Abstract
We report the conversion of amides to carboxylic acids using nonprecious metal catalysis. The methodology strategically employs a nickel-catalyzed esterification using 2-(trimethylsilyl)-ethanol, followed by a fluoride-mediated deprotection in a single-pot operation. This approach circumvents catalyst poisoning observed in attempts to directly hydrolyze amides using nickel catalysis. The selectivity and mildness of this transformation are shown through competition experiments and the net-hydrolysis of a complex valine-derived substrate. This strategy addresses a limitation in the field with regard to functional groups accessible from amides using transition metal-catalyzed C–N bond activation and should prove useful in synthetic applications.
Graphical Abstract
Despite being well-known for their pronounced stability, amides have recently become valuable synthetic building blocks in transition-metal-catalyzed reactions.1 An array of carbon–carbon and carbon–heteroatom bond-forming reactions using amides have now been disclosed using palladium,2 rhodium,3 or nickel4 catalysis. Figure 1 highlights several functional group conversions beginning from amides that can now be achieved using nonprecious metal catalysis.4a–c,g,l,n,s Although several methodologies have been reported in recent years, one of the most fundamental transformations, namely, the conversion of amides to carboxylic acids,5 has not yet been disclosed using transition metal-catalyzed C–N bond activation. We report a means to achieve this transformation using nickel catalysis.
Figure 1.
Select examples of recent advances in the nickel-catalyzed activation of amides.
Our studies commenced with attempts to modify our previously established protocol for the conversion of amides to esters.4a,l Specifically, we evaluated the activation of amide 1 using Ni(cod)2 and the N-heterocyclic carbene ligand SIPr, with water as a nucleophile (Figure 2). Unfortunately, we did not observe the formation of the desired product, benzoic acid (2). This was surprising given that many oxygen nucleophiles have been used in nickel-catalyzed amide esterification reactions. To further assess if the direct conversion to the carboxylic acid was possible, additional experiments were performed involving the nickel-catalyzed esterification of amide 1 using MeOH as the nucleophile. In the absence of any additive, the reaction proceeded as expected to give ester 3 in 85% yield. However, when the reaction was carried out with 0.5 equiv of benzoic acid (2) as an additive, the esterification failed, indicative of catalyst poisoning. Recognizing the incompatibility of the carboxylic acid functional group with the catalyst system, we sought to develop an alternative strategy to effect the conversion of amides to carboxylic acids using nickel catalysis.
Figure 2.
Initial studies and control experiments for the nickel- catalyzed hydrolysis of amides. Conditions: amide 1 (1.0 equiv), Ni(cod)2 (10 mol%), SIPr (10 mol%), methanol or water (1.2 equiv), and toluene (1.0 M) heated at 80 °C for 12 or 16 h in a sealed vial under an atmosphere of N2. aYields were determined by 1H NMR analysis using 1,3,5-trimethoxybenzene as an external standard.
An alternative one-pot approach to achieve the amide to carboxylic acid conversion was conceived, as depicted using amide substrate 4 (Table 1). Strategically, this process was designed to proceed by nickel-catalyzed esterification to give protected carboxylic acid 5, which would then be deprotected in the same reaction vessel through the addition of a mild fluoride source. Table 1 shows select results using two types of nucleophiles, each bearing a silyl group. Although the use of trimethylsilanol (TMS–OH) as a nucleophile failed to generate the desired ester intermediate 5 (entry 1), the use of 2-(trimethylsilyl)ethanol (TMS–ethanol, 7) proved more fruitful (entries 2 and 3). For example, using standard reaction conditions at a temperature of 80 °C, the conversion of amide 4 to carboxylic acid 6 could be achieved in 83% yield using a straightforward esterification/TBAF-mediated deprotection protocol (entry 2).6 Increasing the temperature to 110 °C gave naphthyl carboxylic acid 6 in a slightly improved yield of 87% (entry 3).
Table 1.
Optimization of Reaction Conditionsa
 | ||||
|---|---|---|---|---|
| entry | alcohol | temp (°C) | yield of 5b | yield of 6b |
| 1 | TMS-OH | 80 | 0% | - |
| 2 | TMS-ethanol (7) | 80 | 0% | 83% |
| 3 | TMS-ethanol (7) | 110 | 0% | 87% |
Conditions: amide 4(1.0 equiv), Ni(cod)2 (10 mol%), SIPr (10 mol %), alcohol (1.25 equiv), and toluene (1.0 M) heated at 80–110 °C for 24 h in a sealed vial under an atmosphere of N2; TBAF (2.5 equiv) at 23 °C for 2 h.
Yields were determined by 1H NMR analysis using 1,3,5-trimethoxybenzene as an external standard.
Having identified an operationally simple means to achieve the nickel-catalyzed conversion of amides to carboxylic acids, we evaluated several benzamide derivatives7 in the methodology (Figure 3). The use of the parent naphthyl substrate 4 (Table 1) furnished 2-naphthoic acid (6) in 90% isolated yield. Benzoic acids 28 and 10–12 could also be accessed through this transformation. The formation of carboxylic acids 11 and 12, in 84% and 79% yield, respectively, highlights the tolerance of electron-withdrawing and electron-donating groups. Additionally, the use of a quinoline substrate gave rise to 13 in 60% yield, thus demonstrating the tolerance of the methodology toward an important nitrogen-containing heterocycle.
Figure 3.
Scope of the amide substrate. Conditions: amide 8 (1.0 equiv), Ni(cod)2 (10 mol%), SIPr (10 mol%), 7 (1.25 equiv), and toluene (1.0 M) heated at 110 °C for 24 h in a sealed vial under an atmosphere of N2; TBAF (2.5 equiv) at 23 °C for 2 h. Yields reflect the average of two isolation experiments. aYield was determined by 1H NMR analysis using 1,3,5-trimethoxybenzene as an external standard.
As shown in Table 2, variation of the amide N-substituents was also possible. The use of benzamide 14a, bearing an n-butyl group in place of a methyl group, afforded benzoic acid (2) in 77% yield (entry 1). Additionally, the more sterically encumbered N-isopropyl benzamide seen in 14b (entry 2) and the indoline present in 14c (entry 3) were tolerated. Moreover, tosyl derivative 14d could be employed in the methodology to provide 2 in 71% yield (entry 4).
Table 2.
Variation of the N-Substituentsa
 | ||
|---|---|---|
| entry | substrate | yield of 2 |
| 1 |  |
77% |
| 2 |  |
60% |
| 3 |  |
56% |
| 4 |  |
71% |
Conditions: amides 14a–d(1.0 equiv), Ni(cod)2 (10 mol%), SIPr (10 mol%), 7 (1.25 equiv), and toluene (1.0 M) heated at 110 °C for 24 h in a sealed vial under an atmosphere of N2; TBAF (2.5 equiv) at 23 °C for 2 h. Yields reflect the average of two isolation experiments.
Competition experiments were performed to gauge substrate-based selectivity in the nickel-catalyzed conversion of amides to carboxylic acids (Figure 4). The first involved benzamide 1 and cyclohexyl amide 15, which gave a selective reaction of 1 to furnish net-hydrolyzed product 2 in 86% yield. Aliphatic amide 15 was recovered in quantitative yield. We also performed a competition experiment using tertiary amide 1 and secondary amide 16. This led to selective reaction of 1 to give benzoic acid (2), with quantitative recovery of secondary amide 16. The ability to preferentially manipulate subclasses of amides through selective conversion to carboxylic acids should prove useful in synthetic applications.
Figure 4.
Competition experiments demonstrate substrate selectivity. Conditions: amide 1 (1.0 equiv), 15 or 16 (1.0 equiv), Ni(cod)2 (10 mol%), SIPr (10 mol%), 7 (1.25 equiv), and toluene (1.0 M) heated at 110 °C for 24 h in a sealed vial under an atmosphere of N2; TBAF (2.5 equiv) at 23 °C for 2 h. Yields reflect the average of two isolation experiments.
One further evaluation of the methodology to assess mildness and selectivity is shown in Figure 5. Substrate 17 (derived from L-valine)4a bearing an amide, an ester, and an epimerizable stereocenter was subjected to our typical reaction protocol. This gave benzoic acid (2) and amine 18 in 67% and 72% yield, respectively. Of note, amine 18 was recovered in 99% ee, and the ester functional group remained intact. As classical hydrolysis conditions are often incompatible with esters and epimerizable stereocenters,5 this result underscores the mild nature of our strategy for the conversion of amides to carboxylic acids.
Figure 5.
Cleavage of a valine-derived amide in the presence of an ester. Conditions: amide 17 (1.0 equiv), Ni(cod)2 (20 mol%), SIPr (20 mol%), 7 (1.25 equiv), and toluene (1.0 M) heated at 110 °C for 24 h in a sealed vial under an atmosphere of N2; TBAF (2.5 equiv) at 23 °C for 2 h. Yields reflect the average of two isolation experiments.
We have developed an operationally simple procedure to convert amides to carboxylic acids using nonprecious metal catalysis. The methodology strategically circumvents catalyst poisoning through the use of a nickel-catalyzed esterification, followed by a fluoride-mediated deprotection in a single-pot operation. We have demonstrated that a variety of amides with aryl groups and N-substituents can be employed in this transformation. Additionally, we have shown the process can be utilized to cleave amides in a mild and selective manner. This strategy offers a practical means to convert subclasses of amides to carboxylic acids while addressing a limitation with regard to functional groups accessible using transition-metal-catalyzed amide C–N bond activation.
Supplementary Material
ACKNOWLEDGMENTS
The authors thank the NIH-NIGMS (R01-GM117016 to N.K.G. and Supplement to R.R.K), the Trueblood Family (N.K.G.), the Foote family (A.S.B), and the University of California, Los Angeles, for financial support. These studies were supported by shared instrumentation grants from the NSF (CHE-1048804) and the NIH NCRR (S10RR025631).
Footnotes
Supporting Information
The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.orglett.0c00885.
Experimental details and compound characterization data (PDF)
Complete contact information is available at: https://pubs.acs.org/10.1021/acs.orglett.0c00885
The authors declare no competing financial interest.
Contributor Information
Rachel R. Knapp, Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095-1569, United States
Ana S. Bulger, Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095-1569, United States
Neil K. Garg, Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095-1569, United States;.
REFERENCES
- (1).For recent reviews, see:; (a) Dander JE; Garg NK Breaking amides using nickel catalysis. ACS Catal. 2017, 7, 1413–1423. [DOI] [PMC free article] [PubMed] [Google Scholar]; (b) Meng G; Shi S; Szostak M Cross-coupling of amides by N–C bond activation. Synlett 2016, 27, 2530–2540. [Google Scholar]; (c) Takise R; Muto K; Yamaguchi J Cross-coupling of aromatic esters and amides. Chem. Soc. Rev 2017, 46, 5864–5888. [DOI] [PubMed] [Google Scholar]; (d) Kaiser D; Bauer A; Lemmerer M; Maulide N Amide activation: an emerging tool for chemoselective synthesis. Chem. Soc. Rev 2018, 47, 7899–7925. [DOI] [PubMed] [Google Scholar]
- (2).For Pd-catalyzed amide C–N bond activations, see:; (a) Li X; Zou G Acylative Suzuki coupling of amides: acyl-nitrogen activation via synergy of independently modifiable activating groups. Chem. Commun 2015, 51, 5089–5092. [DOI] [PubMed] [Google Scholar]; (b) Yada A; Okajima S; Murakami M Palladium-catalyzed intramolecular insertion of alkenes into the carbon–nitrogen bond of β-lactams. J. Am. Chem. Soc 2015, 137, 8708–8711. [DOI] [PubMed] [Google Scholar]; (c) Meng G; Szostak M Palladium-catalyzed Suzuki–Miyaura coupling of amides by carbon–nitrogen cleavage: general strategy for amide N–C bond activation. Org. Biomol. Chem 2016, 14, 5690–5705. [DOI] [PubMed] [Google Scholar]; (d) Meng G; Szostak M General olefin synthesis by the palladium-catalyzed Heck reaction of amides: sterically-controlled chemoselective N–C activation. Angew. Chem., Int. Ed 2015, 54, 14518–14522. [DOI] [PubMed] [Google Scholar]; (e) Meng G; Szostak M Sterically controlled Pd-catalyzed chemoselective ketone synthesis via N–C cleavage in twisted amides. Org. Lett 2015, 17, 4364–4367. [DOI] [PubMed] [Google Scholar]; (f) Liu C; Meng G; Liu Y; Liu R; Lalancette R; Szostak R; Szostak M N-Acylsaccharins: stable electrophilic amide-based acyl transfer reagents in Pd-catalyzed Suzuki–Miyaura coupling via N–C cleavage. Org. Lett 2016, 18, 4194–4197. [DOI] [PubMed] [Google Scholar]; (g) Lei P; Meng G; Szostak M General method for the Suzuki–Miyaura cross-coupling of amides using commercially available, air- and moisture-stable palladium/ NHC (NHC = N-heterocyclic carbene) complexes. ACS Catal. 2017, 7, 1960–1965. [DOI] [PubMed] [Google Scholar]; (h) Liu C; Liu Y; Liu R; Lalancette R; Szostak R; Szostak M Palladium-catalyzed Suzuki–Miyaura cross-coupling of N-mesylamides by N–C cleavage: electronic effect of the mesyl group. Org. Lett 2017, 19, 1434–1437. [DOI] [PubMed] [Google Scholar]; (i) Liu C; Meng G; Szostak M N-Acylsaccharins as amide-based arylating reagents via chemoselective N–C cleavage: Pd-catalyzed decarbonylative Heck reaction. J. Org. Chem 2016, 81, 12023–12030. [DOI] [PubMed] [Google Scholar]; (j) Meng G; Shi S; Szostak M Palladium-catalyzed Suzuki–Miyaura cross-coupling of amides via site-selective N–C bond cleavage by cooperative catalysis. ACS Catal. 2016, 6, 7335–7339. [Google Scholar]; (k) Cui M; Wu H; Jian J; Wang H; Liu C; Stelck D; Zeng Z Palladium-catalyzed Sonogashira coupling of amides: access to ynones via C–N bond cleavage. Chem. Commun 2016, 52, 12076–12079. [DOI] [PubMed] [Google Scholar]; (l) Wu H; Li Y; Cui M; Jian J; Zeng Z Suzuki coupling of amides via palladium-catalyzed C–N cleavage of N-acylsaccharins. Adv. Synth. Catal 2016, 358, 3876–3880. [Google Scholar]; (m) Shi S; Szostak M Decarbonylative cyanation of amides by palladium catalysis. Org. Lett 2017, 19, 3095–3098. [DOI] [PubMed] [Google Scholar]; (n) Lei P; Meng G; Ling Y; An J; Szostak M Pd-PEPPSI: Pd-NHC precatalyst for Suzuki– Miyaura cross-coupling reactions of amides. J. Org. Chem 2017, 82, 6638–6646. [DOI] [PubMed] [Google Scholar]; (o) Meng G; Szostak R; Szostak M Suzuki–Miyaura cross-coupling of N-acylpyrroles and pyrazoles: planar, electronically activated amides in catalytic N–C cleavage. Org. Lett 2017, 19, 3596–3599. [DOI] [PubMed] [Google Scholar]; (p) Meng G; Lalancette R; Szostak R; Szostak M N-Methylamino pyrimidyl amides (MAPA): highly reactive, electronically-activated amides in catalytic N–C(O) cleavage. Org. Lett 2017, 19, 4656–4659. [DOI] [PubMed] [Google Scholar]; (q) Osumi Y; Liu C; Szostak M N-Acylsuccinimides: twist-controlled, acyl transfer reagents in Suzuki– Miyaura cross-coupling by N–C amide bond activation. Org. Biomol. Chem 2017, 15, 8867–8871. [DOI] [PubMed] [Google Scholar]; (r) Lei P; Meng G; Ling Y; An J; Nolan SP; Szostak M General method for the Suzuki–Miyaura cross-coupling of primary amide-derived electrophiles enabled by [Pd(NHC)(cin)–Cl] at room temperature. Org. Lett 2017, 19, 6510–6513. [DOI] [PubMed] [Google Scholar]; (s) Li X; Zou G Palladium-catalyzed acylative cross-coupling of amides with diarylboronic acids and sodium tetraarylborates. J. Organomet. Chem 2015, 794, 136–145. [Google Scholar]; (t) Liu C; Li G; Shi S; Meng G; Lalancette R; Szostak R; Szostak M Acyl and decarbonylative Suzuki coupling of N-acetyl amides: Electronic tuning of twisted, acyclic amides in catalytic carbon–nitrogen bond cleavage. ACS Catal. 2018, 8, 9131–9139. [Google Scholar]; (u) Meng G; Szostak M Palladium/NHC (NHC = N-heterocyclic carbene)-catalyzed β-alkyl Suzuki cross-coupling of amides by selective N–C bond cleavage. Org. Lett 2018, 20, 6789–6793. [DOI] [PubMed] [Google Scholar]; (v) Shi S; Szostak M Decarbonylative borylation of amides by palladium catalysis. ACS Omega 2019, 4, 4901–4907. [DOI] [PMC free article] [PubMed] [Google Scholar]; (w) Zhou T; Li G; Nolan SP; Szostak M [Pd(NHC)(acac)Cl]: well-defined, air-stable, and readily available precatalysts for Suzuki and Buchwald–Hartwig cross-coupling (transamidation) of amides and esters by N–C/O–C activation. Org. Lett 2019, 21, 3304–3309. [DOI] [PubMed] [Google Scholar]; (x) Rahman MM; Buchspies J; Szostak M N-Acylphthalimides: efficient acyl coupling reagents in Suzuki–Miyaura cross-coupling by N–C cleavage catalyzed by Pd-PEPPSI precatalysts. Catalysts 2019, 9, 129. [Google Scholar]; (y) Liu C; Lalancette R; Szostak R; Szostak M Sterically hindered ketones via palladium-catalyzed Suzuki–Miyaura cross-coupling of amides by N–C(O) activation. Org. Lett 2019, 21, 7976–7981. [DOI] [PubMed] [Google Scholar]; (z) Li G; Zhou T; Poater A; Cavallo L; Nolan SP; Szostak M Buchwald–Hartwig cross-coupling by air- and moisture-stable [Pd(NHC)(allyl)Cl] pre-catalysts: catalyst evaluation and mechanism. Catal. Sci. Technol 2020, 10, 710–716. [DOI] [PMC free article] [PubMed] [Google Scholar]
- (3).Meng G; Szostak M Rhodium-catalyzed C–H bond functionalization with amides by double C–H/C–N bond activation. Org. Lett 2016, 18, 796–799. [DOI] [PubMed] [Google Scholar]
- (4).For nickel-catalyzed reactions proceeding with cleavage of the amide C–N bond, see:; (a) Hie L; Fine Nathel NF; Shah TK; Baker EL; Hong X; Yang Y-F; Liu P; Houk KN; Garg NK Conversion of amides to esters by the nickel-catalysed activation of amide C–N bonds. Nature 2015, 524, 79–83. [DOI] [PMC free article] [PubMed] [Google Scholar]; (b) Weires NA; Baker EL; Garg NK Nickel-catalysed Suzuki–Miyaura coupling of amides. Nat. Chem 2016, 8, 75–79. [DOI] [PubMed] [Google Scholar]; (c) Baker EL; Yamano MM; Zhou Y; Anthony SM; Garg NK A two-step approach to achieve secondary amide transamidation enabled by nickel catalysis. Nat. Commun 2016, 7, 11554. [DOI] [PMC free article] [PubMed] [Google Scholar]; (d) Simmons BJ; Weires NA; Dander JE; Garg NK Nickel-catalyzed alkylation of amide derivatives. ACS Catal. 2016, 6, 3176–3179. [DOI] [PMC free article] [PubMed] [Google Scholar]; (e) Shi S; Szostak M Nickel-catalyzed diaryl ketone synthesis by N–C bond cleavage: direct Negishi cross-coupling of primary amides by site-selective N,N-di-Boc activation. Org. Lett 2016, 18, 5872–5875. [DOI] [PubMed] [Google Scholar]; (f) Shi S; Szostak M Efficient synthesis of diaryl ketones by nickel-catalyzed Negishi cross-coupling of amides via carbon–nitrogen bond cleavage at room temperature accelerated by solvent effect. Chem. - Eur. J 2016, 22, 10420–10424. [DOI] [PubMed] [Google Scholar]; (g) Hie L; Baker EL; Anthony SM; Desrosiers J-N; Senanayake C; Garg NK Nickel-catalyzed esterification of aliphatic amides. Angew. Chem., Int. Ed 2016, 55, 15129–15132. [DOI] [PMC free article] [PubMed] [Google Scholar]; (h) Dey A; Sasmal S; Seth K; Lahiri GK; Maiti D Nickel- catalyzed deamidative step-down reduction of amides to aromatic hydrocarbons. ACS Catal. 2017, 7, 433–437. [Google Scholar]; (i) Ni S; Zhang W; Mei H; Han J; Pan Y Ni-catalyzed reductive cross-coupling of amides with aryl iodide electrophiles via C–N bond activation. Org. Lett 2017, 19, 2536–2539. [DOI] [PubMed] [Google Scholar]; (j) Medina JM; Moreno J; Racine S; Du S; Garg NK Mizoroki–Heck cyclizations of amide derivatives for the introduction of quaternary centers. Angew. Chem., Int. Ed 2017, 56, 6567–6571. [DOI] [PMC free article] [PubMed] [Google Scholar]; (k) Hu J; Wang M; Pu X; Shi Z Nickel-catalysed retro-hydroamidocarbonylation of aliphatic amides to olefins. Nat. Commun 2017, 8, 14993. [DOI] [PMC free article] [PubMed] [Google Scholar]; (l) Weires NA; Caspi DD; Garg NK Kinetic modeling of the nickel-catalyzed esterification of amides. ACS Catal. 2017, 7, 4381–4385. [DOI] [PMC free article] [PubMed] [Google Scholar]; (m) Shi S; Szostak M Nickel-catalyzed Negishi cross-coupling of N-acylsuccinimides: stable, amide-based, twist-controlled acyl transfer reagents via N–C activation. Synthesis 2017, 49, 3602–3608. [Google Scholar]; (n) Dander JE; Baker EL; Garg NK Nickel-catalyzed transamidation of aliphatic amide derivatives. Chem. Sci 2017, 8, 6433–6438. [DOI] [PMC free article] [PubMed] [Google Scholar]; (o) Huang P-Q; Chen H Ni-catalyzed cross-coupling reactions of N-acylpyrrole-type amides with organoboron reagents. Chem. Commun 2017, 53, 12584–12587. [DOI] [PubMed] [Google Scholar]; (p) Deguchi T; Xin H-L; Morimoto H; Ohshima T Direct catalytic alcoholysis of unactivated 8-aminoquinoline amides. ACS Catal. 2017, 7, 3157–3161. [Google Scholar]; (q) Dander JE; Giroud M; Racine S; Darzi ER; Alvizo O; Entwistle D; Garg NK Chemoenzymatic conversion of amides to enantioenriched alcohols in aqueous medium. Commun. Chem 2019, 2, 82. [DOI] [PMC free article] [PubMed] [Google Scholar]; (r) Wang H; Zhang S; Hong X Computational studies on Ni-catalyzed amide C–N bond activation. Chem. Commun 2019, 55, 11330–11341. [DOI] [PubMed] [Google Scholar]; (s) Mehta MM; Boit TB; Dander JE; Garg NK Ni-catalyzed Suzuki–Miyaura cross- coupling of aliphatic amides on the benchtop. Org. Lett 2020, 22, 1–5. [DOI] [PMC free article] [PubMed] [Google Scholar]; (t) Yu C; Matsuo Y Nickel-catalyzed deaminative acylation of activated aliphatic amines with aromatic amides via C–N bond activation. Org. Lett 2020, 22, 950–955. [DOI] [PubMed] [Google Scholar]
- (5).(a) Steiger RE α-Aminodiethylacetic acid. Org. Synth 1942, 22, 13. [Google Scholar]; (b) Brown RS; Bennet AJ; Slebocka-Tilk H Recent perspectives concerning the mechanism of H3O+− and OH− promoted amide hydrolysis. Acc. Chem. Res 1992, 25, 481–488. [Google Scholar]; (c) Smith MB; March J Aliphatic nucleophilic substitution.” March’s Advanced Organic Chemistry; John Wiley & Sons, Inc.; 2001; pp 474–477. [Google Scholar]; (d) Slebocka-Tilk H; Neverov A; Brown RS Proton inventory study of the base-catalyzed hydrolysis of formamide. Consideration of the nucleophilic and general base mechanisms. J. Am. Chem. Soc 2003, 125, 1851–1858. [DOI] [PubMed] [Google Scholar]
- (6).See SI for experimental details.
- (7).Consistent with prior studies, this methodology using Ni/SIPr requires the use of benzamide-type substrates. Density functional theory (DFT) calculations suggest that the presence of an aromatic ring attached to the carbonyl enables nickel coordination and amide C–N bond cleavage; see reference 4a.
- (8).Reaction was also run on a 1.0 mmol scale, affording benzoic acid (2) in 72% isolated yield.
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