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Application of the gold(I)‐Catalyzed aldol reaction to a stereoselective synthesis of (2 S , 3 R , 4 R , 6 E )‐3‐Hydroxy‐4‐methyl‐2‐(methylamino)oct‐6‐enoic Acid ( = MeBmt ), Cyclosporin's unusual amino acid
Author(s) -
Togni Antonio,
Pastor Stephen D.,
Rihs Grety
Publication year - 1989
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19890720707
Subject(s) - stereocenter , chemistry , stereoselectivity , aldol reaction , aldehyde , catalysis , stereochemistry , absolute configuration , hydrolysis , ring (chemistry) , enantioselective synthesis , organic chemistry
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.