The Mukaiyama-Michael addition of a β,β-dimethyl substituted silyl ketene acetal to α,β-unsaturated ketones using tetra-n-butylammonium bibenzoate as a nucleophilic catalyst

The Michael addition of a β,β-dimethyl substituted silyl ketene acetal [Me₂CC(OMe)OSiMe₃] to α,β-unsaturated ketones, namely, 2-cyclopentenone, 2-cyclohexenone, 3-methyl-2-cyclohexenone, isophorone, methyl vinyl ketone and mesityl oxide occurs smoothly in the presence of the nucleophilic catalyst, tetra-n-butyl ammonium bibenzoate (TBABB) in THF giving the corresponding 1,4-adducts in excellent yields.     

Synthesis of a chiral steroid ring D precursor starting from carvone

A chiral five-membered, silyl enol ether containing, steroid ring D precursor has been synthesized from carvone. This silyl enol ether has been applied in the synthesis of a chiral C17 functionalized steroid skeleton using the addition of a carbocation, generated with ZnBr₂ from a Torgov reagent, followed by cyclization of the adduct by treatment with acid.     

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 from 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.     

Development of a general, enantioselective organocatalytic Mukaiyama-Michael reaction with α,β-unsaturated aldehydes

LUMO-lowering organocatalysis has been extended to promote the conjugate addition of S-alkyl and 1-pyrrolyl silylketene acetals to α,β-unsaturated aldehydes, yielding both, syn and anti Mukaiyama-Michael products with high levels of enantioselectivity. This strategy allows for the generation of chemically useful 1,5-dicarbonyl systems and again highlights the utility of organocatalysis.     

A new approach toward the synthesis of C,D-cis coupled steroid and C,D-cis coupled d-homosteroid skeletons

A short and efficient procedure has been developed for the synthesis of C,D-cis coupled steroid and d-homo steroid skeletons. A Mukaiyama reaction with transfer of the silyl group of the starting silyl enol ether to the enol of the adduct followed by addition of vinyl magnesium bromide to the unprotected carbonyl group leads to adducts which can be cyclized with ZnBr₂. The synthesis of functionalized steroid skeletons in overall yields of about 50% in four steps can be achieved in this way.     

Domino Mukaiyama-Michael reactions in the synthesis of polycyclic systems

Good results were obtained in the Mukaiyama-Michael reaction of the silyl enol ether of cyclohexanone with 2-methyl-2-cyclopentenone 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.     

Solvent-free Mukaiyama and Mukaiyama-Michael vinylogous reactions of a dioxinone-derived silyl enol ether promoted by Lewis bases

The vinylogous aldol-type addition of a dienolsilyl ether, derived from 2,2,6-trimethyl-4H-1,3-dioxin-4-one, showed to occur with complete γ-selectivity by enolate activation promoted by neutral Lewis bases under solvent-free conditions. Moderate to high yields were obtained with aromatic, hetero-aromatic, and aliphatic aldehydes, as well as activated ketones. Under the same conditions and in the absence of catalyst, the first Mukaiyama-Michael addition of the masked acetoacetate ester to α,β-unsaturated aldehydes took place in satisfactory way.