Evaluation of titanium alkoxides and aryloxides in the Kulinkovich cyclopropanation of carboxylic esters

Lee, Jae Chol; Sung, Moo Je; Kun, Jin

doi:10.1016/s0040-4039(01)00145-9

Cited by 45 publications

(10 citation statements)

References 16 publications

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“…Thus, the reactions of formamides, acetamides, and propion-and n-butyramides with ethylmagnesium bromide (6 a) in the presence of stoichiometric amounts of titanium tetraisopropoxide readily furnish the corresponding 1-alkyl-N,N-cyclopropylamines in 20-76 % yield (Table 1, entries 1-10). Likewise, applications of 2-alkyl-or 2-alkenyl-substituted Grignard reagents, respectively, provide the corresponding 2-substituted as well as 1,2-disubstituted cyclopropylamines in 35-63 % yield (entries [11][12][13][14][15][16][17][18], and the 2,2-dialkyl-substituted isobutylmagnesium bromide gave rise to the corresponding 1,2,2-trisubstituted cyclopropylamine (entry 19). Even 1-phosphorylethylsubstituted cyclopropylamines could be synthesized in moderate yields (39-47 %) by reaction of the correspondingly substituted carboxamides with either unsubstituted or 2-alkyl-substituted ethylmagnesium bromides (entries [20][21][22], and employment of cyclic Grignard reagents furnished bicyclic, that is, ring-annelated cyclopropylamines in low to very good yields of 34-92 % (entries 23 and 24).…”

Section: Resultsmentioning

confidence: 99%

Cyclopropylamines from N,N‐Dialkylcarboxamides and Grignard Reagents in the Presence of Titanium Tetraisopropoxide or Methyltitanium Triisopropoxide

Meijere

Chaplinski

Winsel

et al. 2010

Chemistry A European J

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Thirty-three different N,N-dialkyl- and N-alkyl-N-phosphorylalkyl-substituted carboxamides 9-17 were treated with unsubstituted as well as with 2-alkyl-, 2,2-dialkyl-, and 3-alkenyl-substituted ethylmagnesium bromides 6 in the presence of stoichiometric amounts of titanium tetraisopropoxide or methyltitanium triisopropoxide to furnish substituted cyclopropylamines 20-25 in 20-98% yield, depending on the substituents with no (1:1) to excellent (>25:1) diastereoselectivities. Generally higher yields (up to 98%) of the cyclopropylamines 20-28 without loss of the diastereoselectivity were obtained with methyltitanium triisopropoxide as the titanium mediator. Under these conditions, even dioxolane-protected ketones and halogen-substituted and chiral as well as achiral alkyloxyalkyl-substituted carboxamides could be converted to the correspondingly substituted cyclopropylamines with unsubstituted as well as phenyl- and a variety of alkyl-substituted ethylmagnesium bromides in addition to numerous heteroatom-containing (e.g., halogen-, trityloxy-, tetrahydropyranyloxy-substituted) Grignard reagents (62 examples altogether). The transformation of N,N-diformylalkylamines 54 with ethylmagnesium bromide in the presence of methyltitanium triisopropoxide to N,N-dicyclopropyl-N-alkylamines 55 can be brought about in up to 82% yield (6 examples). An asymmetric variant of the titanium-mediated cyclopropanation of N,N-dialkylcarboxamides has been developed by applying chiral titanium mediators generated from stoichiometric amounts of titanium tetraisopropoxide and chiral diamino or diol ligands, respectively. The most efficient chiral mediators turned out to be titanium bistaddolates that provided the corresponding cyclopropylamines with enantiomeric excesses (ee) of up to 84%. Evaluation of several silyl-based additives revealed that the reaction can also efficiently be carried out with substoichiometric amounts (down to 25 mol%) of the titanium reagent, as long as 2-aryl- or 2-ethenyl-substituted ethylmagnesium halides are used and a concomitant slight decrease in yields is accepted. The newly developed methodology was successfully applied for the preparation of analogues with cyclopropylamine moieties of known drugs and natural products such as the nicotine metabolite (S)-Cotinine as well as the insecticides Dinotefuran and Imidacloprid.

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Section: Resultsmentioning

confidence: 99%

Cyclopropylamines from N,N‐Dialkylcarboxamides and Grignard Reagents in the Presence of Titanium Tetraisopropoxide or Methyltitanium Triisopropoxide

Meijere

Chaplinski

Winsel

et al. 2010

Chemistry A European J

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“…34 Cyclopropanation of carboxylic acids using titanium alkoxides has been studied in some detail. 35 The Tebbe reagent is well-known for the methylenation of carbonyl derivatives. Recently this has been extended to the methylenation of β-lactams.…”

Section: Organotitanium-based Methodologymentioning

confidence: 99%

Applications of stoichiometric transition metal complexes in organic synthesis

Fryatt

Christie

2002

J. Chem. Soc., Perkin Trans. 1

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“…In a manner opposite to that of the carbonyl compounds, intermolecular alkylation of olefins by alkoxytitanacyclopropane species often proceeds via the formation of the carbon–carbon bond with the secondary carbon of the metallacycle. For example, titanacyclopropane intermediate 7 , which was formed by the displacement of the alkene ligand in alkoxytitanacyclopropane species 8 with silylated homoallyl alcohol 9 , afforded the reductive dimerization product 10 (Scheme ) 11. The observed regioselectivity of the carbon–carbon bond formation is probably caused by the formation of a less sterically hindered trans ‐configured titanacyclopentane intermediate 11 with distant disposition between the titanium and alkyl substituents of the metallacycle.…”

Section: Regioselectivitymentioning

confidence: 99%

Stereocontrolled alkylation of unsaturated compounds with alkoxytitanacyclopropane reagents

Kulinkovich

Isakov

Kananovich

2008

The Chemical Record

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Interaction of titanium(IV) isopropoxide with ethylmagnesium bromide and its higher homologs leads to the generation of alkoxytitanacyclopropane species, which are able to act in the reactions with unsaturated compounds as 1,2-dicarbanionic alkylating agents. The present review is focused on the processes of intermolecular regio- and stereoselective alkylation of carboxylic esters and allylic alcohol derivatives with alkoxytitanacyclopropane reagents. The oxophilicity of the titanium atom and its tendency to form sterically crowded ate complexes are probably the main factors providing a high level of selectivity of these transformations.

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Evaluation of titanium alkoxides and aryloxides in the Kulinkovich cyclopropanation of carboxylic esters

Cited by 45 publications

References 16 publications

Cyclopropylamines from N,N‐Dialkylcarboxamides and Grignard Reagents in the Presence of Titanium Tetraisopropoxide or Methyltitanium Triisopropoxide

Cyclopropylamines from N,N‐Dialkylcarboxamides and Grignard Reagents in the Presence of Titanium Tetraisopropoxide or Methyltitanium Triisopropoxide

Applications of stoichiometric transition metal complexes in organic synthesis

Stereocontrolled alkylation of unsaturated compounds with alkoxytitanacyclopropane reagents

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