Cooperative Catalytic Reactions Using Lewis Acids and Organocatalysts: Enantioselective Propargylic Alkylation of Propargylic Alcohols Bearing an Internal Alkyne with Aldehydes

Abstract

The enantioselective propargylic alkylation of propargylic alcohols bearing an internal alkyne moiety with aldehydes in the presence of a metal salt as the Lewis acid and an optically active secondary amine as the co‐catalyst has been found to give the corresponding propargylic alkylated products in high yields as a mixture of two diastereoisomers with high enantioselectivity.

SN1‐Type Reactions in the Presence of Water: Indium(III)‐Promoted Highly Enantioselective Organocatalytic Propargylation of Aldehydes

“…The possibility to induce the formation of carbenium ion in the presence of water by merging an organo- [a] The reactions were performed at 0 8C with alcohol 4 d www.chemeurj.org catalytic process with a Lewis acid [29] opens up several new opportunities in the area of organocatalysis. [30] Experimental Section General procedure: The compounds 4 c-s (0.1 mmol, 1 equiv) and aldehyde (0.3 mmol, 3 equiv) were added to a vial containing the MacMillan catalyst 6 c (0.02 mmol, 20 mol %) in H 2 O (0.5 mL) at 0 8C. The mixture was stirred for 1 min and at the same temperature a solution of InA C H T U N G T R E N N U N G (OTf) 3 (20 mol %, 0.33 m in acetonitrile) was slowly added.…”

Asymmetric α Alkylation of Aldehydes: Efficiency with Elegance

“…Even though the S N 1 strategy is a new addition in asymmetric organocatalysis the principle is quickly gaining popularity in the development of novel methods. [10] …”

Indium(III)‐Promoted Organocatalytic Enantioselective α‐Alkylation of Aldehydes with Benzylic and Benzhydrylic Alcohols

“…[7] Recently, we introduced the concept of enantioselective S N 1-type alkylations to organocatalysis, [8,9] and also established the compatibility of indiumA C H T U N G T R E N N U N G (III) Lewis acids with organocatalytic processes mediated by the MacMillan catalyst. [10,11] The compatibility of indiumA C H T U N G T R E N N U N G (III) salts in these processes creates the possibility of using carbocations that cannot be generated in the presence of Brønsted acids. [12] The stability of the carbocation involved in the process is the primary driving force for these S N 1-type reactions, and their use can be easily rationalized by the work of Mayr et al [13] In the presence of InBr 3 , allylic alcohols can provide straightforward access to alkylated aldehydes without the use of palladium or iridium salts.…”

“…Alternatively, by using indiumA C H T U N G T R E N N U N G (III) salts (triflate or bromide), the corresponding carbenium ion can be generated from the alcohols and intercepted by the enamine formed in situ with the MacMillan catalyst. [10][11] The compatibility of indiumA C H T U N G T R E N N U N G (III) salts with water, the amine, and an excess of aldehyde is the motivation for investigating this chemistry.…”

“…In our preceding publications we have established that steric hindrance of the incoming carbenium ion controls the stereoselectivity of the reaction. [11] Therefore, to increase the stereoselectivity and reactivity, derivatives 2 b and 2 c were tested. The reaction conditions were carefully optimized by varying the solvent, Lewis acid, and MacMillan catalyst used in the reaction.…”