Rhodium-catalyzed synthesis pyrrole

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>. 

The synthesis of bicyclo[3.2.1]octadienes 86 has been accomplished by refluxing divinyl-cyclopropanes 85 in xylene. Subsequent research led to the development of conditions employing a rhodium-catalyzed step for the synthesis of bridged systems via the cyclopropanation of cyclopentadienes, furans and pyrroles (see section on transition-metal-mediated rearrangements). 

A rhodium-catalyzed transannulation of tosyl-triazoles 9 with silyl or alkyl enol ethers 10 was developed that allows for the synthesis of substituted pyrroles 11 with regiocontrol.The addition ofTsOH promotes the final dehydration step to afford pyrroles with different functionality. The method can also be adjusted to allow for the synthesis of 3-pyrrolin-2-ones by using silyl ketene acetals as one of the coupling partners (14TL6455). 

Rhodium catalyzed reactions of ethyl isocyanoacetate 353 with 3-fluoroacetylacetone 352 provides a new facile method for the catalytic synthesis of substituted pyrroles. The key step of the reaction is the activation of the C-H bond of isonitrile 353 induced by the a-heteroatom effect. 3-Fluoropyrrole 44 was obtained in 40 % by this method [115]. The mechanism of the transformation includes rhodium promoted decarbonylation of formamide 354 followed by cyclocondensation of intermediate 355 to form the corresponding pyrrole 44. 

In 2015, Yamaguchi, Itami, Davies, and coworkers accomplished the synthesis of dictyodendrins A and F, pyrrole-carbazole alkaloids, by catalytic C-H functionalization (Scheme 16.15 compare to Section 16.2.1.7) [32]. This synthesis also utilized a rhodium-catalyzed -selective C-H arylation of pyrroles with aryl iodides as the initial reaction. Pyrrole 84 was coupled with aryl iodide 85 in the presence of the same electron-deficient rhodium catalyst to afford... 

The rhodium(ii)-catalyzed intramolecular reaction between linked vinyldiazomethanes and pyrroles leads to a novel synthesis of fused tropanes <1996JOC2305>. The reaction occurs by a stepwise [3- -4]-annulation mechanism between a rhodium-stabilized vinylcarbenoid intermediate and the pyrrole rather than by the typical tandem cyclopropanation/Cope rearrangement sequence. The outcome of the reaction is very sensitive to the vinylcarbenoid structure. In particular, the presence of a siloxy substituent on the vinylcarbenoid strongly favors the formation of fused tropanes 1063 or 1064 (Scheme 206) <1996JOC2305>. 

Rhodium acetate-catalyzed diazo decomposition has been used in a synthesis of the pyrrole 51, illustrating a route to several similar 3-oxypyrrole systems (Equation 11) <2002SL1913>. Similar annulations of some related fluorine containing substrates resulted in various unusual fluoropyrrole derivatives <20030L745>. 

A considerable number of pyrroles 30 with alkyl, alkenyl, or aryl substituents were synthesized by spontaneous cyclization of the enyne precursors 31 (when R = H, Ph, CH2OTHP), or upon treatment of 31 with the catalytic system PdCV KCl (when = H), or alternatively, by treatment of 31 with CuCb (when R H) <03JOC7853>. Treatment of y-ketoalkynes with amines in the presence of catalytic amounts of platinum dichloride constitutes a new route to 1,2,3,5-substituted pyrroles <03AG(E)2681>. An intramolecular rhodium(lI)-catalyzed N-H insertion reaction of 5-amino-7,Y-difluoro-a-diazo-P-ketoesters has been used for the synthesis of a series of 3-fluoropyrroles <03OL745>. 

Two short syntheses of racemic ipalbidine ( )-(842) are shown in Scheme 109. The synthesis by Jefford et al. commenced with conjugate addition between pyrrole and Ae atropate ester 849 followed by homologation of the acid 850 with diazomethane and rhodium-induced intramolecular carbene cyclization of the resulting diazoketone 851 (574). The bicyclic product 852 was converted into ( )-842 in a further four steps. The approach taken by Danishefsky and Vogel centered on acid-catalyzed cyclocondensation between the silyl ketene acetal 853 and A -pyrroline (854) to give indolizidinone 855 (575). Reduction of the lactam and cleavage of the aryl ether completed the synthesis of ( )-842. 

Rhodium(II) octanoate catalyzed decomposition of vinyldiazomethane 174 in the presence of pyrrole 177 has been applied in the synthesis of naturally occurring ferruginine899. 

Davies has reported the synthesis of enantiomerically enriched tropanes 42 by the rhodium(II) octanaote catalyzed reaction of various N-Boc pyrroles 40 with vinyldiazomethanes 41 bearing chiral auxiliaries <97JOC1095, 97AA107>. This overall 3+4 annulation occurs by a tandem cyclopropanatlon/Cope rearrangement and was applied by the author to the synthesis of (-)-anhydroecgonine methyl ester and (-)-ferruginine. 

Murahashi described a new pyrrole synthesis involving a rhodium complex-catalyzed reaction of isonitriles (e.g., 3) with 13-dicarbonyl compounds 4 to afford the pyrroles 5 <01OL421>. This process is believed to proceed by chemoselective activation of the a-C-H bond of the isonitrile even in the presence of the more acidic dicarbonyl derivative. 

The first total synthesis of the intricate Stemona alkaloid (+ /—)-isostemofoline (224) was reported by Kende and coworkers 81) starting from 1,2-hexanediol (225) which was straightforwardly converted to 227 (Scheme 22) 82). Reductive cycUzation with sodium hydrosulfite in refluxing aqueous ethanol, and protection of the unstable pyrrole as tert-butyl carbamate, afforded 228 in five steps with 12% overall )deld. The key bicyclic ketone 231 was assembled by [4 + 3] cycloaddition of pyrrole 228 and diazoester 229 promoted by rhodium octanoate dimer, followed by enol silane deprotection, exo-specific hydrogenation, and nucleophilic decarboxylation (47% overall yield). Sodium methoxide-catalyzed aldol condensation of ketone 231 and furfural provided the Q-j/i-unsaturated ketone 232 whose olefin configuration was established by nOe studies. Allylation of 232 provided a 2.4 1 mixture of ketone 234 and the corresponding allylic enol ether 233, which could be converted to the former via a stereoselective Claisen rearrangement. 

R =aryl) in aprotic solvents, for example, xylene at 140 °C, is more important and has been applied very frequently to prepare indoles of type 176 via intermediate 172. This method is connected with the names of Hemetsberger and Knittel and can be transferred to the synthesis of azaindoles, fused indoles, and fused pyrrol derivatives. Quite recently, reactions like 171 (R =Ph) —> 176 have been conducted in a rhodium(II)-catalyzed way, which allows to decrease the necessary temperature into a range of 25-60 C. The transformation of 171 into isoquinolines is also possible if one or both ortho positions of the aryl group R are substituted appropriately. ... 

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