Enantioselective Syntheses of α‐Silyl Amines via a Copper‐N‐Heterocyclic Carbene Catalyzed Nucleophilic Silicon Transfer to Imines

Abstract

We developed an efficient and enantioselective method for the synthesis of chiral α‐silyl amines. In the presence of a copper(I)‐chiral monodentate N‐heterocyclic carbene complex (5 mol %), smooth nucleophilic silicon transfer from Me2PhSiBpin (pin=pinacolato) to tosyl‐protected aldimines affords the corresponding α‐silyl amines in 77–93 % yields over 15 examples and satisfactory ee of 79–99 %. The asymmetric silylation of ketimines was also explored.

Recent advances in Cu-catalyzed C(sp3)–Si and C(sp3)–B bond formation

“…CuCl. Here again, reactions could be performed on numerous albeit activated aldimines 62, failing to use unactivated educts [40]. Likewise, the α-silylated sulfonamide 67 was obtained in modest ee, although the chemical yield of the transformation was very low (15%).…”

Copper-Catalyzed Silylation of C(sp3)–H Bonds Adjacent to Amide Nitrogen Atoms

“…We therefore targeted an oxidative procedure that would convert those C­(sp 3 )–H into C­(sp 3 )–Si bonds without the structural bias of the aforementioned examples (Scheme C). Our approach is intended to complement the existing methods for the catalytic preparation of α-silylated amines, particularly the addition of silicon nucleophiles to imines and carbon nucleophiles to silylated imines, respectively. , …”

“…On the basis of these control experiments and previous experimental observations, we believe that the catalysis proceeds through the imine (gray box, Scheme ) that, in turn, undergoes conventional copper-catalyzed 1,2-addition of the silicon nucleophile (not shown) . That would also explain the higher yields seen with aldimines compared to the ketimine (see Table , entry 11).…”

Catalytic enantioselective addition of Grignard reagents to aromatic silyl ketimines

“…In contrast, chiral α-silyl amines with tetrasubstituted carbon have not been investigated yet, due to a lack of synthetic methods to access them. So far, only a handful of examples of catalytic asymmetric synthesis of chiral α-silyl amines with trisubstituted carbon stereocentres have been reported21222324. For the formation of α-silyl amines with tetrasubstituted carbon stereocentre, no efficient methods have been developed yet, with two examples of racemic synthesis having been reported until now2526.…”

“…For the formation of α-silyl amines with tetrasubstituted carbon stereocentre, no efficient methods have been developed yet, with two examples of racemic synthesis having been reported until now2526. The only report23 in which synthesis of chiral α-silyl amines with tetrasubstituted carbon was presented is based on silyl transfer strategy and describes few products with low yields (13–20%) and e.e. 's (60–79%).…”