Organocatalytic Transannular Approach to Stereodefined Bicyclo[3.1.0]hexanes

Abstract

A diastereodivergent approach to highly substituted bicyclo[3.1.0]hexanes has been developed through a transannular alkylation reaction that builds up the bicyclic core employing asymmetric organocatalysis as the tool for the installation of all stereocenters. On one hand, a Michael/Michael cascade process between enals and 4-alkenyl sulfamidate imines under the iminium/enamine activation manifold provides an oxathiazole-2,2-dioxide-fused cyclohexane adduct that, after isolation, is subsequently engaged in a transannular alkylation/hydrolysis through enamine activation by the use of a primary amine. On the other hand, the corresponding C-2 epimers are directly obtained from the same starting materials in a single operation through a cascade Michael/Michael/transannular alkylation/hydrolysis sequence through sequential iminium/enamine/enamine combination of aminocatalytic activation manifolds.

Asymmetric Organocatalysis Revisited: Taming Hydrindanes with Jørgensen–Hayashi Catalyst

“…A thermodynamically driven tautomerization as the final step was also proposed by Carrillo and Vicario in the synthesis of trans-decalines. 51 Furthermore, upon prolonged storage of tetracycle 18 in CDCl 3 the equilibrium shifted from (4R)-keto-18/enol-18 = 44:56 to 57:43.…”

Recent Developments in Transannular Reactions

“…A similar ring contraction on densely functionalized oxathiazole 2,2-dioxide-fused cyclohexanecarbaldehydes has also been described, in this case proceeding through the generation of an enamine intermediate as the reactive nucleophilic species upon condensation with benzydrylamine (Scheme 45 ). 69 This reaction also makes use of the leaving group ability of the alkylsulfamate imine moiety, which underwent the transannular alkylation through an S N 2 process that took place with complete inversion of configuration. The resulting N -sulfonylimine formed after the alkylation was hydrolyzed in situ by acidic aqueous work-up leading to the final highly substituted bicyclo[3.1.0]hexane family of products.…”

Stereodivergent routes in organic synthesis: marine natural products, lactones, other natural products, heterocycles and unnatural compounds

“…enantioselective organocatalytic routes to bicyclo[3.1.0]hexanes from enals and 4-alkenyl sulfamidate imines have been reported by Carrillo, Vicario and co-workers. 116 Using TMS-protected (S)diphenylprolinol, when the reaction was carried out at -30 ºC, the cyclohexane derivatives were isolated by means of a Michael/Michael cascade reaction. These compounds were treated with benzydrylamine to provide the bicyclic adducts up to 87:13 dr (Scheme 73).…”