Domino Mukaiyama-Michael reactions in the synthesis of polycyclic systems
Sarabèr, F.C.E. ; Dratch, S. ; Bosselaar, G. ; Jansen, B.J.M. ; Groot, Æ. de - \ 2006
Tetrahedron 62 (2006)8. - ISSN 0040-4020 - p. 1717 - 1725.
silyl enol ethers - catalyzed conjugate addition - vitamin-d-3 northern portion - ring closure reactions - one-pot - acyclic stereoselection - titanium tetrachloride - 2+2+2 construction - carbonyl-compounds - organic-synthesis
Good results were obtained in the Mukaiyama-Michael reaction of the silyl enol ether of cyclohexanone with 2-methyl-2cyclopentenone and carvone, with transfer of the silyl group to the receiving enone and with TrSbCl6 as catalyst. A second Mukaiyama-Michael reaction of this new silyl enol ether with methyl vinyl ketone and cyclization of the resulting adduct leads to tricyclic compounds in one-pot domino sequences. The scope and limitations of this domino reaction have been investigated.
New approaches toward the synthesis of (D-homo) steroid skeletons using Mukaiyama reactions
Sarabèr, F.C.E. ; Baranovsky, A. ; Jansen, B.J.M. ; Posthumus, M.A. ; Groot, Æ. de - \ 2006
Tetrahedron 62 (2006)8. - ISSN 0040-4020 - p. 1726 - 1742.
(+)-9(11)-dehydroestrone methyl-ether - vitamin-d-3 northern portion - optically-active steroids - ring closure reactions - claisen-ene strategy - conjugate addition - one-pot - alpha,beta-unsaturated ketones - enantioselective synthesis - 2+2+2 construction
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.