Stereochemistry of addition of carbanion reagents to 'diacetone fructose aldehyde'. Configurational assignment of a 1-deoxyheptulose derivative by X-ray crystallography and NMR studies directed to the assignment of isomeric adducts

摘要

The addition of carbanionic reagents to 'diacetone fructose aldehyde' (6) was investigated with a focus on the stereocontrol. The Grignard reagents, MeMgBr, EtMgBr, i-PrMgBr, and MeMgI, gave a high bias (>=90%) for one diastereomer, assigned as the R-isomer, in ether at -78 to 0 dreg C. The reaction of PhMgBr showed diminished diastereoselectivity under these conditions, with a significant dependence of the isomer ratio on temperature and solvent. PhCH_2MgBr only afforded the adduct of 'allylic rearrangement', namely 13, with poor diastereocontrol (ca. 60:40). MeLi, t-BuLi, PhLi, and LiCH_2CO_2-t-Bu provided adducts of 6 enriched in the R-isomer in the range of 80-89%, whereas 2-lithio-2-ethyl-1,3-dithiane gave a 94:6 ratio of R:S adducts (15a:15b). The R absolute stereochemistry at the carbinol C1 center of 4a was established through X-ray analysis of sulfamate derivative 2a. Carbon-13 NMR chemical shift criteria (the chemical shifts for Cl and C3) were identified to facilitate the stereochemical assignment of C1 adducts of 6.