Cyclopropyl acetylen

Quite a wide variety of alkenes have been subjected to this carbene addition [148] the products are multifunctional small ring molecules which may not only be reduced to simple vinylcyclopropanes, but to various substituted cyclopropyl-acetylenes and cyclopropylideneacetates which are particularly useful and versatile building blocks for organic synthesis [155],... 

Structural features of 1 are an oxazinone moiety and a cyclopropyl acetylene unit connected to a chiral quaternary carbon center. 

First, 7 is converted into its dianion 23 by two equivalents of n-butyllithium. Not only the terminal hydrogen of alkyne 7 but also the propargylic one is acidic. 23 then undergoes intramolecular nucleophilic attack of the terminal chlorine. NH4C1 work-up yields the desired cyclopropyl acetylene 25.8... 

The reaction of basic ZnEt2 with pyrrolidine norephedrine 10 and one equivalent of trifluoroethanol as auxiliary ligand leads to the chiral zinc alkoxide 309 under loss of ethane after deprotonation of the hydroxy groups of 10 and trifluoro ethanol as additive. 30 is not isolated but subjected to addition of cyclopropyl acetylene magnesium... 

Some cyclopropylcarbinyl cations, such as aromatic cyclopropyl cyclopropenium ions (4a and 4b), have been prepared by the addition of the corresponding carbenes to cyclopropyl acetylenes (equation 8). 

A novel iron-catalyzed, cationic cyclopropane ring opening was reported. Aryl-substituted cyclopropyl acetylenes gave ring-opened allene intermediates by a cationic rearrangement. In some cases, this gave functionalized naphthalene products. 

Completely different reaction conditions for the synthesis of enantiopure quinazolines 1153 relied on Lewis acid catalysis. In particular, treatment of quinazoline 1163 with cyclopropyl acetylene and Zn(OTf)2 in the presence of chiral additive 1164 (Scheme 247) [706] was extended to enantioselective diynylation of quinazolines [707]. An example of using organocatalysis included enantioselective Mannich-type reaction of 1166 or its analogues with ketones in the presence of chiral diamine 1167 and L-dibenzoyltartaric acid (L-DBT) (Scheme 248) [708]. In the latter case, the enantioselectivity was moderate, it might be improved to >99 % by a single recrystallization of the product. 

In the first preparations of 128 and 129, 191 reacted with TMSNCO to give adducts 192, which were transformed to cyclic imines 193 upon dehydratation. Reaction of 193 with lithium cyclopropylacetylenide gave racemic 128 and 129, which were subjected to chiral stationary phase HPLC to isolate 128 and 129 as pure enantiomers [136, 137]. Several improvements were reported for this synthetic scheme. In particular, diastereoselective additions of lithium cyclopropyl acetylenide to the derivatives of 193 containing residues of a-phenylethyl amine or campheic acid were developed [154,155]. Moreover, an enantioselective modification of this method employing amino alcohol 194 as an asymmetric catalyst was discovered [156, 157]. Another enantioselective method involved reaction of the derivatives of 193 and cyclopropyl acetylene itself, catalysed by amino alcohol derivatives (e.g. 195) and Zn(OTf)2 [158]. 

Acetylene, where the carbon is sp hybridized with 50% s character, is much more acidic than ethylene (sp, 33% s), which in turn is more acidic than ethane, with 25% 5 character. Increased s character means that the electrons are closer to the nucleus and hence of lower energy. As previously mentioned, cyclopropyl carbanions are more stable than methyl, owing to the larger amount of s character as a result of strain (see p. 181). 

The well documented synthetic method for 37 is chlorination of cyclopropyl-methylketone followed by base treatment [29]. However, this method did not provide a suitable impurity profile. The most convenient and suitable method we found was the one-step synthesis from 5-chloro-l-pentyne (49) by addition of 2equiv of base, as shown in Scheme 1.18 [21, 30]. Two major impurities, starting material 49 and reduced pentyne, had to be controlled below 0.2% each in the final bulk of 37, to ensure the final purity of Efavirenz . Acetylene 37 was isolated by distillation after standard work-up procedure. 

Much early effort in 5-LO inhibition centered on substrate and product analogues. One goal, especially of the Corey group at Harvard, was to study the 5-LO reaction by creating mechanism-based irreversible inhibitors, or by removing the substrate protons which are abstracted by the enzyme. These approaches, which included preparation of acetylenic, methylated, cyclized, or thia-analogues of arachidonic acid, and cyclopropyl analogues... 

Substituted cyclopropyl rings conjugated with a triple bond system have recently received attention as C5 building blocks. The procedure described here is a modification of the decarboxylation-elimination reaction for the preparation of a.3 acetylenic acids from enol sulfonates of acyl malonates. Addition of aqueous alkali to the enol sulfonate of diethyl cyclopropyl carbonyl malonate gives cycl opropyl propiol ic acid, but the yield is 1 ow. 

The effects of selected fatty acid (Cio-Cia) methyl esters on the pink bollworm (Pectinophora qossypiella). bollworm (Heliothis zea) and tobacco budworm (Heliothis virescens) were determined, and a number of cyclopropyl, olefinic and acetylenic methyl esters were also tested (115). Methyl (Z,Z)-deca-2,8-diene-4,6-diynoate (matricaria ester) was lethal at low concentrations to all three insects. This last ester was isolated from Conyza canadensis but is found in vegetative matter of many plants of the Asteraceae. 

In the area of reaction energetics. Baker, Muir, and Andzehn have compared six levels of theory for the enthalpies of forward activation and reaction for 12 organic reactions the unimolecular rearrangements vinyl alcohol -> acetaldehyde, cyclobutene -> s-trans butadiene, s-cis butadiene s-trans butadiene, and cyclopropyl radical allyl radical the unimolecular decompositions tetrazine -> 2HCN -F N2 and trifluoromethanol -> carbonyl difluoride -F HF the bimolecular condensation reactions butadiene -F ethylene -> cyclohexene (the Diels-Alder reaction), methyl radical -F ethylene -> propyl radical, and methyl radical -F formaldehyde -> ethoxyl radical and the bimolecular exchange reactions FO -F H2 FOH -F H, HO -F H2 H2O -F H, and H -F acetylene H2 -F HC2. Their results are summarized in Table 8.3 (Reaction Set 1). One feature noted by these authors is... 

The related lithium(phenylthio)cyclopropylcuprate, prepared from cyclopropyllithium and PhSCu, has been extensively used in the synthesis of /1-cyclopropyl enones by coupling with the corresponding fl-iodo enones (equation 10)34 36. Repetitive regioselective coupling of ethynylcyclopropane units by this method led to polyspirocyclopropyl acetylenes as precursors to [NJpericyclynes37. 

The organometallic chemistry of alkynylcyclopropanes involves primarily the formation and reactions of carbon-metal er-bonds. Metals come essentially from the main group elements, with lithium playing a major role. The two metallation sites are the cyclopropyl and the acetylenic positions, which are expected to differ considerably in their acidity values (t-butylacetylene, pKa = 25230, cyclopropane, pKa = 46183) but less in the reactivity of their metal conjugated bases towards electrophiles. 

Metallation of alkynylcyclopropanes at the acetylenic end is accomplished either by deprotonation or via metal-halide exchange reaction with strong bases. Metallation of ethynylcyclopropane may be affected by KOH in DMF, ethereal EtMgBr or preferably BuLi in THF (equation 151)231. All three metal acetyl ides react with methyl ketones to give the corresponding alcohols. However, the instability of cyclopropyl ketones towards bases, especially at the reaction conditions required by KOH (20 °C, 6h), and the sensitivity of cyclopropenyl double bonds in cyclopropenyl ketone derivatives towards addition reactions of alkylmagnesium compounds, make the alkyllithium (-78 °C, instant reaction) superior to the other reagents. 

Ethynylcyclopropanes, like normal acetylenes, react with dicobalt octacarbonyl in ether to form stable dinuclear cluster-like hexacarbonyl complexes (equation 170)236. The complex with l-chIoro-2,2,3,3-tetramethylethynylcyclopropane reacts stereo- and regioselec-tively with norbomene in a typical Pauson-Khand reaction to give the exn-2-cyclopropyl substituted cyclopentenone (equation 171). Similarly, the reaction of 2-ethoxycyclo-propylacetylene with cyclopentene in the presence of Co2(CO)8 under CO gave 3-(2-ethoxycyclopropyl)-cw-bicyclo[3.3.0]oct-3-en-2-one (equation 172)242. 

An a-cyclopropylvinyl cation, l-cyclopropyl-3-methylbuta-l,2-dienyl cation 38, has been prepared by Siehl by ionizing the corresponding acetylenic alcohol with SbF5 (equation 32)68. 

This condensation helps one understand why the yield of pyrroles from ketoximes and acetylene is reduced in some cases and consequently allows a more directed search for ways to overcome this obstacle. Optimization of this side reaction would make possible a one-pot preparation of valuable dipyrroles with cyclopropyl or vinyl substituents, such as 98a,c for example. 

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