Clemmensen Reduction
The Clemmensen reduction allows the conversion of a carbonyl group to the corresponding methylene group using zinc amalgam and concentrated hydrochloric acid.
General features:
1. Due to the harsh conditions of the Clemmensen reduction, acid-sensitive substrates and polyfunctional ketones rarely deliver the expected alkanes. 2. Milder procedures have been developed to make the synthesis appropriate for acid- and heat-sensitive compounds (e.g., organic solvents saturated with dry HCl and activated zinc dust at ice-bath temperature).
Clemmensen Reduction
Reaction Mechanism
1. Attack of zinc and chloride ion on the carbonyl group. 2. Loss of water. 3. Formation of the carbanion and protonation.
Example
Experimental Procedure
To a stirred solution of the hydroxy ketone (17.2 mmol, 1.0 eq) and zinc powder (10.0 eq) in dichloromethane and methanol (1:1, 180 mL) was added trimethylsilyl chloride (10.0 eq) dropwise at 0 °C. The reaction mixture was stirred at room temperature for 2 h. The zinc powder was removed by filtration. The filtrate was neutralized with saturated solution of sodium bicarbonate. The reaction mixture was extracted with dichloromethane. The combined organic layer was washed with H2O and brine, dried over Na2SO4. The crude product was concentrated under reduced pressure without further purification (≥ 72% yield, ≥ 99% ee).
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