Cyclopropanol l-

Preparation by treatment of the /3-chloroethyl ester of formic acid with PC15.1 Preparation of cyclopropanols,2 When the ether is heated with methyllithium in ether solution a reactive carbenoid intermediate is formed and reacts with an olefin to form a 2-chloroethyl ether of a cyclopropanol (l).3 The product can be converted into the cyclopropanol itself in two ways either by splitting by an organolithium reagent (2a), or by dehydrochlorination followed by acid hydrolysis (2b) ... 

Substituted cyclopropanols were also obtained, albeit in moderate yields, upon reaction of esters such as methyl pentanoate with l,4-bis(bromomagnesium)butane (38) in the presence of titanium tetraisopropoxide. This corroborates the formation of a titanacy-clopropane—ethylene complex 40 from an initially formed titanacyclopentane derivative 39 (Scheme 11.12) [103], Apparently, an ester molecule readily displaces the ethylene ligand from 40, and a subsequent insertion of the carbonyl group into the Ti—C bond, a formal [2S + 2J cycloaddition, leads to the oxatitanacyclopentane 42, the precursor to 1-butylcyclopropanol (43). 

This methodology offers the best means of preparing the key precursors to bicyclopro-pylidene (89) [59,60] and its bis-spirocyclopropanated analogue 92 [59], since methyl cyclopropanecarboxylate (87) and ethyl dispiro[2.0.2.1]heptane-7-carboxylate (90) are virtually quantitatively converted to 1-cyclopropylcyclopropanol (88) and l-(dispiro[2.0.2.1]-hept-7-yl)cyclopropanol (91), respectively (Scheme 11.25) [59]. The same approach has successfully been applied for the preparation of other strained bicyclopropylidene derivatives [72,121],... 

A carbonyl group in the P-position of a cyclopropanol tosylate fragment, as in 99, facilitates the elimination so that it occurs upon treatment of the tosylate 99 with a primary or secondary amine. An ensuing Michael addition of the amine to the a,f5-un-saturated ketone 100 then yields the P-(l-aminocydopropyl)ketone 101, the product of a formal substitution of the hydroxy group in the cyclopropanol precursor to 99 (Scheme 11.27) [123],... 

Diethoxyethyl)-l-methyl-1-cyclopropanol (94) [93] To a gently boiling solution of vinylacetaldehyde diethyl acetal (7.73 mL, 44.4 mmol), ethyl acetate (4.42 mL, 44.4 mmol), and Ti(OiPr)4 (6.53 mL, 22.2 mmol) in anhydrous Et20 (30 mL), a solution of nBuMgBr (133.2 mmol) in Et20 (110 mL) was added dropwise over a period of 3 h. After the addition was complete, the reaction mixture was stirred for an additional 1 h and then poured into 10% aqueous NaOH (150 mL). The aqueous layer was extracted... 

Progress has also been reported in applying titanium-mediated cydopropanation reactions as a key step in the preparation of natural products. For example, racemic stigmo-lone (8-hydroxy-2,5,8-trimethylnonan-4-one) 163, a pheromone of the myxobacterium Stigmatella aurantiaca, has been synthesized in 67% overall yield by the titanium-mediated hydroxycyclopropanation of 2-methyl-5-hexen-2-ol 161 with ethyl isovalerate 160 followed by base-induced ring-opening of the resulting 2-(3-hydroxy-3-methylbutyl)-1-isobutyl-l-cyclopropanol 162 (Scheme 11.41) [139]. 

The alkaloid whitasomnine 44 was prepared according two different routes. The first approach (route A) was based on the cyclization of the l-(3-chloropropyl)cyclopropanol 41 (Scheme 3). The final cyclization involved the reaction of 3-(3-chloropropyl)pyrazole 42 to form the final pyrazole 43 in 40% yield, which is then transformed to the natural product <1996TL1095>. The second approach (route B) is based on the radical cyclization of the substituted pyrazole 45 in the presence of Bu3SnH in acetonitrile under refluxing toluene. Whitasomnine 44 was isolated in 38% yield <2002TL4191>. 

The most satisfactory procedure for obtaining cyclopropanol itself is that of ( ottle which is also recommended for the synthesis of l-arylcyclopropanols. l-Alkylcyclopropanols are best prepared via the correspoiiding acetates which are obtained... 

A hitherto unknown type of rearrangement of l-(l-alkynyl)cyclopropanols (321) to cyclopent-2-en-l-ones (322) mediated by octacarbonyldicobalt" and hexacarbonyldicobalt" complexes has been described. A possible pathway for the transformation is outlined in Scheme 101. A -proton transfer accompanied by a metal-mediated Stevens rearrangement, which converts a coordinated dimethylsulfane... 

Treatment of l-(l-octynyl)cyclopropanol (11a) (R = n-QHjj) with 1.1 molar amounts of Co2(CO)8 in tetrahydrofuran (THF) at room temperature gives the corresponding Co2(CO)6 complex 12 a. This complex is stable at room temperature but when the solution is heated to reflux for 8 h under argon, 3-hexyl-2-... 

The generality of these observations is supported by the data in Scheme 8. In the case of the reactions of monosubstituted l-(l-alkynyl)cyclopropanols 15, 5-substituted cyclopentenones 17 are obtained with complete selectivity when trans-15 are used as substrates. On the other hand, 4-substituted cyclopentenones 16 are obtained with good to high regioselectivity by employing ferf-butyl-dimethylsilyl ethers of cis-l5 as substrates. Furthermore, 5,5-disubstituted cyclopentenones 20 including a spirocyclic derivative are obtained selectively starting from 2,2-disubstituted l-(l-alkynyl)cyclopropanols 18. 

The reactions of various l-(l-alkynyl)cyclopropanols were examined using 5-10 mol% of Co2(CO)8 and 10 mol% of tri(o-isopropylphenyl) phosphite. 1-Phenylethynylcyclopropanol (11b), as well as the alkyl- or silyl-substituted derivatives, gave the corresponding 3-substituted 2-cyclopentenones in good to high yields (Scheme 13). 

When l-[o-(phenylethynyl)phenyl]cyclopropanol-Co2(CO)6 complex (36) is heated at 50 °C in 2-propanol under argon in the presence of DABCO, a completely different product, 3a,4-dihydro-3ff-cyclopenta[a]inden-2-one derivative 40, is produced as a 95 5 diastereomeric mixture in 72% yield. As shown in Scheme 18, not only aryl-substituted alkynyl derivatives, but also alkyl-substituted alkynyl derivatives, give the corresponding cyclopenta[a]inden-2-one derivatives 40 in moderate to good yields. 

Reactions of various l-(l,2-propadienyl)cyclopropanols having a substituent at the 1- or 3-position of the propadienyl moiety 55 proceed smoothly at between 0°C and room temperature with 1.1 mole amounts of Co2(CO)8 in either THF or ethyl acetate, and various 2-monosubstituted or 2,3-disubstituted 1,4-hydro-quinone derivatives 58 are obtained in good yields (Scheme 25). In particular, 1-(1,2-propadienyI)cycIopropanoI having the ferf-butyldimethylsilyl group at the 1-position of the 1,2-prop adienyl moiety gives a high yield of the silylated hydroquinone. 

Unlike their enolate counterparts, homoenolates have been underrated because of a prior lack of synthetic accessibility. Many of the previously known homoenolates cyclize readily to the cyclopropanolate tautomer and behave chemically as the latter. 1-Alkoxy-l-silyloxycyclopropanes have provided,... 

Alternatively, the reaction of cyclopropylethynylmagnesium bromide with cyclo-propanone hemiacetal gives l-(cyclopropylethynyl)cyclopropanol (equation 152)232. The reaction of cyclopropanone acetal with other alkynyl Grignard reagents serves as a general route to alkynylcyclopropanols. Similarly, alkynyllithium derivatives of vitamin D were coupled with cyclopropane carbonyl isoxazolidine to give the corresponding alkynyl-cyclopropyl ketones (equation 153). 

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