Lithium Chloride-Hexamethylphosphoric Triamide1

LiCl-(Me2N)3PO
(LiCl)

[7447-41-8]  · ClLi  · Lithium Chloride-Hexamethylphosphoric Triamide  · (MW 42.39) (HMPA)

[680-31-9]  · C6H18N3OP  · Lithium Chloride-Hexamethylphosphoric Triamide  · (MW 170.24)

(chloride displacement reactions, dehydrohalogenation reactions, and decarboxylative alkylations)

Physical Data: see Lithium Chloride and Hexamethylphosphoric Triamide.

Chloride Displacement.

In an early example, SN2 attack of chloride ion on an (S)-tosylate produced the (R)-alkyl chloride in 62% yield with nearly complete inversion of stereochemistry (98% ee) without rearrangement of the neopentyl group (eq 1).2 Allylic chlorides can be easily prepared from the corresponding allylic alcohols (eq 2).3 Attempts to use a mesitoate nucleophile failed under these conditions.4 In situ generation of the allylic tosylate and subsequent displacement by chloride led to good yields of allylic chlorides that were further used for Grignard coupling reactions. Utilization of these conditions precluded any formation of the tertiary halide via SN2-like reactions.

Dehydrohalogenation.

Lithium chloride, with HMPA as solvent and Lithium Carbonate as a buffer, has been used for large-scale dehydrobromination reactions to prepare 1,3-cyclohexadiene (eq 3).5 The same reaction sequence has been used to prepare a mixture of two deuterium-labeled cyclohexadienes that have been further reacted with Maleic Anhydride to prepare labeled Diels-Alder adducts (eq 4).5

A similar protocol has been used in more substituted examples to provide substrates that can be utilized for bis-epoxidation (eq 5).6 Diepoxide compounds of this type are novel antitumor agents.

Decarboxylative Alkylation.

It has been reported that the decarboxylation of b-diesters with LiCl and HMPA provided evidence that it was possible to alkylate the putative anion with various electrophiles such as Benzyl Bromide.7 Further, it was shown that replacement of HMPA with Dimethyl Sulfoxide as the solvent retarded the rate of the reaction. The use of any base other than LiCl gave poorer yields.8 b-Vetivone has been prepared utilizing an intramolecular alkylation via an anion derived from the induced decarboxylation of a b-keto ester (eq 6).9 Similar results can be achieved using 1-Methyl-2-pyrrolidinone, but replacement of this solvent with N,N-Dimethylformamide resulted in a substantial reduction in yield.


1. Normant, J.; Deshayes, H. BSF 1967, 2455.
2. Stephenson, B.; Solladie, G.; Mosher, H. S. JACS 1972, 94, 4184.
3. Stork, G.; Grieco, P. A.; Gregson, M. TL 1969, 1393.
4. Arnold, R. T.; Searles, S. JACS 1949, 71, 2021.
5. Weisz, A.; Mandelbaum, A. JOC 1984, 49, 2648.
6. Demuth, M. R.; Garrett, P. E.; White, J. D. JACS 1976, 98, 634.
7. Asaoka, M.; Miyake, K.; Takei, H. CL 1975, 1149.
8. Takei, S.; Kawano, Y. TL 1975, 4389.
9. Eilerman, R. G.; Willis, B. J. CC 1981, 30.

Dennis Wright & Mark C. McMills

Ohio University, Athens, OH, USA



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