Decarboxylative Benzylations of Alkynes and Ketones

Abstract

Benzyl esters of propiolic and beta-keto acids undergo catalytic decarboxylative coupling when treated with appropriate palladium catalysts. Such decarboxylative couplings allow the benzylation of alkynes without the use of strong bases and/or organometallics. This allows the synthesis of sensitive benzylic alkynes that are prone to undergo isomerizations under basic conditions. Additionally, decarboxylation facilitates the site-specific benzylation of diketones and ketoesters under mild, base-free conditions. Ultimately, the methodology described expands our ability to cross-couple medicinally relevant heterocycles.

Transition Metal-Catalyzed Decarboxylative Allylation and Benzylation Reactions

“…157b Conversely, decarboxylative benzylations are still in their infancy; decarboxylative benzylations of phenols, 161 diphenylglycinate imines, 164 acetylides, 165 and ketones 165 have only recently been reported.…”

Production of Csp3–Csp3 Bonds through Palladium‐Catalyzed Tsuji–Trost‐Type Reactions of (Hetero)Benzylic Substrates

“…[41] The formation of Csp 3 -Csp 3 bonds, even those containing hindered quaternary carbon centers, occurred in fair to high yields [Equations (44) and (45)], the efficiency being, however, sensitive to the electronic properties of the aryl substituents [Equation (46)]. …”

“…[41] Either Pd(PPh 3 ) 4 or (η (78) to (81)]. [34] A domino reaction of this kind can lead mainly to the formation of a Csp The Chruma/Fields decarboxylative benzylation procedure for benzyl diphenylglycinate imines [Equation (48) and Equation (49)] has been extended to heteroaromatic benzylic substrates [Equation (82)], [42] whereas the Murakami domino reaction of 2-(alkynyl)aryl isocyanates [Equation (52)] has also been carried out with pyridin-3-ylmethanol [Equation (83)].…”

β‐Aryl Nitrile Construction via Palladium‐Catalyzed Decarboxylative Benzylation of α‐Cyano Aliphatic Carboxylate Salts

“…[8] Recently, Tunge et al reported an intramolecular decarboxylative benzylation of b-keto esters, but the benzyl groups participating in this chemistry were limited to benzyls with extend conjugations. [9] To the best of our knowledge, intermolecular decarboxylative benzylation of aliphatic carboxylates has not been explored. Because catalytic reactions involving pbenzyl-Pd intermediates are important and have drawn broad attention, [10] we were interested in the intermolecular decarboxylative benzylation of acyano aliphatic carboxylates.…”