Synthesis of Optically Active Bifunctional Isoprenoid Building Blocks by Rhodium(I)‐Catalyzed Asymmetric Allylamine to Enamine Isomerization

Abstract

AbstractThe application of the known asymmetric allylamine to enamine isomerization methodology to bifunctional C5‐isoprenoid allylic amines of types IId and IIe (Scheme 1) is described. It is shown that a number of such substrates can be isomerized with enantioselectivities of > 90% ee. using cationie Rh1 complexes containing (6. 6′‐dimethylbiphenyl′2, 2′‐diyl)bis(dipheny phosphine) (BIPHEMP; 9) as asymmetry‐inducing ligand (Scheme 2, Tables 1 and 2). Synthetically most useful is the isomerization of the benzyloxy derivative 10a into the (E)‐enamine 11a. This isomerization proceeds with very high enantioselectivity (98‐99% ee) and affords, after enamine hydrolysis, the optically active 4‐(benzyloxy)‐3‐methylbutanals ((R)‐ or (S)‐12) in chemical yields of ca. 90%. In conjunction, a short synthetic route to the starting material 10a has been developed which has a Pd‐catalyzed amination of isoprene epoxide (30) as the key step. Thus, convenient and practical access to the optically active aldehydes (R)‐and (S)‐12 is now at hand. These aldehydes are useful optically active bifunctional building blocks for isoprenoid homologation.