[102-69-2]  · C9H21N  · Tripropylamine  · (MW 143.31)

(in combination with trichlorosilane, for silylations, reductive silylations, and reductions;1 used as base in preparation of activated esters with 2-chloro-N-methylpyridinium iodide;2 used as base in preparation of b-lactams from activated esters and imines3)

Physical Data: mp -93.5 °C; bp 155-158 °C; d 0.753 g cm-3.

Solubility: sol alcohol, ether.

Form Supplied in: liquid, widely available.

Handling, Storage, and Precautions: handle with care; wear gloves and avoid breathing vapors. Use in a fume hood.

Reductive Silylations; Reductions.

Tripropylamine in combination with Trichlorosilane is an excellent reagent for reductive silylations and reductions in organic synthesis.1 Benzylic halides are readily converted into benzylic silanes (eq 1),4 while aromatic ketones,5 aldehydes,5 acid chlorides,6 and aromatic acids7 undergo reductive silylations with the tripropylamine-trichlorosilane combination. Aromatic ketones and aromatic aldehydes are converted to benzylic silanes which upon base hydrolysis are converted to the fully reduced compounds (eq 2).1 The reductive silylation and hydrolysis sequence can be carried out in one pot without isolation of the intermediate benzylsilane. Aromatic carboxylic acid groups are efficiently converted into methyl groups using the reductive silylation-hydrolysis protocol.8 The tripropylamine-trichlorosilane combination is used to reduce an aromatic carboxylic acid group selectively in the presence of an ester group (eq 3).9 The initially formed benzylic silane esters can be isolated if desired.

Activated Esters.

The reaction of a carboxylic acid with Mukaiyama's reagent 2-Chloro-1-methylpyridinium Iodide and a tertiary amine is a convenient method for preparing activated esters. In Mukaiyama's original work,10 Triethylamine, Tri-n-butylamine, and 2,6-Lutidine were shown to give good results; tripropylamine was not examined. Tripropylamine has now been used with Mukaiyama's reagent and acrylic acid to efficiently prepare sulfonamidoisobornyl acrylates, nonracemic chiral intermediates for asymmetric Diels-Alder reactions (eq 4).2 The reaction of activated esters and imines provides an important stereoselective synthesis of b-lactams via the Staudinger reaction. The use of Mukaiyama's reagent with tripropylamine (3 equiv) gives higher yields and greater stereoselectivity when compared with triethylamine or tributylamine (eq 5).3

Heterocyclic Synthesis.

The reaction of quinazoline-2,4-dione or 2,4-dichloroquinazoline with a mixture of Phosphorus Oxychloride, tripropylamine, and a cyclic tertiary amine (N-methylpiperidine, for example) gives an excellent yield of the 4-chloro-2-substituted quinazoline.11 The yield was substantially reduced without the use of tripropylamine. Interestingly, the regiochemistry is opposite to that observed for the reaction of 2,4-dichloroquinazoline with primary and secondary amines, where a 4-substituted-2-chloroquinazoline is obtained.

1. Benkeser, R. A. ACR 1971, 4, 94.
2. Oppolzer, W.; Chapuis, C.; Bernardinelli, G. TL 1984, 25, 5885.
3. Georg, G. I.; Mashava, P. M.; Guan, X. TL 1991, 32, 581.
4. (a) Benkeser, R. A.; Gaul, J. M.; Smith, W. E. JACS 1969, 91, 3666. (b) Furuya, N.; Sukawa, T. JOM 1975, 96, C1.
5. Benkeser, R. A.; Smith, W. E. JACS 1969, 91, 1556.
6. Benkeser, R. A.; Foley, K. M.; Gaul, J. M.; Li, G. S.; Smith, W. E. JACS 1969, 91, 4578.
7. Benkeser, R. A.; Gaul, J. M. JACS 1970, 92, 720.
8. (a) Benkeser, R. A.; Foley, K. M.; Gaul, J. M.; Li, G. S. JACS 1970, 92, 3232. (b) Li, G. S.; Ehler, D. F.; Benkeser, R. A. OS 1977, 56, 83; OSC 1988, 6, 747. (c) Pindur, U.; Pfeuffer, L. TL 1987, 28, 3079. (d) Pindur, U.; Pfeuffer, L. H 1987, 26, 325.
9. Benkeser, R. A.; Ehler, D. F. JOC 1973, 38, 3660.
10. Saigo, K.; Usui, M.; Kikuchi, K.; Shimada, E.; Mukaiyama, T. BCJ 1977, 50, 1863.
11. Yoshida, K.; Tanaka, T.; Ohtaka, H. JCS(P1) 1991, 1279.

Richard A. Conley

The R. W. Johnson Pharmaceutical Research Institute, Raritan, NJ, USA

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