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

Abstract

Silyl ketene imines derived from a variety of α-branched nitriles have been developed as highly useful reagents for the construction of quaternary stereogenic centers via the aldol addition reaction. In the presence of SiCl4 and the catalytic action of a chiral phosphoramide, silyl ketene imines undergo extremely rapid and high yielding addition to a wide variety of aromatic aldehydes with excellent diastereo- and enantioselectivity. Of particular note are the high yields and selectivities obtained from electron-rich, electron-poor, and hindered aldehydes. Linear aliphatic aldehydes did react with good diastereo- and enantioselectivity in the presence of nBu4N(+)I(-), but branched aldehydes were much less reactive. Semiempirical calculations provided a rationalization of the observed diastereo- and enantioselectivity via open transitions states.

Nickel‐Catalyzed Conjugate Addition of Silyl Ketene Imines to In Situ Generated Indol‐2‐ones: Highly Enantioselective Construction of Vicinal All‐Carbon Quaternary Stereocenters

“…[2] Since the pioneering research of Fu and coworkers, [3] significant progress has been made in the asymmetric 1,2-additions of SKIs.T he Denmark group have disclosed enantioselective aldol reactions of SKIs with aldehydes promoted by SiCl 4 and chiral bisphosphoramide catalyst, which afforded b-hydroxy nitriles in excellent results. [4] Asymmetric Mannich reactions of SKIs with imines have been documented by Leighton et al and our group. [5] Furthermore,t he implementation of SKIs in asymmetric protonation reactions has been reported by the List group.…”

Pyrrole-Based Conjugated Microporous Polymers as Efficient Heterogeneous Catalysts for Knoevenagel Condensation

“…Considering the presence of weakly basic pyrrole moieties within both CMPs, the CMPs might be used as heterogeneous catalysts for base-catalyzed reactions which are extremely important in catalyzing the synthesis of various small molecules for chemical and pharmaceutical industries ( Perryman et al, 2013 ; Volchkov and Lee, 2013 ; Denmark et al, 2014 ). In this respect, base-catalyzed Knoevenagel condensation was selected as the model reaction to evaluate the catalytic activity of both CMPs.…”

Stereodefined Acyclic Polysubstituted Silyl Ketene Aminals: Asymmetric Formation of Aldol Products with Quaternary Carbon Stereocenters

“…Although these strategies proved that challenging motifs such as quaternary carbon stereocenters in acyclic systems could be prepared from simple α‐heterosubstituted alkynes in a single‐pot operation with the concomitant creation of several new bonds,14 the aldol reaction with aliphatic aldehydes proceeded sluggishly with only low diastereomeric ratios. Whereas Lewis base catalyzed additions of silyl ketene imines to aliphatic aldehydes proceed with good results,15 in all other cases, useful yields and diastereoselectivities were only achieved by using α,β‐unsaturated aldehydes which could eventually serve as surrogates for saturated aldehyde substrates through hydrogenation 7. 9, 13 The development of a new approach to aldol products by reaction of stereodefined trisubstituted acyclic enolates with aliphatic aldehydes leading to the expected quaternary carbon stereocenters was therefore needed.…”