Annelations of cyclic Beta-cyanoketones in the synthesis of functionalized polycyclic compounds and steroids

Cyclic ß-cyano ketones like cyanocarvone and 3-cyano-2-methylcyclopentanone can be annelated in high yields with methyl vinyl ketone, ethyl vinyl ketone and 6(3- methoxyphenyl)hex-1-en-3-one to cyano-substituted decalones and indanones. Computational studies at the B3LYP/6-31+G(d,p)//B3LYP/6-31G(d,p) level of theory show that thermodynamic rather than kinetic factors can explain the high yields. The annelated products are suitable intermediates for the synthesis of isoprenoid, steroid and homo steroid skeleton

(3R,5S,6S,8R,10S)-8-Acetyl-7-hydroxy-3-isopropenyl-10-methylperhydrophenanthren-1-one

In the crystal structure of the title compound, C20H30O3, there is an intramolecular hydrogen bond between the hydroxyl and acetyl groups [O...O = 2.722 (3) A

17-Isopropyl-3-methoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene

The steroid ring B of the title compound, C22H32O, is in a half-chair conformation. The five-membered ring is in an intermediate form between the envelope and half-chair conformation

New approaches toward the synthesis of (D-homo) steroid skeletons using Mukaiyama reactions

New, short, and flexible procedures have been developed for syntheses of steroid and D-homo steroid skeletons. A Mukaiyama reaction between the silyl enol ether of 6-methoxytetralone and 2-methyl-2-cyclopentenone or carvone, with transfer of the silyl group to the receiving enone, gave a second silyl enol ether. Addition of a carbocation, generated under Lewis acid conditions from 3-methoxy-2-butenol, 3-ethoxy-3-phenyl-2-propenol or 3-methoxy-2-propenol to this second silyl enol ether gave adducts, which could not be cyclized by aldol condensation to (D-homo) steroid skeletons. The Mukaiyama-Michael reaction of the silyl enol ether of 6-methoxy tetralone with 2-methyl-2-cylopentenone gave a second silyl enol ether, which reacted in high yield with a carbocation generated from 3-hydroxy-3-(4-methoxyphenyl)propene. Ozonolysis of the double bond in this adduct gave a tricarbonyl compound (Zieglers triketone), which has been used before in the synthesis of 9, 11-dehydroestrone methyl ether. A second synthesis of C17 substituted CD-trans coupled (D-homo) steroid skeletons has been developed via addition of a carbocation, generated with ZnBr2 front a Torgov reagent, to a silyl enol ether containing ring D precursor. The obtained seco steroids have been cyclized under formation of the 8-14 bond by treatment with acid. The double bonds in one of the cyclized products have been reduced to a C17-substituted all trans steroid skeleton

Mukaiyama and Torgov Chemistry in the Synthesis of (D-homo) Steroid Skeletons

Three new, short, and efficient procedures have been developed for syntheses of steroid and D-homo steroid skeletons by application of Mukaiyama and Torgov chemistry. An important element in the first and in the second route is a Mukaiyama-Michael reaction with transfer of the silyl group from the starting silyl enol ether to the carbonyl group of the receiving enone. In this way a new silyl enol ether is obtained which enables either a selective reaction with the silyl enol ether in ring D as in route 1, or a selective reaction with the unprotected carbonyl group in ring B as in route 2. In all three approaches the C12-C13 bond is constructed using a Mukaiyama reaction of a Torgov type carbocation precursor with a silyl enol ether as the key transformation. In route 1, Zieglers triketone, which has been used before in the synthesis of 9,11 -dehydroestrone methyl ether, has been prepared in four easy steps and in 70% overall yield, using the reactions mentioned above. In the second route a selective Grignard reaction of vinyl magnesium bromide with the unprotected carbonyl group of methoxy tetralone leads to a Torgov type intermediate. This can be converted easily into a carbocation, which then reacts intramolecularly with the silyl enol ether in ring D, under formation of the C12-C13 bond to complete the synthesis of cis (D-homo) steroid skeletons. In the third route, C 17 substituted C,D trans coupled (D-homo) steroid skeletons have been prepared via an intermolecular addition of a carbocation, generated with ZnBr2 from a Torgov reagent, to a silyl enol ether containing ring D precursor. The adducts have been cyclized under formation of the C8-C14 bond by treatment with acid and the double bonds in the cyclized products have been reduced to all trans steroid skeletons. A chiral five membered silyl enol ether containing ring D precursor has been synthesized from carvone, and used as starting compound in the synthesis of a chiral C 17 functionalized steroid