[217459-11-5]  · C22H28FeN2  · (MW 376.90)

(chiral catalyst for the O-to-C rearrangement of O-acylated enolates, the kinetic resolution of primary amines, and the dynamic kinetic resolution/ring opening of azlactones)

Physical Data: mp 165-172 °C.

Solubility: soluble in t-amyl alcohol, chlorinated, aromatic, and ethereal solvents.

Form Supplied in: burgundy crystals.

Handling, Storage, and Precautions: can be handled in air; best if stored under nitrogen.

O-to-C Rearrangement of O-Acylated Enolates

This chiral derivative of 4-(pyrrolidino)pyridine (PPY) serves as an enantio-selective catalyst for the rearrangement of O-acylated enolates to their C-acylated isomers, a process first described by Steglich using PPY and DMAP.1 With the chiral PPY derivative, a new quaternary stereocenter is produced in excellent yield and very good enantiomeric excess (1).2,3 The reaction products function as protected a-alkylated a-amino acid equivalents (2).4 Preliminary mechanistic studies are consistent with the pathway illustrated in 3. This is the first example of a stereoselective variant of the Steglich rearrangement.

Kinetic Resolution of Primary Amines

This chiral PPY derivative also serves as an effective catalyst for the kinetic resolution of primary amines.5 O-Acylated azlactones are the acyl-ating agents of choice -with more conventional reagents such as acid chlorides and anhydrides, the uncatalyzed background reaction is significant. Selectivity factors (selectivity factor = (rate of fast-reacting enantiomer)/(rate of slow-reacting enantiomer)) ranging from 11 to 27 are obtained for aryl/alkyl-substituted primary amines (4).6

Dynamic Kinetic Resolution/Ring Opening of Azlactones

A closely related catalyst 2 (NMe2 in place of the pyrrolidino group) effects the dynamic kinetic resolution/ring opening of azlactones with moderate enantioselection (5).7

1. Steglich, W.; Höfle, G., Tetrahedron Lett. 1970, 4727.
2. Ruble, J. C.; Fu, G. C., J. Am. Chem. Soc. 1998, 120, 11532.
3. Corey, E. J.; Guzman-Perez, A., Angew. Chem., Int. Ed. Engl. 1998, 37, 388.
4. Wirth, T., Angew. Chem., Int. Ed. Engl. 1997, 36, 225.
5. Johansson, A., Contemp. Org. Synth. 1995, 2, 393.
6. Arai, S.; Bellemin-Laponnaz, S.; Fu, G. C., Angew. Chem. Int. Ed. 2001, 40, 234.
7. Liang, J.; Ruble, J. C.; Fu, G. C., J. Org. Chem. 1998, 63, 3154.

Gregory C. Fu

Massachusetts Institute of Technology, Cambridge, MA, USA

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