A Metal-Catalyzed Intermolecular [5+2] Cycloaddition/Nazarov Cyclization Sequence and Cascade

Abstract

The bicyclo[5.3.0]decane skeleton is one of the most commonly encountered bicyclic subunits in nature and the core scaffold of a wide range of targets of structural, biological, and therapeutic importance. Prompted by the interest in such structures, we report the first studies of metal-catalyzed [5+2] cycloadditions of vinylcyclopropanes (VCPs) and enynones. The resultant efficiently formed dienone cycloadducts serve as substrates for subsequent Nazarov cyclizations and as intermediates for single-operation [5+2]/Nazarov serial reactions and catalytic cascades. In many cases the one-flask process can be carried out in shorter reaction times and with comparable or superior yields to the two-flask procedure. Significantly, a single catalyst can be used to mediate both transformations. These [5+2]/Nazarov reaction sequences and cascades collectively provide strategically novel and facile access to the bicyclo[5.3.0]decane skeleton from simple and readily available components.

Catalytic Nazarov Cyclization: The State of the Art

“…Wender et al developed an intramolecular [5+2] cycloaddition and Nazarov cyclization cascade, the steps of which are catalyzed by rhodium(I) complexes and AgSbF 6 , respectively (Scheme 50) [127]. Upon completion of the cycloaddition between enynones (236) and vinylcyclopropane (237) to yield Nazarov precursors (238), catalytic AgSbF 6 was added to the reaction mixture for the formation of bicyclo[5.3.0]decane products (239) with 54-89 % yield and diastereomeric ratios of up to > 20:1.…”

Recent Developments in the [5+2] Cycloaddition

“…[30] Recently, Wender et al have developed the reaction of a variety of these substrates with a commercially available oxygen-substituted VCP 37, using [RhCl(CO) 2 ] 2 as catalyst. Significantly, aryl-alkynones 38a-e, enynones 38f, g, and a-alkoxy-enynones 38h, i, were all found to react readily at 80 8C, furnishing upon brief hydrolytic work-up the corresponding aryl-enones 39a-e and dienones 39f-i in good to excellent yields, as shown in Scheme 16.…”

3-Acyloxy-1,4-enyne: A new five-carbon synthon for rhodium-catalyzed [5 + 2] cycloadditions

“…These two reactions provided easy access to diverse cycloheptenones and cycloheptadienes. By coupling with [4+2] cycloaddition [19] and Nazarov cyclization [20], more complex polycyclic products were prepared conveniently. Both three-component (5+2+1) [21] and four-component (5+1+2+1) [22] cycloadditions were also developed using VCP, alkyne, and CO as the starting materials.…”