Diazoacetamides

Chiral dirhodium(II) carboxamidate catalysts are, by far, the most effective for reactions of allylic diazoacetates [44, 45] and allylic diazoacetamides [46]. Product yields are high, catalyst loading is low (less than 1 mol%), and enan-tioselectivities are exceptional (Scheme 6). The catalysts of choice are the two... 

Optical induction emanating from a chiral diazoacetamide is apparently not much higher. The 2-phenylcyclopropanecarboxylates cis-222 and trans-222, obtained in low yield from (N-diazoacetyl)oxazolidones 220,221 and styrene in the presence of Rh2(OAe)4 followed by ethanolysis, showed only small enantiomeric excesses 215). Starting with either diazo compound, the (1/ ) enantiomer was predominant in both cis- and trans-222. 

Doyle s rhodium(n) carboxamidate complexes are undisputedly the best catalysts for enantioselective cyclizations of acceptor-substituted carbenoids derived from diazo esters and diazoacetamides, displaying outstanding regio- and stereocontrol.4 These carboxamidate catalysts consist of four classes of complexes pyrrolidinones... 

The dirhodium(n)-catalyzed asymmetric C-H insertion has been recognized as a powerful procedure for the preparation of many interesting compounds.35,43,68,179 Doyle et al. developed an efficient procedure for the enantio-selective syntheses of lactams. - The acyclic terminal diazoacetamides gave moderate enantioselectivity... 

Recently, Yu and co-workers developed an operationally simple catalytic system based on [RuCl2(/>-cymene)]2 for stereoselective cyclization of a-diazoacetamides by intramolecular carbenoid C-H insertion.192 /3-Lactams were produced in excellent yields and >99% m-stereoselectivity (Equation (53)). The Ru-catalyzed reactions can be performed without the need for slow addition of diazo compounds and inert atmosphere. With a-diazoanilide as a substrate, the carbenoid insertion was directed selectively to an aromatic C-H bond leading to y-lactam formation (Equation (54)). 

Although diazoacetamides are usually converted into p-lactams upon diazodecomposition, with some substrates pyrrolidinones can be the main product (Table 4.6) [1101,1102,1140,1141]. For instance, l-diazoacetyl-2-ethylpyrrolidine yields, upon treatment with rhodium(II) complexes only l-methyl-3-pyrrolizidinone (i.e. 

The starting diazoacetamide is prepared by N-arylation of /-phenylalanine methyl ester (DMP, 5.5 M 4-fluoronitrobenzene, 110°C, lOh, 30%), acetoa-cetylation (2,2,6-triraethyl-4/7-l,3-dioxin-4-one, toluene, 110 °C, 4h, 71%) and diazo group transfer (tosyl azide, triethylamine, acetonitrile, 20 °C, 1.5 h, 90%). 

Chiral dicarboxylic acid (R)-5g (5 mol%, R = Mes) bearing simpler mesityl-substituents at the 3,3 -positions was found to catalyze efficiently the trans-selective asymmetric aziridination of iV-aryl-monosubstituted diazoacetamides 177 and aromatic (V-Boc imines 11 (Scheme 75) [94], In sharp contrast to previous reports on this generally dx-selective sort of aziridination, this method exhibited unique fran -selectivity and afforded exclusively the fran -aziridines 178 in moderate to good yields along with excellent enantioselectivities (<20-71%, 89-99% ee). The 1,2-aryl shift products 179 were observed as side products in varying ratios (178 179= 56 44-90 10). Diazoacetamides were chosen instead of diazoesters. Due... 

Diazoacetamides undergo intramolecular cyclopropanation with similarly high enantios-electivities (Eq. 4) [33, 36, 37]. In these cases, however, competition from intramolecular dipolar cycloaddition can compHcate the reaction process. Therefore, the use of R = Me or Bu has been required to achieve good yields of reaction products. Representative examples of applications of chiral dirhodium(II) carboxamidates for enantioselective intramolecular cyclopropanation of diazoacetamides are compiled in Scheme 15.2. 

With respect to the large number of unsaturated diazo and diazocarbonyl compounds that have recently been used for intramolecular transition metal catalyzed cyclopropanation reactions (6-8), it is remarkable that 1,3-dipolar cycloadditions with retention of the azo moiety have only been occasionally observed. This finding is probably due to the fact that these [3+2]-cycloaddition reactions require thermal activation while the catalytic reactions are carried out at ambient temperature. A7-AUyl carboxamides appear to be rather amenable to intramolecular cycloaddition. Compounds 254—256 (Scheme 8.61) cyclize intra-molecularly even at room temperature. The faster reaction of 254c (310) and diethoxyphosphoryl-substituted diazoamides 255 (311) as compared with diazoacetamides 254a (312) (xy2 25 h at 22 °C) and 254b (310), points to a LUMO (dipole) — HOMO(dipolarophile) controlled process. The A -pyrazolines expected... 

Catalysed cyclopropanation using diazoacetamides is rather less well developed. Doyle and coworkers have reported the intermolecular cyclopropanation of styrene with N,N-dimethyl diazoacetamide to give a cyclopropyl adduct in 74% yield (equation 3S)64. A further example is found in a synthesis of a-(carboxycyclopropyl)glycine 27 where an intramolecular cyclopropanation of the diazoacetamide is the key step (equations 39)65,66. 

Once again, cis-disubstituted olefins lead to higher enantioselectivities than do trans-disubstituted olefins, but here the differences are not as great as they were with allyl diazoacetates. Both allylic and homoallylic diazoacetamides also undergo highly enantioselective intramolecular cyclopropanation (40-43) [93,94], However, with allylic a-diazopropionates enantiocontrol i s lower by 10-30% ee [95], The composite data suggest that chi ral dirhodium(II) carboxamide catalysts are superior to chiral Cu or Ru catalysts for intramolecular cyclopropanation reactions of allylic and homoallylic diazoacetates. 

As a result of these developments, Doyle and co-workers have synthesized several lignans, among which are (-)-enterolactone, (+)-isodeoxypodophyllotoxin, and (-)-arctigenin [126], Selected examples have been reported of impressive results from C-H insertion reactions of diazoacetamides that result in [3-lactams. For example, [3-lactam formation was the sole C-H insertion process to occur with 51 (Eq. 5.33) [128] or other seven-membered ring diazoacetamides. 

In 2005, the group of Choi has reported a catalytic system based on [RuC12 (p-cymene)2] that produced the stereoselective cyclization of a-diazoacetamides by intramolecular carbenoid C-H insertion and afforded [I-lactams in excellent yield (>97%) with m-stereoselectivity (>99%), (Scheme 110), [239]. 

Doyle et al.344 and Wee and Liu345 have reported the ring-closing transformation of a-diazoacetamides 108 and 109 to yield 2(3//)-indolinones over Nafion-H [Eq. (5.136)]. In the transformation of compounds 109 the electrophilic intramolecular substitution is followed by decarboxylation.345 Small amounts of 2-azetidinone derivatives (4—10%) formed through a carbene intermediate were also detected. The yield of products from compounds 108 are even higher than observed in the presence of Rh(OAc)2 often applied in the decomposition of diazo compounds.344... 

The Rh(II)-catalysed intramolecular C-H insertion of diazoacetamide in water has been studied.49 This study assessed the factors governing the preferential intramolecular C-H insertion versus O-H insertion with the solvent. The hydrophobic/hydrophilic nature of the amide substituent appeared to be the most significant contribution driving the reaction towards C-H insertion. The nature of the rhodium catalyst precursor also modifies the reaction outcome [Rh2(OAc)4 enhancing the O-H insertion],... 

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