Cyclopropanation rhodium-catalysed

Cyclopropanes 13 have been prepared from a NHC-rhodium catalysed decarbonylation of cyclobutanones 11 (Scheme 5.4) [6]. The isolated complex 12... 

In 2004, a series of other chiral thioether-phosphine ligands based on a cyclopropane backbone were evaluated in the rhodium-catalysed hydrogenation of a dehydroamino acid by Molander el al As shown in Scheme 8.2, even if these ligands were generally active, only moderate enantioselectivities of up to 47% ee were obtained. 

Where the carbon-carbon double bond is a part of an aromatic system, in general, cyclopropanation of diazoketones results in the formation of unstable cyclopropane adducts. For example, Saba140 has shown that in the intramolecular cyclopropanation of diazoketone 57 the norcaradiene ketone 58 can be detected by low-temperature NMR and can be trapped in a Diels Alder reaction with 4-phenyl-l,2,4-triazoline-3,5-dione (equation 69). In addition, Wenkert and Liu have isolated the stable norcaradiene 60 from the rhodium catalysed decomposition of diazoketone 59 (equation 70)105. Cyclopropyl ketones derived from intramolecular cyclopropanation of hetereoaromatic diazoketones are also known and two representative examples are shown in equations 71 and 72106. Rhodium(II) compounds are the most suitable catalysts for the cyclopropanation of aromatic diazoketones. 

An unusual rhodium-catalysed addition of a dienylboronate ester to highly strained alkenes, such as norbornene, has been reported, resulting in the formation of vinyl-cyclopropane-fused tricyclic products (Scheme 7). Preliminary mechanistic studies have been presented.246... 

Lower temperatures are enough with a strong Lewis acid like Et2AlCl. The cyclopropane 52 comes from available dihydrofuran 50 by rhodium-catalysed carbene insertion. Rearrangement at very low temperatures gives the cyclopentene 53 that actually has three five-membered rings fused together.13... 

Enantioselective rhodium-catalysed cyclopropanation reactions have enjoyed considerable success for intramolecular cases. However, by suitable choice of catalyst, intermolecular reactions have also been highly selective in some instances. 

The direct rhodium-catalysed cyclopropanation is limited to relatively electron-rich alkenes, as the metallocarbenoids formed in situ are electrophilic, j garwal and coworkers have developed a strategy for the catalytic enantioselective epoxidation of aldehydes utilising catalytic quantities of enantiomerically pure sulfides such as... 

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). 

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... 

For cyclopropanation of very electron-rich alkenes such as vinyl ethers copper(II) trifluoroacetate, copper(II) hexafluoroacetylacetonate or rhodium(II) acetate are the catalysts of choice. Copper trifluoroacetate catalysed cyclopropanation of vinyldia-zomethane with dihydropyran gives the corresponding vinyl cyclopropane adduct in low yield (equation 17). In contrast, catalytic decomposition of phenyldiazomethane in the presence of various vinyl ethers results in high-yield phenylcyclopropane formation (equations 18 and 19)27. 

Palladium(II) compounds have unique characteristics suitable for efficient catalysed cyclopropanation of electron-deficient alkenes using diazoalkanes. Neither copper nor rhodium(II) catalysts have shown comparable reactivity with diazoalkanes, although these catalysts are superior to palladium(II) catalysts for cyclopropanation with diazocarbonyl compounds. A few examples of palladium(II) catalysed cyclopropanation of a,fl-unsaturated carbonyl compounds with diazoalkanes are shown in equations 20-242 °. 

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. 

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. 

Thus changing the ligands on dirhodium(II) can provide a switch which, in some cases, can turn competitive transformations on or ofT146. Other examples include the use of dirhodium(II) carboxamides to promote cyclopropanation and suppress aromatic cycloaddition146. For example, catalytic decomposition of diazoketone 105 with dirhodium(II) caprolactamate [Rh2(cap)4] provides only cyclopropanation product 106. In contrast, dirhodium(II) perfluorobutyrate [Rh2(pfb)4] or dirhodium(II)triphenylacetate [Rh2(tpa)4] gave the aromatic cycloaddition product 107 exclusively (equation 100)l46 148. Although we have already seen that rhodium(II) acetate catalysed decomposition of diazoketone 59, which bears both aromatic and olefinic functionalities, afforded stable norcaradiene 60 (equation 70)105, the rhodium(II) acetate catalysed carbenoid transformation within an acyclic system (108) showed no chemoselectivity (equation 101). However, when dirhodi-um(II) carboxamides were employed as catalysts for this type of transformation, only cyclopropanation product 109 was obtained (equation 101). ... 

Carbenoid transformations involving competition between intramolecular cyclopropa-nation and /8-hydride elimination have been investigated149. The chemoselectivity of these catalytic transformations can be effectively controlled by the choice of catalyst. Rhodium(II) trifluoroacetate catalysed decomposition of diazoketone 111 proceeds cleanly to give only enone 112. However, rhodium(II) acetate or bis-(iV-t-butylsalicyladiminato) copper(II) cu(TBs)2 provides exclusively cyclopropanation product 113 (equation 102)149. 

Intermolecular cyclopropanation of 2-substituted terminal diene 121 with rhodium or copper catalysts occurs preferentially at the more electron-rich double bond (equation 109)37162. With a palladium catalyst, considerable differences in regiocontrol can occur, depending on the substituent of the diene. In general, palladium catalysed cyclopropanation occurs preferentially at the less substituted double bond (equation 110). However, with a stronger electron-donating substituent present in the diene, e.g. as in 2-methoxy-l, 3-butadiene, the catalytic process results in exclusive cyclopropanation at the unsubstituted double bond (equation 110)162. 

Stereosectivity is a broad term. The stereoselectivity in cyclopropanation which has been discussed in the above subsection, in fact, can also be referred to as diastereoselectivity. In this section, for convenience, the description of diastereoselectivity will be reserved for selectivity in cyclopropanation of diazo compounds or alkenes that are bound to a chiral auxiliary. Chiral diazoesters or chiral Ar-(diazoacetyl)oxazolidinone have been applied in metal catalysed cyclopropanation. However, these chiral diazo precursors and styrene yield cyclopropane products whose diastereomeric excess are less than 15% (equation 129)183,184. The use of several a-hydroxy esters as chiral auxiliaries for asymmetric inter-molecular cyclopropanation with rhodium(II)-stabilized vinylcarbenoids have been reported by Davies and coworkers. With (R)-pantolactone as the chiral auxiliary, cyclopropanation of diazoester 144 with a range of alkenes provided c yield with diastereomeric excess at levels of 90% (equation 130)1... 

The inclusion of a separate chapter on catalysed cyclopropanation in this latest volume of the series is indicative of the very high level of activity in the area of metal catalysed reactions of diazo compounds. Excellent, reproducible catalytic systems, based mainly on rhodium, copper or palladium, are now readily available for cyclopropanation of a wide variety of alkenes. Both intermolecular and intramolecular reactions have been explored extensively in the synthesis of novel cyclopropanes including natural products. Major advances have been made in both regiocontrol and stereocontrol, the latter leading to the growing use of chiral catalysts for producing enantiopure cyclopropane derivatives. 

Rhodium- and copper-catalysed cyclopropanation of 8-oxabicyclo[3.2.1]octane by diazocarbonyl compounds was achieved in poor to moderate yields. Ring opening of the cyclopropane (40) upon treatment with Sml2 offered a desymmetrization of the original bicycle. 

An enantioselective rhodium(II)-catalysed intramolecular cyclopropanation, follow- (g) ed by a regioselective allylic alkylation and a diastereoselective rhodium(I)-catalysed 5 + 2-cycloaddition has been reported.102 ... 

Several iodonium ylides, thermally or photochemically, transferred their carbene moiety to alkenes which were converted into cyclopropane derivatives. The thermal decomposition of ylides was usually catalysed by copper or rhodium salts and was most efficient in intramolecular cyclopropanation. Reactions of PhI=C(C02Me)2 with styrenes, allylbenzene and phenylacetylene have established the intermediacy of carbenes in the presence of a chiral catalyst, intramolecular cyclopropanation resulted in the preparation of a product in 67% enantiomeric excess [12]. 

Substituted bicyclo[ . 1.0]alkanes may also be obtained by condensation of secondary amines with 2-haloketones. A variety of nucleophilic reactions can be carried out on the intermediate cyclopropaniminium salt 116251 (Scheme 108). Competing alkene scission and cyclopropanation occurs on reaction of enamines with pentacarbonyl-chromium carbene complexes252 (Scheme 109). N-Silylated allylamines and their derived N-silylated enamines undergo rhodium or copper catalysed cyclopropanation by methyl diazoacetate253 (Scheme 110). 

Numerous synthetic methods have been developed for the synthesis of cyclopropanes, which represent an important core structure in a number of biologically active compounds. Of these techniques, metal-catalysed cyclopropanation of alkenes with ethyl diazoacetate constitutes a particularly simple and straightforward approach. The metal reacts with the azo compound to form a carbene complex which in turn reacts with the olefin, via formation of a metallabutacycle. Copper-complexes are most commonly employed, but other metals like rhodium and palladium are also used. 

---