Asymmetric Direct Vinylogous Michael Addition to 2-Enoylpyridine N-Oxides Catalyzed by Bifunctional Thio-Urea

Abstract

Catalytic enantioselective direct vinylogous Michael addition of α,α-dicyanoalkenes to 2-enoylpyridine N-oxides with a bifunctional organocatalyst is described. The methodology offers an efficient way to install an asymmetric carbon-carbon bond at the γ-position of α,α-dicyanoalkenes in excellent regio-, diastereo-, and enantioselectivity. Further, application in desymmetrization of achiral α,α-dicyanoalkene to access highly functionalized enantioenriched cyclohexylidenemalononitrile derivatives has been demonstrated.

Organocatalytic Enantioselective Michael Addition of Oxazolones to 2‐Enoylpyridine N‐Oxides for Assembling of Pyridine N‐Oxides Featuring Vicinal Oxygen‐Containing Tetrasubstituted Stereocenters

“…In 2014, Singh et al. disclosed a chiral bifunctional thiourea catalyzed direct vinylogous Michael addition of 2‐enoylpyridine N ‐oxides with α,α‐dicyanoalkenes (Scheme A) . Using 5‐phenylfuran‐2(3 H )‐one as partner, Yuan and Xu et al.…”

Cinchona Derivatives as Bifunctional H‐bonding Organocatalysts in Asymmetric Vinylogous Conjugate Addition Reactions

“…Our research group investigated the worth of bifunctional 2-enoylpyridin-N-oxide 32 in tertiary amine-thiourea promoted γ-functionalization of α,α-dicyanoalkenes. [27] Double H-bonding activation is of great use with this type of acceptor containing two Lewis basic sites. Cinchonidine-derived amine-thiourea catalyst C9 was found efficient enough to catalyze this transformation yielding highly enantioenriched adducts 33 (Scheme 13).…”

“…Our research group investigated the worth of bifunctional 2‐enoylpyridin‐ N ‐oxide 32 in tertiary amine‐thiourea promoted γ‐functionalization of α,α‐dicyanoalkenes [27] . Double H‐bonding activation is of great use with this type of acceptor containing two Lewis basic sites.…”

Organocatalytic Asymmetric Vinylogous Michael Reactions

“…The direct AVM addition of α,α‐dicyanoalkenes ( 64 and 70 ) to 2‐enoylpyridine N ‐oxides 71 was then reported by Singh and co‐workers (Scheme ) . In the presence of 10 mol % of cinchonidine‐derived thiourea 72 in toluene at 0 °C, the reactions could be finished within a period from 24 to 96 hours, leading to a wide range of adducts 73 with up to 99 % ee and >99:1 d.r.…”