The transformation of the carbonyl group of aldehydes and ketones to methylene derivatives can be achieved by chemical methods such as Clemmensen reduction³, Wolff-Kishner reduction⁴, LiAlH₄-AlCl₃⁵, NaBH₄-CF₃CO₂H⁶, Et₃SiH-BF₃ or CF₃CO₂H^7-9, HI-Phosphorus^10-11 or by catalytic hydrogenation¹². Catalytic transfer hydrogenation of the carbonyl group, however, has been reported only by Brieger and covorkers^13-14 using various hydrogen donors, palladium-carbon as the catalyst and ferric chloride as the Lewis acid promoter. In general, this reaction requires 3-12 hrs for completion. Recently, the effectiveness of ammonium formate as a catalytic hydrogen transfer agent in organic synthesis has been reviewed¹⁵. This agent has previously been employed in the Leuckart Reaction¹⁶ for conversion of aldehydes and ketones into primary and secondary amines.

In our ongoing program to develop efficient and fast synthetic methods for ¹¹C-α-amino acids (¹¹C t_½=20.4 min) such as [¹¹C-carboxyl]phenylalanine, [¹¹C-carboxyl]tyrosine, etc., via reductive carboxylation of acylnitromethane derivatives, we have developed a mild and rapid reduction of aromatic aldehydes and ketones to the corresponding methylene derivatives using ammonium formate as shown in Table I.

In most cases, the reaction is over within 10-30 min; however, in the case of 1-benzosuberone (11) and dibenzosuberone (10), reaction did not proceed to completion, and 40-45% of the ketone starting materials were observed on GC analysis [5% methyl silicone oil OV-101, column size 50 cm x 1/8", temperature programmed 50°C (1 min hold) to 280°C (3 min hold) at a rate of 25°C/min, helium flow rate 30 ml/min]. Neither increasing the reflux time (30 min to 4 hrs) nor adding an additional amount of ammonium formate changes the product/substrate ratio in the reaction mixture. The reduction of acetophenone was sluggish. After a 30 min reaction time interval, the product/substrate ratio in the reaction mixture was 1/5 observed by GC analysis (as described above, except initial temperature hold time 3 min). However, upon adding an additional amount of HCO₂NH₄ and increasing the reaction time up to 4 hr, the product/substrate ratio changed to 55/44. In the case of benzaldehyde, 1.5% toluene, 34% benzyl alcohol (retention time 4.9 min) and 60% high boiling byproduct (retention time 8.9 min) were observed in the reaction mixture after 20 min at 85°C. Prolonging the reaction time slowly increases the concentration of toluene (Table I) with reduction of benzyl alcohol. This important observation provides evidence that reduction of aldehydes and ketones to hydrocarbons proceeds via the alcohol intermediate, which is further confirmed by our finding that diphenylmethanol is rapidly converted to diphenylmethane under the experimental conditions reported here. The poor yield of toluene may be due to its low boiling point.

These results demonstrate a rapid, mild and selective reduction of a wide variety of aromatic aldehydes and ketones to methylene derivatives under moderate reaction conditions and can be an attractive alternative for Wolff-Kishner or Clemmensen reduction, provided other functionalities such as nitro or halo substituents are not present in the substrate, since these groups are readily reduced or displaced^17-18. We have found, however, this procedure is not applicable for reduction of conjugated olefinic carbonyl groups, as evidenced by the reduction of the double bond of debenzylideneacetone (12) to diphenethyl ketone in preference to the carbonyl group. It should also be noted in Table I that this procedure is useful for the synthesis of 2,4-dimethoxyethylbenzene, which is a key intermediate in the synthesis of Eticlopride¹⁹, a selective dopamine D₂-receptor antagonist.