Cyclopropyl alcohols, synthesis

The conformation of the hydroxy group relative to the afkene and the relative steric hindrance around it must also be taken into consideration when planning a synthesis. For example, the cyclopropanation of a tricyclic precursor in the synthesis of myrocin produced the anti cyclopropyl alcohol derivative (equation 51). This reaction is probably still hydroxy directed by the fixed equatorial OH group, but the attack on the less hindered face of the alkene is favored. 

Alternatively, 1-phenylsulfanylcydopropyllithium (58), prepared by metalation of cyclopropyl phenyl sulfide (57) with butyllithium, has also been used successfully for the synthesis of cy-clobutanones. Addition to ketones, both saturated and unsaturated, leads to the desired 1,2-adducts 59 in high yield. Subsequent treatment of these cyclopropyl alcohols with either aqueous tetrafluoroboric acid at room temperature or anhydrous tin(IV) chloride in di-chloromethane afforded the corresponding cyclobutanones 60 in 65-88% yield. ... 

The synthesis of agarospirol (epihinesol) portrays an efficient stereoselective approach to spiro[4-5] decanes based on the intramolecular keto-carbene insertion reaction (A— B) and cleavage of the derived cyclopropyl alcohol (C) to give a spiroketone. 

Scheme 23 Synthesis of cyclopropyl alcohols from vinyloxiranes...

A second convergent synthesis of haliclamine A (64) was achieved in a stepwise sequence from cyclopropyl(thiophen-2-yl)methanone (76) (Scheme 7) [37]. The protected thiophene 77 was condensed with formyl-piperidine to give 78, suitable for a Wittig olefination with 79. After desulfurization of the product 80, the deprotected alcohol 82 was subjected to homoallylic rearrangement using MesSiBr in the presence of ZnBr2. The re-... 

The discovery of carbene and carbenoid additions to olefins was the major breakthrough that initiated the tapping of this structural resource for synthetic purposes. Even so, designed applications of cyclopropane chemistry in total syntheses remain limited. Most revolve around electrophilic type reactions such as acid induced ring opening or solvolysis of cyclopropyl carbinyl alcohol derivatives. One notable application apart from these electrophilic reactions is the excellent synthesis of allenes from dibromocyclopropanes 2). 

A related synthesis of highly substituted furans was reported by Schmalz and Zhang from cyclopropyl alkynyl ketones. The reaction scope included a great variety of nucleophiles such as several alcohols, indole or even acetic acid [140]. 

The synthesis of amitriptyline starts from the key intermediate dibenzo-suberone (manufactured from phthalic anhydride) and can proceed by two pathways (Fig. 1). Treatment of dibenzosuberone with cyclopropyl Grignard gives the tertiary alcohol after hydrolysis. Reaction of the alco-... 

The ate complexes prepared from 4-tosyloxy-l-butyne and trialkylboranes also provides a selective synthesis of cyclopropyl ketones and homopropargylic alcohols simply by changing the reaction temperature (Eq. 53)... 

A stereoselective Li-NHs reduction of a cyclopentenone has been employed in two different syntheses of the cytotoxic sesquiterpene coriolin (69 Scheme 2). In one synthesis, tricyclic ketone (70) was reduced stereoselectively to alcohol (71) using Li-NHs-methanol. In the second synthesis, tetracyclic enone (72) was converted in a single step to (71). This reduction proceeds by initial cleavage of the cyclopropyl ketone unit of (72) to give ketone (70), which is then reduced to (71). 

Another interesting alkene synthesis starts from a cyclopropyl-substituted alcohol, which, on reaction with magnesium halides, is converted to a haloalkene MesSiX has also been used in this type of reaction (Scheme 22). ... 

The combination of diethylzinc and chloroiodomethane was employed in the synthesis of carbo-cyclic cyclopropyl nucleosides projected for biological evaluation. Attempts to cyclopropanate the intermediate a,j8-unsaturated ester, methyl (Z)-4,5-(isopropylidenedioxy)pent-2-enoate, gave a low yield (10%) of the desired cyclopropyl product. However, hydroxy-directed cyclo-propanation vide infra) of the reduced allyl alcohol 21 with diethylzinc/chloroiodomethane at 0°C afforded the cyclopropane derivative 22 in 54% yield. 

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