Direct Enantioselective Addition of Alkynes to Imines by a Highly Efficient Palladacycle Catalyst

Abstract

Enantiopure propargylic amines are highly valuable synthetic building blocks. Much effort has been devoted to develop methods for their preparation. The arguably most important strategy is the 1,2-addition of alkynes to imines. Despite remarkable progress, the known methods using Zn and Cu catalysts suffer from the need for high catalyst loadings, typically ranging from 2-60 mol % for neutral aldimine substrates. Here we report a planar chiral Pd complex acting as very efficient catalyst for direct asymmetric alkyne additions to imines, requiring very low catalyst loadings. Turnover numbers of up to 8700 were accomplished. Our investigation suggests that a Pd-acetylide complex is generated as a catalytically relevant intermediate by the aid of an acac ligand acting as internal catalytic base. It is shown that the catalyst is quite stable under the reaction conditions and that product inhibition is not an issue. A total of 39 examples is shown which all yielded almost enantiopure products.

Keywords: 1,2-Addition; Asymmetric Catalysis; Ferrocenes; Palladacycles; Propargylic Amines.

Scheme 1

State‐of‐the‐art compared to this work.

Scheme 2

Investigation of the catalyst recycling and reuse.

Scheme 3

Application of decreased catalyst amounts (reaction conditions like in Table 4).

Figure 1

Reaction profiles of 2 A under the conditions of Table 5.