The PGA Research Group

Thomas Morsch

 

The Birch reduction1 is a very useful and widely-used method for the dearomatization of benzene derivatives. The products of the reaction are non-conjugated dienes, and the regioselectivity is determined by the electronic nature of the substituents on the aromatic ring (Scheme 1).

Scheme 1

TMM1

The non-conjugated dienes from the Birch reduction are excellent substrates for the highly enantioselective Ir-catalyzed hydrogenation reactions2 developed in the Andersson group (Scheme 2). The prochiral dienes are chemoselectively reduced in high yield and with exquisite levels of enantioselectivity (ee).
           
Scheme 2

TMM2

The chiral alkenes from the Ir-catalyzed hydrogenation are amenable to further manipulation to useful chiral building blocks2, and the overall process has great potential for complex molecule synthesis. This potential remains relatively unexplored, however, and the objective of the present project3 is to employ the Birch-Andersson sequence in the enantioselective synthesis of biologically active and structurally complex natural products.

References

  1. (a) Birch, A. J. J. Chem Soc. 1944, 430; (b) Review: Rabideau, P. W.; Marcinow, Z. Org. React. 1992, 42, 1-334.
  2. See, e.g., Paptchikhine, A.; Itto, K.; Andersson, P. G. Chem. Commun. 2011, 47, 3989.
  3. Peters, B. K.; Liu, J.; Margarita, C.; Rabten, W.; Kerdphon, S.; Orebom, A.; Morsch, T.; Andersson, P. G. J. Am. Chem. Soc. 2016, 138, 11930.