US EPA

5699585 

Dissertation 

Silicon-directed Nazarov cyclization: Stereochemical, mechanistic, and substituent-compatibility studies 

Habermas, KL 

1993 

Urbana-Champaign, IL 

University of Illinois 

Doctoral Dissertation 

English 

In the Silicon-Directed Nazarov Cyclization (SDNC) an organosilyl group, attached to a divinyl ketone at a position beta to the carbonyl, directs the location of the double bond in the cyclopentenone ring. Various studies are described that explore the stereochemistry, scope, and mechanism of the reaction. The cyclization proceeds with good to excellent stereoselectivity in cyclohexenyl systems bearing a variety of ring substituents. In all cases the trans family of isomers predominates; cis ring-fused products are formed almost exclusively. The stereoselectivity is high ($>$9:1) with bulky substituents. The potential for improving stereocontrol by increasing the bulk of silicon substituents was explored with 3-methyl-substituted cyclopentenyl-, cyclohexenyl-, and cycloheptenyl-vinyl ketones. Augmenting the bulk of the silyl group enhances the stereoselectivity with five- and six-membered rings. Selectivity is poor in cycloheptenyl systems with a methyl group on the stereogenic center, irrespective of the bulk of the silicon appendage. However, with cycloheptenyl- and cyclooctenyl-substrates bearing a 3-benzyloxymethyl group the products are principally ($>$92%) of the cis stereochemical family. Stereochemical results in the five- and six-ring systems are consistent with a steric approach control model, in which the vinylsilane prefers to attack the least-hindered face of the internal olefin. The ability to incorporate alkyl, alkenyl, aryl, and heteroatomic groups into substrates for the SDNC and their subsequent reactions is reported. The reaction is compatible with vinyl, allyl, or phenyl groups attached to the alpha position of the vinylsilane, and to most other positions of the substrate. Alkyl groups at the beta position of the internal or external olefin retard the reaction, while allyl or phenyl substituents on an alpha position dramatically accelerate cyclization. Oxygen- and nitrogen-containing functions are tolerated except when attached to the $\alpha$-vinyl carbon atom of the divinyl ketone. The influence of various substituents on the rate of reaction is consistent with the rate-determining step of the SDNC being cyclization of the pentadienylic cation to the cyclopentenylic cation. A novel cationic cyclization that forms the bicyclo (3.3.1) nonane ring system is also described.