Cyclopropanes unsaturated derivatives

In summary, the method described here provides an efficient and convenient route to a variety of a-diazo ketones including unsaturated derivatives that were not previously available by diazo transfer. a-Diazo ketones serve as key intermediates in a number of important synthetic methods including the Arndt-Eistert homologation, the photo-Woltf ring contraction strategy, and the carbenoid-mediated cyclopropanation reaction. We anticipate that improved access to a-diazo ketones will serve to enhance the utility of these valuable synthetic strategies. 

An attempt has been made to extend the discussion to the unsaturated derivatives of cyclopropane, i.e cyclopropene and methylenecyclopropane however, the treatment is not extensive either due to a paucity of pertinent chemistry or to coverage elsewhere in this volume (Cyclopropenes, Chapter 21 Cyclopropenyl derivatives. Chapter 24). The reader will also note that the discussion on basicity of cyclopropanes is considerably more extensive due to the wealth of new chemistry and conceptualizations in the past dozen or so years. 

Cyclopropanation. Unsaturated amidt lam are found to undergo Pd(II)-catalyzed c tonyl group. For the access of 1-aminocyclc a./3-didehydroamino acid derivatives with d... 

Changes in Jc-h of the unsaturated carbons were again found to be small, consistent with little rehybridization (or rehybridization to a cyclopropane type derivative) of the alkene carbons. 

A variety of carboxamides not carrying further functionalities has been transformed into the corresponding thiocarboxamides by the use of LR, including the cyclopropane derivatives (63), dithiooxamide, A(A -disubstituted dimethylmalonic acid bisthioamides, the dibenzo[16]crown ether thioamides (66), and the calix[4]arene thioamide 67. Also the somewhat labile unsaturated derivatives of the acryloyl- (64) and... 

The marine metabolite 6a was isolated from the marine sponge Halichondria okadai and first reported in 1989 along with the unsaturated derivative 6b [7]. These compounds, both weak lipoxygenase inhibitors, contain 20 carbon atoms, and their biosynthesis from arachidonic acid and eicosapentaenoic acid, respectively, has been proposed. In addition to having important physiological properties, they also contain a number of unusual structural features, including a nine-membered lactone and a cyclopropane ring. The relative stereochemistry of aU the chiral centers... 

Pyrolysis at 190° of the resulting diastereomeric A -pyrazolines (8) and (11) leads to elimination of nitrogen and formation of the cis- and tmns-cydo-propanecarboxylates (9) and (12), respectively. Thermal decomposition of the A -pyrazoline (13) affords methyl tiglate (14) in addition to the cyclopropane derivative (15) in a ratio 2 1, while A -pyrazolines such as (3) give only 0L,[i- or, y-unsaturated esters, and no cyclopropane derivatives. 

High vacuum pyrolysis, heating in organic bases, contact with acidic adsorbents and reaction at room temperature with perchloric acid or boron trifluoride etherate cleaves the pyrazoline to give a 45-60% yield of the cyclopropane derivative (13) as well as 9 % of the unsaturated methyl compound (14). ° ... 

Epoxidation of aldehydes and ketones is the most profound utility of the Corey-Chaykovsky reaction. As noted in section 1.1.1, for an a,P-unsaturated carbonyl compound, 1 adds preferentially to the olefin to provide the cyclopropane derivative. On the other hand, the more reactive 2 generally undergoes the methylene transfer to the carbonyl, giving rise to the corresponding epoxide. For instance, treatment of P-ionone (26) with 2, derived from trimethylsulfonium chloride and NaOH in the presence of a phase-transfer catalyst Et4BnNCl, gave rise to vinyl epoxide 27 exclusively. ... 

The cyclopropane cyclizations by elimination of triflinic acid (CF3S02H) are readily effected by basic treatment of triflones (trifluoromethyl alkyl sulfones) with activated /-protons (equations 46 and 47)39. The cyclopropane diesters 45 are formed on treatment of 44 with potassium hydride in DMSO or sodium methoxide in methanol (equation 48). In contrast, the monoester 46 failed to give the desired cyclopropane40. Addition of carbanions derived from /f, y-unsaturated phenyl sulfones to a, /i-unsaturated carboxylic esters and subsequent elimination of benzenesulfinate ion give cyclopropanes possessing the unsaturated side chain and the ester function in trans positions (equation 49)41. 

Much of the early work into the rhodium(II)-catalysed formation of oxazoles from diazocarbonyl compounds was pioneered by the group of Helquist. They first reported, in 1986, the rhodium(II) acetate catalysed reaction of dimethyl diazomalonate with nitriles.<86TL5559, 93T5445, 960S(74)229> A range of nitriles was screened, including aromatic, alkyl and vinyl derivatives with unsaturated nitriles, cyclopropanation was found to be a competing reaction (Table 3). 

Intramolecular oxonium ylide formation is assumed to initialize the copper-catalyzed transformation of a, (3-epoxy diazomethyl ketones 341 to olefins 342 in the presence of an alcohol 333 . The reaction may be described as an intramolecular oxygen transfer from the epoxide ring to the carbenoid carbon atom, yielding a p,y-unsaturated a-ketoaldehyde which is then acetalized. A detailed reaction mechanism has been proposed. In some cases, the oxonium-ylide pathway gives rise to additional products when the reaction is catalyzed by copper powder. If, on the other hand, diazoketones of type 341 are heated in the presence of olefins (e.g. styrene, cyclohexene, cyclopen-tene, but not isopropenyl acetate or 2,3-dimethyl-2-butene) and palladium(II) acetate, intermolecular cyclopropanation rather than oxonium ylide derived chemistry takes place 334 ). 

This wide range of transformations includes many reactions which are one way or another connected with cyclopropane derivatives. The cyclopropane moieties can be part of the structure of both the linear dienes or of annulated polycyclic unsaturated systems as well as being part of a spiro compound. 

With the exception of the parent compounds, where the Michael adducts are isolated, acrylic esters [see, e.g. 6,7,31,105,111 ] and nitriles [6,7], and vinyl ketones [26, 113, 115] generally yield the cyclopropanes (Table 7.6) under the standard Makosza conditions with chloroform. Mesityl oxide produces a trichlorocyclopropy-lpropyne in low yield (10%) [7]. When there is no substituent, other than the electron-withdrawing group at the a-position of the alkene, further reaction occurs with the trichloromethyl anion to produce spiro systems (35-48%) (Scheme 7.12) [7, 31]. Under analogous conditions, similar spiro systems are formed with a,p-unsaturated steroidal ketones [39]. Generally, bromoform produces cyclo adducts with all alkenes. Vinyl sulphones are converted into the dichlorocyclopropane derivatives either directly or via the base-catalysed cyclization of intermediate trichloromethyl deriva-... 

Otherwise, dibromomalonates (and nitriles) react with a-unsaturated carbonyl compounds in the presence of only 1 equiv of dibutyl telluride, giving cyclopropane derivates. 

Trimethylsilyl diisobutyltelluronium prop-2-enylide reacts with a,)3-unsaturated esters and amides to give trimethylsilylvinyl cyclopropane derivatives. ... 

The ODPM reactivity of (B.y-unsaturated aldehydes is not restricted to y-phenyl-substituted compounds but can also be extended to systems in which the intermediate biradicals are stabilized by conjugation with a vinyl group. Thus, m-methoxyacetophenone-sensitized irradiation of 40 (Structures 40-49) for 20 min, affords the cyclopropane derivative 41 (47%) as a 1 8 mixture of cisitrans isomers. Similarly, irradiation of 42, for 15 min, under the same conditions, yields 43 (52%) as the trans isomer exclusively [51]. 

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