US EPA

1954812 

Journal Article 

TOTAL SYNTHESIS OF SPATANE DITERPENES - THE TRICYCLIC NUCLEUS 

Salomon, RG; Sachinvala, ND; Roy, S; Basu, B; Raychaudhuri, , SR; Miller, DB; Sharma, RB 

1991 

Yes 

Journal of the American Chemical Society
ISSN: 0002-7863
EISSN: 1520-5126 

113 

8 

3085-3095 

WOS:A1991FG03200043 

A convergent, stereocontrolled construction of the cis,anti,cis-tricyclo[5.3.0.0(2,6)]decane nucleus of spatane diterpenes was achieved by 2-pi + 2-pi photocycloaddition of 2-cyclopenten-1-one, as an A-ring precursor, with a carbonyl-masked derivative of 6-methylbicyclo[2.2.1]hept-5-en-2-one as a temporarily bridged C-ring precursor. By design, the temporary bridge assures the correct stereochemical relationship between the B-ring stereocenters and the C-ring hydroxyl substituent that is present in latent form in the oxoethano bridge. Serendipitously, the bridge also fosters a favorable orientation of the photocycloaddition that contrasts with the nonselective 2-pi + 2-pi-photocycloadditions of unbridged 1-methylcyclopentenes with 2-cyclopenten-1-one. Wittig methylenation of the A-ring carbonyl in photoproduct 24 followed by hydrolysis to 25 and catalytic hydrogenation introduces a methyl group at position 1 with a 10:1 preference for the requisite stereochemistry in 26. Even higher stereoselectivity was achieved by SO2-promoted isomerization of the exocyclic C=C bond in 25 to an endocyclic disposition in 29 prior to catalytic hydrogenation. Johnson's sulfoximine method is especially effective for resolution of ketone 29. The oxoethano bridge in ketone 26n is oxidized rapidly but nonregioselectively by an H2SO4-catalyzed reaction with peracetic acid, producing a 57:43 mixture of 14 and 34. Regioselective generation of the desired lactone 14 could be accomplished by a much slower oxidation with peracetic acid and no added H2SO4. The necessary configuration at position 7 in 49 was generated stereoselectively by a novel homoallylic hydroxyl-directed, pseudointramolecular delivery of hydride to the methylenemalonic ester in the precursor 48. Conversion of the malonic ester moiety in 49 into an allylic alcohol was accomplished in 92% overall yield by monosaponification, decarboxylative condensation with formaldehyde and reduction of the resulting acrylic ester with i-Bu2AlH. Selective oxidation of the allylic hydroxyl followed by acetylation delivered acetate (+)-11a, which is identical with an oxidative degradation product from spatane diterpenes.