Metal-dependent reaction tuning with cyclopentylmetal reagents: application to the asymmetric synthesis of (+)-alpha-conhydrine and (S)-2-cyclopentyl-2-phenylglycolic acid.
The reaction profile of the cyclopentyl organometallic reagents with the aliphatic ketones can be tuned to reduction or addition by changing the metal atom. Cyclopentylmagnesium bromide (CPMB) reduces aromatic and aliphatic aldehydes and ketones to the corresponding alcohols without any C-C bond formation and shows good diastereoselectivity in the reduction of the substituted cyclic and polycyclic ketones as well as chiral alpha-oxygenated aliphatic ketones. However, in the presence of 10 mol % of ZnCl(2), the cyclopentylmagnesium halides follow a normal Grignard addition to the ketones to give tertiary alcohols with complete diastereoselectivity. The reductive as well as the addition protocols were used for the asymmetric synthesis of two medicinally important compounds, (+)-alpha-conhydrine and (S)-2-cyclopentyl-2-phenylglycolic acid.
Roy
Siddharth
S
Bio-Organic Division, Bhabha Atomic Research Centre, Mumbai 400 085, India.
Sharma
Anubha
A
Mula
Soumyaditya
S
Chattopadhyay
Subrata
S
D000447:Aldehydes / Q000737:chemistry; D003517:Cyclopentanes / Q000138:chemical synthesis*; D006016:Glycolates / Q000138:chemical synthesis*; D007659:Ketones / Q000737:chemistry; D008670:Metals / Q000737:chemistry; D009942:Organometallic Compounds / Q000138:chemical synthesis*; D010084:Oxidation-Reduction; D010880:Piperidines / Q000138:chemical synthesis*; D013237:Stereoisomerism
C538785:(S)-2-cyclopentyl-2-phenylglycolic acid; D000447:Aldehydes; D003517:Cyclopentanes; D006016:Glycolates; D007659:Ketones; D008670:Metals; D009942:Organometallic Compounds; D010880:Piperidines; C520251:alpha-conhydrine; C538704:cyclopentylmagnesium bromide