Convergent enantioselective synthesis of vinigrol, an architecturally novel diterpenoid with potent platelet aggregation inhibitory and antihypertensive properties. 1. Application of anionic sigmatropy to construction of the octalin substructure.
The coupling of building blocks 15 and 36e in the presence of MgBr(2).OEt(2) at 0 degrees C proceeds with an exo stereoselectivity (3.2:1) considerably more advantageous for the acquisition of carbinol 37e than in the absence of the additive (exo/endo = 1:5.7). The pivotal transformation that sets all of the relevant stereocenters of the cis-octalin 55 is the oxyanionic-accelerated [3,3]-sigmatropic rearrangement of 37e. A salient feature is the structurally enforced adoption of a boatlike transition state that serves to properly set four vicinal methine hydrogens in an all-cis arrangement. The ensuing conversion of 55 into iodo sulfone 62 has permitted X-ray crystallographic confirmation of all absolute stereochemical assignments since the isopropyl substituent was initially installed enantioselectively via the Evans oxazolidinone protocol. No intramolecular anionic cyclization of 62 to generate the tricyclic framework was seen. This absence of reactivity is attributed to conformational factors that inhibit attainment of the proper S(N)2 reaction trajectory.
Paquette
Leo A
LA
Department of Chemistry, The Ohio State University, Columbus, Ohio 43210, USA. paquette.1@osu.edu
Guevel
Ronan
R
Sakamoto
Shuichi
S
Kim
In Ho
IH
Crawford
Jason
J
D000959:Antihypertensive Agents / Q000138:chemical synthesis*; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis; D018360:Crystallography, X-Ray; D003500:Cyclization; D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000959:Antihypertensive Agents; D001643:Bridged Bicyclo Compounds; D004224:Diterpenes; D007202:Indicators and Reagents; D010975:Platelet Aggregation Inhibitors; C055112:vinigrol