US EPA

1071415 

Journal Article 

Mitsunobu Reaction of Unbiased Cyclic Allylic Alcohols 

Shull, BK; Sakai, T; Nichols, JB; Koreeda, M 

1997 

Yes 

Journal of Organic Chemistry
ISSN: 0022-3263
EISSN: 1520-6904 

62 

24 

8294-8303 

English 

11671964 

The stereochemical inversion of unbiased allylic alcohols using triphenylphosphine, diethyl azodicarboxylate, and benzoic acid, commonly known as the Mitsunobu reaction, was studied in three different solvents with specific attention toward the product composition. The results generated for the Mitsunobu reaction of (R)-3-deuterio-2-cyclohexen-1-ol and the cis and trans isomers of 1-deuterio-5-methyl-2-cyclohexen-1-ol, 1-deuterio-5-tert-butyl-2-cyclohexen-1-ol, and optically active cis and trans 5-isopropyl-2-methyl-2-cyclohexen-1-ol all gave similar product distributions with respect to inversion and retention at the carbinol center as well-as syn and anti S(N)2' type addition when THF or benzene was used as the solvent (CH(2)Cl(2) gave less selective product distributions). Interestingly, it was found that the quasi-equatorial and quasi-axial nature of the starting allylic alcohol does not appear to affect the product distribution for this reaction, nor does methyl substitution at the central carbon of the allylic alcohol. In all cases, significant amounts (8-28%) of non-S(N)2 type products were detected for these sterically unbiased allylic alcohols; only 72-77% of the product was from S(N)2 type reaction when sterically undemanding (R)-3-deuterio-2-cyclohexen-1-ol was subjected to Mitsunobu conditions.