide complex (Table 1, entry 2), the iodide complex provided 4a and iso-4a in a ratio of 17:1 but an increased proportion of allyl-4a was observed (Table 1, entry 3). Thus, to promote formation of a single isomeric product, use of the iodide complex alone was insufficient, prompting consideration of additional optimization strategies.

Table 1.

The effect of the counterion on the regio- and stereoselectivity of the catalytic reductive coupling reaction of phenylpropyne (1a) to aldehyde 2b through ruthenium-catalyzed transfer hydrogenation.[a]

graphic file with name nihms332293u2.jpg
Ru complex Additive Yield [%] 4a/iso-4a 4a/allyl-4a
1 graphic file with name nihms332293t1.jpg – 23 2:1 5:1
2 graphic file with name nihms332293t2.jpg – 31 2:1 6:1
3 graphic file with name nihms332293t3.jpg – 40 17:1 2:1
4 graphic file with name nihms332293t1.jpg C7F15CO2H 36 1:1 7:1
5 graphic file with name nihms332293t2.jpg C7F15CO2H 35 2:1 8:1
6 graphic file with name nihms332293t3.jpg C7F15CO2H 71 >20:1 8:1
Open in a new tab
[a]

Yields are of combined isomeric materials. Regio- and stereoselectivity was determined by 1H NMR analysis of the crude reaction mixtures. In general, low yields are due to incomplete conversion.

It is known that [RuH2(CO)(PPh3)3] reacts with trifluoro-acetic acid (HO2CCF3, TFAA) to form [RuH(TFA)(CO)-(PPh3)3] and elemental hydrogen [Eq. (1)],[16a] as is the reaction of [RuHCl(CO)(PPh3)3] with trifluoroacetic acid to form [RuCl(TFA)(CO)(PPh3)3] [Eq. (2)].[16b] Additionally, stoichiometric and catalytic reactions of [Ru(TFA)2(CO)-(PPh3)2] with alcohols are known to produce [RuH-(TFA)(CO)(PPh3)2] and an aldehyde or ketone [Eq. (3)].[17] Hence, the catalytic coupling of phenylpropyne (1a) to aldehyde 2b was attempted by using the ruthenium complexes [RuHX(CO)(PPh3)3] (X=Cl, Br, and I) in the presence of C7F15CO2H. It was hypothesized that counterion exchange would be rapid, and that different counterions might assist different steps in the catalytic cycle.

graphic file with name nihms332293e1.jpg (1)
graphic file with name nihms332293e2.jpg (2)
graphic file with name nihms332293e3.jpg (3)

In the event, addition of C7F15CO2H promoted no significant enhancement in regioselectivity in combination with the ruthenium-chloride or -bromide complexes, nor was the ratio of 4a/allyl-4a significantly improved (Table 1, entries 4 and 5). In contrast, the use of the ruthenium iodide complex in the presence of C7F15CO2H delivered 4a as a single regioisomer in 71% isolated yield with an enhanced 8:1 ratio of 4a/allyl-4a (Table 1, entry 6). These data suggest that the specific combination of iodide and carboxylate counterions is necessary to promote high levels of regioselectivity and conversion.

As attempts to prepare the discrete complex [Ru-(O2CR)2(I)(CO)(PPh3)2] (R=C7F15, CF3) were unsuccessful, experiments conducted from this point onward employed the catalyst generated in situ upon combination of [Ru-(TFA)2(CO)(PPh3)2] and Bu4NI. It was found that at lower concentrations, formation of allyl-4a was suppressed and good regiocontrol was retained. A minimum of two equivalents of the terminal reductant, formic acid, were necessary to achieve optimal yields of 4a. At lower loadings of formic acid, the yield of 4a and the ratio of 4a/allyl-4a deteriorate. Finally, the precise loading of iodide is also crucial in terms of suppressing the formation of both iso-4a and allyl-4a. Thus, by using [Ru(TFA)2(CO)(PPh3)2] (5 mol%), Bu4NI (10 mol%), and formic acid (200 mol%) in THF at 65°C, the desired trisubstituted allylic alcohol product 4a was generated as a single regioisomer in 75% yield with complete stereocontrol and in the absence of allyl-4a (Table 2).

Table 2.

The regio- and stereoselective catalytic reductive coupling reaction of nonsymmetric alkynes 1a–1f to aldehydes 2a–2d through ruthenium-catalyzed transfer hydrogenation.[a]

graphic file with name nihms332293f3.jpg
Open in a new tab
[a]

Yields are of the isolated material. Regio- and stereoselectivity was determined through 1H NMR analysis of the crude reaction mixtures.

[b]

The reaction was conducted for 16 h.

[c]

Bu4NI (5 mol%) was employed.

[d]

The reaction was conducted at a concentration of 1.0m.

[e]

The reaction was conducted at a concentration of 0.5m.

[f]

The reaction was conducted for 15 h.

[g]

The reaction was conducted at a concentration of 2.0m for 24 h.

[h]

The reaction was conducted at 45°C for 48 h.

[i]

HCO2H (150 mol%) was employed. See the Supporting Information for further experimental details.

To evaluate the generality of these conditions, the catalytic vinylation of aldehydes 2a–2d was conducted by using phenylpropyne (1a). The desired trisubstituted allylic alcohols 3a–6a were obtained in good yield with nearly exclusive formation of a single isomeric adduct and with complete stereocontrol. Encouraged by these results, 1,2-disubstituted alkynes 1b–1f, which possess aryl, heteroaryl, or alkyl substituents, were coupled to aldehydes 2a–2d. The corresponding trisubstituted allylic alcohols 4a–4f, 5a–5f, and 6a–6f were formed in moderate to good yields, and in most cases a single isomeric adduct predominates (Table 2). The remarkable regioselectivity of this catalytic system is underscored by the ability to differentiate the acetylenic termini of alkyne 1f, which incorporates CH2CH2OBn and CH3 groups, to form adducts 3f–6f in good yields and as single regioisomers in all cases, notwithstanding adduct 4f. Finally, whereas the aforementioned transformations were conducted by using 0.3 mmol of the aldehyde, the coupling of phenylpropyne (1a) to aldehyde 2b on a 3.0 mmol scale provided allylic alcohol 4a in a slightly higher 79% isolated yield with a comparable level of selectivity.

In previous studies on the coupling of 2-butyne to alcohols and aldehydes under the conditions of ruthenium-catalyzed C–C bond-forming transfer hydrogenation, it was found that dehydrogenation of the initially formed allylic alcohols could be induced to provide products of intermolecular alkyne hydroacylation from the alcohol or aldehyde oxidation level [Eq. (4)].[12b] These products of alkyne hydroacylation are not formed under the conditions used here. As previously observed, dehydrogenation of the initially formed allylic alcohol is suppressed by lower reaction temperatures (65 vs. 110°C) and shorter reaction times (20 vs. 30 h). Also, the presence of iodide and the use of formic acid, rather than isopropanol, as the terminal reductant may be significant, because these species may occupy a coordination site on ruthenium that would be required for β-hydride elimination.

graphic file with name nihms332293e4.jpg (4)

To gain further insight into the reaction mechanism a series of deuterium labeling experiments were performed. Exposure of phenylpropyne (1a) to deuterated aldehyde [D1]-2b under the standard conditions results in the formation of allylic alcohol [Dn]-4a with essentially complete retention of deuterium at the carbinol position (>98% D; Table 3, entry 1). This result suggests that 4a does not experience significant reversible oxidation–reduction by way of enone intermediates, which is important with regard to the potential development of related enantioselective processes. In a kinetic competition experiment, phenylpropyne (1a) reacts with [D1]-2b (50% D) under standard conditions to deliver [Dn]-4a (48% D), revealing no significant kinetic effect within the error limits of this experiment (Table 3, entry 2).

Table 3.

Deuterium labeling and competition kinetics experiments.[a]

graphic file with name nihms332293f4.jpg
Open in a new tab
[a]

The extent of D incorporation was evaluated by using 1H and D NMR spectroscopy. The indicated values represent the average of two runs. [D2]-formic acid in D2O (95 wt%); [D1]-formic acid in H2O (95 wt%).

Interestingly, exposure of phenylpropyne (1a) to 2b under standard conditions employing [D2]-formic acid results in partial deuterium incorporation of [Dn]-4a at the vinylic position (21% D) and, remarkably, at the vinylic methyl group (50% D with respect to all three hydrogen atoms; Table 3, entry 3). Given the likelihood that adventitious water compromises the extent of deuterium incorporation, results arising from the use of [D2]-formic acid and [D1]-formic acid were compared. Indeed, by using [D1]-formic acid, substantially less deuterium incorporation is observed at the vinylic position (1% D) and at the vinylic methyl group (8% D; Table 3, entry 4). This result suggests that it is primarily the acidic OD deuterium atom in [D2]-formic acid that is incorporated at the vinylic position of the product.

Reaction of the deuterated alkyne, [D3]-1a, and aldehyde 2b under the standard conditions delivers [Dn]-4a, which retains approximately half of the isotopic label at the vinylic methyl group (56% D with respect to all three hydrogen atoms) without significant transfer of deuterium to any other position (Table 3, entry 5). As anticipated in view of the initial labeling experiment (Table 3, entry 1), exposure of [D3]-1a to [D1]-2b under the standard conditions does not reduce the loss of deuterium at the vinylic methyl group (53 % D with respect to all three hydrogen atoms) and deuterium is retained at the carbinol position (>99% D; Table 3, entry 6). Coupling of the deuterated alkyne, [D3]-1a, and aldehyde 2b by using [D1]-formic acid does little to mitigate the loss of deuterium at the vinylic methyl group (60% D; Table 3, entry 7). In contrast, the use of [D2]-formic acid significantly suppresses the loss of deuterium at the vinylic methyl group (83 % D; Table 3, entry 8).

The accumulation of deuterium at the vinylic methyl group in [Dn]-4a (Table 3, entries 3 and 4) and the loss of deuterium at the vinylic methyl observed in the conversion of [D3]-1a into [Dn]-4a (Table 3, entries 5 and 6) may be accounted for on the basis of the indicated catalytic mechanism for H–D exchange (Scheme 1, right). Therein, a ruthenium(0) complex, generated upon H–I reductive elimination, engages alkyne 1a in C–H or C–D oxidative addition to the propargylic C–H or C–D bond, which results in the formation of a propargylruthenium hydride. Hydrogen–deuterium exchange then occurs with formic acid through discrete reversible protonation–deprotonation (equivalent to O–H oxidative addition/reductive elimination) or by way of six-centered transition state A. Subsequent C–H or C–D reductive elimination of the propargylruthenium hydride or deuteride releases the alkyne, which can enter the catalytic cycle for C–C coupling (see below).

Scheme 1.

Scheme 1

Open in a new tab

A plausible catalytic mechanism for the C–C coupling and the catalytic mechanism accounting for H–D exchange at the propargylic position of alkyne [D3]-1a in the specific case of deuterium loss.

This interpretation suggests that any accumulation or loss of deuterium at the propargylic position of alkyne 1a occurs prior to C–C coupling. To challenge this hypothesis, coupling product 4a was resubjected to the standard reaction conditions employing [D1]-formic acid or [D2]-formic acid. Analysis of the recovered 4a by 1H and D NMR spectroscopy revealed no incorporation of deuterium [Eq. (5)]. Additionally, alkyne 1a was exposed to the standard reaction conditions by using [D1]-formic acid in the absence of aldehyde 2b. The product of alkyne reduction, trans-β-methyl-styrene, was formed in 70% isolated yield in this reaction [Eq. (6)].

graphic file with name nihms332293e5.jpg (5)
graphic file with name nihms332293e6.jpg (6)

Although the extent of deuterium incorporation at the vinylic methyl group in trans-β-methylstyrene (4% D with respect to all three hydrogen atoms; Table 3, entry 5) is anticipated on the basis of previous observations (Table 3, entry 4), the extent of deuterium incorporation at the vinylic positions (25% D) is higher than that observed in the C–C coupling product [Dn]-4a under the same conditions. This is due to the fact that deuterium incorporation at the vinylic positions occurs after the initial reduction of 1a. Consistent with this interpretation, cis-β-methylstyrene is the major reduction product at low conversion. Thus, it would appear that the initially formed cis-olefin engages in hydrometallation to generate alkyl ruthenium species, which upon β-hydride elimination delivers trans-β-methylstyrene as the sole reduction product. Reversible hydrometallation–β-hydride elimination accounts for the increase in deuterium incorporation at the vinylic positions [Eq. (5)].

The collective results on isotopic labeling (Table 3, entries 4 and 5) are consistent with the indicated catalytic mechanism for aldehyde vinylation (Scheme 1). Therein, [Ru(TFA)(I)(CO)(PPh3)2], generated in situ through counterion exchange between [Ru(TFA)2(CO)(PPh3)2] and Bu4NI, engages in carboxylate exchange with formic acid to release trifluoroacetic acid and generate a ruthenium formate (not shown), which eliminates carbon dioxide to furnish [RuH(I)(CO)(PPh3)2]. This species may eliminate HI to generate zero-valent ruthenium, which catalyzes the H–D exchange at the propargylic position, as previously described. Alternatively, regioselective alkyne hydrometallation occurs to deliver a vinylruthenium intermediate that, upon carbonyl addition, provides the indicated ruthenium alkoxide. Trifluoroacetic acid mediated protonolysis of the ruthenium alkoxide releases the product of carbonyl vinylation and regenerates [Ru(TFA)(I)(CO)(PPh3)2] (Scheme 1).

The proposed hydrometallative mechanism for alkyne–carbonyl reductive coupling is corroborated by the stoichiometric conversion of [Ru(TFA)2(CO)(PPh3)2] into [Ru-(TFA)(H)(CO)(PPh3)2] under transfer hydrogenation conditions employing ethanol as the terminal reductant,[17b] and the subsequent reaction of [Ru(TFA)(H)(CO)(PPh3)2] with PhC≡CPh to provide the corresponding vinylruthenium complex (Scheme 2).[18b] The regioselectivity of hydrometallation, which favors placement of ruthenium adjacent to the aryl substituent in alkynes 1a–1e, may be driven by additional stabilization associated with the π-benzyl character of this intermediate. For alkyne 1f, the Lewis basic benzyl ether moiety is anticipated to direct the regioselectivity of the hydrometallation.[19] It should be noted that oxidative coupling pathways cannot be excluded on the basis of the available data and may account for contra-steric regiocontrol in the C–C coupling event.

Scheme 2.

Scheme 2

Open in a new tab

Established stoichiometric transformations that corroborate the proposed hydrometallative mechanism for alkyne-carbonyl reductive coupling.

Conclusion

A highly regio- and stereoselective alkyne-aldehyde reductive coupling protocol for the synthesis of trisubstituted allylic alcohols has been developed. Iodide counterions were shown to play an essential role in directing the regioselectivity of the C–C bond formation. Isotopic labeling studies corroborate the reversible catalytic propargyl C–H oxidative addition in advance of C–C coupling, and demonstrate that the C–C coupling products do not experience reversible dehydrogenation by way of enone intermediates. Based on these findings, asymmetric variants of this vinylation process appear feasible.

Experimental Section

See the Supporting Information for full experimental details.

Supplementary Material

Supplementary Information

Acknowledgments

Acknowledgement is made to the Robert A. Welch Foundation (F-0038), the NIH-NIGMS (RO1-GM069445) and the University of Texas at Austin Center for Green Chemistry and Catalysis.

Footnotes

Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201101554.

References

  • 1.For selected reviews on C–C bond-forming hydrogenation and transfer hydrogenation, see: Ngai MY, Kong JR, Krische MJ. J Org Chem. 2007;72:1063–1072. doi: 10.1021/jo061895m.Skucas E, Ngai MY, Komanduri V, Krische MJ. Acc Chem Res. 2007;40:1394–1401. doi: 10.1021/ar7001123.Patman RL, Bower JF, Kim IS, Krische MJ. Aldrichimica Acta. 2008;41:95–104.Shibahara F, Krische MJ. Chem Lett. 2008;37:1102–1107. doi: 10.1246/cl.2008.1102.Bower JF, Kim IS, Patman RL, Krische MJ. Angew Chem. 2008;121:36–48.Angew Chem Int Ed. 2008;48:34–46.Han SB, Kim IS, Krische MJ. Chem Commun. 2009:7278–7287. doi: 10.1039/b917243m.
  • 2.For hydrogen-mediated coupling of nonconjugated alkynes to carbonyl compounds and imines, see: Rhee JU, Krische MJ. J Am Chem Soc. 2006;128:10674–10675. doi: 10.1021/ja0637954.Skucas E, Kong JR, Krische MJ. J Am Chem Soc. 2007;129:7242–7743. doi: 10.1021/ja0715896.Barchuk A, Ngai MY, Krische MJ. J Am Chem Soc. 2007;129:8432–8433. doi: 10.1021/ja073018j.Ngai MY, Barchuk A, Krische MJ. J Am Chem Soc. 2007;129:12644–12645. doi: 10.1021/ja075438e.Han SB, Kong JR, Krische MJ. Org Lett. 2008;10:4133–4135. doi: 10.1021/ol8018874.Williams VM, Kong JR, Ko BJ, Mantri Y, Brodbelt JS, Baik MH, Krische MJ. J Am Chem Soc. 2009;131:16054–16062. doi: 10.1021/ja906225n.
  • 3.For hydrogen-mediated coupling of 1,3-enynes to carbonyl compounds and imines, see: Jang HY, Huddleston RR, Krische MJ. J Am Chem Soc. 2004;126:4664–4648. doi: 10.1021/ja0316566.Kong JR, Cho CW, Krische MJ. J Am Chem Soc. 2005;127:11269–11276. doi: 10.1021/ja051104i.Kong JR, Ngai MY, Krische MJ. J Am Chem Soc. 2006;128:718–719. doi: 10.1021/ja056474l.Komanduri V, Krische MJ. J Am Chem Soc. 2006;128:16448–16449. doi: 10.1021/ja0673027.Cho CW, Krische MJ. Org Lett. 2006;8:891–894. doi: 10.1021/ol052976s.Hong YT, Cho CW, Skucas E, Krische MJ. Org Lett. 2007;9:3745–3748. doi: 10.1021/ol7015548.Liu P, Krische MJ, Houk KN. Chem Eur J. 2011;17:4021–4029. doi: 10.1002/chem.201002741.
  • 4.For selected reviews on alkyne hydrometallation and carbometallation, see: Winterfeldt E. Synthesis. 1975:617–630.Zweifel G, Miller JA. In: Organic Reactions. Dauben WG, editor. Vol. 32. Wiley; New York: 1984. pp. 377–517.Knochel P. In: Comprehensive Organic Synthesis. Trost BM, Fleming I, editors. Vol. 4. Pergamon Press; Oxford: 1991. pp. 865–912.Eisch JJ. In: Comprehensive Organic Synthesis. Trost BM, Fleming I, Schreiber SL, editors. Vol. 8. Pergamon Press; Oxford: 1991. pp. 733–761.Negishi Ei, Kondakov DY. Chem Soc Rev. 1996;25:417–426.Dzhemilev UM, Ibragimov AG. In: Modern Reduction Methods. Andersson PG, Munslow PJ, editors. Wiley-VCH; Weinheim: 2008. pp. 447–489.
  • 5.Enantioselective aldehyde vinylation has been accomplished by using organozinc reagents, which are prepared by alkyne hydrometallation (R2BH or Cp2ZrHCl) with subsequent transmetallation to zinc by using ZnMe2. For reviews, see: Wipf P, Kendall C. Chem Eur J. 2002;8:1778–1784. doi: 10.1002/1521-3765(20020415)8:8<1778::aid-chem1778>3.0.co;2-h.Wipf P, Nunes RL. Tetrahedron. 2004;60:1269–1279.
  • 6.Isolated examples of rhodium-catalyzed addition reactions of vinylmetal reagents to aldehydes have been reported. References [a] and [f] report asymmetric transformations, however only modest enantioselectivities are observed: Sakai M, Ueda M, Miyaura N. Angew Chem. 1998;110:3475–3477. doi: 10.1002/(SICI)1521-3773(19981217)37:23<3279::AID-ANIE3279>3.0.CO;2-M.Angew Chem Int Ed. 1998;37:3279–3281. doi: 10.1002/(SICI)1521-3773(19981217)37:23<3279::AID-ANIE3279>3.0.CO;2-M.Batey RA, Thadani AN, Smil DV. Org Lett. 1999;1:1683–1686.Fürstner A, Krause H. Adv Synth Catal. 2001;343:343–350.Fujii T, Koike T, Mori A, Osakada K. Synlett. 2002:298–300.Takezawa A, Yamaguchi K, Ohmura T, Yamamoto Y, Miyaura N. Synlett. 2002:1733–1735.Duan HF, Xie JH, Shi WJ, Zhang Q, Zhou QL. Org Lett. 2006;8:1479–1481. doi: 10.1021/ol060360c.Xing CH, Liu TP, Zheng JR, Ng J, Eposito M, Hu QS. Tetrahedron Lett. 2009;50:4953–4957.
  • 7.For intramolecular rhodium-catalyzed alkyne –carbonyl reductive coupling employing silane as the reductant, see: Ojima I, Tzamarioudaki M, Tsai CY. J Am Chem Soc. 1994;116:3643–3644.
  • 8.a) For intramolecular titanium-catalyzed alkyne –carbonyl reductive coupling employing silane as the reductant, see: Crowe WE, Rachita MJ. J Am Chem Soc. 1995;117:6787–6788. b) for an associated study, see: Kablaoui NM, Buchwald SL. J Am Chem Soc. 1995;117:6785–6786.
  • 9.For intramolecular nickel-catalyzed alkyne-carbonyl reductive coupling employing organozinc reagents or silane as the reductant, see: Oblinger E, Montgomery J. J Am Chem Soc. 1997;119:9065–9066.Tang XQ, Montgomery J. J Am Chem Soc. 1999;121:6098–6099.Tang XQ, Montgomery J. J Am Chem Soc. 2000;122:6950–6954.Knapp-Reed B, Mahandru GM, Montgomery J. J Am Chem Soc. 2005;127:13156–13157. doi: 10.1021/ja054590i.
  • 10.For intermolecular nickel-catalyzed alkyne–carbonyl reductive coupling, see: Huang WS, Chan J, Jamison TF. Org Lett. 2000;2:4221–4223. doi: 10.1021/ol006781q.Miller KM, Huang WS, Jamison TF. J Am Chem Soc. 2003;125:3442–3443. doi: 10.1021/ja034366y.Takai K, Sakamoto S, Isshiki T. Org Lett. 2003;5:653–655. doi: 10.1021/ol0272996.Mahandru GM, Liu G, Montgomery J. J Am Chem Soc. 2004;126:3698–3699. doi: 10.1021/ja049644n.Luanphaisarnnont T, Nbubaku CO, Jamison TF. Org Lett. 2005;7:2937–2940. doi: 10.1021/ol050881k.Sa-ei K, Montgomery J. Org Lett. 2006;8:4441–4443. doi: 10.1021/ol061579u.Chaulagain MR, Sormunen GJ, Montgomery J. J Am Chem Soc. 2007;129:9568–9569. doi: 10.1021/ja072992f.
  • 11.For reviews of nickel-catalyzed alkyne–carbonyl reductive coupling, see: Montgomery J, Sormunen GJ. Top Curr Chem. 2007;279:1–23.Moslin RM, Miller-Moslin K, Jamison TF. Chem Commun. 2007:4441–4449. doi: 10.1039/b707737h.
  • 12.For ruthenium-catalyzed alkyne-carbonyl C–C coupling, see: Patman RL, Chaulagain MR, Williams VM, Krische MJ. J Am Chem Soc. 2009;131:2066–2067. doi: 10.1021/ja809456u.Williams VM, Leung JC, Patman RL, Krische MJ. Tetrahedron. 2009;65:5024–5029. doi: 10.1016/j.tet.2009.03.068.Bausch CC, Patman RL, Breit B, Krische MJ. Angew Chem. 2011;123:5805–5808. doi: 10.1002/anie.201101496.Angew Chem Int Ed. 2011;50:5687–5690. doi: 10.1002/anie.201101496.
  • 13.For other ruthenium-catalyzed C–C coupling reactions under transfer hydrogenation conditions, see: for dienes: Shibahara F, Bower JF, Krische MJ. J Am Chem Soc. 2008;130:6338–6339. doi: 10.1021/ja801213x.Shibahara F, Bower JF, Krische MJ. J Am Chem Soc. 2008;130:14120–14122. doi: 10.1021/ja805356j.Han H, Krische MJ. Org Lett. 2010;12:2844–2846. doi: 10.1021/ol101077v. for allenes and allenamides: Skucas E, Zbieg JR, Krische MJ. J Am Chem Soc. 2009;131:5054–5055. doi: 10.1021/ja900827p.Zbieg JR, McInturff EL. Org Lett. 2010;12:2514–2516. doi: 10.1021/ol1007235.Zbieg JR, McInturff EL, Leung JC, Krische MJ. J Am Chem Soc. 2011;133:1141–1144. doi: 10.1021/ja1104156.
  • 14.For related iridium-catalyzed C–C coupling reactions under transfer hydrogenation conditions, see: for dienes: Bower JF, Patman RL, Krische MJ. Org Lett. 2008;10:1033–1035. doi: 10.1021/ol800159w.Zbieg JR, Fukuzumi T. Adv Synth Catal. 2010;352:2416–2420. doi: 10.1002/adsc.201000599. for allylic carboxylates: Kim IS, Ngai MY, Krische MJ. J Am Chem Soc. 2008;130:6340–6341. doi: 10.1021/ja802001b.Kim IS, Ngai MY, Krische MJ. J Am Chem Soc. 2008;130:14891–14899. doi: 10.1021/ja805722e.Kim IS, Han SB, Krische MJ. J Am Chem Soc. 2009;131:2514–2520. doi: 10.1021/ja808857w.Lu Y, Kim IS, Hassan A, Del Valle DJ, Krische MJ. Angew Chem. 2009;121:5118–5121. doi: 10.1002/anie.200901648.Angew Chem Int Ed. 2009;48:5018–5021. doi: 10.1002/anie.200901648.Itoh J, Han SB, Krische MJ. Angew Chem. 2009;121:6431–6434.Angew Chem Int Ed. 2009;48:6313–6316. doi: 10.1002/anie.200902328.Hassan A, Lu Y, Krische MJ. Org Lett. 2009;11:3112–3115. doi: 10.1021/ol901136w.Bechem B, Patman RL, Hashmi S, Krische MJ. J Org Chem. 2010;75:1795–1798. doi: 10.1021/jo902697g.Zhang YJ, Yang JH, Kim SH, Krische MJ. J Am Chem Soc. 2010;132:4562. doi: 10.1021/ja100949e.Han SB, Han H, Krische MJ. J Am Chem Soc. 2010;132:1760–1761. doi: 10.1021/ja9097675.Han SB, Gao X, Krische MJ. J Am Chem Soc. 2010;132:9153–9156. doi: 10.1021/ja103299f. for allenes : Han SB, Kim IS, Han H, Krische MJ. J Am Chem Soc. 2009;131:6916–6917. doi: 10.1021/ja902437k. for recent applications in total synthesis: Lu Y, Krische MJ. Org Lett. 2009;11:3108–3111. doi: 10.1021/ol901096d.Harsh P, O'Doherty GA. Tetrahedron. 2009;65:5051–5055. doi: 10.1016/j.tet.2009.03.097.Han SB, Hassan A, Kim IS, Krische MJ. J Am Chem Soc. 2010;132:15559–15561. doi: 10.1021/ja1082798.Moran J, Preetz A, Mesch RA, Krische MJ. Nature Chem. 2011;3:287–290. doi: 10.1038/nchem.1001.
  • 15.In “hydrogen auto-transfer” reactions, alcohol dehydrogenation and nucleophile generation occur independently. Hence, conventional preactivated nucleophiles are required. These processes deliver products of formal alcohol substitution rather than carbonyl addition. For selected reviews, see: Guillena G, Ramón DJ, Yus M. Angew Chem. 2007;119:2410–2416. doi: 10.1002/anie.200603794.Angew Chem Int Ed. 2007;46:2358–2364. doi: 10.1002/anie.200603794.Hamid MHSA, Slatford PA, Williams JMJ. Adv Synth Catal. 2007;349:1555–1575.Nixon TD, Whittlesey MK, Williams JMJ. Dalton Trans. 2009:753–762. doi: 10.1039/b813383b.Dobereiner GE, Crabtree RH. Chem Rev. 2010;110:681–703. doi: 10.1021/cr900202j.Guillena G, Ramón DJ, Yus M. Chem Rev. 2010;110:1611–1641. doi: 10.1021/cr9002159. for related dehydrogenative coupling reactions of amines that also require preactivated nucleophiles, see: Li CJ. Acc Chem Res. 2009;42:335–344. doi: 10.1021/ar800164n.
  • 16.a) Dobson A, Robinson SD, Uttley MF. J Chem Soc Dalton Trans. 1975:370–377. [Google Scholar]; b) Robinson SR, Uttley MF. J Chem Soc Dalton Trans. 1973:1912–1920. [Google Scholar]
  • 17.For stoichiometric and catalytic reactions of [Ru(TFA)2(CO)-(PPh3)2] with alcohols to produce [RuH(TFA)(CO)(PPh3)2] and an aldehyde or ketone, see: Dobson A, Robinson SD, Uttley MF. J Chem Soc Dalton Trans. 1975:370–377.Dobson A, Robinson SD. Inorg Chem. 1977;16:137–142.
  • 18.For stoichiometric reactions of [HXRu(CO)(PR3)3] (X = halide or carboxylate) with alkynes to furnish vinylruthenium complexes, see: Dobson A, Moore DS, Robinson SD, Hursthouse MB, New L. J Organomet Chem. 1979;177:C8–C12.Dobson A, Moore DS, Robinson SD, Hursthouse MB, New L. Polyhedron. 1985;4:1119–1130.Deshpande SS, Gopinathan S, Gopinathan C. J Organomet Chem. 1991;415:265–270.Santos A, López J, Matas L, Ros J, Galán A, Echavarren AM. Organometallics. 1993;12:4215–4218.Santos A, López J, Montoya J, Noheda P, Romero A, Echavarren AM. Organometallics. 1994;13:3605–3615.
  • 19.Trost BM, Gutierrez AC, Ferreira EM. J Am Chem Soc. 2010;132:9206–9218. doi: 10.1021/ja103663h. [DOI] [PMC free article] [PubMed] [Google Scholar]; b) Trost BM, Ferreira EM, Gutierrez AC. J Am Chem Soc. 2008;130:16176–16177. doi: 10.1021/ja8078835. [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplementary Information
NIHMS332293-supplement-Supplementary_Information.pdf (11.5MB, pdf)

RESOURCES