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Dibal reduction of an amino acid derived methyl ester; Garner's Aldehyde

SyntheticPage 161 (2001)
Submitted 5th Sep 2001, published 5th Sep 2001

Rob Stockman (,
A contribution from the Stockman Group, UEA

Reaction Scheme

Chemicals Used
DIBAL (1 M solution in toluene) Potassium sodium tartrate (Rochelle's salt)

A solution of 3-(1,1-dimethyl-4-methyl)-(S)-2,2-dimethyloxazolidine-3,4-dicarboxylate (22.4 g, 86.15 mmol) in dry toluene (180 mL) in a 1 litre round bottomed flask was cooled under an atmosphere of argon to -78°C. A solution of DIBAL in toluene (147 mL of a 1 M solution) was added over 1 hour (see notes). The reaction was stirred for a further 2 hours at -78°C, before being quenched by the dropwise addition of dry methanol (33 mL). The reaction was allowed to warm to about -20°C internal temperature, and then poured into a vigorously stirred solution of Rochelle's salt (1.2M aqueous potassium sodium tartrate, 600 mL). The viscous solution was stirred vigorously for 2 hours, after which time it settled to two clear phases. The organic layer was separated, and the aqeous layer extracted three times with diethyl ether (150 mL each extraction). The combined organics were dried over magnesium sulfate and evaporated. Purification by distillation (83-85 °C, 0.2 mmHg) gave Garner's aldehyde (16.30g, 82%) as a colourless oil.

Author's Comments
It is important to keep the reaction solution as near -78°C at all times. An oversized flask is used, with the cooling bath level several inches above the level of the solution inside the flask. The DIBAL was added very slowly (over 1 hour) into the flask by "dribbling" down the inside wall of the flask. The DIBAL is thus cooled on it's way to the reaction solution. In this way, any over-reduction is avoided. This procedure has been carried out many times (>10) by the author on scales up to that described. Yields are reproducibly in the range 80-85%. DIBAL in hexanes also works.

1H (CDCl3, 300 MHz) 9.62 and 9.55 (1H, br s, CHO), 4.36 and 4.20 (1H, m), 4.09 (2H, m), 1.63 and 1.60 (3H, s), 1.57 and 1.51 (3H, s), 1.52 and 1.45 (9H, s). Most peaks are doubled due to restricted rotation of NBOC group. IR (thin film, cm-1) 1740 (CHO), 1710 (BOC).

Lead Reference
P. Garner and J. M. Park, Org Synth. 1991, 70, 18.

Other References
P. Garner and J. M. Park, J. Org. Chem. 1987, 52, 2361. A. McKillop, R. J. K. Taylor, R. J. Watson and N. lewis, Synthesis, 1994, 31. A. Dondoni and D. Perrone, Synthesis 1997, 527.

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