Red-Al^® Reducing Agent

Red-Al^®, or sodium bis(2-methoxyethoxy)aluminum dihydride (Vitride^®, SMEAH), is a versatile reducing agent and a good substitute for LiAlH₄ in many reactions. Red-Al^® is nonpyrophoric, although still moisture-sensitive, and is available in solution, allowing for easier handling compared to LiAlH₄.

Red-Al^® is particularly effective at the reduction of epoxides. A recent example employs Red-Al^® in a key step in the asymmetric synthesis of (R)-fluoxetine hydrochloride. The enantiomerically pure α,β-epoxyamide was reduced by Red-Al^® in the presence of 15-crown-5 to produce the β-hydroxyamide in good yield and excellent selectivity (Scheme 23).¹

Cao and co-workers utilized Red-Al^® to convert propargyl chlorides to allenes, which were subsequently used in a tandem Pauson-Khand reaction to create 3,7-diisopropylsilyldicyclopenta-[a,e]pentalene, a 14π annulene (Scheme 24).²

The preparation of highly functionalized α,β-disubstituted alkenoates can be achieved under mild conditions by reducing an acetylenic ester with Red-Al^® and quenching the reaction with iodine to yield the vinyl iodide. The vinyl iodide can be subsequently transformed via Sonogashira or Stille coupling to form the desired α,β-disubstituted alkenoates (Scheme 25).

Red-Al^® displays excellent (E)-selectivity in the reduction and does not reduce the methyl ester.³ Red-Al^® reduction can selectively produce dialdehydes from aromatic diesters in the presence of N-methylpiperazine (Scheme 26). Although Red-Al^® is regularly employed in the reduction of esters to aldehydes, reduction of the diester without the addition of the amine produced only the dicarbinol.⁴