Stereoselective synthesis of (+)-nephrosteranic acid, (+)-trans-cognac lactone, and (+)-trans-whisky lactone using a chiral cyclohexadienyl Ti compound.
We present the stereoselective transfer of cyclohexadienyl from 3-metalated 1,4-cyclohexadienes to various aldehydes. Lewis-acid-mediated "allylation" of aldehydes by treatment with 3-silylated and 3-stannylated 1,4-cyclohexadienes could not be achieved with high diastereoselectivity. In contrast, cyclohexadienyl titanium compounds reacted with both aliphatic and aromatic aldehydes with good-to-excellent diastereoselectivities. Reaction of a chiral TADDOL-derived (TADDOL, 2,2-dimethyl-alpha,alpha,alpha',alpha'-tetraphenyl-1,3-dioxolandimethanol) cyclohexadienyl Ti derivative with various aldehydes led to the corresponding homoallylic alcohols with excellent diastereo- and enantioselectivities. Lower selectivities were obtained with chiral B-cyclohexadienyldiisopinocampheylborane. The 1,3-cyclohexadienes are very useful building blocks for the preparation of biologically important gamma-butyrolactones. Short efficient syntheses of (+)-nephrosteranic acid, (+)-trans-whisky lactone, and (+)-trans-cognac lactone by desymmetrization of 1,4-cyclohexadiene are described.
Schleth
Florian
F
Fachbereich Chemie der Universität Marburg, Hans-Meerwein-Strasse, 35032 Marburg, Germany.
Vogler
Thomas
T
Harms
Klaus
K
Studer
Armido
A
D000447:Aldehydes / Q000737:chemistry; D018360:Crystallography, X-Ray; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry; D007202:Indicators and Reagents; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000737:chemistry*; D013237:Stereoisomerism
D000447:Aldehydes; D005663:Furans; D007202:Indicators and Reagents; D007783:Lactones; D009942:Organometallic Compounds; C505946:cyclohexadienyl titanium; C456480:nephrosteranic acid