ChemInform Abstract: Functionalized Diorganozinc Compounds: Key Reagents for the Synthesis of Enantiomerically Pure 2,5‐Disubstituted cis‐ and trans‐ Tetrahydrofurans.

Abstract

~ 1,4-Diol derivatives 4a-i were synthesized stereoselectively by either reagent-or catalyst-controlled routes using the addition of functionalized diorganozinc reagents to aldehydes. The stereoselectivities along the reagent-controlled synthetic path were in the range between 80:20 and 95:5. The stereoselectivities along the catalyst route exceeded 95:5. The 1,4-diol derivatives 4 thus obtained were transformed into enantiomerically pure cis-and trons-2,5-disubstituted tetrahydrofurans In this paper we report on a general solution to this problem by using functionalized diorganozinc reagentsLs], which allow the synthesis of both stereoisomers starting from common building blocks.Assuming that an intramolecular Williamson reaction will be used to close the THF ring, the following retrosynthetic scheme results (Scheme 1).The cis-THF 1 could be obtained from the dihydroxy tosylate syn-3, while the trans-THF 2 could be generated from the dihydroxy tosylate anti-3. Compound syn-3 should be available from the alcohol syn-4, which can either be obtained from the diorganozinc compound 5 and the aldehyde 6 (path A) or the diorganozinc compound 9 and the aldehyde 7 (path B). In path A a stereodirecting effect of the chiral center of the organozinc reagent 5 isIn contrast, path B makes use of the stereodirecting effect of a chiral catalyst 8['O] after blocking of the chiral center in 7 with a sterically demanding silyl ether. By use of the other enantiomer of the catalyst, ent-8, the dihydroxy tosylate anti3 should be available via the alcohol anti-4 from the building blocks 7 and 9 (path C). Reagent Control: Path APrevious studies had revealed that the organozinc iodide prepared from the enantiomerically pure acetonide iodide 10 showed a stereodirecting effect of the chiral center in the acetonide group in Lewis acid-catalyzed addition reactions with achiral and chiral aldehyded91. In this paper we report