Synthesis of monoprotected 2-alkylidene-1,3-propanediols by an unusual SN2′ Mitsunobu reaction

✍ Scribed by André B. Charette; Bernard Côté

• Publisher: Elsevier Science
• Year: 1993
• Tongue: French
• Weight: 250 KB
• Volume: 34
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)91807-0

✦ Synopsis

A simple and efficient route to monoprotected E-and Z-2-alkylidene-1 ,Zpropanediols was developed. The key step involves an unusual regio-and stereoselective SR2' Mitsunobu reaction of substituted 3-hydtoxy-2methylenealkenoate. We recently reported that 3.4,~tri-0-benzyl-D-glucose could be used as an efficient and practical chiral auxiliary for the cyclopropanation of variety of substituted allylic alcohols.2 In connection with an ongoing synthetic program, we were interested in the unexplored cyclopropanation of protected 2-alkylidene-1,3propanediols using our chiral auxiliary (Scheme 1). Scheme 1 We were surprised to find very little investigation in the chemistry of the required Zalkylidene-13propanediol precursors 1.3 Furthermore. the few approaches available do not allow stereochemical control of the olefin and differentiation of the oxygenated positions: two essentials requirements in our system. The first approach we investigated was based on Hoffmann's protocol4 that produces 2-bromomethyl-2-alkenoate 3 in 2 steps from methyl acrylate (Scheme 2). The bromide could be subsequently displaced with either ammonium fonnatr? or NaOAce to produce ester 4a or 4b , two suitable precursors to monoprotected diol 1.' Scheme 2

Based on the regioselectivity and stereoselectivity of the bromination reaction in these systems, we envisioned that under the Mitsunobu conditions.8 the Michael acceptor nature of the oxophosphonium salt 5 derived from 2 should be increased and potential for y-attack may be favored over a-attack (Figure 1).