Roush crotylboration

What is Roush crotylboration?

The Roush crotylboration reaction, also known as Roush asymmetric crotylboration or Roush crotylboronate chemistry, was first reported by Roush (Massachusetts Institute of Technology, MIT) in 1985. The reaction is an enantioselective synthesis of a chiral alcohol through the condensation of a crotylboronate, derived from diisopropyl-(R,R)-tartrate, with an achiral aldehyde.

Roush crotylboration - general reaction scheme - Roush asymmetric crotylboration - Roush crotylboronate chemistry
Roush crotylboration
  • R = alkyl, aryl
  • R1 = H, R2 = Me
  • or R1 = Me, R2 = H

The crotylboronates, which are derived from cis-2-butene or trans-2-butene through a series of treatments with n-BuLi/KO-t-Bu, B(i-Pr)3, acid, and diisopropyl tartrate, are referred to as Roush crotylboranes or Roush crotyl boronate reagents. These reagents can be conveniently stored in toluene solution in the freezer and do not require an extra oxidation step during the workup stage after the addition to the aldehyde.

The (Z)- and (E)-crotylboronates derived from diisopropyl-(R,R)-tartrate result in syn-homoallylic and anti-allylic alcohols, respectively. However, the crotylboronates generally yield only good to moderate enantioselectivity for the addition to most achiral aldehydes, with typical enantiomeric excess (e.e.) ranging between 60% and approximately 87%. Notably, the crotylboration reaction with metal carbonyl-complexed unsaturated aldehydes gives e.e. in the range of 83–98%.

To improve the enantioselectivity of the reaction, Roush’s group has developed a second generation of crotylboronates with a chiral auxiliary of (R,R)-N,N-bis-(2,2,2-trifluoroethyl)-N,N-ethylenetartramide. These reagents are among the most highly enantioselective and the auxiliary group can be easily recycled after the reaction.

References

Diastereo- and enantioselective aldehyde addition reactions of 2-allyl-1,3,2-dioxaborolane-4,5-dicarboxylic esters, a useful class of tartrate ester modified allylboronates
William R. Roush, Alan E. Walts, and Lee K. Hoong
Journal of the American Chemical Society 1985 107 (26), 8186-8190
DOI: 10.1021/ja00312a062

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