Rhodium -catalyzed annulation

Isoquinohnes were prepared by a rhodium-catalyzed annulation of pic-ohnamides with alkynes. A number of aryl alkynes are tolerated in this reaction (Scheme 52).With an asymmetric alkyne, the larger group (phenyl) is found distal to the amide. When the alkynes have alkyl groups instead of aryl, the yield is lowered.While some variation is also tolerated on the pico-linamide, when groups are placed at C-5, the yield is lowered, presumably due to steric hindrance (14SL1036). 

Annulation reactions between unactivated alkynes and a range of heteroatom-containing substrates have facilitated the preparation of a host of heterocycles. For example, the preparation of isoquinolones was achieved through a rhodium-catalyzed annulation of internal acetylenes with 0-methyl hydroxamates (Scheme 3.78 and Example 3.12) [81]. The reaction conditions were quite mild, and most reactions were complete within 16 h. The overall process was redox neutral and used a catalytic amount of cesium acetate to promote the reaction. Additionally, the process was not appreciably sensitive to the electronic composition of the 0-methyl hydroxamates. One of the more attractive aspects of this chemistry was the observation that the rhodium-catalyzed reaction... 

SCHEME 3.78 Synthesis of isoquinolones through rhodium-catalyzed annulation [81]. 

The rhodium-catalyzed annulation of internal alkynes with naphthylcarbamates was found to afford either benzoindole or benzoquinoline derivatives depending upon the additives used in the reaction (Scheme 3.91) [94]. The key component in this chemistry was copper acetate. In the presence of this copper salt (0.5equiv), benzoindoles were preferentially formed in high yield. If the copper salt was never added to the reaction mixture, benzoquinolines were formed in high yield. This chemoselective reaction is an attractive approach to the synthesis of these compounds due to the operational simplicity of the process and the ease in which either substrate could be selected. 

IV-Phenylanthranilic acid (52) reveals dual reactivity upon the rhodium-catalyzed annulation (Scheme 25.29) [24]. Under conditions similar to those in Scheme 25.28... 

Oshima et al. explored a cationic rhodium-catalyzed intramolecular [4+2] annulation of l,3-dien-8-ynes in water in the presence of sodium dodecyl sulfate (SDS), an anionic surfactant.132 When the substrate l,3-dien-8-yne was a terminal alkyne, the reaction provided an inter-molecular [2+2+2] product (Eq. 4.68). In water, a reactive cationic rhodium species was formed by the dissociation of the Rh-Cl bond in the presence of SDS. The SDS forms negatively charged micelles, which would concentrate the cationic rhodium species (Scheme 4.15). 

Wender et al. s [5 + 2] metal-catalyzed annulation strategy has also been applied to the total synthesis of (+)-aphanamol I (154) [34]. The scope of this method was expanded by using a tetrasubstituted allene that resulted in the stereoselective formation of an angular methyl group. The reaction of allene 149 with 0.5 mol% of rhodium biscarbonyl choride dimer afforded the fused bicyclic product 152 in 93% yield with complete exo/endo and diastereoselectivity (Scheme 19.28). The stereoselectivity of this process was attributed to a preference for formation of the cis-fused metallo-... 

The synthesis of thiiranes with subsequent elimination of sulfur is an important procedure for the creation of C=C bonds, especially for sterically crowded systems (47,48), in analogy to the Eschenmoser-sulfide-contraction reaction (116). The spontaneous elimination of sulfur was observed in the rhodium-catalyzed reaction of diazo compound 62, which gave rise to the formation of cyclopentenone derivative 63 (117) (Scheme 5.24). A synthesis of indolizomycin was published by Danishefsky and co-workers (118) and involved a similar annulation step. In this case, however, the desulfurization reaction was achieved by treatment with Raney Ni. 

Regio- and diastereoselective rhodium-catalyzed tandem allylic alkylation of 71 with stabilized carbon and heteroatom nucleophiles 72 followed by the PK annulation by the same catalyst was described by Evans and co-workers. Alkylation of an optically active allylic alcohol carbonate 71 proceeds in a regio- and stereospecific manner successfully at 30 °C by 7r-acidic Rh(i) catalysts (Equation (41)). The resultant product then undergoes the PKR with the aid of the pre-existing catalyst under GO pressure at elevated temperature. ... 

Transition-metal-catalyzed annulation reactions of anilines with tertiary amines is another protocol for the catalytic functionalization of sp- C-H bonds (Eq. 45). Several reaction systems resulting in the formation of heteroaromatic compounds which are modifications of the preceding annulation reaction using aniline and ethylene with the aid of rhodium catalyst [71] have recently been developed [72]. 

A synthesis of a set of 2-pyridylpyrroles has been described, involving annulation of 1,3-dicarbonyl compounds with 2-(aminomethyl)pyridine under acidic conditions, as illustrated by the construction of compound 437 (Equation 121) <20020L435>. Likewise, pyrroles have also been obtained from reactions between 1,3-diaryl-l,3-dicarbonyl compounds and imines or oximes promoted by the TiCU/Zn-system <2004SL2239>. Yet another approach involves rhodium-catalyzed reactions of isonitriles with 1,3-dicarbonyl synthons, which enables for instance preparation of fluorinated pyrroles <20010L421>. 

Annulated linearly fused cycloheptadienes 6 are prepared by intramolecular cyclopropanation of dienic esters with a,) -unsaturated diazo compounds, followed by in situ rhodium-catalyzed rearrangement. ... 

Tan KL, Bergman RG, Ellman JA (2001) Annulation of alkenyl-substituted heterocycles via rhodium-catalyzed intramolecular C-H activated coupling reactions. J Am Chem Soc 123 ... 

Regioselective aza-annulation with acrylonitrile met with somewhat limited success. Aza-annulation of 10 with acrylonitrile resulted in the formation of a 75 25 mixture of 11 (eq. I).4 The mixture of 11 was taken on to 12, which was used in the synthesis of optically active 2,2 -bipyridines and 1,10-phenanthrolines. A more selective route to 11a was reported, and this approach started from optically pure (/ )-(+)-pu egone (13, eq. 2).5 In this case, regioselective Michael addition to give 14 was accomplished due to the presence of the isopropylidene moiety of the (/ )-(+)-pulegone. Subsequent rhodium catalyzed deisopropylidenation, nitrile hydration, and cyclization gave lib, which was taken on to (-)-pumiliotoxin C (15). 

Oshima et al. explored a cationic rhodium-catalyzed intramolecular [4+2] annulation of l,3-dien-8-ynes in water in the presence of sodium dodecyl sulfate (SDS), an anionic surfactant. When the substrate... 

On standing in solution, 119 slowly undergoes a Cope rearrangement to 120. When the rhodium catalyzed reaction is carried out at 40 °C, the [3+4] annulation product 120 is isolated directly in 72% yield. In solution, 120 is also of limited stability, and over several days at room temperature rearranges to the formal [3+2] annulation product... 

Under rhodium-catalyzed conditions, hydrazine 137 undergoes oxidative annulation with alkyne 135 to furnish 1,2,3-tri-substituted indole 138 in moderate to excellent yield. The 1-aminoindole products can be substituted at C2 and C3 with aryl, heteroaryl, alkyl, and alkynyl groups (free hydroxyls and alkyl chlorides are also tolerated). 1,3-Dinitrobenzene acts as the stoichiometric oxidant and this is believed to be the first report of its use as such in a transition metal-catalyzed C-H activation (140L6176). 

Rhodium-catalyzed chelation-assisted C—H bond functionalization reactions (enantioselective annulation of aryl imines, dihydropyridine synthesis from imines and ahcynes, one-pot synthesis of pyridines from imines and alkynes, 2-arylpyridine alkylation with imines) 12ACR814. Synthesis of pyridine and dihydropyridine derivatives by regjo- and stereoselective addition to N-activated pyridines 12CRV2642. 

The Rh-catalyzed annulation of triazoles has been explored by several investigators as a novel indole synthesis. Fokin s team generated azavinyl carbenes with rhodium and parlayed this reaction into an indole synthesis (equation 3) [54], Davies and colleagues described a one-pot indole synthesis from tosyl azide and cyclohexenyl derivatives involving an in situ triazole formation (equation 4) [55], and Lin reported a synthesis of 3-indolylimines using a similar approach (equation 5) [56]. Miura and coworkers effected the Rh-cat-alyzed intramolecular synthesis of 3,4-fused indoles... 

Scheme 19.77 Rhodium-catalyzed intramolecular annulation of aromatic imines.

A rhodium-catalyzed tandem annulation and [5 + 1] cycloaddition were used to prepare carbazole 257.3-Hydroxy-l, 4-enyne served as the 5-carbon component of the cycloaddition while carbon monoxide was the reaction partner (16 examples, 36—82% yield) (13JA16797). Collins reported the visible light-mediated synthesis of Al-phenylcarbazole 258. The aryl—aryl... 

Rhodium(lll)-catalyzed redox—neutral coupling of N-phenoxyacet-amides and alkynes led to benzo[l)]furan derivatives (13AGE6033). Furo[2,3-l)]pyran-6-one derivatives were prepared via rhodium(II)-catalyzed reactions of diazo compounds and ethynyl compounds (13T9294). Copper-mediated oxidative annulation of phenols and unactivated internal alkynes afforded benzo[l ]furan derivatives (13CS3706). E t-kaurane maoecrystalV was produced via C-H functionalization (13JA14552). Rhodium-catalyzed intramolecular C-H... 

Allyl amines and alkynes were explored as starting materials for pyridines synthesis by Jun and coworkers as well [109]. The reaction proceeded through a sequential Cu(II)-promoted dehydrogenation of the allylamine and Rh(III)-catalyzed iV-annulation of the resulting a,/3-unsaturated imine and alkyne. Moderate to good yields of pyridines can be isolated (Scheme 3.52). This transformation was later on explored with ruthenium catalyst [110]. In the presence of [ RuCl2(p-cymene) 2] (0.1 equiv.), KPFe (0.1 equiv.), and Cu(OAc)2 (1 equiv.) in tAmOH at 100°C, the desired pyridine derivatives were formed in good yields. In this case, the reaction started with C-H activation and then insertion to alkynes which is different from the rhodium catalyzed case. 

Hojo, D. Tanaka, K. Rhodium-catalyzed C—H bond activation/[4-I-2 annulation/ aromatization cascade to produce phenol, naphthol, phenanthrenol, and triphenylenol derivatives. Org. Lett. 2012, 14, 1492-1495. 

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