Cyclopropyl carbinols

J ULIA-BRUYLANTS Cyclopropyl Carbinol Rearrangement Synthesis ot allyl halides (usually E] by rearrangement ol cyciopropyl carbirKils acid catalyzed)... 

The first substance examined in the steroid field was 3j6-hydroxycholest-4-ene (1) and the epimeric 3a-alcohol (3). These compounds react stereospecifically in dry ether with the Simmons-Smith reagent to yield the isomeric cyclopropyl carbinols (2) and (4) in 90 % and 67 % yields, respectively. The rate of this reaction is about one fifth of that observed with simple cyclic car-binols. ... 

Treatment of (70a) with methanesulfonyl chloride in pyridine gives rise to vinylcylopropane (73) which can be converted back to the homoallylic alcohol (70a) under conditions similar to those used for converting cyclopropyl carbinol (69a) to the B-homo-7)5-ol (70a). 

Another carbocationic domino process by the same group resulted in the formation of indane derivatives using cyclopropyl carbinol compounds as starting mate-... 

The analogous process involving allylic epoxides is more complex, as issues such as the stereochemistry of substituents on the ring and on the alkene play major roles in determining the course of the reaction [38]. Addition of the Schwartz reagent to the alkene only occurs when an unsubstituted vinyl moiety is present and, in the absence of a Lewis acid, intramolecular attack in an anti fashion leads to cyclopropane formation as the major pathway (Scheme 4.10). cis-Epoxides 13 afford cis-cyclopropyl carbinols, while trans-oxiranes 14 give mixtures of anti-trans and anti-cis isomers. The product of (S-elimi-... 

These electrophilic conjunctive reagents require donor reactants. The cyclopropyl-carbinols as precursors to cyclobutanones arise by simple addition of organometallics. For example, the cyclobutanone 47 derives by addition of vinyllithium to 44 followed by rearrangement with aqueous fluoroboric acid 92). In some cases, this route to cyclopropylcarbinols is preferred. Addition of 41 to aldehydes or ketones... 

Julia and co-workers (87, 88) have developed a novel synthesis of homoallyl-ic bromides by rearrangement of cyclopropyl carbinols on treatment with hydrobromic acid. For instance, the secondary cyclopropyl carbinols 301 have been converted into trans-bromo olefins 302 with 90-95% stereoselectivity. 

The 1-alkoxycyclopropyllithiums 136 and 140 have been added to a variety of conjugated aldehydes and ketones to produce cyclopropyl carbinols such as 141,... 

In 1997, Taguchi, Hanzawa and coworkers described the formation of cyclopropyl carbinols from alkenyl oxiranes through chemoselective hydrozirconation followed by intramolecular attack of the generated alkylzirconocene on the epoxide ring (Scheme 18) [27]. Both the reactivity and the selectivity patterns are worthy of note. The sequence was made possible owing to the chemoselective hydrozirconation of the alkene in the presence of oxirane. Despite the poor nu-... 

The stereochemical outcome of the reaction (inversion of the configuration at the oxirane carbon) was explained by the approach of Cp2ZrHCl from the less hindered side of the stable gauche conformer of the vinyloxirane (Scheme 19). Cis-epoxides gave only syn-trans cyclopropyl carbinols, whereas trans-oxiranes gave mixtures of anti-trans and anti-cis isomers. 

The bromide was prepared from the cyclopropyl carbinol obtained by reduction and from the halide a rignard confound was forsted. This compound treated with formaldehyde gave among other products cyclobutylcarbinol, Whether this is to be attributed to isomerization or to the presence of cyclobutanol in the cyclopropjl alcohol is uncertain. 

The transition metal-catalyzed allylation of carbon nucleophiles was a widely used method until Grieco and Pearson discovered LPDE-mediated allylic substitutions in 1992. Grieco investigated substitution reactions of cyclic allyl alcohols with silyl ketene acetals such as Si-1 by use of LPDE solution [95]. The concentration of LPDE seems to be important. For example, the use of 2.0 M LPDE resulted in formation of silyl ether 88 with 86 and 87 in the ratio 2 6.4 1. In contrast, 3.0 m LPDE afforded an excellent yield (90 %) of 86 and 87 (5.8 1), and the less hindered side of the allylic unit is alkylated regioselectively. It is of interest to note that this chemistry is also applicable to cyclopropyl carbinol 89 (Sch. 44). 

Due to the higher oxidation level cyclopropylcarbinyl-homoallyl rearrangement (see also Section IV.C) of oxycyclopropanes gives, y-unsaturated carbonyl compounds. This feature has been discovered by Julia and coworkers, who reacted certain esters with Grignard reagents or LiAlH4. The corresponding cyclopropyl carbinol opens under acidic conditions to j5,y-unsaturated aldehydes (equation This conversion also works for... 

Solution phase heats of reaction AH for conversion of carbinols to cations in SO2CIF according to equation 19 have been measured for several cyclopropyl carbinols, and are given in Table 16 with data for suitable reference compounds for comparisons . As can be seen ionization of c-Pr3COH is 10.2 kcal mol" more exothermic than for Ph3COH, which is in turn 13.5 kcal mol" more exothermic than Me3COH. However, for the carbinols Ph2CROH the order is Ph > c-Pr > Me. 

Orthoesters of acrylic acid are converted to y.y-dialkoxyallylzirconocene ethoxides with CpjZr. These latter species serve as 2,2-dialkoxycyclopropyl anion synthon, showing y-addition reactivity toward carbonyl compounds to afford homoallylic alcohols. In the presence of MejSiOTf cyclopropyl carbinols are formed, due to a switch to the -addition mode conjugate addition to enones leads to P-cyclopropyl ketones (e.g., from 2-cyclopen tenone)... 

Cyclopropyl carbinols Alkenyl epoxides are converted to cyclopropyl carbinols stereoselectively. 

Their synthesis from l(l-silyl)cyclopropyl carbinols 77,78,81) which is closely related to the methods just presented will also be reported in (Section 4.1.2.1.2). 

Synthesis of Alkylidene and Allylidene cyclopropanes from l-( 1-silyl) cyclopropyl carbinols... 

The synthesis of alkylidene and allylidene cyclopropanes reported in this section takes advantage of the availability 77 78,81 a-82) of l-(l-silyl) cyclopropyl carbinols from a-lithio cyclopropylsilanes and carbonyl compounds. It, however, suffers from the sometimes modest yields obtained when ketones are involved (Schemes 21 a, 47) in the Peterson olefination reaction 77,78,81a) (Schemes 21, 48). This reaction seems much more difficult to achieve than when straight-chain analogs are involved and resembles the cases of allenes 1211 and chlorocyclopropenes120) reported by Chan. For example, thionyl chloride alone is not suitable for that purpose 77,136) but further addition of tetra-n-butylammonium fluoride (20 °C, 15 hrs) leads to the formation of undecylidene cyclopropane77,136 in 46% yield from the corresponding l-(l-silyl)cyclopropyl... 

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