Cyclopropanation metal-catalysed

Scheme 6.1 Catalytic cycle of metal-catalysed carbenoid cyclopropanation reactions with diazo compounds.

The highly strained nature of methylene- and alkylidenecyclopropanes has been evidenced by spectroscopic measurements and X-ray analysis. The presence of the exocyclic double bond imposes a lengthening of the C(2)-C(3) bond as a result of an increase of the C(2)-C(l)-C(3) angle (compared to cyclopropane). This structural feature is reflected in a typical reactivity of these compounds which is a thermal or transition metal catalysed [3 + 2] cycloaddition with alkenes. This chemistry, usually referred to as TMM chemistry , has been the object of many studies and thoroughly reviewed by Binger and Buch [2] and Trost [8]. 

More recent reports from Cordova [155] and Wang [156] have described the cyclopropanation of a, P-unsaturated aldehydes 99 with diethyl bromomalonates 100 and 2-bromo ethyl acetoacetate catalysed by a series of diaryIprolinol derivatives. Both describe 30 as being the most efficient catalyst in many cases and optimal reaction conditions are similar. Some representative examples of this cyclopropanation are shown in Scheme 40. The transformation results in the formation of two new C-C bonds, a new quaternary carbon centre and a densely functionalised product ripe for further synthetic manipulation. Triethylamine or 2,6-lutidine are required as a stoichiometric additive in order to remove the HBr produced during the reaction sequence. The use of sodium acetate (4.0 equivalents) as an additive led to subsequent stereoselective ring opening of the cyclopropane to give a,P-unsaturated aldehydes 101. It can be envisioned that these highly functionalised materials may prove useful substrates in a variety of imin-ium ion or metal catalysed transformations. 

The metal-catalysed hydrogenation of cyclopropane has been extensively studied. Although the reaction was first reported in 1907 [242], it was not until some 50 years later that the first kinetic studies were reported by Bond et al. [26,243—245] who used pumice-supported nickel, rhodium, palladium, iridium and platinum, by Hayes and Taylor [246] who used K20-promoted iron catalysts, and by Benson and Kwan [247] who used nickel on silica—alumina. From these studies, it was concluded that the behaviour of cyclopropane was intermediate between that of alkenes and alkanes. With iron and nickel catalysts, the initial rate law is... 

Although a metal catalysed decomposition of ethyl diazoacetate was originally described by Silberrad and Roy in 19061, it was to be many years before the value of this type of process for cyclopropanation of alkenes using transition metal catalysts was widely appreciated and reliable, efficient methods were developed. By the early 1960s, the reaction had become important in organic synthesis. Various transition metal compounds have been screened for catalytic cyclopropanation. Copper, rhodium and palladium compounds have... 

Diazoalkanes, in particular diazomethane, can efficiently transfer a methylene unit to olefinic double bonds via a metal catalysed process. The range of alkenes that may be used as substrates in this cyclopropanation is vast. The efficiency of the cyclopropanation of various types of alkenes can be very dependent upon the particular catalyst chosen for the reaction. 

Metal catalysed decomposition of diazocarbonyl compounds in the presence of alkenes provides a facile and powerful means of constructing electrophilic cyclopropanes. The cyclopropanation process can proceed intermolecularly or intramolecularly. Early work on the topic of intramolecular cyclopropanation (mainly using diazoketones as precursors) has been surveyed31. With the discovery of powerful group VIII metal catalysts, in particular the rhodium(II) derivatives, metal catalysed cyclopropanation of diazocarbonyls is currently the most fertile area in cyclopropyl chemistry. In this section, we will review the efficiency and versatility of the various catalysts employed in the cyclopropanation of diazocarbonyls. Cyclopropanations have been organized according to the types of diazocarbonyl precursors. Emphasis is placed on recent examples. 

Metal catalysed cyclopropanation using alkyl diazoesters has been confirmed as a useful synthetic method since an earlier review dealing with cyclopropanation chemistry... 

Metal catalysed decomposition of dienoic diazoketones can give rise to vinyl cyclopropanes89"92. This cyclopropanation process is ring size dependent and only closures to... 

Electron-withdrawing substituents generally increase diazo compounds stability toward decomposition. Dicarbonyl diazomethane, which bears two carbonyl groups flanking the diazomethane carbon, are more stable than diazo compounds with only one carbonyl substituent. In general, metal catalysed decomposition of dicarbonyl diazomethane requires higher temperature than does monocarbonyl substituted diazomethane. As indicated before, rhodium(II) carboxylates are the most active catalysts for diazo decomposition. With dicarbonyl diazomethane, the rhodium(II) carboxylate-promoted cyclopropanation process can also be carried out under ambient conditions to afford a high yield of products. 

A few natural products which contain the cyclopropyl ring have been synthesized through metal catalysed cyclopropanation using dicarbonyl diazomethanes. ( )-Cycloeudesmol 63, isolated from marine alga Chondria oppositiclada, was synthesized via a sequence involving a copper catalysed cyclopropanation of a-diazo-/8-ketoester 61 to give the key intermediate 62 (equation 73)1 7,108. Similarly, the bicyclo[3.1.0]hexane derivative 65 was synthesized from the corresponding a-diazo-/8-ketoester 64 via the catalytic method and was converted into ( )-trinoranastreptene 66 (equation 74)109. Intramolecular cyclopropanation of -diazo-/i-ketoesters 67 results in lactones 68 which are precursors to 1-aminocyclopropane-l-carboxylic acids 69 (equation 75)110. 

Metal catalysed cyclopropanation IV. CYCLOPROPANATION USING OTHER PRECURSORS... 

Metal catalysed cyclopropanation using other types of intermediate is also possible. Lithiated tert-butyl alkyl sulphones bring about the cyclopropanation of various nonactivated alkenes under nickel(II) acetylacetonate catalysis (equation 88)131,132. Sulphonium ylides of type 90 react with simple alkenes under copper catalysis to give the corresponding cyclopropane adduct (equation 89)113,134. In this example the ylide (90) is the sulphonium equivalent of ethyl diazoacetate134. 

Carbenoids derived from the metal catalysed decomposition of diazo compounds undergo various chemical transformations. Control of chemoselectivity by choice of the appropriate catalyst has significantly increased the synthetic viability of catalytic cyclopropanation reactions. Intermolecular reaction of unsaturated alcohols with carbenoids derived from catalytic decomposition of alkyl diazoesters has been reported by Noels and... 

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