Rhodium carbenoid

For an example of a rhodium carbenoid mediated [4S+1C] cycloaddition, see Schnau-belt J, Marks E, Reissig HU (1996) Chem Ber 129 73... 

An alternative strategy for selective intermolecular G-H insertions has been the use of rhodium carbenoid systems that are more stable than the conventional carbenoids derived from ethyl diazoacetate. Garbenoids derived from aryldiazoacetates and vinyldiazoacetates, so-called donor/acceptor-substituted carbenoids, have been found to display a very different reactivity profile compared to the traditional carbenoids.44 A clear example of this effect is the rhodium pivalate-catalyzed G-H insertion into cyclohexane.77 The reaction with ethyl diazoacetate gave the product only in 10% yield, while the parallel reaction with ethyl phenyldiazoacetate gave the product in 94% yield (Equation (10)). In the first case, carbene dimerization was the dominant reaction, while this was not observed with the donor/acceptor-substituted carbenoids. 

The reaction of aryldiazoacetates with cyclohexene is a good example of the influence of steric effects on the chemistry of the donor/acceptor-substituted rhodium carbenoids. The Rh2(reaction with cyclohexene resulted in the formation of a mixture of the cyclopropane and the G-H insertion products. The enantios-electivity of the C-H insertion was high but the diastereoselectivity was very low (Equation (31)). 0 In contrast, the introduction of a silyl group on the cyclohexene, as in 15, totally blocked the cyclopropanation, and, furthermore, added sufficient size differentiation between the two substituents at the methylene site to make the reaction to form 16 proceed with high diastereoselectivity (Equation (32)).90 The allylic C-H insertion is applicable to a wide array of cyclic and acyclic substrates, and even systems capable of achieving high levels of kinetic resolution are known.90... 

The cyclopropanation utilizing donor/acceptor rhodium carbenoids can be extended to a range of monosubstituted alkenes, occurring with very high asymmetric induction (Tab. 14.4) [40]. Reactions with electron-rich alkenes, where low enantioselectivity was observed at room temperature, could be drastically improved using the more hydrocarbon-soluble Rh2(S-DOSP)4 catalyst at -78°C. The highest enantioselectivity is obtained when a small ester group such as a methyl ester is used [40], a trend which is the opposite to that seen with the unsubstituted diazoacetate system [16]. 

Asymmetric allylic C-H activation of more complex substrates reveals some intrinsic features of the Rh2(S-DOSP)4 donor/acceptor carbenoids [135, 136]. Cyclopropanation of trans-disubstituted or highly substituted alkenes is rarely observed, due to the steric demands of these carbenoids [16]. Therefore, the C-H activation pathway is inherently enhanced at substituted allylic sites and the bulky rhodium carbenoid discriminates between accessible secondary sites for diastereoselective C-H insertion. As a result, the asymmetric allylic C-H activation provides alternative methods for the preparation of chiral molecules traditionally derived from classic C-C bond-forming reactions such as the Michael reaction and the Claisen rearrangement [135, 136]. 

In summary, the chemistry of the donor/acceptor-substituted carbenoids represents a new avenue of research for metal-catalyzed decomposition of diazo compounds. The resulting carbenoids are more chemoselective than the conventional carbenoids, which allows reactions to be achieved that were previously inaccessible. The discovery of pan-tolactone as an effective chiral auxiliary, and rhodium prolinates as exceptional chiral catalysts for this class of rhodium-carbenoid intermediate, broadens the synthetic utility of this chemistry. The successful development of the asymmetric intermolecular C-H activation process underscores the potential of this class of carbenoids for organic synthesis. 

While we have had some success, we are aware of the hmitations inherent in a transition state model for rhodium-mediated C-H insertion that attempts to predict product ratios on the basis of Mechanics calculations. Arbitrary decisions limiting the several degrees of freedom possible in the transition state could lead one to a model for the point of commitmenf to cyclization that would be far from reahty. The work described herein is important because it offers experimental evidence for a key rotational degree of freedom in the dihedral angle between the ester carbonyl and the rhodium carbenoid. 

The ratio of the insertion (Tab. 16.5) to the /9-hydride eHmination product (If A) was determined for each of the catalysts. Two factors are beheved to govern the ratio of insertion to elimination (1) the earliness versus lateness of the transition state, and (2) the steric bulk of the ligand on the rhodium carbenoid. 

The steric effects become clear on inspecting the Newman projections of the transition states. The conformation 43 a leads to cyclopentane formation, while the conformation 43 b would give / -H elimination. As the rhodium carbenoid becomes larger, conformation 43 b is increasingly favored. Thus, as the steric bulk of the ligands on the Rh carbenoid increases on going from acetate (entry 1) to the TPA catalyst (entry 4), there is a significant increase in the proportion of /9-hydride elimination. 

We believe that the selectivity of methine (CH) insertion over methylene (CH2) insertion (Tab. 16.6) is a reflection of the polarizabihty of the rhodium carbenoid. As the carbenoid approaches the target C-H, the methine C-H is more electron-rich than the methylene C-H. A more easily polarized carbenoid would respond more fully to this and give proportionally more of the methine insertion product. Our design of the a-diazo ester 32 included the p-methoxy group on the benzene ring, so that the reactivity of the methylene benzylic C-H would approach that of the methine. Statistically, due to geometric constraints, only one of the two benzyhc methylene C-H groups is available for the insertion necessary for the cyclization to 36/37. 

For the cyclization of diazo ester 32 there are four competing diastereomeric chair transition states leading to CH2 insertion products. In the transition state, the Rh-C bond is aligned with the target C-H bond leading to C-C bond formation. The two most stable of these transition states are depicted in Scheme 16.8. The actual product from cyclization is determined as the intermediate carbenoid commits to a particular diastereomeric transition state. If the C-C distance is short at the point of commitment (tight transition state), there will be a substantial steric interaction between the arene and the ester, and 32 b will be disfavored. If the C-C distance is longer, this interaction will not be as severe and more of 32 a will be formed. Thus, it seems reasonable that the ratio of 3 a to 36b is a measure of the C-C bond distance at the point of commitment of the rhodium carbenoid. 

Dipoles can also be generated from rearrangements that take place after the formation of an initial rhodium carbenoid product ]40, 70, 71]. One example of this type of transmutation, also known as a dipole cascade process, involves the formation of an azomethine ylide via the initial formation of a carbonyl ylide [72]. This process was... 

Another approach to substituted 2,3-dihydro-l,4-dioxins 239 involves the reaction between 1,2-diols 238 and rhodium carbenoids generated from a-diazo-/ -ketoester 237 (Scheme 23) <1999H(51)1073>. This method complements the intramolecular reactions described earlier <1997JOC3902>. 

Doyle et al. (34) were the first group to generate isomiinchnones from diazo imides using Rh(II) catalysis. For example, isomiinchnone 60 was produced from diazo imide 59, but attempts to trap this species with ethyl acrylate were unsuccessful. The only material identified was the isomiinchnone hydrolysis product. This use of Rh(II) to generate a rhodium-carbenoid species from an a-diazo carbonyl compound is reminiscent of the first successful synthesis of... 

The furo[3,4-ri]oxazoie 54, constracted by cyclisation of a rhodium carbenoid, is a useful compound for the production of unusual benzoxazoles for example, cycloaddition of Al-phenylmaleimide gave the benzoxazole 55 <98JOC7680>. Simpler benzoxazole syntheses include the base catalysed cyclizsation (with loss of the trifluoromethyl anion) of the imines 56 <99TL4119> and the acid catalysed cyclisation of diacylated aminophenols 57 <99H(51)979>. ... 

The total synthesis of the antifungal alkaloid K252a has been reported in which the indolocarbazole nucleus is constructed using novel rhodium carbenoid chemistry <1995JA10413, 1997JA9641>. Thus, reaction of 2,2 -biindole with diazolactam 173 in the presence of rhodium acetate in degassed pinacolone produces indolocarbazoles in moderate yields (Equation 107). 

Rhodium(II) acetate catalyzes C—H insertion, olefin addition, heteroatom-H insertion, and ylide formation of a-diazocarbonyls via a rhodium carbenoid species (144—147). Intramolecular cyclopentane formation via C—H insertion occurs with retention of stereochemistry (143). Chiral rhodium (TT) carboxamides catalyze enantioselective cyclopropanation and intramolecular C—N insertions of CC-diazoketones (148). Other reactions catalyzed by rhodium complexes include double-bond migration (140), hydrogenation of aromatic aldehydes and ketones to hydrocarbons (150), homologation of esters (151), carbonylation of formaldehyde (152) and amines (140), reductive carbonylation of dimethyl ether or methyl acetate to 1,1-diacetoxy ethane (153), decarbonylation of aldehydes (140), water gas shift reaction (69,154), C—C skeletal rearrangements (132,140), oxidation of olefins to ketones (155) and aldehydes (156), and oxidation of substituted anthracenes to anthraquinones (157). Rhodium-catalyzed hydrosilation of olefins, alkynes, carbonyls, alcohols, and imines is facile and may also be accomplished enantioselectively (140). Rhodium complexes are moderately active alkene and alkyne polymerization catalysts (140). In some cases polymer-supported versions of homogeneous rhodium catalysts have improved activity, compared to their homogenous counterparts. This is the case for the conversion of alkenes direcdy to alcohols under oxo conditions by rhodium—amine polymer catalysts... 

In recent years there has been a growing interest in the use of carbonyl ylides as 1,3-dipoles for total synthesis.127-130 Their dipolar cycloaddition to alkenic, alkynic and hetero multiple bonded dipolaro-philes has been well documented.6 Methods for the generation of carbonyl ylides include the thermal and photochemical opening of oxiranes,131 the thermal fragmentation of certain heterocyclic structures such as A3-l,3,4-oxadiazolines (141) or l,3-dioxolan-4-ones132-134 (142) and the reaction of carbenes or car-benoids with carbonyl derivatives.133-138 Formation of a carbonyl ylide by attack of a rhodium carbenoid... 

Various y-azido-d-hydroxydiazo keto esters, e.g. (125), have been found to undergo smooth Rh(II)-catalysed cyclization to afford 2-carboethoxy substituted 3(2//)-furanones as a single diastereoisomer. The authors165 proposed that the formation of e.g. (128) involves insertion of the rhodium carbenoid into the adjacent O—H bond to... 

There has been great interest in recent years in methods for the generation of azomethine ylides and in exploitation of these reactive species in tandem/cascade processes for the rapid assembly of polyaza, polycyclic, multifunctional systems. a-Diazo ketones have featured greatly in such studies, treatment with a catalytic amount of rhodium(II) acetate generating transient rhodium carbenoids. A very common feature of many investigations of this type is the occurrence of quite unexpected reactions. For example, treatment of the diazo ketone 1 with a catalytic amount of... 

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