Overman Rearrangement

The Overman Rearrangement allows the conversion of readily available allylic alcohols into allylic amines by a two-step synthesis involving the rearrangement of an allylic trichloroacetimidate to an allylic trichloroacetamide with clean 1,3-transposition of the alkenyl moiety.

Allylic amines are useful precursor of a variety of nitrogen-containing molecules, such as alkaloids, antibiotics and unnatural amino acids.

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Mechanism of the Overman Rearrangement

The deprotonated alcohol adds to trichloroacetonitrile to give a trichloroacetimidate anion. As this latter intermediate can readily deprotonate the starting alcohol, only a catalytic amount of a strong base is needed.

The formation of the allylic amine can involve a thermal [3,3]-sigmatropic rearrangement - comparable to the Claisen Rearrangement - that prefers to proceed via a chair-like transition state:

Alternatively, the rearrangement can be induced by a transition metal catalyst such as Pd(II) or Hg(II):

Some chiral transition metal catalysts bind with face-selectivity toward the substrate, which enables the enantioselective conversion of prochiral starting materials:

C. E. Anderson, L. E. Overman, J. Am. Chem. Soc., 2003, 125, 12412-12413.

For a more detailed explanation of the reaction mechanism and the stereoselection induced by transition metal catalysts along with some early examples of Pd-catalyzed chiral conversions, please refer to a recent publication by L. E. Overman (J. Org. Chem. 1997, 62, 1449. DOI).

Recent Literature

Catalytic Asymmetric Rearrangement of Allylic Trichloroacetimidates. A Practical Method for Preparing Allylic Amines and Congeners of High Enantiomeric Purity
C. E. Anderson, L. E. Overman, J. Am. Chem. Soc., 2003, 125, 12412-12413.

Catalytic Asymmetric Formation of Secondary Allylic Amines by Aza-Claisen Rearrangement of Trifluoroacetimidates
Z.-q. Xin, D. F. Fischer, R. Peters, Synlett, 2008, 1495-1499.

Improved Conditions for Facile Overman Rearrangement
T. Nishikawa, M. Asai, N. Ohyabu, M. Isobe, J. Org. Chem., 1998, 63, 188-192.

A General, Highly Enantioselective Method for the Synthesis of D and L α-Amino Acids and Allylic Amines
Y. K. Chen. A. E. Lurain, P. J. Walsh, J. Am. Chem. Soc., 2002, 124, 12225-12231.

[(NHC)Au^I]-Catalyzed Rearrangement of Allylic Acetates
N. Marion, R. Gealageas, S. P. Nolan, Org. Lett., 2007, 9, 2653-2656.