Enals transfer hydrogenation

Organocatalytic transfer hydrogenation of enals has been discussed as a route for synthesis of some lepidopteran pheromones. 

A primary alcohol and amines can be used as an aldehyde precursor, because it can be oxidized by transfer hydrogenation. For example, the reaction of benzyl alcohol with excess olefin afforded the corresponding ketone in good yield in the presence of Rh complex and 2-amino-4-picoline [18]. Similarly, primary amines, which were transformed into imines by dehydrogenation, were also employed as a substrate instead of aldehydes [19]. Although various terminal olefins, alkynes [20], and even dienes [21] have been commonly used as a reaction partner in hydroiminoacylation reactions, internal olefins were ineffective. Recently, methyl sulfide-substituted aldehydes were successfully applied to the intermolecu-lar hydroacylation reaction [22], Also in the intramolecular hydroacylation, extension of substrates such as cyclopropane-substituted 4-enal [23], 4-alkynal [24], and 4,6-dienal [25] has been developed (Table 1). 

General Procedure for Transfer Hydrogenation of Enals Using Symmetric Hantzsch Ester [97] (pp. 110 and 394)... 

Scheme 25. Asymmetric counteranion-directed catalysis transfer hydrogenation of enals...

Asymmetric Reduction of Enals by Transfer Hydrogenation. The metal-free reduction of olefins relies on the use of Hantzsch-type dihydropyridines, as hydrogen donors. The asymmetric variant of this reaction can be mediated by catalyst 1. The reduction is enantioconvergent both stereoisomers of... 

Since the first catalyst (7) used in the organocatalytic Diels-Alder reaction, several modificahons have been made to improve its catalytic properties. In 2002 the commonly called MacMillan second-generation catalyst (25) was used in the addihon of indoles to enals [10]. A few years later, MacMillan s third-generation catalyst (26) was used for the enantioselective transfer hydrogenation of enals (Figure 33.3) [11]. 

Scheme 33.24 Transfer hydrogenation of enals reported by MacMillan...

BOTH (Enantioselective Organocatalytic Transfer Hydrogenation) The group led by MacMillan showed that the combination of an imidazolidine catalyst 3 and a Hantzsch ester 4a is a powerful and versatile reducing agent (Scheme 32.2). They were able to selectively reduce 1,4-unsaturated enals and enones with yields up to 95% and ees up to 97%. 

SCHEME 32.3. Enantioselective organocatal)dic transfer hydrogenation (BOTH) of enals. 

Desulfurization through a-cleavage was shown to be the major product for a series of compounds 34 illustrated below [30]. These compounds, both benzylic and allylic, consistently showed cleavage on the benzylic side but suffered E/Z isomerization in the enal products 36 and 37 when not constrained by substitution. Deuterium labeling was consistent with the internal hydrogen transfer proposed to reach the sulEne 35. 

---