Rhodium-carbenoid addition

The cyclopropane intermediate results from the rhodium-carbenoid addition to the less-hindered terminal double bond of the diene. This generates the cyclopropane in which both alkenes are cis related, which allows the subsequent Cope rearrangement of the divinyl cyclopropane (see Section 3.6.1). The conformation of the boat-shaped transition state for the rearrangement must have the methyl and acetate groups trans to one another. See W. R. Cantrell and H. M. L. Davies, J. Org. Chem., 56 (1991), 723. 

As would be expected for a highly electrophilic species, rhodium-catalyzed carbenoid additions are accelerated by aryl substituents, as well as by other cation-stabilizing groups on the alkene reactant.205 When applied to 1,1-diarylethenes, ERG substituents favor the position trans to the ester group.206 This can be understood in terms of maximizing the interaction between this ring and the reacting double bond. 

Carbenoid additions to y,y-difluoroallylic compounds represent valuable methodology complementary to the difluorocarbene chemistry described in Sect. 2.1. One example was provided by Boger and Jenkins [353] at Scripps during a synthesis of a duocarmycin analogue. Intramolecular rhodium-catalysed carbenoid addition of a p-quinonediazide to a protected difluoroallylic amine formed a key intermediate (Eq. 137). 

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... 

Bis(phosphoranimine) ligands, chromium complexes, 5, 359 Bis(pinacolato)diboranes activated alkene additions, 10, 731—732 for alkyl group functionalization, 10, 110 alkyne additions, 10, 728 allene additions, 10, 730 carbenoid additions, 10, 733 diazoalkane additions, 10, 733 imine additions, 10, 733 methylenecyclopropane additions, 10, 733 Bisporphyrins, in organometallic synthesis, 1, 71 Bis(pyrazol-l-yl)borane acetyl complexes, with iron, 6, 88 Bis(pyrazolyl)borates, in platinum(II) complexes, 8, 503 Bispyrazolyl-methane rhodium complex, preparation, 7, 185 Bis(pyrazolyl)methanes, in platinum(II) complexes, 8, 503 Bis(3-pyrazolyl)nickel complexes, preparation, 8, 80-81 Bis(2-pyridyl)amines... 

Addition of a rhodium carbenoid to an alkyne leads to a cyclopropene derivative. In an intramolecular context, the fused cyclopropene moiety is unstable and undergoes ring opening to generate a rhodium vinyl carbenoid entity, which can then undergo cyclopropanation or cyclopropena-tion, carbon hydrogen insertion, and ylide generation. This is illustrated... 

Other complementary methodologies include the preparation of substituted cyclopropanes from glycals using rhodium acetate carbenoid additions [65,66]. Additionally, acid catalyzed cyclopropane opening reactions in alcoholic solutions afford the 2-C-branched-glycosides. These combined reactions were used to prepare a key intermediate in marine diterpene norrisolide synthesis from D-mannose [67]. 

Decomposition of a-diazo ketoamides 208 in the presence of substituted propiolic esters gives spirocyclic oxiranes 209. The reaction involves intramolecular addition of a rhodium carbenoid onto the oxygen atom of the amide group to yield the carbonyl ylide, which, after 1,4-H-migration, produces a cyclic ketene N,0-acetal 210. The latter further reacts with the activated triple bond of the dipolarophile to form a zwitterionic intermediate and, finally, a spirocycloadduct (Scheme 26) (90JA2037). 

Another application of rhodium carbenoid chemistry relates to the synthesis of strained-ring nitro compounds as high energy-density materials. Nitrocyclo-propanes are the simplest members of this class of compounds and catalyzed additions of a nitrocarbene to an olefin have only been described recently [40], Detailed studies have shown that the success of the reaction is, as expected, dependent on both the alkene and the nitrodiazo precursor. Consistently with the electrophilic character of rhodium carbenoids, only electron-rich alkenes are cyclopropanated. The reaction has been extended to the synthesis of nitrocyclo-propenes but the yields are good for terminal acetylenes only [41]. 

Diazocarboxylate esters can be transformed by transition metal catalysts such as rhodium(II) acetate into alkoxycarbonylcarbenes that undergo a wide variety of synthetically useful C-H, C-C, C-X, X-H and X-X insertion reactions (where X = heteroatom) [99]. Chemoselectivity of rhodium carbenoids derived from Rh(II) carboxylates and carboxamides has been found to exhibit striking ligand dependency, for example in work by Padwa showing that perfluorocar-boxamide ligands exclusively promoted aromatic C-H insertions in Rh(II)-cat-alyzed decomposition of diazoamides to give oxindoles, whereas a carboxylate-based rhodium catalyst promoted other types of insertions and addition reactions [100]. 

In addition to the formation and reactions of carbonyl ylides discussed in the previous section, carbenoids also react intramolecularly with ethereal oxygen atoms to generate oxonium intermediates. When the ether is part of a ring as in substrates 63 a-b, the intramolecular addition of rhodium carbenoids produces bicyclic oxonium intermediates, which generated [5.2.1] oxabicycles 64a-b upon rearrangement by a [2,3]-sigmatropic pathway, Eq. 44 [74]. 

Benzo[b]thiophenes and Benzo[b]furans Reactions and Synthesis 437 Rhodium-catalysed carbenoid addition to benzofuran using a chiral catalyst proceeds with high ee. ... 

Fig. 10.3-9 Tryptophan modification using addition to reacting with the aqueous rhodium carbenoids. (a) These species can solvent. Control experiments that were run be formed in situ through the reaction of in the absence of rhodium catalyst afford no...

The addition of a diazocarbonyl compound to an alkene with metal catalysis is an effective method for the formation of cyclopropanes, as discussed above. However, direct addition to aldehydes, ketones or imines is normally poor. Epoxide or aziridine formation can be promoted by trapping the carbene with a sulfide to give an intermediate sulfur ylide, which then adds to the aldehyde or imine. For example, addition of tetrahydrothiophene to the rhodium carbenoid generated from phenyldiazomethane gave the ylide 131, which adds to benzaldehyde to give the trans epoxide 132 in high yield (4.104). On formation of the epoxide, the sulfide is released and hence the sulfide (and the rhodium complex) can be used in substoichiometric amounts. 

Tryptophan offers an indole side chain that can be used for ligation chemistry. A water-compatible rhodium carbene can be added to the indole ring (19) [105,139]. The reactive species is generated in situ by a conjugated diazo compound by a rhodium catalyst like rhodium(II) acetate [63,139,149]. The reaction takes place in the two- and three-position of indole. Thus, a mixture of N-alkylated and C-alkylated product is obtained. It is necessary to add hydroxylamine hydrochloride as an additive to bind to the distal rhodium carbenoid complex. The usage of this salt lowers the pH value below 3.5 and therefore limits the scope of this methodology. As a side reaction, the carbene inserts into the O-H bond of water (Table 6). 

The combination of reactions of rhodium carbenoids with polyether-macrocycle synthesis offered interesting procednres for the synthesis of this important class of compounds. One elegant example is the Rh-catalyzed four-component reaction of two a-diazo- 3-keto esters and two cyclic ethers, such as tetrahydrofuran or 1,4-dioxane, to yield functionalized 16- to 18-membered macrocycles 65 (Scheme 5.44) [42]. The process involves the generation of electrophilic rhodium carbenoid A, the addition of cyclic ether to this intermediate, as well as the formation and dimerization of the oxonium ylide intermediate B. Another example is the Rh-catalyzed macrocyclization of oxetanes with a-diazocarbonyls (Scheme 5.45) [43]. In this case, three oxetanes and one rhodium carbenoid intermediate condense in a one-step process. It is noteworthy that these macrocyclizations could proceed under high-concentration conditions (1M). 

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