Lithium Morpholide

[37828-58-3]  · C4H8LiNO  · Lithium Morpholide  · (MW 93.07)

(in situ protection of aromatic aldehydes via a-amino alkoxides;1 nucleophile capable of adding to activated triple bonds6-8)

Preparative Methods: prepared in situ by adding n-Butyllithium to Morpholine in anhydrous organic solvents at -40 °C.

Handling, Storage, and Precautions: highly flammable; should be kept under a nitrogen or argon atmosphere. Use in a fume hood.

Lithium morpholide (1) is conveniently used for in situ protection of aldehydes as a-amino alkoxides.1a This method has been used to regioselectively alkylate substituted benzaldehydes (eq 1)2 and furaldehydes. Better solubility of (1) and the corresponding a-amino alkoxide in THF at low temperature makes (1) more convenient to use than other reagents such as lithium N-methylanilide and Lithium Piperidide.2

N-Formylmorpholine can be prepared by reacting (1) with Carbon Monoxide in THF.3,4 Electrochemically, (1) can react with THF to give the aminotetrahydrofuran (2) (eq 2).5

Like other lithium amides, lithium morpholide adds to various activated triple bonds to give vinyllithiums (3) (eq 3)6 or allenes (4) (eq 4).7

The morpholyl imine (5) is the product from the reaction of triethoxyacetonitrile with lithium morpholide (1) (eq 5).8

N-(a-Cyanoacetyl)morpholine is prepared by the nucleophilic substitution of ethyl cyanoacetate with lithium morpholide.9 Dimerization resulting in bimorpholine has been observed when (1) is treated with Copper(I) Chloride.10

Related Reagents.

N-Lithio-N,N,N-trimethylethylenediamine; Lithium N-Methylpiperazide; Lithium Piperidide.

1. (a) Comins, D. L. SL 1992, 615. (b) Denat, F.; Gaspard-Iloughmane, H.; Dubac, J. S 1992, 954. (c) Lee, G. C. M.; Holmes, J. M.; Harcourt, D. A.; Garst, M. E. JOC 1992, 57, 3126.
2. Comins, D. L.; Brown, J. D. TL 1981, 22, 4213.
3. Perez, D. G.; Nudelman, N. S. JOC 1988, 53, 408.
4. Furlong, J. J. P.; Lewkowicz, E. S.; Nudelman, N. S. JCS(P2) 1990, 1461.
5. Fuchigami, T.; Sato, T.; Nonaka, T. JOC 1986, 51, 366.
6. Feit, B.-A.; Dickerman, S.; Masrawe, D.; Fishman, A. JCS(P1) 1988, 927.
7. Maas, G.; Würthwein, E-U.; Singer, B.; Mayer, T.; Krauss, D. CB 1989, 122, 2311.
8. Kantlehner, W.; Maier, T.; Kapassakalidis, J. J. S 1982, 276.
9. Bhawal, B. M.; Khanapure, S. P.; Biehl, E. R. SC 1990, 20, 3235.
10. Jackisch, J.; Legler, J.; Kauffmann, T. CB 1982, 115, 659.

Daniel L. Comins & Sajan P. Joseph

North Carolina State University, Raleigh, NC, USA

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.