Highly Enantioselective Cascade Transformations by Merging Heterogeneous Transition Metal Catalysis with Asymmetric Aminocatalysis

Abstract

The concept of combining heterogeneous transition metal and amine catalysis for enantioselective cascade reactions has not yet been realized. This is of great advantage since it would allow for the recycling of expensive and non-environmentally friendly transition metals. We disclose that the use of a heterogeneous Pd-catalyst in combination with a simple chiral amine co-catalyst allows for highly enantioselective cascade transformations. The preparative power of this process has been demonstrated in the context of asymmetric cascade Michael/carbocyclization transformations that delivers cyclopentenes bearing an all carbon quaternary stereocenters in high yields with up to 30:1 dr and 99% ee. Moreover, a variety of highly enantioselective cascade hetero-Michael/carbocyclizations were developed for the one-pot synthesis of valuable dihydrofurans and pyrrolidines (up to 98% ee) by using bench-stable heterogeneous Pd and chiral amines as co-catalysts.

The Use of Porous Palladium(II)‐polyimine in Cooperatively‐ catalyzed Highly Enantioselective Cascade Transformations

“…The spirocyclic oxindole structural motif 7, with an all carbon quaternary stereocenter, is a valuable structural motif present in several natural products and pharmaceuticals. [21] With the Pd 2+ /PP-1, we achieved similar (or better), as compared with aminemodified silica supported Pd 2+ , [13] enantioselective formation of such spirocyclic oxindoles 7 (up to > 99.5:0.5 er) by the conjugate/carbocyclization cascade transformation between enals 1 and 6 (Scheme 2).…”

“…[12] Consequently, it is relevant to investigate such eventual advantages for porous organic polymers as substrates for catalyzed asymmetric cascade transformations. Guided by our previous work on porous organic polymers, [7d] we envisioned the synthesis of a Lewis acidic (Pd 2+ ) based porous polyimine polymer that we could investigate as a catalyst for the dynamic kinetic asymmetric transformations (DYKAT) of enals 1 with propargylic nucleophiles 2 (E ¼ 6 E 1 ) [13,14] in cooperation with an amine catalyst [13] (Scheme 1a). This reac- [13] or homogeneous metal [14] /chiral amine (5) catalyst systems a predominant stereoisomer of the corresponding poly-functionalized product 4 containing a quaternary stereocenter, can be assembled in high yield, diastereomeric ratio (dr) and enantiometric ratio (er).…”

Combined heterogeneous metal/organic catalysts for eco-friendly synthesis

“…Palladium is a powerful and versatile transition metal, which can be immobilized on various solid supports and next be used as a heterogeneous catalyst for efficient chemical reactions [49][50][51][52][53][54][55][56]. In this context, we recently disclosed that enantioselective carbocyclizations could be performed by the synergistic action of a heterogeneous palladium catalyst and a chiral amine co-catalyst [57]. The above results in metal/ organo cooperative catalysis inspired us to design and explore the multicatalysis relay strategy using palladium nanoparticles as the heterogeneous catalysts and the aerobic oxidation of alcohols to aldehydes as the initial entry transformation (Scheme 1, level 1).…”

Asymmetric one-pot reactions using heterogeneous chemical catalysis: recent steps towards sustainable processes

“…96 Recently, asymmetric cascade reactions using combinations of a soluble chiral organocatalyst and supported Pd catalysts were developed for the preparation of chiral five membered unsaturated cyclic compounds. 97 Good yields and high stereoselectivities were obtained in reactions of cinnamaldehyde derivatives (6) with propargylic C-, O-or N-nucleophiles (7,9,11), leading to the formation of cyclopentene, dihydrofuran or pyrroline derivatives (Scheme 3). Combinations of two catalysts were used in these reactions.…”