Practical and Highly Enantioselective Synthesis of β‐Alkynyl‐β‐amino Esters Through Ag‐Catalyzed Asymmetric Mannich Reactions of Silylketene Acetals and Alkynyl Imines.

Abstract

Practical and Highly Enantioselective Synthesis of β-Alkynyl-β-amino Esters Through Ag-Catalyzed Asymmetric Mannich Reactions of Silylketene Acetals and Alkynyl Imines. -A highly efficient Ag-catalyzed enantioselective method for the addition of silylketene acetals to a variety of alkynyl imines is developed. The enantioselective processes can be carried out in air without the need for purified solvent. The catalytic asymmetric protocol delivers the desired β-alkynyl-β-amino esters in up to 94% e.e. Optically enriched products are readily converted to a number of synthetically useful derivatives. Ag-catalyzed reactions involving silylketene acetals of alkyl esters proceed with lower enantioselectivity. -(JOSEPHSOHN, N. S.; CARSWELL, E. L.; SNAPPER, M. L.; HOVEYDA*, A. H.; Org. Lett. 7 (2005) 13, 2711-2713;

Synthesis and Reactivity of Propargylamines in Organic Chemistry

“…As a result of this approach, a series of propargylamine derivatives 302 has been synthesized in high yields and obtained with excellent ee, as determined by chiral HPLC analysis. 212,213 Another interesting silver-catalyzed approach to enantioenriched propargylamines has been developed in 2007 by Rueping and co-workers who used a combination of a chiral phosphoric acid 303 and Ag(I) catalyst. 214 The authors investigated the alkynylation of α-imino esters via a dual catalysis procedure, in which an enantioselective activation, catalyzed by a Brønsted acid 303, is combined with a metalcatalyzed alkynylation.…”

“…Relatively few examples for the synthesis of propargylamines using organocatalytic methods have been described in the literature. These approaches resemble the Ag-catalyzed reaction previously developed by Hoveyda and Snapper, 212,213 where propargylamines are synthesized through the addition of carbon nucleophiles to alkynyl imines. Maruoka and co-workers developed a stereoselective Mannich-type reaction of in situ generated C-alkynyl imines 380 with acetylacetone 257,258 and aliphatic aldehydes 259 Another similar organocatalytic approach to propargylamines has been developed by Palomo and co-workers, who combined a proline-based catalyst and a Brønsted acid to promote the Mannich reaction of aldehydes with inactivated alkynyl imines (Table 24).…”

Ultrasonic synthesis, characterization of β-aminoketones by bismuth(III) triflate and determination of antigenotoxic properties

“…However, in most cases these protocols use hazardous organic solvents and suffer from long reaction time with low yields. Therefore, it is necessary to develop the modern versions of the reaction that could work under simple and mild conditions (Josephsohn et al, 2005).…”