Asymmetric Synthesis of Cyclopentane‐Substituted Oxindoles via Organocatalytic Desymmetrization of Cyclopent‐4‐ene‐1,3‐diones

Abstract

The highly enantioselective desymmetrization of prochiral cyclopent‐4‐ene‐1,3‐diones has been developed via an organocatalytic Michael reaction. This desymmetrization protocol is efficiently catalyzed by 10 mol% of a bifunctional squaramide, offering a short entry into a series of cyclopentane‐substituted oxindoles bearing two quaternary and one tertiary stereocenters in good yields and high stereoselectivities.magnified image

Recent advances towards organocatalytic enantioselective desymmetrizing reactions

“…This thiourea-catalyzed process proceeded via cascade Michael addition/ oxidation to forge functionalized compounds (33) in 14-95% yields with 50-87% enantioselectivities. Additionally, the same group simultaneously realized an organocatalytic Michael addition reaction of 3-substituted oxindoles with cyclopentenediones in the same year [52]. Later in 2019, the Wang group observed that the application of N-methoxy amides as nucleophiles and commercially available cinchonidine as the catalyst could lead to a formal C(sp 2 )−H amidation of cyclopentenediones [53] and a practically identical case was reported by Chegondi [54].…”

Organocatalytic Enantioselective Desymmetrization of Prochiral 2,2‐Disubstituted Cyclic 1,3‐Diones

“…The same research group further reported an organocatalytic Michael addition of oxindoles 12 on prochiral cyclopentene‐1,3‐diones 3 via enantioselective desymmetrization (Scheme 6). [19] This reaction was efficiently catalyzed by a bifunctional squaramide C4 to yield cyclopentane‐substituted oxindoles 13 having two quaternary stereocenters with good diastero‐ and enantioselectivities (up to 97 : 3 er) in high yields (71–95% yield). To highlight the practical applicability of this protocol, substrates with electronically and sterically diverse functional groups were investigated ( 13 a – d ) and a gram scale reaction was also demonstrated with excellent yield and enantioselectivity under standard reaction conditions.…”

Desymmetrization of Cyclopentene‐1,3‐Diones via Alkylation, Arylation, Amidation and Cycloaddition Reactions

“…In the year 2017, Dieter Enders and co-workers developed an enantioselective desymmetrization protocol of prochiral cyclopentene-1,3-diones (1) through an organocatalytic approach. [32] Bifunctional squaramide [33] (C8) (10 mol%) was used as an organocatalyst in this asymmetric Michael addition. The reaction of 3-aryloxindoles (35) and substrate 1 occurred in very simple conditions with organocatalyst (C8) in DCM at room temperature within 12 h (Scheme 8).…”

“…Squaramide catalyzed Michael addition of 3-aryloxindoles to cyclopentene-1,3-diones. [32] [3 + 2] cycloaddition of prochiral cyclopentene-1,3-diones (1) with azomethine ylide (46) by using Ag(I)/TF-BiphamPhos (L14) for the synthesis of bicyclic-pyrrolidine derivatives (47) via enantioselective desymmetrization protocol under mild reaction condition (Scheme 13). [39] Synthesis of highly functionalized enantioenriched bicyclic-cyclopentane/pyrrolidine was very well explained through 1,3 dipolar cycloaddition of azomethine ylide with excellent yield and diastereoselectivity.…”

“…In the year 2017, Dieter Enders and co‐workers developed an enantioselective desymmetrization protocol of prochiral cyclopentene‐1,3‐diones ( 1 ) through an organocatalytic approach [32] . Bifunctional squaramide [33] ( C8 ) (10 mol%) was used as an organocatalyst in this asymmetric Michael addition.…”