Highly Chemoselective Reduction of Amides (primary, Secondary, Tertiary) to Alcohols Using SmI2/amine/H2O Under Mild Conditions

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2014 Jan 28

PMID 24460078

Citations 21

Authors

Michal Szostak

Malcolm Spain

Andrew J Eberhart

David J Procter

Affiliations

Soon will be listed here.

Abstract

Highly chemoselective direct reduction of primary, secondary, and tertiary amides to alcohols using SmI2/amine/H2O is reported. The reaction proceeds with C-N bond cleavage in the carbinolamine intermediate, shows excellent functional group tolerance, and delivers the alcohol products in very high yields. The expected C-O cleavage products are not formed under the reaction conditions. The observed reactivity is opposite to the electrophilicity of polar carbonyl groups resulting from the n(X) → π*(C═O) (X = O, N) conjugation. Mechanistic studies suggest that coordination of Sm to the carbonyl and then to Lewis basic nitrogen in the tetrahedral intermediate facilitate electron transfer and control the selectivity of the C-N/C-O cleavage. Notably, the method provides direct access to acyl-type radicals from unactivated amides under mild electron transfer conditions.

Citing Articles

Direct synthesis of α-functionalized amides via heteroatom-hydrogen insertion reactions using amide-sulfoxonium ylides.

Wu H, Xu Y, Lin A, Wang Z, Chen H, Zhu X Nat Commun. 2024; 15(1):10207.

PMID: 39587080 PMC: 11589769. DOI: 10.1038/s41467-024-54532-3.

Catalytic Enantioselective Intramolecular Oxa-Michael Reaction to α,β-Unsaturated Esters and Amides.

Su G, Formica M, Yamazaki K, Hamlin T, Dixon D J Am Chem Soc. 2023; 145(23):12771-12782.

PMID: 37253087 PMC: 10273320. DOI: 10.1021/jacs.3c03182.

Sequential Iron-Catalyzed C(sp)-C(sp) Cross-Coupling of Chlorobenzamides/Chemoselective Amide Reduction and Reductive Deuteration to Benzylic Alcohols.

Bisz E, Podchorodecka P, Li H, Ochedzan-Siodlak W, An J, Szostak M Molecules. 2023; 28(1).

PMID: 36615417 PMC: 9821805. DOI: 10.3390/molecules28010223.

Benzoates as photosensitization catalysts and auxiliaries in efficient, practical, light-powered direct C(sp)-H fluorinations.

Yakubov S, Stockerl W, Tian X, Shahin A, Mandigma M, Gschwind R Chem Sci. 2022; 13(47):14041-14051.

PMID: 36540818 PMC: 9728569. DOI: 10.1039/d2sc05735b.

Synthesis of (-)-halichonic acid and (-)-halichonic acid B.

Reber K, Niner E Beilstein J Org Chem. 2022; 18:1629-1635.

PMID: 36530535 PMC: 9727271. DOI: 10.3762/bjoc.18.174.

References

Spletstoser J, White J, Tunoori A, Georg G . Mild and selective hydrozirconation of amides to aldehydes using Cp2Zr(H)Cl: scope and mechanistic insight. J Am Chem Soc. 2007; 129(11):3408-19. PMC: 2626624. DOI: 10.1021/ja066362+. View

Sautier B, Lyons S, Webb M, Procter D . Radical cyclization cascades of unsaturated Meldrum's acid derivatives. Org Lett. 2011; 14(1):146-9. DOI: 10.1021/ol2029367. View

Balaraman E, Gunanathan C, Zhang J, Shimon L, Milstein D . Efficient hydrogenation of organic carbonates, carbamates and formates indicates alternative routes to methanol based on CO2 and CO. Nat Chem. 2011; 3(8):609-14. DOI: 10.1038/nchem.1089. View

Park S, Brookhart M . Development and mechanistic investigation of a highly efficient iridium(V) silyl complex for the reduction of tertiary amides to amines. J Am Chem Soc. 2011; 134(1):640-53. DOI: 10.1021/ja209567m. View

Carey J, Laffan D, Thomson C, Williams M . Analysis of the reactions used for the preparation of drug candidate molecules. Org Biomol Chem. 2006; 4(12):2337-47. DOI: 10.1039/b602413k. View

Dahlen A, Hilmersson G . Instantaneous SmI2/H2O/amine-mediated reductions in THF. Chemistry. 2003; 9(5):1123-8. DOI: 10.1002/chem.200390129. View

Addis D, Das S, Junge K, Beller M . Selective reduction of carboxylic acid derivatives by catalytic hydrosilylation. Angew Chem Int Ed Engl. 2011; 50(27):6004-11. DOI: 10.1002/anie.201100145. View

Szostak M, Spain M, Procter D . Recent advances in the chemoselective reduction of functional groups mediated by samarium(II) iodide: a single electron transfer approach. Chem Soc Rev. 2013; 42(23):9155-83. DOI: 10.1039/c3cs60223k. View

Barbe G, Charette A . Highly chemoselective metal-free reduction of tertiary amides. J Am Chem Soc. 2007; 130(1):18-9. DOI: 10.1021/ja077463q. View

10.

Das S, Join B, Junge K, Beller M . A general and selective copper-catalyzed reduction of secondary amides. Chem Commun (Camb). 2012; 48(21):2683-5. DOI: 10.1039/c2cc17209g. View

11.

Motoyama Y, Mitsui K, Ishida T, Nagashima H . Self-encapsulation of homogeneous catalyst species into polymer gel leading to a facile and efficient separation system of amine products in the Ru-catalyzed reduction of carboxamides with polymethylhydrosiloxane (PMHS). J Am Chem Soc. 2005; 127(38):13150-1. DOI: 10.1021/ja054453l. View

12.

Ankner T, Said Stalsmeden A, Hilmersson G . Selective cleavage of 3,5-bis-(trifluoromethyl)benzylcarbamate by SmI2-Et3N-H2O. Chem Commun (Camb). 2013; 49(61):6867-9. DOI: 10.1039/c3cc41642a. View

13.

Pelletier G, Bechara W, Charette A . Controlled and chemoselective reduction of secondary amides. J Am Chem Soc. 2010; 132(37):12817-9. DOI: 10.1021/ja105194s. View

14.

Das S, Addis D, Junge K, Beller M . Zinc-catalyzed chemoselective reduction of tertiary and secondary amides to amines. Chemistry. 2011; 17(43):12186-92. DOI: 10.1002/chem.201101143. View

15.

John J, Bergens S . A highly active catalyst for the hydrogenation of amides to alcohols and amines. Angew Chem Int Ed Engl. 2011; 50(44):10377-80. DOI: 10.1002/anie.201103137. View

16.

Ito M, Ootsuka T, Watari R, Shiibashi A, Himizu A, Ikariya T . Catalytic hydrogenation of carboxamides and esters by well-defined Cp*Ru complexes bearing a protic amine ligand. J Am Chem Soc. 2011; 133(12):4240-2. DOI: 10.1021/ja1117254. View

17.

Molander G, Harris C . Sequencing Reactions with Samarium(II) Iodide. Chem Rev. 1996; 96(1):307-338. DOI: 10.1021/cr950019y. View

18.

Krackl S, Someya C, Enthaler S . Reductive cleavage of amides to alcohols and amines catalyzed by well-defined bimetallic molybdenum complexes. Chemistry. 2012; 18(48):15267-71. DOI: 10.1002/chem.201202857. View

19.

Das S, Wendt B, Moller K, Junge K, Beller M . Two iron catalysts are better than one: a general and convenient reduction of aromatic and aliphatic primary amides. Angew Chem Int Ed Engl. 2012; 51(7):1662-6. DOI: 10.1002/anie.201108155. View

20.

Evans W . The importance of questioning scientific assumptions: some lessons from f element chemistry. Inorg Chem. 2007; 46(9):3435-49. DOI: 10.1021/ic062011k. View