Direct Intramolecular Conjugate Addition of Simple Alkenes to α,β-Unsaturated Carbonyls Catalyzed by Cu(OTf)₂

Abstract

An unprecedented intramolecular conjugate addition of simple alkenes to α,β-unsaturated carbonyl compounds has been developed. A simple Lewis acid such as Cu(OTf)2 was found to effectively catalyze the reaction, and six- and five-membered cyclic products were obtained in moderate to high yields.

Synthesis of 1‐Aminoindenes through Aza‐Prins‐Type Cyclization

“…On the other hand, the aza‐Prins‐type exo cyclization of an imine bearing an alkene moiety on the imine carbon is relatively rare, while useful cyclic compounds having a protected amino group can be obtained (Scheme b) . To the best of our knowledge, there have been few reports on the endo cyclization and no descriptions on the catalytic asymmetric variant (Scheme c) . In this context, we became interested in the formation of 1‐aminoindene derivatives 3 by the acid‐catalyzed aza‐Prins‐type endo cyclization by using 2‐alkenylbenzaldehydes 1 through the in situ generation of the iminium salt 2 .…”

“…This result suggested that the present cyclization can proceed through aza‐Prins reaction including the carbocation intermediate as shown in Scheme , whereas an alternative pathway via electrocyclic reaction cannot be ruled out. When p ‐toluenesulfonamide (TsNH 2 ) was used instead of BocNH 2 , 1‐aminoindene derivative 3 q was obtained in good yield …”

“…In most cases, an iminium carbon reacts with an alkene moiety on the iminium nitrogen to give the nitrogen heterocycles, whicha re frequently used in alkaloid synthesis (Scheme 1a). [3] In this context, we became interested in the formationof 1aminoindene derivatives 3 by the acid-catalyzed aza-Prins-type endo cyclization by using 2-alkenylbenzaldehydes 1 through the in situ generation of the iminium salt 2.T he 1-aminoindane substructure is found in biologically active drug candidates, such as an ew pain-reliever UKH-1114, [4,5] and development of an efficient and useful catalytic method for synthesis of 1-aminoindene derivatives is highly desirable. [2] To the best of our knowledge, there have been few reports on the endo cyclization and no descriptions on the catalytic asymmetricv ariant (Scheme1c).…”

“…[2] To the best of our knowledge, there have been few reports on the endo cyclization and no descriptions on the catalytic asymmetricv ariant (Scheme1c). [3] In this context, we became interested in the formationof 1aminoindene derivatives 3 by the acid-catalyzed aza-Prins-type endo cyclization by using 2-alkenylbenzaldehydes 1 through the in situ generation of the iminium salt 2.T he 1-aminoindane substructure is found in biologically active drug candidates, such as an ew pain-reliever UKH-1114, [4,5] and development of an efficient and useful catalytic method for synthesis of 1-aminoindene derivatives is highly desirable. [6] We first tested variousa cid catalysts (10 mol %) in the cyclization of 2-isopropenylbenzaldehyde (1a)w ith tert-butyl carbamate (BocNH 2 )i nC H 2 Cl 2 at room temperature (Table 1).…”

“…When p-toluenesulfonamide (TsNH 2 )w as used instead of BocNH 2 ,1 -aminoindened erivative 3q was obtained in good yield. [3] Scheme2.PTSA-catalyzed cyclization using 1a and protectedamines. [a] Reactions were performed on a0 .1 mmols cale in 1.0 mL of CH 2 Cl 2 .…”