[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.
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
John M. McGill
Eli Lilly and Company, Lafayette, IN USA