Mitsunobu Reaction of Unbiased Cyclic Allylic Alcohols

Abstract

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.

Simple strategy for synthesis of optically active allylic alcohols and amines by using enantioselective organocatalysis

“…Among the simplest and most applied methods is the palladium-catalyzed π-allyl substitution. However, stereo-selective π-allyl substitution is mostly carried out on cis-substituted substrates giving retention of the relative stereochemistry of the products, while the corresponding trans-product is obtained usually by Mitsunobu inversion (43). Consequently, we believe that the described diastereoselective reaction can serve as a complementary method to the palladium-catalyzed reactions for the formation of both cis and trans-substituted allylic products.…”

Synthesis of polyhydroxylated decalins via two consecutive one-pot reactions: 1,4-addition/aldol reaction followed by RCM/syn-dihydroxylation

“…Despite the fact that the use of allylic alcohols as substrates in Mitsunobu reactions can be a challenging task, some successful examples can be found in the literature [49–50]. However, the reaction with benzoic acid did not proceed at all, whereas application of p -nitrobenzoic acid yielded a complicated mixture of products.…”

Stereoselective synthesis of trans-dihydronarciclasine derivatives containing a 1,4-benzodioxane moiety

“…However, the structure of the title compounds requires the inversion of this asymmetry centre. For this purpose, the Mitsunobu reaction [58] (triphenylphosphine, diethyl azodicarboxylate, anhydrous THF) seemed to be an obvious choice. Thus, compound (-)-33 or (-)-34 was converted to (?…”