Cyclopropanol derivs., syntheses

A general synthesis of cyclopropylboranes has been developed and its use as a stereocontrolled route to substituted cyclopropanol derivatives demonstrated.The reaction of lithium dichloro-methane with organoboranes has been studied systematically with a view to preparing homologated primary and secondary alcohols. ... 

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-... 

Sato et al. developed an interesting enantioselective synthesis of bicyclic cyclopropanols 37 from N-acylcamphorsultam derivatives 36. Products with enantiomeric excesses of up to 98% were obtained (Scheme 11.11) [102]. 

This reaction was applied to the synthesis of quinonoid natural products [34]. Propargyl bromides 62 a and 62b, which were prepared from prenyl bromide and phytyl bromide by a standard procedure, were converted to the corresponding aluminum reagents by reaction with powdered aluminum and a catalytic amount of mercuric chloride [35]. Then the iodomagnesium salt of cyclopropanol hemiacetal was treated with these reagents [36] affording the prenyl derivative 63 a and the phytyl derivative 63 b in 49 and 50% yield, respectively (Scheme 26). 

In the course of studies on cyclopropanone—)5-lactam conversions, Wasserman and coworkers developed a route to the nocardicins by taking advantage of the reactivity of primary amines with cyclopropanone. The unusual susceptibility of the carbonyl group of cyclopropanone to attack by nucleophiles is well exemplified in this synthesis which involves the addition of the highly hindered malonate derivative (156) to generate the cyclopropanol adduct (157). The hindered amine (156) was previously found to be completely unreactive as a nucleophile in a displacement reaction with dibromoester (158) in an attempt to form the azetidine carboxylate (159). The further conversion of the amino malonate adduct (157) to the -lactam through a nitrenium ion rearrangement is illustrated in Scheme 59. 

Wasserman and Clagett effected the synthesis of 1-substituted cyclopropanols starting with a 1-alkoxyvinyl ester (2) derivable from an alkoxyacetylene (1). In the... 

Cyclopropanols can be converted to various cyclopropyloxy derivatives (esters, e.g. acetates, ethers, e.g. methyl and ethyl ethers, and acetals, e.g. tetrahydropyran-2-yloxy derivatives) under the appropriate reaction conditions. In most cases the synthesis of cyclopropyl esters by the reaction between a cyclopropanol and an acid chloride (e.g. formation of 1 ) or acetic anhydride (e.g. formation of 2 ) have been reported. The yields were particularly good (84-95%) when acetic anhydride was used, although a drawback of the reaction can be byproduct formation. When a reactive moiety is attached to the cyclopropane ring in addition to the hydroxy group, other reactions can also occur m-l-(aminomethyl)-2,2-dimethyl-3-(2-methylprop-l-enyl)cyclopropanol (3) reacted with phosgene in benzene to give the corresponding carbamate l,l-dimethyl-2-(2-methylprop-l-enyl)-4-oxa-6-azaspiro[2.4]heptan-5-one (4) in 31% yield. ... 

Cyclopropanols and their derivatives (ethers, esters) constitute the most important class of cyclopropanes which undergo this type of ring enlargement. Synthetically useful strategies to cyclobutanones have been devised based upon an efficient synthesis of appropriate cyclopropanols (see Sections 1.A.1.2.1.2. and 1.A.1.2.1.4.) or oxaspiropentanes. 

The synthesis of the steroidal 2a,3a-cyclopropanol (137b) has been described. The 3-bis-(2-chloroethoxy)-derivative (135) was pyrolysed in vacuo to give the olefin (136). This with excess Simmons-Smith reagent gave the cyclopropyl steroid (137a), which with butyl-lithium liberated the free cyclopropanol (137b) this was converted into 17j8-hydroxy-2a-methyl-5a-androstan-3-one (138) by base. 

In 2009, Chiba s group reported a manganese-mediated synthesis of pyridines from cyclopropanols with vinyl azides [70]. In the presence of 1.7 equivalents of Mn(AcAc)3, a variety of pyridine derivatives have been prepared in good yields at room temperature. In their further studies, they realized this transformation in a catalytic manner [71]. In their mechanistic studies, they found the reactions were initiated by a radical addition of /3-carbonyl radicals, generated by the one-electron oxidation of cyclopropanols with Mn(III), to vinyl azides to give imi-nyl radicals, which cyclized with the intramolecular carbonyl groups. Additionally, the application of this newly developed methodology in the synthesis of quaternary indole alkaloid, melinonine-E, was accomplished as well (Scheme 3.33). 

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