Rhodium, from diazo carbonyl

Chapter 4 concerns the cycloaddition of carbonyl ylides generated from diazo carbonyl compounds and rhodium or copper catalysts. In this framework chemoselective and enantioselective transformations leading to the formation of various heterocycles such as tetrahydrofurans, oxazolidines, mesoionic and bicyclic compoxmds, alkaloids, and other natural products are described. 

The examples described so far clearly show the value of the rhodium-catalyzed carbene transfer obtained from diazo compounds onto carbonyl and imino groups. However, the scope is even broader, as the formed carbene can also undergo an ad-... 

An understanding of the mechanism [10] for rhodium-mediated intramolecular C-H insertion begins with the recognition that these a-diazo carbonyl derivatives can also be seen as stabilized ylides, such as 15 (Scheme 16.4). The catalytic rhodium(II) car-boxylate 16 is Lewis acidic, with vacant coordination sites at the apical positions, as shown. The first step in the mechanism, carbene transfer from the diazo ester to the rhodium, begins with complexation of the electron density at the diazo carbon with an open rhodium coordination site, to give 17. Back-donation of electron density from the proximal rhodium to the carbene carbon, with concomitant loss of N2, then gives the intermediate rhodium carbene complex 18. 

Only a few methods are available for the synthesis of isomilnchnones, and the original techniques are summarized by Gingrich and Baum (10). Padwa and coworkers (25) provided a more recent historical account of the synthesis of isomilnchnones. The major new development is the generation of isomilnchnones using the rhodium(II)-catalyzed decomposition of a-diazo carbonyl compounds. In continuation of earlier work (28), Haddadin and Tannus (29) extended their new synthesis of isomilnchnones 51 from A(-benzoylphenylglyoxanilides (50) as illustrated in Scheme 10.6 to a series of new compounds. 

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... 

Rhodium compounds and complexes are also commercially important catalysts. The hydroformylation of propene to butanal (a precursor of hfr(2-ethyUiexyl) phthalate, the PVC plasticizer) is catalyzed by hydridocarbonylrhodium(I) complexes. Iodo(carbonyl)rhodium(I) species catalyze the production of acetic acid from methanol. In the flne chemical industry, rhodium complexes with chiral ligands catalyze the production of L-DOPA, used in the treatment of Parkinson s disease. Rhodium(II) carboxylates are increasingly important as catalysts in the synthesis of cyclopropyl compounds from diazo compounds. Many of the products are used as synthetic, pyrethroid insecticides. Hexacyanorhodate(III) salts are used to dope silver halides in photographic emulsions to reduce grain size and improve gradation. 

The interception of the transient rhodium carbenoid formed from diazo compound 601 by a carbonyl oxygen produces carbonyl ylides that, upon dimerization and subsequent rearrangement, give 56% of compound 602 (92JA593),... 

Addition of carbenoids derived from a-diazo carbonyl compounds to prostereogenic olefins can furnish two diastereomeric cyclopropane derivatives (dsjtrans- or euefo/exo-isomers). The metal-catalyzed transfer of alkoxycarbonyl carbenes has been closely investigated it usually furnishes the mwv-substituted cyclopropanes with moderate to good preference. The rhodium(II/-catalyzed reaction of ethyl diazoacetate with various olefins typically demonstrates that the d.r. (trans/cis) increases when the substituent on the olefin becomes sterically more demanding5. 

A-Phthaloyl-protected (S)-phenylalanine has been used as a ligand for rhodium in the formation of metallocarbenes from diazo compounds for C-H insertion reactions (Section D.1.2.2.3.2.). Ar-Sulfonyl-protected (S)-alanine and (S)-valine are efficient ligands for chiral Lewis acids used in the Diels-Alder reaction (Section D.1.6.1.1.1.3.). A -Sulfonyl-pro-tected (S)-phenylalanine methyl ester has been used for the enantioselective protonation of lactone enolates (Section D.2.I.). The terf-butyl ester of (S)-valine readily forms imines with carbonyl compounds which are used for the highly efficient alkylations of their azaenolates (Sections D.1.1.1.4.1D.1.5.2.4.). All these derivatives can be obtained by the standard methods described in Houben-Weyl3. 

Padwa and Prein presented an extensive experimental and theoretical study of the 1,3-dipolar cycloaddition reactions of isomunchnones with olefinic dipolaro-philes. The a-diazo carbonyl isomunchnone precursors were synthesized in the usual fashion from amides and diazoethylmalonyl chloride. For example, isomunchnone 457 was readily generated from 456 using rhodium catalysis to form... 

Asymmetric cyclopropanation. The ability to effect ligand exchange between rhodium(II) acetate and various amides has lead to a search for novel, chiral rhodium(II) catalysts for enantioselective cyclopropanation with diazo carbonyl compounds. The most promising to date are prepared from methyl (S)- or (R)-pyroglutamate (1), [dirhodium(ll) tetrakis(methyl 2-pyrrolidone-5-carboxylate)]. Thus these complexes, Rh2[(S)- or (R)-l]4, effect intramolecular cyclopropanation of allylic diazoacetates (2) to give the cyclo-propanated y-lactones 3 in 65 S 94% ee (equation 1). In general, the enantioselectivity is higher in cyclopropanation of (Z)-alkenes. 

After copper and palladium, rhodium is the third most important transition metal for the synthesis of the indole ring. For a 2007 review on this reaction, see Patil and Paiil [1], Some early examples (Scheme 1) are Alper s rhodium reaction of 2-aryl-2/7-azirines to give 2-styiylindoles (equation 1) [2], Watanabe s Rh-catalyzed Fischer indole synthesis (equation 2) [3], Ucciani s 3-methylindole synthesis via the hydroformylation of o-nitrostyrene (equation 3) [4], and Burst s preparation of 3-acetyl-2-hydrox-yindoles from the Rh-catalyzed decomposition and carbenoid aromatic C-H bond insertion (equation 4) [5]. Narasaka extended Alper s 2-aryl-2//-azirine reaction to a Rh(II)-catalyzed synthesis of 2,3-disubstituted indoles [6], and both Cenini [7] and Alper [8] stretched the deoxygenation of o-nitrostyrenes to give indoles. Burst s Rh-catalyzed decomposition of a-diazo carbonyl compounds was used by Bauban [9] and Jha [10] in the synthesis of substituted oxindoles. 

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 rhodium-catalyzed conversion of a-diazo-p-hydroxy carbonyl into P-dicarbonyl compounds (Table 23, Entries 6-8) in general seems to be preferable to the acid-catalyzed reaction because of higher yields and absence of side-reactions 37S,377). From a screening of 20 metal salts and complexes, Rh2(OAc)4, RhCl(PPh3)3, PdCl2 and CoCl2 emerged as the most efficient catalysts for the transformation of a-diazo-P-hydroxy esters into P-ketoesters 376). This reaction has become part of... 

Mejla-Oneto and Padwa have explored intramolecular [3+2] cycloaddition reactions of push-pull dipoles across heteroaromatic jr-systems induced by microwave irradiation [465]. The push-pull dipoles were generated from the rhodium(II)-cata-lyzed reaction of a diazo imide precursor containing a tethered heteroaromatic ring. In the example shown in Scheme 6.276, microwave heating of a solution of the diazo imide precursor in dry benzene in the presence of a catalytic amount of rhodium I) pivalate and 4 A molecular sieves for 2 h at 70 °C produced a transient cyclic carbonyl ylide dipole, which spontaneously underwent cydoaddition across the tethered benzofuran Jt-system to form a pentacyclic structure related to alkaloids of the vindoline type. 

Padwa and Prein (105,106) applied chiral, but racemic, isomiinchnone dipoles in diastereoselective 1,3-dipolar cycloadditions. The carbonyl ylide related isomiinch-none derivative rac-70 was obtained from the rhodium-catalyzed cyclization of diazo-derivative rac-69 (Scheme 12.24) (105). The reactions of the in situ formed dipole with a series of alkenes was described and in particular the reaction with maleic acid derivatives 71a-c gave rise to reaction with high selectivities. The tetracyclic products 72a-c were all obtained in good yield with high endo/ exo and diastereofacial selectivities. In another paper by the same authors, the reactions of racemic isomilnchnones having an exo-cyclic chirality was described (106). 

With the long chain a-diazo ketone. 6-diazo-7-tridecanone, 1,5-insertion could proceed with placement of the carbonyl outside the ring, or included in the ring. In fact, only the product 7, from the first of these two cyclization modes, is observed67. The alternative cyclopentane 9 is not formed. As with the a-diazo ester, the relative proportion of 1,2- and 1,5-products depends on the rhodium carboxylate employed. Throughout these studies, it has been observed that the olefin 8, obtained from 1,2-elimination, is cleanly Z-configured67 68. 

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