Discovery of 2-aminobuta-1,3-enynes in asymmetric organocascade catalysis: construction of drug-like spirocyclic cyclohexanes having five to six contiguous stereocenters

Abstract

We present herein for the first time the asymmetric synthesis of drug-like spiranes through reflexive-Michael reaction by using 2-aminobuta-1,3-enyne catalysis under mild conditions.

Asymmetric Synthesis of Nature‐Inspired Bioactive Spiro Compounds through Organocatalytic Diels–Alder Reactions

“…In optimizing the reaction, we chose 9‐amino‐9‐deoxyepiquinine ( 4 a , 10 mol %) as the catalyst in toluene for the three‐component [4+2] cycloaddition reaction, as 4 a has proven suitable for cycloaddition reactions and aminoenyne catalysis . Interestingly, the three‐component one‐pot reaction of benzylideneacetone ( 1 a ) and 4‐nitrobezaldehyde ( 2 a ) with 1,3‐indandione ( 3 ) at room temperature for 26 h under the catalysis of 4 a (10 mol %), furnished the spirocyclic exo ‐product anti ‐(+)‐ 6 aa in only 26 % yield with 81 % ee and endo ‐product syn ‐(−)‐ 7 aa in only 8 % yield with 33 % ee and 3:1 dr (Table , entry 1).…”

Organocatalytic transformations of alkynals, alkynones, propriolates, and related electron-deficient alkynes

“…19 This work is based on aforementioned Ramachary's 18 MacMillan's group have recently synthetized (À)-minovincine in nine steps by ketone activation through a cascade catalysis. 20 This work is based on the previous synthesis of minfiensine described in Scheme 2.…”

“…18 In this work, the authors studied a MichaeleMichael tandem reaction through the use of dienyne intermediate G, which attacked to the in situ formed indane-1,3-dione 42. The reaction proceeded quite well for a large variety of cyclohexenones 43 with ee's higher than 90%.…”

Streamlined asymmetric α-difunctionalization of ynones

“…The unique property and reactivity of alkynes, coupled with the chemical versatility of carbonyl compounds, makes ynones an indispensable template for rapid structural proliferation and diversification 4 – 7 . Consequently, ynones possessing an α-chiral center are highly attractive chiral synthetic building blocks 8 , 9 . Although numerous synthetic approaches to ynones have been reported, the synthesis of chiral ynones remains a significant challenge due to multiple chemically reactive sites that interfere with common catalysts.…”