The Stereoselective Preparation of an Enantiomerically Pure Cyclopentane Using Intramolecular Aldol Cyclopentaannulation of a Glucose Derivative

Abstract

Methods for the annulation of carbohydrates have found extensive applications in organic synthesis. We report here a new protocol for the stereoselective conversion of glucose into an enantiomerically pure cyclopentane aldehyde 22. The readily available epoxide 15 was reacted with allyl Grignard to produce alcohol 16 in 86% yield. Swern oxidation followed by epimerization using triethylamine in N,N-dimethylformamide furnished the ketone 17 also in 86% yield. Regioselective deprotonation with lithium hexamethyldisilazane in THF was followed by methylation with methyl iodide and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidone as cosolvent to give 80% yield of ketone 18. Oxidation of ketone 18 by the Wacker procedure gave the 1,4-diketone 19 in 56% yield. Intramolecular aldol condensation occurred readily on treatment of diketone 19 with potassium tert-butoxide in toluene to furnish a 90% yield of enone 20. Treatment with N-bromosuccinimide produced the bromoester 21 in 72% yield, which was reduced to a mixture of aldehydes 22 (61%) and 23 (14%) with zinc shot in 2-propanol.

Synthesis of Chiral Cyclopentenones

“…A protocol for the stereoselective conversion of glucose into enantiomerically pure cyclopentenone 722 was reported by Wood et al (Scheme ). The epoxide 717 , readily available from glucose, was subjected to Grignard reaction followed by Swern oxidation of 718 and epimerization using triethylamine in N , N -dimethylformamide, regioselective deprotonation of 719 with lithium hexamethyldisilazane (LiHMDS) and methylation with methyl iodide in the presence of 1,3-dimethyl-3,4,5,6-tetrahydro-2­(1 H )-pyrimidone (DMPU) as cosolvent, and oxidation of ketone 720 by the Wacker procedure.…”

Synthesis of new iso-C-nucleoside analogues from 2-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-α-d-altropyranosid-3-yl)ethanal

“…20,21 Benzylation of the 2-hydroxy group in THF with benzyl bromide and sodium hydride in the presence of tetrabutylammonium iodide 22,23 gave the branchedchain sugar 3. Postema et al have described the oxidation of similar unsaturated compounds with ozone in CH 2 Cl 2 followed by reduction with Zn/acetic acid to give the corresponding aldehydes.…”

Nucleoside Analogues from Branched-Chain Pyranosides

“…[20] Reaction of the branched-chain monosaccharide 2 with ethynylmagnesium bromide or lithium phenylacetylide in THF afforded, after 4 h at room temperature, butynols 3a and 3b as an inseparable mixture of diastereoisomers in 85 and 87% yield, respectively (Scheme 1). Disappearance of the aldehyde signals concurrently with the appearance of the new resonances for the alkyne carbon atoms in the 13 C NMR spectra clearly demonstrated the formation of the expected alcohols as R,S mixtures.…”