Dynamic Diastereoselectivity during Iron Carbonyl Mediated Spirocyclization Reactions

Abstract

Dynamic diastereoselectivity during Fe(CO)3 promoted [6+2] ene spirocyclization of 35a and 35b, having a chiral center on the pendent side chain, was investigated and gave rise to products 28a and 28b instead of four possible isomers. From this reaction, two chiral centers are generated, with absolute stereochemistry determined by the double bond geometry and the chiral center already present. 28a/b and the diene product from demetallation of 28a are proposed as potential intermediates for total synthesis of 18-deoxycytochalasin H. Furthermore, a stepwise second cyclization and a tandem double cyclization mediated by the Fe(CO)3 moiety was investigated.

Advances in Stereoconvergent Catalysis from 2005 to 2015: Transition-Metal-Mediated Stereoablative Reactions, Dynamic Kinetic Resolutions, and Dynamic Kinetic Asymmetric Transformations

“…255 The precursor can be easily synthesized from the corresponding chiral amino ester and the racemic carboxylic acid as a diastereomeric mixture of 328 and 329 . Under photolytic conditions, the iron-center loses coordination to the diene, eventually establishing an equilibrium between the two π-faces that allows for the dynamic interconversion of 328 and 329 .…”

“…In 2005, the Pearson group reported a novel intramolecular ene-type reaction between a diene−Fe(CO) 3 complex and an alkene, resulting in the stereospecific generation of the corresponding spirolactam (Scheme 68). 255 The precursor can be easily synthesized from the corresponding chiral amino ester and the racemic carboxylic acid as a diastereomeric mixture of 328 and 329. Under photolytic conditions, the ironcenter loses coordination to the diene, eventually establishing an equilibrium between the two π-faces that allows for the dynamic interconversion of 328 and 329.…”

Synthesis of Enantiopure Bicyclic α,α-Disubstituted Spirolactams via Asymmetric Birch Reductive Alkylation

“…The stereoselective construction of quaternary spirocyclic carbon centers is a challenging problem in organic synthesis . A limited number of methods for the stereoselective construction of bicyclic α,α-disubstituted spirolactams have been reported to date including use of a photochemical iron carbonyl [6 + 2] ene-type reaction, reduction of a bridged bicyclic lactone, and oxidative spirocyclization of a phenolic oxazoline . In the case of spirolactams containing a 7-membered lactam ring, regioselective alkylation of an aminocaprolactam proceeding via a benzylidiene Schiff base intermediate has only furnished a racemic quaternary lactam .…”

Asymmetric organic synthesis with stoichiometric transition metal complexes

“…Studies by Pearson, 22 Knöelke, 23 and Stephenson 24 developed iron cyclohexadienyl complexes into valuable synthetic templates with planar chirality, suitable for iterative 1,1-and 1,2-bisfunctionalization, thus opening new pathways for complex natural product syntheses (Schemes 17 and 18). Racemic  4cyclohexadienyl iron complexes were activated by oxidation to  5 -cationic iron complexes that acted as electrophiles poised for nucleophilic attack proceeding with exquisite selectivity from the diastereotopic face opposite to the iron center.…”