Syntheses of Vinylcyclopropanes

The mutual interaction between the carbon-carbon double bond and the cyclopropane ring of vinylcyclopropanes confers to this class of compounds a particularly high reactivity which has been used, inter alia, for the synthesis of cyclopentenes or 1,4-dienes Ring functionalized derivatives are also known for adding some 

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Rhodium-catalyzed [5 + 2]-cycloaddition of an allene and a vinylcyclopropane proceeds with complete chemo-, endo/exo- and diastereoselectivity, representing an effective general route to bicyclo[5.3.0]decane derivatives (Scheme 16.75) [81]. This cydoaddition protocol has been applied successfully to asymmetric total syntheses of natural products [82, 83]. 

A range of vinylcyclopropanes were synthesized in good to excellent yield (see Table 10.4). Good enantioselectivities (77-88% ee) and moderate diastereoselectiv-... 

Cycloheptane derivatives (7, 192-193). Wender et a/. have applied their cycloheptane annelation procedure to total syntheses of the pseudoguaianolides damsinic acid (1) and confertin (2). The paper describes the synthesis of 1-lithio-l-methyl-2-vinylcyclopropane, which is the annelation reagent utilized in the pseudo-guaianolide syntheses. 

Otter syntheses of 1-beterosubstituted vinylcyclopropanes have teen proposed, especially in the silyl series. They involve the Ramberg-Backlund methodology136,186) (Scheme 57b) or the McMurry strategy 136,138 187-188) (Schemes 65, 69). 

A vast number of vinylcyclopropanes have been synthesized by performing condensation reactions between nucleophilic reagents and cyclopropanecarbaldehydes and cyclopropyl ketones. A range of reaction conditions have been employed, but in most syntheses the carbonyl function has been converted to an alkene moiety by using a Wittig reagent. 

Table 2. Examples of Fused Carbocyclic and Oxaeyelic Ring Systems Synthesized from Vinylcyclopropanes...

Endocyclic vinylcyclopropanes yield bicyclo[3.2.0]heptenes 4 and 5 under irradiation with either 200- or 450- medium-pressure Hanovia lamps, or in a Rayonet photoreactor (254-nm lamps). This methodology was used in the syntheses of the terpenes grandisol and capnellene. ... 

Initial studies toward the syntheses of natural products using the [3-1-2] strategy have been described. An approach to a key intermediate in the synthesis of (+)-rocglamide is shown in Scheme 8 [12]. Tricyclic [5.5.n] ring systems have been obtained from bicyclic vinylcyclopropanes (Scheme 8) [13]. 

Cycloaddition reactions of cyclopropanes via cleavage of the C—C bond have been apphed to the synthesis of a wide variety of natural products, particularly terpenoids. For example, (-H)-dictamnol [5], (-H)-aphanamol I [6], (-H)-tremulenolide A [7], and (-l-)-lirondosin A [8] were synthesized through a [5-h2] cycloaddition reaction of vinylcyclopropanes with C—C unsaturated bonds. ( )-Hirsutene [9], ( )-pentalenene [10], ( )-asterisca-3(15),6-diene [10], ( )-hirsutic acid [11], and (-l-)-asteriscanohde [12] were synthesized via rhodium(l)-catalyzed [5-H2-H1] cycloaddition of vinylcyclopropanes with alkenes and carbon monoxide. Total syntheses of ( )-a-agarofuran [13], and ( )-pyrovellerolactone [14] were also achieved through cycloaddition reactions of cyclopropane derivatives. For these syntheses, reference to the papers should be made directly. 

The Fe(CO)5-mediated [5-1-1] carbonylation of vinylcyclopropanes and CO had also been used in the synthesis of natural products by Taber et al. (Scheme 17.9) [13]. For example, this method was used to synthesize the cyclohex-enone core of sesquiterpene (—)-delobabone [13a]. In the... 

Cycloheptanes.— The C-1—C-2 bond in -y-thujaplicin is essentially single, Co"-/3-thujaplicin-amine complexes have been described, and thermodynamic data on the U -/3-thujaplicin complex have been calculated. The biomimetic cyclization of the silyl enol ether (191) to karahanaenone (192), using methyl-aluminium bis(trifluoroacetate) is almost quantitative (192) is also synthesized by thermolysis followed by desilylation of the silyl enol ether (193) which is readily available from l-bromo-2-methyl-2-vinylcyclopropane and isobutyraldehyde. Dehalogenation of 3-bromo-l-iodo-3-methylbutan-2-one with Zn-Cu couple on alumina in the presence of isoprene yields (192) and minor amounts of the isomers (194) and (195) however, dehalogenation with Fc2(CO)9 favours (195). Acetolysis of karahanaenol tosylate yields anticipated p-menthane derivatives and no filifolene. ... 

Finally a general approach to synthesize 42-pyrrolines must be mentioned. This is tl add-catalyzed (NH4C1 or catalytic amounts of HBr) and thermally (150°C) induced rea rangement of cyclopropyl imines These educts may be obtained from commerdal cyan acetate, cyclopropyl cyanide, or benzyl cyanide derivatives by the routes outlined below. Tl rearrangement is reminiscent of the rearrangement of 1 -silyloxy-1 -vinylcyclopropanes (p. 7 83) but since it is add-catalyzed it occurs at much lower temperatures. A2-Pyrrolines constitut reactive enamines and may be used in further addition reactions such as the Robinson anei lation with methyl vinyl ketone (R.V. Stevens, 1967, 1968, 1971). 

A summary of the synthetic methods based on the vinylcyclopropane rearrangements s pears in Section 8.1.8. The listing of total syntheses featuring this rearrangement and its heteroatom variants is compiled in Section 8.1.9. 

Various reactions discussed so far have been applied to cleave complex vinylcyclopropanes which are available by a novel method of extreme convergency. In 1981 Wender and Howbert reported their first example for an intramolecular 1,3-photoaddition of an olefin unit to an adjacent arene moiety This ingenious strategy generates functionalized polycyclic vinylcyclopropanes in a regio- and stereocontrolled fashion which is perfect to synthesize certain terpenes. The key steps of a short route to a-cedrene are displayed in equation 182. ... 

The iridoid sesquiterpene (-)-specionin, an antifeedant to the spruce budworm, was synthesized by T. Hudlicky et al. using the low-temperature vinylcyclopropane-cyclopentene rearrangement as the key step. The substituted cyclopentenone precursor was first exposed to the lithium dienolate derived from ethyl 4-(dimethyl-fert-butylsilyloxy)-2-bromocrotonate at -110 °C to afford silyloxyvinylcyclopropanes as a mixture of exo and endo isomers (with respect to the vinyl group). The mixture was not separated but immediately subjected to TMSI/HMDS, and the corresponding tricyclic ketones were obtained in good yield. Similar results were obtained when TBAF in THF was used instead of TMSI. 

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