An Efficient and General Method for the Synthesis of α,ω-Difunctional Reduced Polypropionates by Zr-Catalyzed Asymmetric Carboalumination: Synthesis of the Scyphostatin Side Chain

✍ Scribed by Ze Tan; Ei-ichi Negishi

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 138 KB
• Volume: 43
• Category: Article
• ISSN: 0044-8249
• DOI: 10.1002/anie.200353429

✦ Synopsis

We recently reported an efficient and general method for the synthesis of reduced polypropionates with a single heterofunction [1] through the application of Zr-catalyzed asymmetric carboalumination. [2, 3] In view of the large number of complex natural products that are of medicinal and biological interest, such as scyphostatin (1), [4] ionomycin, [5] doliculide, [6] and borrelidin, [7] we thought it worthwhile to search for a related method for the synthesis of terminally differentiated a,w-difunctional reduced polypropionates through the use of Zr-catalyzed asymmetric carboalumination. [1][2][3] We report herein one such method involving 1) just one relatively inexpensive and enantiomerically pure (! 99 % ee) methyl (R)-or (S)-3-hydroxy-2-methylpropionate and 2) a catalytic and reagent-controlled asymmetric carbometalation [1][2][3] with Me 3 Al and either enantiomer of [ZrCl 2 (nmi) 2 ] (nmi = 1neomenthylindenyl; see 2). [8] We also report the application of this method to the synthesis of the scyphostatin side chain.

Preparation of 3 (Scheme 1) started with protection of methyl (S)-3-hydroxy-2-methylpropionate (! 99 % ee; TCI,