Palladium-Catalyzed Diastereoselective Synthesis of 3-Arylbutanoic Acid Derivatives

Abstract

The first palladium-catalyzed diastereoselective conjugate addition of arylboronic acids to chiral imides is reported. The catalytic system employing 4-tert-butyloxazolidin-2-one as the chiral auxiliary in a mixed solvent system of MeOH/HO (1:3) under an air atmosphere provides the optically active 3-arylbutanoic acid derivatives in excellent yields with high diastereoselectivity.

Protodepalladation as a Strategic Elementary Step in Catalysis

“…60 Alternatively, a chiral amine co-catalyst can be used to activate the carbonyl and impart enantioselectivity. 61 Finally, addition of 4- tert -butyloxazolidin-2-one to the carbonyl as a chiral auxiliary also afforded enantioselective conjugate addition of arylboronic acids to linear alkenes with moderate to high ee’ s. 62 Recently, Yang and Zhang demonstrated the use of nitrostyrene and dienes derived from Meldrum’s acid as viable Michael acceptors for the asymmetric conjugate addition of arylboronic acids under Pd(II) catalysis using Pyox-derived ligands (Scheme 21iv and v). 63 Alkoxylation, acetoxylation and amidation of alkenes have been developed with alcohols, acetic acid and Cbz-protected amines as external nucleophiles, respectively.…”

Enantiopure 4‐oxazolin‐2‐ones and 4‐methylene‐2‐oxazolidinones as chiral building blocks in a divergent asymmetric synthesis of heterocycles

“…Chiral 1,3‐oxazolidin‐2‐ones have been widely used as efficient auxiliaries for the asymmetric synthesis of a large variety of enantiopure and highly functionalized carbonylic compounds . Likewise, the preparation of α‐amino alcohols and α‐amino acids has been designed based on the approach of the transformation of chiral 1,3‐oxazolidin‐2‐ones, which in turn can be obtained from optically pure α‐amino alcohols and α‐amino acids, among other substrates . The synthetic applicability of these heterocycles has increased with the development of new methods for their construction .…”

“…[1][2][3][4][5][6][7][8][9] Likewise, the preparation of α-amino alcohols and α-amino acids has been designed based on the approach of the transformation of chiral 1,3-oxazolidin-2-ones, [10][11][12][13] which in turn can be obtained from optically pure α-amino alcohols 10 and α-amino acids, among other substrates. [1][2][3][4][5][6][7][8][9] The synthetic applicability of these heterocycles has increased with the development of new methods for their construction. [14][15][16][17][18][19][20][21] Functionalized 4-methylene-1,3-oxazolidin-2-ones have also proven to be versatile synthons in the formation of diverse molecular systems.…”

Oxadiazinones As Chiral Auxiliaries: Chiral Templates For Asymmetric Conjugate Addition In The Synthesis Of (R)-(+)-Tolterodine

“…While this chiral template has proven to be very useful, the dominant chiral auxiliary that has been employed in chiral auxiliary mediated asymmetric conjugate additions is the Evans' oxazolidinone (10). [31][32][33][34][35][36][37][38] The Evans' auxiliary has proven to be the most versatile of all of the auxiliaries presented here. While catalytic asymmetric conjugate addition methods are continuing to increase in their applications, the Evans' oxazolidinone remains as a viable option to achieve asymmetric synthetic ends.…”

“…The use of the Evans' chiral auxiliary in asymmetric synthesis follows a general pathway of acylation and conjugate addition reactions (Scheme 4). [31][32][33][34][35][36] For the oxazolidinones, the C4position is the stereochemical controlling element. Figure 6.…”