Gold Catalyzed Cyclopropanation/[5+3] Cycloaddition of 1,4,9‐ and 1,4,10‐Allenenynes to Bicyclo[3.3.1]nonane Derivatives

Abstract

A synthetic method to prepare cycloalkyl‐ and (hetero)aryl‐fused bicyclo[3.3.1]nonane derivatives from gold(I)‐catalyzed cyclopropanation/[5+3] cycloaddition of 1,4,9‐ and 1,4,10‐allenenynes is described. The suggested double cycloisomerization mechanism delineates the first example of a stepwise [5+3] cycloaddition pathway in gold catalysis, a mode of reactivity that is also sparse in organic chemistry. Experimental and Density Functional Theory (DFT) computational studies based on a proposed gold carbenoid species provides insight into this unique selectivity that leads to the assembly of the architecturally challenging bridged carbocyclic motif.

Controlling the Gold(I)-Catalyzed 1,5-Allenene Reaction: Construction of Fused Rings with Excellent Diastereoselectivity

“…In general, the nucleophile is a carbon atom of the allenic unit leading to a [2 + 2] or [2 + 3] carbocycloaddition . Whereas interception of the intermediate carbocation by heteronucleophiles was possible in the case of 1,7-allenenes, in nonactivated 1,5-allenenes, the cationic intermediate Int1 , which is formed through 6- endo -cyclization, cyclizes to the gold carbene Int2 (Scheme a). ,, After removal of the gold catalyst, bicycle 2 is obtained. Depending on the substituent pattern, 2 can undergo further gold-catalyzed cyclization reactions, leading to polycycles. , In this work, we intended to favor the 5- exo -cyclization by introducing an aromatic moiety stabilizing the benzylic cation Int3 .…”

Engaging Yne‐Allenes in Cycloaddition Reactions: Recent Developments

“…in 2020, demonstrates that the effective construction of conformationally restricted and facially biased bridged fused ring systems could be finished through gold‐self relay catalysis merged cyclopropanation with [5 + 3] cycloaddition (Scheme 23). [ 80 ] Gold catalyst 72 efficiently promoted bicyclization reaction of ene‐yne‐allene substrates 71 with (hetero)aryl groups linked to the alkyne moiety, furnishing tetracyclic bicyclo[3.3.1]nonanes 75 in 55%—82% yields. This gold catalysis could tolerate a wide range of substrates bearing various functional groups such as methyl, phenyl, anilinyl and ether at the alkenyl carbon center and different substituents at various positions of the benzene ring.…”

Gold-catalyzed cycloadditions of allenesviametal carbenes

“…Recently, Chan and co-workers discovered a novel method for the gold-catalyzed double cycloisomerization of 1,4,9- and 1,4,10-allenenynes involving formal [3 + 2] cycloaddition between the allene and alkene to afford cycloalkyl- and (hetero)aryl-fused bicyclo[3.3.1]nonane derivatives. 22 The architecturally challenging bridged carbocyclic motif was constructed through in situ -generated gold carbene species. In the presence of 5 mol% of the gold catalyst, allenenynes 17 could be transformed successfully into the bicyclo[3.3.1]nonane derivatives 18 (Scheme 15).…”