Application of the gold(I)‐Catalyzed aldol reaction to a stereoselective synthesis of (2<i>S</i>, 3<i>R</i>, 4<i>R</i>, 6<i>E</i>)‐3‐Hydroxy‐4‐methyl‐2‐(methylamino)oct‐6‐enoic Acid ( = MeBmt), Cyclosporin's unusual amino acid

Abstract

Abstract The title compound 8 was prepared in three steps starting from the optically pure aldehyde (2 R , 4 E )‐2‐methyl‐hex‐4‐enal ( 3 ), thus constituting the shortest synthetic approach reported. Two of the three stereogenic centers in the product were generated in a coupling reaction of 3 with ethyl isocyanoacetate, catalyzed by a gold(I)/chiral ferrocenylphosphine system, giving the dihydrooxazole 5 in 85% diastereoselectivity (mismatchedcase). The weak effect of double stereodifferentiation in this reaction (matched case 90% ds) is discussed. N ‐Methylation and hydrolytic ring opening of 5 gave the protected form 7 of MeBmt, The X‐ray diffraction study carried out on 7 confirms the absolute configuration of the two stereogenic centers formed in the gold(I)‐catalytic reaction.