Cyclopropanol

For most combinations of atoms, a number of molecular structures that differ fk m each other in the sequence of bonding of the atoms are possible. Each individual molecular assembly is called an isomer, and the constitution of a compound is the particular combination of bonds between atoms (molecular connectivity) which is characteristic of that structure. Propanal, allyl alcohol, acetone, 2-methyloxinine, and cyclopropanol each correspond to the molecular formula CjH O, but differ in constitution and are isomers of one another. 

The procedure can be adapted to the preparation, in comparable yield, of a variety of 1-substituted cyclopropanols, alkyl as well as aryl. 

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-... 

The procedure involves C-alkylation of an a-sulfonyl carbanion derived from 245 with alkyl halides or carbonyl compounds, followed by cleavage of the cyclopropanols 247 produced by deprotection of the hydroxy group of 246 to give (E)-substituted aldehydes141. 

Cyclopropanol, 1-amino- (8, 9), hydrochloride (58939-46-1) Cyclopropylamine, 1-ethoxy- (8) Cyclopropanamine, 1-ethoxy-(9), hydrochloride (58939-48-3)... 

The anions of vinyl cyclopropanols (16), conveniently released from ethers (15) with BuLi, rearrange rapidly to cyclopentenes (17). 

In a new version of the Simmons-Smith reaction allyl or aUenic alcohols such as cyclohexenol are converted by Sm/CH2l2/Me3SiCl 14 in THF at -78°C into syn cyclopropanols such as 2135 [63] (Scheme 13.17). 

Cp2TiCl . Hydrogen atom abstraction from THF seems possible, also. Most remarkably, the reaction can be employed in the efficient synthesis of cyclopropanols and cyclobutanols as shown in Scheme 28. 

A similar ring expansion has been reported in the oxidation of cyclopropanol 225 with manganese(III) tris(2-pyridinecarboxylate) to generate the / -keto radical, which is allowed to add to the silyl enol ether 226 [124], The... 

Another example is the asymmetric synthesis of ( )-pinidine 208 and its isomers. These syntheses are achieved via asymmetric enolization, stereoselective cyclopropanation, and oxidative ring cleavage of the resulting cyclopropanol system (Scheme 5-68).123... 

Cyclopropane, 1,1-diphenyl-, 48, 75 Cyclopropanols, synthesis of 1-substi-tuted, 47,110 Cyclotetradecanone, 48, 58... 

Asymmetric cyclopropanol formation has been achieved with olefmic acylsulfonamides, which act like olefmic esters. Thus, their reaction with 1 provides a method for synthesizing cyclopropanols in an optically active form. As represented by Eq. 9.41, alkylation of Oppolzer s camphor sultam and reaction of the resulting unsaturated acylsulfonamides with 1 provides optically active bicyclic cyclopropanols having exclusively the structure shown in the equation [76],... 

This cyclopropanol formation proceeds smoothly with alkenyl- (except ethenyl) [74], cycloalkyl- [58—60,72], and arylcarboxylates [56,58], as well as with carboxylates containing a P- [65,75] or y-halogen [66], an acetal [71,76], and quite a number of other functional substituents, including dialkoxyphosphonyl groups [69] (see Table 11.1). 

Diesters and even triesters have been converted to bis- and tris(cyclopropanol)s, respectively. Dimethyl succinate gave the bis (cyclopropanol) derivative 17 in 80% yield, while triethyl trans-cyclopropanetricarboxylate (18) yields the tris (cyclopropanol) 19 (90%) (Scheme 11.4 selected examples in Table 11.2) [77,78], Higher homologous dicarboxylic acid diesters are likewise smoothly converted with ethylmagnesium bromide in the presence of Ti(OiPr)4 to provide the corresponding bis (cyclopropanol) s [71,78]. 

Table 11.2. Bis- and tris(cyclopropanol)s from di- and tricarboxylic acid ethyl esters and ethylmagnesium bromide in the presence of titanium tetraisopropoxide.

In the recently reported reaction of differently substituted p-, y-, and 5-lactones 20 [80], 20 mol% of Ti(OiPr)4 proved sufficient to obtain the corresponding p-, y-, and 5-hydro-xyalkyl cydopropanols 21 in 60—70% yield (Scheme 11.5, Table 11.3, entries 1—3). However, 36 mol% of the titanium reagent was found to be necessary to obtain N-protected (aminohydroxyalkyl)cyclopropanols (Table 11.3, entries 5 and 6) from the corresponding 2-N-Boc- and 3-N-Cbz-2-butyrolactones in yields of 65% and 70%, respectively. 

Scheme 11.6. Routine and enantiose-lective preparation of 1,2-disubstituted cyclopropanols from esters and 2-substituted ethylmagnesium halides. For details, see Table 11.4.

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) ...

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