Graduate student Rambabu Sankranti will present his dissertation research “Exploration of Novel Synthetic Utility of Lithiated Acetonitrile” to the department.

Abstract:

Exploring “green” chemical technologies is of great importance in the synthetic community.¹ In particular, the one-pot reaction approach is a highly efficient and environmentally friendly protocol, which often (1) minimizes total process waste, (2) reduces operational complexity, and (3) improves cost effectiveness. Our research group has been interested in such practical “one-pot” methods, which enable easy access to a variety of useful organic molecules. Lithiated acetonitrile (LiCH₂CN) is a readily-available chemical reagent, originally introduced by Kaiser and Seebach in 1968 (Scheme 1).² Due to its synthetic versatility, the utilization of this reagent in organic synthesis has been continuously increasing. Our group has explored novel and practical “one-pot” reactions using LiCH₂CN and its derivatives. In one project, a one-pot stereoselective olefination for use in the synthesis of α,β-disubstituted acrylonitriles has been developed.³ The protocol efficiently produced a variety of α-substituted-α-diaminoboryl acetonitrile reagents in situ that underwent subsequent olefination with an aldehyde. The use of an aryl or conjugated aldehyde preferentially led to a (Z)-acrylonitrile, where as an aliphatic aldehyde gave an (E)-isomer as the major product. In another project, a mixture of n-butyllithium and lithiated acetonitrile (LiCH₂CN) unexpectedly converted styrene oxide into a C1-homologated allyl alcohol in an unusual regioselective manner.⁴  The reaction seems to involve a carbene-like intermediate which undergoes subsequent methylenation with LiCH₂CN. This protocol was extended to prepare a variety of 2,3-diaryl allyl alcohols. The use of 2-aryl acetonitriles in place of simple acetonitrile for the homologation reaction successfully provided the corresponding 2,3-diaryl allyl alcohols in a stereoselective manner with the (Z)-isomer predominating. The prepared allyl alcohols were subsequently utilized for the synthesis of the respective indene derivatives by means of the Lautens’ intramolecular Friedel-Crafts alkylation.

References:

1. (a) Chem. Rev. 2007, 107, 2169. (b) Chem. Res. 2002, 35, 686.
2. (a) Ber. 1968, 101, 3113. (b) J. Org. Chem. 1968, 33(9), 3402.
3. Org. Chem., 2011, 76(19), 8053
4. Lett., 2013, 15, 5099