α,α-Disubstituted Boron Enolates in the Asymmetric Synthesis of Quaternary Carbon Centers

Abstract

[reaction: see text] Reduction of alpha,alpha-disubstituted thioglycolate amides with lithium di-tert-butylbiphenylide affords alpha,alpha-disubstituted enolates with high Z/E selectivity. Transmetalation of the enolates with dicyclohexylboron bromide facilitates highly diastereoselective aldol reaction with aromatic and alpha,beta-unsaturated aldehydes.

Enantioselective synthesis of all-carbon quaternary stereogenic centers in acyclic systems

“…As Gleason found a solution to the general inaccessibility of acyclic a,a-disubstituted enolates of defined stereochemistry The absolute configuration of all created stereogenic centers is consistent with a chair-like transition state. 79 When the condensation of the a,a-disubstituted lithium enolates, derived from bicyclic thioglycolate lactams as described in Scheme 47, is performed with benzenesulfonyl imines, the Mannich addition products are obtained with excellent diastereoselectivities. 80 As the direct analysis of cyclic amides is difficult due to the presence of amide rotamers, they were partially hydrolyzed to provide stable valinol amides as described in Scheme 63.…”

Enantioselective Construction of Quaternary Stereogenic Carbon Atoms by the Lewis Base Catalyzed Additions of Silyl Ketene Imines to Aldehydes

“…With the ability to selectively access trisubstituted amide enolates, Gleason then developed a diastereoselective aldol reaction for the synthesis of quaternary stereogenic centers. [9] The success of this reaction relies on the ability to convert the lithium enolate to a boron enolate using dicyclohexylboron bromide. The in situ formed boron enolate then undergoes diastereoselective syn aldol additions with aromatic and olefinic aldehydes in good yield and excellent stereoselectivities (Scheme 3).…”

“…With the ability to selectively access trisubstituted amide enolates, Gleason then developed a diastereoselective aldol reaction for the synthesis of quaternary stereogenic centers 9. The success of this reaction relies on the ability to convert the lithium enolate to a boron enolate using dicyclohexylboron bromide.…”

Reductive Lithiation and Multilithiated Compounds in Synthesis

“…However, transmetallation of this intermediate with dicyclohexylboron bromide (2.1 equiv) allowed the recovery of the desired product with good yield in a 91 : 9 syn/anti ratio (Scheme 12.7). Under these conditions, the reaction was successfully extended to several aromatic and α,β-unsaturated aldehydes, as well as to different amides [24]. Subsequently, the same authors investigated the reactivity under similar reaction conditions of a more easily accessible class of 5,7-bicyclic thioglycolate lactams, 23, derived from (S)-valinol [25].…”