Diene-Transmissive Diels–Alder Sequences with Benzynes

Abstract

Diene-transmissive Diels–Alder (DTDA) sequences are extraordinarily powerful processes for the generation of fused bicyclic systems. Nonetheless, only stable dienophiles have previously been deployed. Herein we report DTDA sequences with a variety of substituted [3]­dendralenes in the first study to deploy arynes as dienophiles. We demonstrate the one-flask generation of complex, aromatic-ring-containing, multicyclic systems of relevance to medicinal chemistry. These synthetic operations provide numerous successful examples of the otherwise challenging and rarely reported intermolecular Diels–Alder reaction of acyclic 1,3-butadienes with arynes, which is made possible due to the exalted reactivity of dendralenic dienes.

Stereoselective Synthesis of Highly Substituted 1,3‐Dienes via “à la carte” Multifunctionalization of Borylated Dendralenes

“…It is important to note that few examples of carbolithiation of dendralenes have been described. Besides anionic polymerization [15] and a carbolithiation/electrocyclization of cyclic [3]dendralenes, [16] only one example involving carbolithiation/electrophilic trapping of dendralenes has been reported to date [17] . Interestingly, in our system carbolithiation occurs via a regioselective addition of the organolithium reagent to the vinyl moiety of the borylated dendralene which generates an allyllithium intermediate.…”

“…Besides anionic polymerization [15] and a carbolithiation/electrocyclization of cyclic [3]dendralenes, [16] only one example involving carbolithiation/electrophilic trapping of dendralenes has been reported to date. [17] Interestingly, in our system carbolithiation occurs via a regioselective addition of the organolithium reagent to the vinyl moiety of the borylated dendralene which generates an allyllithium intermediate. This is in sharp contrast with previous examples where dendralene carboli- thiation generates a stabilized pentadienyllithium intermediate.…”

“…This is in sharp contrast with previous examples where dendralene carboli- thiation generates a stabilized pentadienyllithium intermediate. [15][16][17] We hypothesized that the presence of the polarized C À B bond in our system might hamper both the formation of the pentadienyllithium intermediate and the carbolithiation at the alkenyl boronate moiety, thus providing a favored scenario for nucleophilic addition at the vinylic terminus. Another important feature of the carbolithiation step is the high level of regio-and stereoselectivity achieved after the electrophilic trapping.…”

Stereoselective Synthesis of Highly Substituted 1,3‐Dienes via “à la carte” Multifunctionalization of Borylated Dendralenes

“…Besides anionic polymerization [15] and a carbolithiation/electrocyclization of cyclic [3]dendralenes, [16] only one example involving carbolithiation/electrophilic trapping of dendralenes has been reported to date. [17] Interestingly, in our system carbolithiation occurs via a regioselective addition of the organolithium reagent to the vinyl moiety of the borylated dendralene which generates an allyllithium intermediate. This is in sharp contrast with previous examples where dendralene carbolithiation generates a stabilized pentadienyllithium intermediate.…”

“…This is in sharp contrast with previous examples where dendralene carbolithiation generates a stabilized pentadienyllithium intermediate. [ 15 , 16 , 17 ] We hypothesized that the presence of the polarized C−B bond in our system might hamper both the formation of the pentadienyllithium intermediate and the carbolithiation at the alkenyl boronate moiety, thus providing a favored scenario for nucleophilic addition at the vinylic terminus. Another important feature of the carbolithiation step is the high level of regio‐ and stereoselectivity achieved after the electrophilic trapping.…”