Asymmetric Synthesis of (−)-Adaline

Abstract

[reaction: see text] An enantioselective total synthesis of (-)-adaline has been achieved starting from a chiral 6,6-disubstituted piperidone derivative previously prepared by diastereoselective allylation of a chiral tricyclic N-acyl-N,O-acetal. The key steps include lithium ion-activated SN2-type alkynylation of the tricyclic N,O-acetal leading to exclusive formation of the (6S)-ethynylpiperidine and ring-closing olefin metathesis of the (2R,6S)-cis-2,6-dialkenylpiperidine for constructing the bridged azabicyclononane.

Synthesis of Macrocyclic Compounds by Ring Closing Metathesis

“…Amphidinolide A was synthesized by Maleczka group [48] using RCM reaction with high stereoselectivity. Substrate 54 did not give the desired product with catalyst A, but with catalyst B gave the desired product solely in E configuration (Scheme 16).…”

Preparation of cyclic molecules bearing “strained” olefins using olefin metathesis

“…Kibayashi and co-workers have recently described an asymmetric synthesis of (À)-adaline 7 in which RCM was used to afford a [3.3.1] azabicyclic ring system (Scheme 2) [6]. It was found that the hydrochloride salt 8 was unable to induce the same conformational control as a N-acyl group.…”

“…These systems possess added aryl groups fused to the interior of helical structure. Both protocols were found to be quite efficient for the formation of [6,7] required 60 min of microwave irradiation with 6 to undergo complete conversion to [7] helicene (81% isolated yield). Milder conditions with catalyst 34 also produced a 80% isolated yield of [7] helicene.…”

“…Precursor 36 underwent smooth conversion (100%) to the[6] helicene 37 after 60 minutes under microwave irradiation and was isolated in 80% yield. Similar yields were obtained using catalyst 34 at 40°C in a sealed tube (70%).…”

The chemistry of the carbon–transition metal double and triple bond: annual survey covering the year 2002

“…85) for total synthesis of lentiginosine [279]; (7) formation of tetrahydropyridine derivatives [280,281]; (8) asymmetric formation of tetrahydropyridine derivatives [282]; (9) formation of tetrahydropyridine derivatives for total synthesis of aspidosperma alkaloids [283]; (10) formation of 9-azabicyclo[3.3.1]nonane derivatives (e.g. 86) for total synthesis of adaline [284]; (11) formation of methylenedihydropyridines (e.g. 88) via RCM of a conjugated diene with a remote alkene [285]; (12) formation of bicyclic ␦-lactams (e.g.…”