A New Class of Chiral Lewis Basic Metal-Free Catalysts for Stereoselective Allylations of Aldehydes

Abstract

A new class of amine N-oxides derived from trans-2,5-diphenylpyrrolidine were synthesized in enantiomerically pure form and tested as metal-free catalysts in the reaction of aldehydes with allyl(trichloro)silane to afford homoallylic alcohols. The products were obtained in fair to good yields and up to 85% ee. The behavior of structurally different catalysts and the influence of a coordinating unit present in the organocatalyst on controlling the stereochemical efficiency of the reaction were also investigated. Noteworthy a catalyst capable of promoting the allylation of aliphatic aldehydes with an almost unprecedent and unusually high enantioselectivity, up to 85%, was identified.The design and the synthesis of novel chiral Lewis bases which are able to act both as metal ligand as well as metalfree catalysts is a topic of paramount interest in the field of stereoselective catalysis. 1 Recently, special attention has been given to the development of an environmentally benign methodology that involves the use of nontoxic silicon-based reagents. 2 The coordination of a Lewis base to a tetracoordinated silicon atom leads to hypervalent silicate species of increased Lewis acidity at silicon center. As a consequence, such extracoordinated organosilicon compounds become very reactive carbon nucleophiles or hydride donors with a strong electrophilic character at silicon and an enhanced capability to transfer a formally negative-charged group to an acceptor. 3 A paradigmatic example of successful chiral Lewis base catalyzed reaction is represented by the allylation of aldehydes with allyltrichlorosilanes to afford homoallylic alcohols with high enantioselectivity. Among the different classes of compounds which have been employed as chiral Lewis bases to catalyze the reaction, 4 chiral phosphoramides, 5 and less often diphosphine oxides 6 have been employed with excellent results.Among Lewis basic catalysts, one class of compounds that deserve a special attention are chiral N-oxides derived from tertiary amines and pyridines. The high nucleophilicity of the oxygen in N-oxides, coupled with a high affinity of silicon for oxygen represent ideal properties for the development of synthetic methodology based on nucleophilic activation of organosilicon reagents. 7 A few efficient systems were developed, but the high level of stereocontrol achieved was the result of an extensive optimization of the stereochemical features of the catalysts, the synthesis of which required long and tedious procedures, sometimes involving also a resolution step. Furthermore a difficult-to-control stereogenic element such as a stereogenic axis in the catalyst is often required to achieve high levels of stereocontrol.Even if systems of relatively easy synthesis were developed, 8 including chiral bispyridine N,N¢-dioxides, 9 or simple pyridine N-oxides easily assembled from inexpensive aminoacids, 10 the search of new, readily available, efficient chiral organocatalysts for the reaction of trichlorosilyl compounds is still very active.In this field an...