Diazo insertion reactions rhodium-catalyzed

Alternatively, diazotization of ethyl indole-2-carboxylate (179) leads to formation of 2-carboethoxy-3-diazo-3H-indole (180) which undergoes rhodium-catalyzed alcohol O-H insertion reactions leading to 3-alkoxyindoles 181 <00TL6905>. 

In recent work67, it has been demonstrated that simple a-diazo ketones and esters can, in fact, be induced to undergo 1,5-insertion in preparatively useful yields. It was already known51 that in the rhodium-catalyzed insertion process, methyl C-H is electronically less reactive than methylene C-H or methine C-H. It therefore seemed likely that competing -hydride elimination would be least likely with a diazoethyl ketone. Indeed, on cyclization of 2-diazo-3-tetrade-canone, only a trace of the enone product from /J-hydride elimination is observed. The predominant side reaction competing with 1,5-insertion is dimer formation. 

The rhodium-catalyzed CH insertion reaction of the diazo compound 1188 affords 1,3-indandione 1189, the enol tautomer 1190 of which undergoes ring expansion furnishing the six-membered ring dipole 1191 which dimerizes, even in the presence of excess DMAD to produce an unusual isochroman-4-one 1192 (Scheme 294)... 

Intramolecular Carbon-Hydrogen Insertion. The advantages of rhodium(II) catalysts for carbenoid transformations are nowhere more evident than with carbon-hydrogen insertion reactions. Exceptional regio- and diastereocontrol has been observed for Rh2(OAc)4 catalyzed transformations of a broad selection of diazoketones, a-diazo-p-ketoesters, a-diazo-P-keto-sulfones and -phosphonates which yield cyclopentanone derivatives in moderate to good yields (57-54). In contrast, poor yields and low regioselectivities characterize the corresponding copper catalyzed reactions. Applications of dirhodium(II) catalysts for C-H insertion reactions have even been extended to the synthesis of y-lactones (55), 3(2//)-furanones (56,57), P-laetones (58), and P-lactams (59,60). 

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>. 

Primary ureas 1365 are good substrates in rhodium-catalyzed N-H insertion reactions with an array of 2-diazo-l,3-keto esters 1364. The products from the insertion reaction cyclize with the aid of acid to yield imidazolones 1366. This chemistry has been translated onto insoluble polymer resins and utilized to prepare a small array of imidazolones (Scheme 351) <20030L511, 2004JOC8829>. 

Rhodium-catalyzed intramolecular reaction of diazo ketones like 175 leads mainly to carbenoid insertion into the a-C-H bond but a minor product is the 1,3-dioxolane (Equation 49) <1997JOC4910>. 

Some examples of catalytic cyclopropanation reactions with diazoacetamides are given in Table 14. In reactions with a-diazo-A,7V-dimethylacetamide catalyzed by tetraacetatodi-rhodium, cyclopropane yields decrease with decreasing alkene reactivity (ethoxyethene, 82% styrene, 47% cyclohexene, 21%). - Furthermore, with A-alkyl substituents larger than methyl, intramolecular carbenoid C-H insertion is in competition with alkene addition, e.g. formation of 4.i -259... 

Although the formation of three-membered rings by cyclopropanation of olefins with metal carbenoids is commonplace, the construction of such systems via intramolecular C-H insertion is quite rare. This is because 1,2 migration of any hydride atoms a to the carbenoid center is typically very facile, rendering it inactive toward further transformations [56], It was found, however, that [i-tosyl a-diazo carbonyl compounds 37 are suitable substrates for intramolecular 1,3 C-H insertion reactions catalyzed by achiral rhodium carboxylates 25 (Scheme 6) [57],... 

The transition-metal-catalyzed reaction of diazo compounds 702, which have a N—H or O—H bond at an appropriate position, gives nitrogen- and oxygen-containing heterocycles 703 (Scheme 2 1 8).293 Wang and Zhu demonstrated a convenient synthesis of the polyfunctionalized /Tfluoropyrroles by the rhodium-catalyzed intramolecular N—H insertion reaction.2933 The reaction of d-amino-y,y-difluoro-a-diazo-/Tketo esters 704 in the presence of Rh2(OAc)4 gave the... 

A similar strategy starts with an intramolecular alkyne insertion of an a-diazo ketone. Thus, rhodium(II)-catalyzed reaction of 2-(6,8-nonadien-1-ynyl)-or-diazoacetophenones 112 at 0°C in dichloromethanc affords cyclopen%]azulenones 115 in 50-58% yield879. Due to the enhanced solubility, rhodium(II) mandelate has proved to be superior to the acetate. 

More recent approaches include a rhodium(II)-catalyzed intramolecular insertion reaction to form the hve-membered heterocycle. Reformatsky-imine addition of 4-bromo-4,4-difluoroacetoacetate with aldimines gave b-amino-y.y-difluoroacetoa-cetates 67 that were readily converted to the key diazo intermediates 68 through the action of tosyl azide and molecular sieve. Rhodium(II)-catalyzed intramolecular insertion followed by aromatization through loss of HF gave the functionalized pyrroles 69 (Fig. 3.29). 

Sulfur controlled radical cyclization of A -ethenyl-a-bromo-alkanamides occurs in a A-exo-trig manner to give the trans-3,A-Rhodium catalyzed carbene insertion reactions are very useful for the preparation of bicyclic P-lactams but are little used to form monocyclic p-lactams. High yields and exceptional stereocontrol are achieved when a-diazo-amides are decomposed in the presence of rhodium(II) catalysts to give (63) (93BMC2409). 

In 1981, Nordlander demonstrated that acetals 22 can be used as reactants in the Bischler-Mdhlau indole synthesis, providing 2,3-unsubstituted indoles in good yield. Subsequent modification was made by Sundberg in 1984. From 1998 to 2002, Moody and co-workers developed a modified Bischler indole synthesis by using rhodium(II) acetate to catalyze the reaction of N-methylanilines with a-diazo-P-ketoesters via an N-H insertion reaction of a rhodium carbenoid. The resulting a-(A -arylamino)ketones cyclize to give indoles upon treatment with BF3 or an acidic ion exchange resin. ... 

Rhodium-Catalyzed Reactions via Zwitterionic Intermediates Diazo compounds are also known to undergo insertion into C—H bonds by action of a rhodium-based catalyst, giving rise to a zwitterionic species characterized by a similar reactivity to that of onium ylide species [170]. Recently, Hu et al. [171] have described that zwitterionic intermediates 150, obtained by carbene insertion into a C—H bond in indoles, can be trapped by imine 151 activated by a chiral Brpnsted acid. After optimization of conditions, three-component reactions carried out at -10 °C in toluene afforded the desired products 152 in high yields, >20 1 diastereoselectivities for the flnft-isomer, and 84-99% ee (Scheme 3.66). 

In 1989, the Moody s group from UK reported the constmction of seven-membered cyclic ethers (Fig. 3.26) [9] via Rh (Il)-catalyzed intramolecular O-H insertion reaction. With the catalyst of rhodium acetate dimer, the catenulate a-diazo carbonyl substrate containing secondary hydroxyl reacted to obtain seven-membered cyclic ethers under toluene reflux conditions with the yield of 88 %. 

The intramolecular C-H insertion of rhodium carbenoids, described earlier for the synthesis of 2-azetidinones, has also been reported to form pyrrolidinone derivatives [36]. The Rh-catalyzed reactions of a-diazo amides 67 by heating in water afford pyrrolidine derivatives 69 together with 2-azetidinones 68 (Scheme 22). 

Many rhodium(II) complexes are excellent catalysts for metal-carbenoid-mediated enantioselective C-H insertion reactions [101]. In 2002, computational studies by Nakamura and co-workers suggested the dirhodium tetracarboxylate catalyzed diazo compounds insertion reaction to alkanes C-H bonds proceed through a three-centered hydride-transfer-like transition state (Fig. 25) [102]. Only one rhodium atom of the catalyst is involved in the formation of rhodium carbene intermediate, while the other rhodium atom served as a mobile ligand, which enhanced the electrophilicity of the first one and facilitate the cleavage of rhodium-carbon bond. In this case, the metal-metal bond constitutes a special example of Lewis acid activation of Lewis acidic transition-metal catalyst. 

SCHEME 2.90 Rhodium/SPA cooperatively catalyzed N-H insertion reaction of a-diazo-a-arylacetates and carbamates. 

Intermediate 37 can be transformed into ( )-thienamycin [( )-1)] through a sequence of reactions nearly identical to that presented in Scheme 3 (see 22— 1). Thus, exposure of /(-keto ester 37 to tosyl azide and triethylamine results in the facile formation of pure, crystalline diazo keto ester 4 in 65 % yield from 36 (see Scheme 5). Rhodium(n) acetate catalyzed decomposition of 4, followed by intramolecular insertion of the resultant carbene 3 into the proximal N-H bond, affords [3.2.0] bicyclic keto ester 2. Without purification, 2 is converted into enol phosphate 42 and thence into vinyl sulfide 23 (76% yield from 4).18 Finally, catalytic hydrogenation of 23 proceeds smoothly (90%) to afford ( )-thienamycin... 

Wolff rearrangement of a-diazoketones to give ketenes or subsequent products is an often used synthetic procedure the scope and limitations of which are well established 13 390), so that only a few new features of this reaction need to be considered here. Concerning its catalytic version, one knows that copper, rhodium and palladium catalysts tend to suppress the rearrangement390). A recent case to the contrary is provided by the Rh2(OAc)4-catalyzed decomposition of ethyl -2-diazo-3-oxopent-4-enoates 404 from which the p,y-unsaturated esters 405 are ultimately obtained via a Wolff rearrangement 236). The Z-5-aryl-2-diazo-3-oxopent-4-enoates undergo intramolecular insertion into an aromatic C—H bond instead (see Sect. 4.1). 

Silanes can react with acceptor-substituted carbene complexes to yield products resulting from Si-H bond insertion [695,1168-1171]. This reaction has not, however, been extensively used in organic synthesis. Transition metal-catalyzed decomposition of the 2-diazo-2-phenylacetic ester of pantolactone (3-hydroxy-4,4-dimethyltetrahydro-2-furanone) in the presence of dimethyl(phenyl)silane leads to the a-silylester with 80% de (67% yield [991]). Similarly, vinyldiazoacetic esters of pantolactone react with silanes in the presence of rhodium(II) acetate to yield a-silylesters with up to 70% de [956]. 

---