Nucleophilic substitution at the acetalic center of mandelate 1,3-dioxolan-4-ones using magnesio-copper reagents: Application to the synthesis of chiral secondary alcohols.
✍ Scribed by Bertrand Heckmann; Charles Mioskowski; Jurong Yu; J.R. Falck
- Book ID
- 104215785
- Publisher
- Elsevier Science
- Year
- 1992
- Tongue
- French
- Weight
- 222 KB
- Volume
- 33
- Category
- Article
- ISSN
- 0040-4039
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✦ Synopsis
Ethereal magnesia-copper reagents, in contrast to lithio-copper reagents, add stereoselectively to man&lie acid derived 1,3-dioxolawl-ones to dord optically active secondary alcohol &er removal of the chiral auxiliary.
1,3-Dioxan-4-ones' and 1,3-dioxolan-4-one& e.g., (1) and (2). respectively. have been used for the synthesis of chiral secondary alcohols via addition of silicon reagents. In the fotmer case, it was possible to extends this approach to lithium triorganocuprates (higher order cuprates); lithium diorganocuprates, however, tended to react at the carbonyl. Unfortunately, the chiral auxiliary required for (1) is expensive in its monomeric form (Aldrich Chem. Co.) and is only available commercially in its polymeric form as the (R)-antipode4 (Fluka Chem. Co.). We report herein methodology for exploiting 1.3~dioxoland-ones (2) derived from mandehc acid which is inexpensive and commercially available in both enantiomuic forms.
The condensation of mandelic acid with a variety of aldehydes in the presence of catalytic p-TsOH or BF3.Et20 according to literature procedures furnished 2-substituted-5-phenyl-1,3-dioxolan-4-ones (2) in yields of 70 % or better (90-98 % cis). The methodeof Noyori gave (2) nearly quantitatively, but with poorer stereoselectivity in some cases. e.g., pivaldehyde gave rise to an 86:14 cislrranr-mixture. Since the mandelate acetals are generally solids, cis-( 2) was typically obtained pure by recrystallixation7.