Racemization of Homoallyl Alcohols via an Allyl-transfer Reaction

Abstract

Acid-catalyzed asymmetric allylation of 3-phenylpropanal 2a via an allyl-transfer reaction from a chiral allyl donor, (1R,2S,5R)-1-allylmenthol, gave (R)-1-phenylhex-5-en-3-ol 3b enantioselectively. The optical yield (ee) of (R)-3b, however, decreased with increasing chemical yield, and the chemical yield increased with increasing reaction time. The racemization takes place via an acid-catalyzed allyl-transfer reaction from (R)-3b to 2a.

Key words

allyl-transfer reaction - homoallylic alcohol - asymmetric synthesis - racemization

References

• 1 Yamamoto Y. Asao N. Chem. Rev.  1993,  93:  2207 
• 2 Nokami J. Ohga M. Nakamoto H. Matsubara T. Hussain I. Kataoka K. J. Am. Chem. Soc.  2001,  123:  9168 ; references cited therein
• 3a Nokami J. Yoshizane K. Matsuura H. Sumida S. J. Am. Chem. Soc.  1998,  120:  6609 
• 3b Sumida S. Ohga M. Mitani J. Nokami J. J. Am. Chem. Soc.  2000,  122:  1310 
• 4 Loh et al. also observed an allyl-transfer reaction in the absence of aldehyde in their indium-promoted allyl-transfer reaction: Loh T.-P. Tan K.-T. Hu Q.-Y. Tetrahedron Lett.  2001,  42:  8705 

5

Homocrotyl alcohol 3a will be much more stable than homoallyl alcohol 4, because 3a has a thermodynamically more stable internal olefin and sterically less hindered structure. For example, we observed no racemization of 3a (Scheme [5] ) after treatment with 3-phenylpropanal (2a, 10 mol%) in the presence of TSA·H₂O (10 mol%) at 20 °C for 20 h (recovery: 92%).

Scheme 5