Diazoamides

Diazoamide 373 also failed to give sulfonium ylide derived products upon decomposition with Cu(acac)2 or Rh2(OAc)4. When the reaction was carried out... 

Rh-carboxamide complexes (86), (103), and (104) introduced by Doyle el al. are by far the best cata ysts or t e eye ization of 2- and 3-alkenyl diazoesters and diazoamides, although the catalyst... 

Dioxo-derivatives 150 can be efficiently synthesized via Rh(ll)-catalyzed intramolecular C-H insertion from various a-diazoamides. For example, intramolecular C-H insertion occurred readily in 149 under refluxing benzene conditions and produced the corresponding 7-lactams 150 with improved yields and excellent stereoselectivity (Equation 21) <2004JOC9313>. 

The different synthetic applications of acceptor-substituted carbene complexes will be discussed in the following sections. The reactions have been ordered according to their mechanism. Because electrophilic carbene complexes can undergo several different types of reaction, elaborate substrates might be transformed with little chemoselectivity. For instance, the phenylalanine-derived diazoamide shown in Figure 4.5 undergoes simultaneous intramolecular C-H insertion into both benzylic positions, intramolecular cyclopropanation of one phenyl group, and hydride abstraction when treated with rhodium(II) acetate. 

Fig. 4.5. Rhodium(II) acetate-catalyzed decomposition of amino acid-derived diazoamides...

Diazoamides also give triazoles, on heating or by treatment with base. Reaction of the diazoamide (9) with phosphorus pentachloride gave a 5-chlorotriazole derivative through an intermediate imidoyl chloride (Scheme 23). ... 

The methylmalonyl suhstituent at the nitrogen atom could he utilized to form a /3-lactam ring attached to 1,3-oxazine. In a diazo-transfer reaction, iV-methylmalonyl-l,3-oxazine 239 was converted to the corresponding a-diazoamide 240. Treatment of 240 with dirhodium(n) tetrakisliV-phthaloyl-fAl-phenylalaninate] (Rh2(3 -PTA)4) resulted in formation of azeto[l,2-f][l,3]oxazine 241 in good yield and ee (Scheme 44) <1998CC1517>. 

Rhodium-mediated decomposition (60) of diazoamide (158) led to formation of the mesoionic oxazolium ylide 159, which was efficiently trapped by the pendant alkene to produce the oxo-bridged tricyclic amide 160. 

Harwood and co-workers (105) utihzed a phenyloxazine-3-one as a chiral derived template for cycloaddition (Scheme 4.50). An oxazinone template can be formed from phenylglycinol as the template precursor. The diazoamide needed for cycloaddition was generated by addition of diazomalonyl chloride, trimethyl-dioxane-4-one, or succinimidyl diazoacetate, providing the ester, acetyl, or hydrogen R group of the diazoamide 198. After addition of rhodium acetate, A-methylmaleimide was used as the dipolarophile to provide a product that predominantly adds from the less hindered a-face of the template in an endo fashion. The cycloaddition also provided some of the adduct that approaches from the p-face as well. p-Face addition also occurred with complete exo-selectivity. Mono- and disubstituted acetylenic compounds were added as well, providing similar cycloadducts. 

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... 

Diazoamides of type 300 rapidly cyclize to form aziridines 302 (342) (Scheme 8.73). It is conceivable that this reaction proceeds through a 1,2,3-triazoline intermediate 301, which is the consequence of a LUMO(dipole)— HOMO(dipolarophile) controlled intramolecular [3 + 2] cycloaddition. Some remarkable steric effects were encountered for this cyclization. While the piperidine derivative [300, = ( 112)4] readily cyclized by diazo group transfer at... 

C in 88% yield, the pyrrolidine analogue [300, R, R = ( 112)3] had to be heated for 1-2 days in polar solvents. The corresponding acyclic diazoamide (300, R = R = H) possessed a half-life of >10 days at ambient temperamre. The intramolecular aziridination reaction, however, could be readily achieved under catalysis using Rh2(OAc)4. 

The diverse chemistry of carbenes is beyond the scope of this account, but a few typical reactions are shown here to illustrate the usefulness of the photochemical generation of these reactive species. A carbene can insert into a C—H bond, and this finds application in the reaction of an a-diazoamide to produce a P-lactam (5.29). Carbenes derived from o-diazoketones can rearrange to ketenes, and thus a route is opened up to ring-contraction for making more highly strained systems <5.301. Carbenes also react with alkenes, often by cycloaddition to yield cyclopropanes in a process that can be very efficient (5.31) and highly stereoselective (5.321. 

RC=CKWG) yields 2,4-di-EWG-substituted pyrroles in the presence of copper catalyst but 2,3-di-EWG-substituted pyrroles in the presence of a phosphine catalyst.74 The 3 + 2-cycloaddition of diazoalkanes to (6 )-3-p-tolylsulfinylfuran-2(5//)-one produces diastereoisomeric pyrazolines in almost quantitative yield and with des >98%. (g) The sulfinyl group is responsible for the complete control of the n-facial selectivity in all these reactions.75 The Rh(II)-catalysed intramolecular 1,3-dipolar cycloaddition reaction of diazoamides (57) with alkenyl and heteroaromatic n -bonds yields pen-tacyclic compounds (59), via the ylide (58), in good to excellent yields and in a (g) stereocontrolled manner (Scheme 15).76... 

In a related study, Kappe also investigated this phenomenon and found that when diazoamide 147 was treated with Rh2(OAc)4 in the absence of a dipolarophile, ammonium ylide 148 could be isolated as a crystalline solid in 70% yield.67 The structure of the ylide was confirmed by X-ray crystallography. In the presence of DMAD, ylide 148 was converted to cycloadduct 149. 

When diazoimide 19 (or 20) was deacetylated [36] and the resulting diazoamide 23 (or 24) was subjected to rhodium(II) acetate, the yield of the corresponding cycloadduct (i.e. 25 or 26) was significantly diminished. One explanation for this, different reactivity is the inherent decrease in electrophilic character conferred upon the intermediate rhodium carbenoid when the diazo carbon bears a hydrogen atom rather than an acetyl group. This decrease in electrophi-licity may alter the rate of carbenoid attack on the remote carbonyl group to the point where alternative reactions can occur. Another possible explanation to account for the diminished reactivity is that the preferred conformation of the intermediate rhodium carbenoid may not be the one that results in carbonyl ylide formation [35]. 

Rhodium(ll)-catalyzed decomposition of the diazoamide 235 has been shown to provide the indole 236 (Equation 74). In contrast, attempts involving Rh2(OAc)4 failed to give indolic products <1996T2489>. Decomposition of related substrates induced by zeolite K/3 leads to formation of oxindoles <1996J(P1)2793>. 

One of the few examples of an intramolecular carbene addition to an imino-bond is shown in Scheme 6 <19990L667>. Isoquinoline diazoamide 35 was subjected to standard dirhodium catalysis. The resulting aziridino-isoquinoline 36 was isolated in an excellent 87% yield. The N-O invertomers could be isolated chromatographically. Several other cyclic and acyclic systems were also synthesized. A simple acyclic system provided an 86% yield of a bisazabicyclo[3.1.0]hexane system. A pyrrolizidine aziridine was prepared in 60% overall yield. 

Surprisingly, the indolizidine aziridine 39 was synthesized in 88% yield, but was found to be an uncatalyzed reaction, providing the product upon diazo-transfer at 0°C to oxime 37. Two plausible mechanisms are invoked for this carbene reaction sequence (1) a carbenoid insertion process or (2) collapse of the azomethine ylide formed upon addition of the diazoamide. The uncatalyzed process is likely due to a dipolar cycloaddition of the diazo and pendent oxime. 

Heimgartner and co-workers treated a-diazoketones and a-diazoamides 64 with thiones, with and without a catalyst such as Rh(OAc)2 present (1998HCA285). The products were substituted thiiranes 65 and/or substituted 1,3-oxathioles. In all cases, a thiocarbonyl ylide intermediate, which could undergo either a 1,3- or a 1,5-electro-cyclization, was held responsible. The ylide could arise either from addition of a carbene or a carbenoid to S of the thiocarbonyl compound or by loss of N2 from a primary cycloadduct between the diazo and the thiocarbonyl compounds. In one case, such a primary adduct was isolated. The thiirane carboxamides could be desulfurized with (Me2N)3P in tetrahydrofuran (THF) at 60 °C to afford acrylamides 66 (Scheme 11). 

Reactions of thioketones with diazoamides at room temperature in THE for 15-30 min gave corresponding thiiranes in 64-72% yield (Scheme 93) <1998HCA285>. 

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