Oleg G. Kulinkovich

Alkylation of carboxylic acid derivatives with dialkoxytitanacyclopropane reagents

Methods for the generation of dialkoxytitanacyclopropanes (dialkoxytitanium olefin complexes) are surveyed. Alkylation of carboxylic acid derivatives with these reagents giving rise to β-titanio ketones and related species, which are spontaneously transformed into the corresponding cyclopropane compounds or react with external electrophiles, are considered.

Titanium-Mediated Diastereoselective Formation of (E)- or (Z)-2-Substituted 1-Vinylcyclopropanols: Scope and Limitation, Applications

Titanium-mediated cyclopropanation of α,β-unsaturated esters failed to provide 1-vinylcyclopropanol derivatives in useful yields, but (E)-2-substituted-1-vinylcyclopropanols were formed diastereoselectively from O-protected β-oxo- and β-halo esters, with the allylic double bond being created subsequently (Knoevenagel condensation or dehydrohalogenation). Titanium-mediated cyclopropanation of homoallyl alk-2-enoates, on the other hand, directly provided the corresponding Z diastereomers. Palladium(0)-catalysed azidation of their sulfonic esters (tosylate, mesylate), azide reduction, and subsequent double bond cleavage afforded (E)- or (Z)-2-alkyl-2,3-methanoamino acids, although improvements are required to perform the total asymmetric syntheses of molecules with three membered-rings by these methods. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Synthesis of 3-(Trifluoromethyl)benzo[c][1,6]naphthyridines from Substituted 4H-Pyran-4-ones via 4-Amino-5-Aryl-2-(trifluoromethyl)pyridines

Abstract The cyclization of acylated 4-amino-5-aryl-2-(trifluoromethyl)pyridines under the action of P 2 O 5 /POCl 3 smoothly afforded 3-(trifluoromethyl)benzo[ c ][1,6]naphthyridines in good yields. Intermediate aminopyridines were synthesized in a two-step sequence from the corresponding 4 H -pyran-4-ones, which were prepared by reaction of 2-acetyl-2-aryloxiranes and 4-dimethylamino-3-(4-methoxyphenyl)-3-buten-2-one with ethyl trifluoroacetate under basic conditions.

Two-step synthesis of (±)-stigmolone, the pheromone of Stigmatella aurantiaca

Abstract Racemic stigmolone (8-hydroxy-2,5,8-trimethyl-4-nonanone), the pheromone of myxobacterium Stigmatella aurantiaca, was synthesised in 67% overall yield, using titanium-mediated hydroxycyclopropanation of 2-methyl-5-hexen-2-ol with ethyl isovalerate followed by the base-induced ring opening of the resulting 2-(3-hydroxy-3-methylbutyl)-1-isobutyl-1-cyclopropanol.

Stereoselective Synthesis of (7aS)-1-Methylenehexahydro-1H-pyrrolizine and (−)-Heliotridane from N-Diphenylmethyl-(S)-proline Ethyl Ester

Alkaloid (7aS)-1-methylenehexahydro-1H-pyrrolizine was synthesized from N-diphenylmethyl-(S)-proline ethyl ester by cyclopropanation of the ester group with ethylmagnesium bromide in the presence of titanium tetraisopropoxide, replacement of the protecting group on the nitrogen atom, and cationic cyclopropylallyl isomerization of (S)-1-(1-ethoxycarbonylpyrrolidin-2-yl)cyclopropyl sulfonate into the corresponding allyl bromide. Stereoselective reduction of (7aS)-1-methylenehexahydro-1H-pyrrolizine with sodium tetrahydridoborate in the presence of nickel chloride afforded (−)-heliotridane [(1S,7aS]-1-methylhexahydro-1H-pyrrolizine] in high yield.

TITANIUM(IV) ISOPROPOXIDE-CATALYSED REACTION OF ALKYLMAGNESIUM HALIDES WITH ETHYL ACETATE IN THE PRESENCE OF STYRENE. NON-HYDRIDE MECHANISM OF LIGAND EXCHANGE IN THE TITANACYCLOPROPANES

Abstract The dependence of the yields of (E)-1-methyl-2-phenyl-1-cyclopropanol (3) on the structure of the organomagnesium compounds and reagents ratio in the reaction of ethyl acetate with Grignard reagents, in the presence of styrene and catalytic amounts of Ti(OPri)4, has been investigated. Butylmagnesium bromide has been found to be the most suitable organomagnesium for the preparation of3 by this method. The use of (CD3)2CHMgBr for the generation of the titanacyclopropane intermediates led to the formation of3. This result disagreed with the hydride mechanism of the ligand exchange for 2-phenyltitanacyclopropane (4) formation.

Titanium-mediated formation of 1,2-disubstituted cyclopropanols from esters and alkenes. A new approach to the synthesis of 3,11-dimethylnonacosan-2-one, a sex pheromone of the German cockroach

Abstract A convenient new approach to the synthesis of 3,11-dimethylnonacosan-2-one ( 1 ), a component of the sex pheromone of the German cockroach Blattella germanica , using base-induced ring opening of corresponding easily available 1,2-disubstituted cyclopropanols has been performed.

Synthesis of (+)-disparlure from diethyl (−)-malate via opening and fragmentation of the three-membered ring in tertiary cyclopropanols

Abstract(+)-Disparlure [(7R,8S)-7,8-epoxy-2-methyloctadecane, pheromone of the gypsy moth Lymantria dispar L.] was synthesized starting from diethyl (−)-malate via cyclopropanation of the ester groups, selective protection of the 1,3-diol functionality, and successive opening and fragmentation of the three-membered rings in the corresponding tertiary cyclopropanols as key stages.

A convenient approach to substituted 1-(1-alkenyl)cyclopropanols: a new preparation of 2,3-methanoamino acids

Abstract The diastereoselective titanium(IV)-mediated cyclopropanation of ethyl 3,3-diethoxypropionate by Grignard reagents, followed by modified Knoevenagel condensation with malonic acid under microwave irradiation, allow the preparation of ( E )-1-(1-alkenyl)cyclopropanol derivatives, suitable precursors of π-1,1-dimethyleneallylmetal species. The azidation of such complexes, followed by a reduction–oxidation sequence led to pure ( E )-2,3-methanoamino acids.

Reductive ethylation of homoallyl alcohols with a disubstituted double bond with ethylmagnesium bromide in the presence of titanium(IV) isopropoxide

Homoallyl and bishomoallyl alcohols with a disubstituted double bond treated with ethylmagnesium bromide in the presence of titanium(IV) isopropoxide are converted into the products of a reductive ethylation of the olefin fragment. Under similar conditions esters of β,γ-unsaturated carboxylic acids undergo a successive cyclopropanation of the ester group and reductive ethylation of the double carbon-carbon bond and yield 1-(3-ethylalkyl)cyclopropanols. The features of the observed reactions are explained in the framework of the carbometallation mechanism of the double carbon-carbon bond by the action of dialkoxytitanacyclopropane reagents.