Construction of Azabicyclo[6.4.0]dodecatrienes Based on Rhodium(I)-Catalyzed Intramolecular [6+2] Cycloaddition between Azetidine, Allene, and Alkynes

Abstract

Treatment of the allenylazetidine-alkynes with a catalytic amount of [RhCl(CO)dppp] 2 (dppp: 1,3-bis(diphenylphosphino)propane) effected the intramolecular hetero-[6 2]-type ring-closing reaction via the C-C bond cleavage of the azetidine ring to produce azabicyclo[6.4.0]dodecatriene derivatives in good to excellent yields. The formation of the oxa analogue could also be achieved.Key words allene; azetidine; [6+2] cycloaddition; bicyclic compound; alkyne; rhodium Small-sized cycloalkanes are often of significant use from synthetic points of view. [1][2][3][4][5] We recently disclosed that the rhodium(I)-catalyzed cycloaddition of allenylcyclopropanealkynes 1 (n=0) afforded the bicyclo[5.4.0] undecatrienes 2 (n=0) 6) in the [5+2] ring-closing manner (Chart 1). The reaction must have proceeded via cleavage of the cyclopropane ring due to the relief of its high strain energy (27.5 kcal/mol). 7)A similar ring construction was realized using allenylcyclobutane-alkynes 1 (n=1) producing the eight-membered bicyclic compounds 2 (n=1) 8) in high yields ([6+2] cycloaddition). The unfunctionalized simple cyclobutane ring is generally known not to open, let alone being used as a C 4 -building block. [1][2][3][4][5] We tentatively interpreted that the production of 2 (n=1) would initiate the formation of the rhodabicyclo[4.3.0] intermediate 3 (n=1), [8][9][10] which should be susceptible to β-carbon elimination, [1][2][3][4][5] with release of the ring strain energy (26.3 kcal/mol) 11) giving rise to the nine-membered rhodabicyclic species 4. Reductive elimination would occur to provide the final products. The successful application of this methodology to the cyclopentane derivative 1 (n=2) afforded the ninemembered bicyclic compounds 2 (n=2).9) This novel [7+2] cycloaddition involves the unprecedented cleavage of the normal-sized cyclopentane ring by releasing its strain energy (6.3 kcal/mol) 11) via the intermediate 3 (n=2), 8,9) similar to that of the cyclobutane derivatives.We now report the application of a newly developed eightmembered ring formation method for the preparation of the bicyclic azocine derivatives as well as the oxa analogue (Chart 2). The polycyclic skeleton containing an eight-membered heterocycle has been found as the core structure in various natural products and biologically-active compounds. 12-14) Results and DiscussionOur initial study employed the phenylsulfonylallene-alkyne 5a having the N-tosyl-3-azetidine ring 15) at the allenic terminus. After careful screening, we found that the use of [RhCl(CO) dppp] 2 (dppp: 1,3-bis(diphenylphosphino) propane) in toluene at 80°C was suitable for our purpose to provide the expected azabicyclo[6.4.0] dodecatriene derivative 6a (90% yield; Table 1, entry 1). The optimized reaction conditions [5 mol% [RhCl(CO) dppp] 2 in toluene at 80°C] were applied to several other allenylazetidine-alkyne species 5. The substrate 5b, having a methyl group at the allenic position, afforded the desired azabicyclo[6.4.0] product 6b 16) in 99% yield (entry 2). This ring-closing...

Rh^I-Catalyzed Cycloaddition between Allenyl π-Bonds and C-C Triple Bonds

“…The azocine fused bicyclic products 8 could also be obtained in high yields. 22 The use of [RhCl(CO)dppp] 2 in toluene at 80 was suitable in this case to provide the desired 8a in 90% yield. Several other azetidine derivatives 7 23 were exposed to the optimized conditions to afford 8b i in good yields as shown in Table 3.…”