Direct Asymmetric Vinylogous and Bisvinylogous Mannich-Type Reaction Catalyzed by a Copper(I) Complex

Abstract

A direct catalytic asymmetric vinylogous Mannich-type reaction has been disclosed in good yield, excellent regio-, diastereo- and enantioselectivity. The key to control the regioselectivity is the combination of a bulky N-acylpyrazole and a bulky bisphosphine ligand. The catalytic system was extended to a bisvinylogous Mannich-type reaction by changing the ligand. The synthetic utility of the vinylogous products was demonstrated by several transformations.

Leveraging the Knorr Pyrazole Synthesis for the Facile Generation of Thioester Surrogates for use in Native Chemical Ligation

“…N‐acyl heterocycles are known to act as efficient acylating agents but N‐acylpyrazoles have been largely overlooked due to their modest reactivity, which is about 20 times less reactive than the corresponding N‐acylimidazole . Although N‐acylpyrazoles are widely studied in the realm of organic heterocyclic synthesis, their utility has been focused on ligands and mildly activated substrates for organometallic transformations . The relatively low reactivity towards endogenous nucleophiles and the ease of synthetic access presented an opportunity to adapt Knorr's synthesis for mild and selective in situ thioesterification.…”

“…[33,34] Although N-acylpyrazoles are widely studied in the realm of organic heterocyclic synthesis,t heir utility has been focused on ligands and mildly activated substrates for organometallic transformations. [35][36][37][38][39] Ther elatively low reactivity towards endogenous nucleophiles [33] and the ease of synthetic access presented an opportunity to adapt Knorrssynthesis for mild and selective in situ thioesterification.…”

The Vinylogous Michael Addition of 3‐Alkylidene‐2‐oxindoles to β,γ‐Unsaturated α‐Keto Esters by Bifunctional Cinchona Alkaloids

“…Over the last few years, research involving catalytic asymmetric direct vinylogous reactions have been growing rapidly A variety of vinylogous pronucleophiles such as butenolides, butyrolactams, coumarins, allyl alkyl/aryl ketones, 5‐alkyl‐4‐nitroisoxazoles, 3‐alkylidene oxindoles, α‐alkyl/arylidene pyrazolinones, 2‐allylazaarenes, β,γ‐unsaturated amides and esters, oxazole‐2‐thiones, N ‐2,2,2‐trifluoroethyl isatin ketimines, enals and enones, nitrones, and α,α‐dicyanoalkenes (Scheme ). have been explored for direct vinylogous Michael reaction.…”

Lewis acid-catalyzed asymmetric reactions of β,γ-unsaturated 2-acyl imidazoles

“…These compounds and their analogs bearing one potential enolization have been demonstrated as highly active nucleophiles in a number of catalytic asymmetric reactions for the synthesis of natural products and bioactive compounds [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] . Especially, γ-addition as dienolate pronucleophiles with either metal catalysis [17][18][19][20][21][22][23][24][25][26][27][28] or organocatalysis [29][30][31][32][33][34][35][36] has been widely documented during the past several years, and the maintained πconjugation of γ-addition process leading to thermodynamically stable conjugated products (Fig. 1a, A).…”