(a-Triethylsilyl)propionaldehyde Cyclohexylimine

[119711-55-6]  · C15H31NSi  · (a-Triethylsilyl)propionaldehyde Cyclohexylimine  · (MW 253.56)

(reagent used for the selective formation of (E)-a-methyl-a,b-unsaturated aldehydes1)

Physical Data: bp 84-86 °C/0.1 mmHg.

Solubility: sol THF, sol ether.

Analysis of Reagent Purity: 1H NMR (300 MHz, CDCl3) d 7.65 (d, J = 6.7, 1H); 2.87 (tt, J = 10.6 and 4.1 Hz, 1H); 2.03 (pentet, J = 7.0 Hz, 1H); 1.82-1.20 (m, 10H); 1.16 (d, J = 7.0 Hz, 3H); 0.96 (t, J = 7.8 Hz, 9H); 0.60 (q, J = 7.9 Hz, 6H).1

Preparative Methods: prepared from propionaldehyde N-cyclohexylimine1,2 by treatment with Lithium Diisopropylamide in THF at -78 °C for 30 min followed by the addition of Chlorotriethylsilane and gradually warming to 0 °C over a 3-4 h period.2,3

Purification: by fractional distillation.1

Handling, Storage, and Precautions: use in a well-ventilated fume hood.

Formation of (E)-a-Methyl-a,b-unsaturated Aldehydes.

The anions of a-silyl aldimines have been used to prepare unsaturated aldehydes by means of Peterson alkenation reactions.4,5 The anions of a-trimethylsilyl- or a-triethylsilylpropionaldehyde t-butylimine are easily prepared by treatment of the silyl aldimine with LDA or s-Butyllithium (eq 1).4

Condensation of the a-lithio species with aldehydes and ketones conveniently yields a,b-unsaturated aldehydes following hydrolysis of the intermediate unsaturated imines (eqs 2 and 3).3,4

While the trimethyl and triethylsilyl aldimines (1) and (2) showed similar behavior in producing a,b-unsaturated aldehydes, the ability to isolate the triethylsilyl reagent (2) without contamination by the N-silyl enamine isomer makes it the preferred reagent.3 Additionally, the replacement of the t-butylimine with a cyclohexylimine affords a reagent (5) which is easily purified by fractional distillation.1 The anion of a-triethylsilylpropionaldehyde cyclohexylimine (5) is formed by the addition of s-BuLi in THF at -78 °C (eq 4).1 This anion condenses with aldehydes to produce a-methyl-a,b-unsaturated aldehydes in good yield after hydrolysis (eq 4).

The ratio of (E)- to (Z)-alkene products is dependent on the workup conditions. Addition of the a-silylaldimine anion to a carbonyl species gives a mixture of (E)- and (Z)-a-b-unsaturated imines, which upon hydrolysis with aqueous Oxalic Acid affords moderately selective formation of (E)-a,b-unsaturated aldehydes (eqs 4 and 5). Treatment of the mixture of imines with anhydrous Trifluoroacetic Acid in THF for a short period of time prior to aqueous hydrolysis serves to isomerize the imines and produce the trans-aldehyde with high selectivity (eqs 4 and 5).1 The anhydrous trifluoroacetic acid workup protocol thus provides a highly selective method for the preparation of (E)-a-methyl-a,b-unsaturated aldehydes.6

1. Desmond, R.; Mills, S. G.; Volante, R. P.; Shinkai, I. TL 1988, 29, 3895.
2. Campbell, K. N.; Sommers, A. H.; Campbell, B. K. JACS 1944, 66, 82.
3. Schlessinger, R. H.; Poss, M. A.; Richardson, S.; Lin, P. TL 1985, 26, 2391.
4. Corey, E. J.; Enders, D.; Bock, M. G. TL 1976, 7.
5. Peterson, D. J. JOC 1968, 33, 780.
6. (a) Corey, E. J.; Huang, H. C. TL 1989, 30, 5235. (b) Jones, T. K.; Reamer, R. A.; Desmond, R.; Mills, S. G. JACS 1990, 112, 2998. (c) Martin, S. F.; Dodge, J. A.; Burgess, L. E.; Hartmann, M. JOC 1992, 57, 1070.

John M. McGill

Eli Lilly and Company, Lafayette, IN USA

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