Cyclopropanol carboxylic esters

Vicinally donor-acceptor-substituted cyclopropanol carboxylic esters have been proven to be versatile synthetic building blocks in organic synthesis [11]. They readily undergo a retroaldol reaction, thus creating a stable enolate that at the same time can be considered as a homoenolate in relation to the newly formed carbonyl function. Shimada et al. applied this strategy to the preparation of y-substituted lactones starting from cyclopropane 21 (Scheme 3) [12]. 

A number of new methods for the preparation of cyclopropanols has been developed (see Sections II.B and II.E for the preparation of cyclopropanols via 1,3-bond formation see also Section III. A. 1). Treatment of carboxylic esters with ethylmagnesium bromide in the presence of Ti (OPr-z)4 affords 1-substituted cyclopropanols in excellent yields (equation 152)334. Similar transformation of carboxylic esters to cyclopropanols is realized by... 

An impressive reaction of carboxylic esters with an excess of ethylmagnesium bromide in the presence of an equimolar amount of titanium(IV) isopropoxide at — 78 to — 40 °C to form 1-substituted cyclopropanols has been reported, e.g. formation of 1-pentylcyclopropane-l-ol (1). ... 

Synthesis of 1-substituted cyclopropanols from esters and a Grignard reagent or by reductive coupling of carboxylic esters with terminal olefins, catalyzed by Ti(OiPr)4. 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

Table 11.4. 1,2-Disubstituted cyclopropanols 22 from carboxylic acid esters 8 and 2-substituted ethyl-magnesium halides in the presence of titanium tetraisopropoxide or chlorotitanium triisopropoxide. Entry Starting Product Conditions Yield Ref. Ester R1 R3 [mol% (%) R2 Ti(OR)4] (d. r. Z/Eb) ...

Table 11.5. Substituted cyclopropanols 31 from carboxylic acid esters and alkenes via ligand-exchanged titanium intermediates generated from Grignard reagents and XTi(OiPr)3 (X = OiPr, Cl, Me).

The oxidation of 1-methoxycyclopropanol with iron(IIl) nitrate in methanol in the presence of but-3-en-2-one gives the 6-oxo ester in 30% yield.The mechanism may involve addition of a 2-(methoxycarbonyl)ethyl radical, obtained via iron(III) induced oxidation, to but-3-en-2-one resulting in an a-keto radical. A more effective and practical intermolecular addition of cyclopropanols to alkenes was recently performed in the presence of manganese(III) pyridine-2-carboxylate (Table 4)T 32 -phe reaction may proceed by way of (i) generation of 8-acylalkyl... 

Table 11.4. 1,2-Disubstituted cyclopropanols 22 from carboxylic acid esters 8 and 2-substituted ethyl-magnesium halides in the presence of titanium tetraisopropoxide or chlorotitanium triisopropoxide.

Kulinkovich Cyclopropanation. The Kulinkovich method produced cyclopropanols from carboxylic acid esters and ethylmagnesium bromide in the presence of catal3d ic amount of titanium tetraisopropoxide (Scheme 4). The intermediate was proposed to involve titanacyclopropane. Generally, good to excellent yields were observed for 1-alkylcyclopropanols (55). 1,2-Disubstituted cyclo-... 

However, a very useful adaptation of the original protocol for the conversion of esters to cyclopropanols with titanacydopropane towards a highly versatile preparation of cydopropylamines has been developed [68], N,N-dialkylaminocyclopro-panes with up to three additional substituents are readily obtained from carboxylic acid N,N-dialkylamides and ethyl- as well as substituted ethylmagnesium bromide in the presence of titanium tetraisopropoxide. These transformations were also possible with substoidiiometric amounts of Ti(OPr-i)4, but the yields were significantly better with stoichiometric amounts. 

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