Conjugate Addition-Initiated Nazarov Cyclization

Abstract

A reaction sequence involving the 1,6-conjugate addition of a nucleophile to a dienyl diketone followed by Nazarov cyclization is described. Several nucleophiles are identified as competent initiators for the sequence. A different reaction outcome is is observed when catalytic amounts of nucleophile are employed, involving elimination of the nucleophile after the electrocyclization.

The Nazarov Cyclization: A Valuable Method to Synthesize Fully Substituted Carbon Stereocenters

“…In an approach similar to, but distinct from, Tius's work (vide infra), Frontier found that treatment of extended α‐keto enone 21 with a Lewis acid in the presence of a suitable carbon or nitrogen nucleophile such as 22 gives cyclization products such as 25 , containing a tertiary alcohol, in good yields (Scheme ) 14. 1,6‐Conjugate addition by the amine generates the requisite pentadienyl cation 24 , which undergoes Nazarov cyclization forming the fully substituted carbon α to the carbonyl.…”

Beyond the Divinyl Ketone: Innovations in the Generation and Nazarov Cyclization of Pentadienyl Cation Intermediates

“…Frontier, Brooks, and Caruana [20] recently found that various carbon and nitrogen nucleophiles undergo a 1,6-conjugate addition on α-diketone substrates ( 50 , Scheme 10). A subsequent Nazarov cyclization occurs to provide α-hydroxycyclopentenones ( 51 ), [21] which in the presence of Y(OTf) 3 are isolated as a single diastereomer.…”

1,6-Conjugate Addition of Nucleophiles to α,β,γ,δ-Diunsaturated Systems

“…Also, none of the products derived from 1,2-addition of the nucleophile was detected. Frontier and co-workers 41 recently reported a reaction sequence involving the 1,6-conjugate addition of several nucleophiles to dienyl diketone 128 followed by Nazarov cyclization (Scheme 44). The two-step sequence was de- scribed to be catalyzed by Lewis acidic transition-metal complexes and was stereoselective, affording high yields of α-hydroxycyclopentenones 130.…”