title: Stereoselective arylation of substituted cyclopentenes by substrate-directable Heck-Matsuda reactions: a concise total synthesis of the sphingosine 1-phosphate receptor (S1P(1)) agonist VPC01091.
abstract: We describe herein an efficient and diastereoselective substrate-directable Heck-Matsuda reaction with nonactivated five-membered olefins. The carbamate acts as the main directing group in the arylation process allowing the synthesis of several functionalized aryl cyclopentenes in good to excellent diastereoselectivities (>85:15) and in isolated yields ranging from 41 to 90%. No double bond isomerizations were observed in these Heck reactions, and the newly created benzylic centers were preserved in all cases examined. The substrate directable Heck arylation approach was successfully applied in a straightforward total synthesis of the sphingosine 1-phosphate receptor-subtype 1 (S1P(1)) agonist VPC01091 by a concise and practical route involving 5 steps in 40% overall yield.
authors.affiliation: Instituto de Química, Universidade Estadual de Campinas, UNICAMP, C.P. 6154, CEP, 13083-970, Campinas, São Paulo, Brazil.
authors.forename: Caio C
authors.initials: CC
authors.lastname: Oliveira
authors.forename: Emerson A F
authors.initials: EA
authors.lastname: dos Santos
authors.forename: Julia H Bormio
authors.initials: JH
authors.lastname: Nunes
authors.forename: Carlos Roque D
authors.initials: CR
authors.lastname: Correia
mesh_terms: D000475:Alkenes / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D049349:Receptors, Lysosphingolipid / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000475:Alkenes; D003517:Cyclopentanes; D049349:Receptors, Lysosphingolipid; C579735:rac-((1R*,3S*)-1-amino-3-(4-octylphenyl)cyclopentyl)methanol hydrochloride