Imines diazo compounds

Triazoline thermolysis leads to aziridines, diazo compounds, imines, or enamines a diazonium betaine is postulated as the intermediate that can undergo stabilization by different pathways,16,30,806,112,465 as depicted in Scheme 161. Imine and enamine formation may occur directly from the diazonium betaine806,112,226 237 247 or via the diazo compound.32 Acceleration of the rate of thermolysis of 4,5-dialkyl-substituted triazolines in polar solvents is commensurate with the betaine intermediate,100,112,457,466 and attempts to prove a 1,3-zwitterionic intermediate have failed 467-469... 

The same authors have described a related enantioselective three-component Mannich-type reaction of diazo compounds, imines and water in the presence of a combination of Rh2(OAc)4 with a chiral BINOL-derived phosphoric acid. Following the same mechanism as above (with water... 

The addition of diazo compounds generally leads to three membered tings, although in special cases, linear adducts with an intact diazo group [110] or l,3,4-oxadiazol-3-ines [111] can be isolated Most diazo compounds are unstable and yield oxirans and aziridines [112,113,114] Aziridines are obtained exclusively on reaction of certain polyfluorinated acyl imines with diazomethane [115]... 

Of course, the key limitation of the ylide-mediated methods discussed so far is the use of stoichiometric amounts of the chiral reagent. Building on their success with catalytic asymmetric ylide-mediated epoxidation (see Section 1.2.1.2), Aggarwal and co-workers have reported an aza version that provides a highly efficient catalytic asymmetric synthesis of trans-aziridines from imines and diazo compounds or the corresponding tosylhydrazone salts (Scheme 1.43) [68-70]. 

These complexes can be isolated in some cases in others they are generated in situ from appropriate precursors, of which diazo compounds are among the most important. These compounds, including CH2N2 and other diazoalkanes, react with metals or metal salts (copper, palladium, and rhodium are most commonly used) to give the carbene complexes that add CRR to double bonds. Ethyl a-diazoacetate reacts with styrene in the presence of bis(ferrocenyl) bis(imine), for example, to give ethyl 2-phenylcyclopropane-l-carboxylate. Optically active complexes have... 

More recently, Williams has described the one pot synthesis of 2-substituted oxazoles 11 by the thermolysis of triazole amides 9 the reaction does not proceed photo-chemically.<92TL1033> Although the reaction does not involve addition to a nitrile, it is an interesting application of a diazo compound since the proposed zwitterionic intermediate 10 is a resonance form of a diazo imine, so formally the reaction may be thought of as a thermal decomposition of a diazo imine (Scheme 6). 

Aziridines have been synthesized, albeit in low yield, by copper-catalyzed decomposition of ethyl diazoacetate in the presence of an inline 260). It seems that such a carbenoid cyclopropanation reaction has not been realized with other diazo compounds. The recently described preparation of 1,2,3-trisubstituted aziridines by reaction of phenyldiazomethane with N-alkyl aldimines or ketimines in the presence of zinc iodide 261 > most certainly does not proceed through carbenoid intermediates rather, the metal salt serves to activate the imine to nucleophilic attack from the diazo carbon. Replacement of Znl2 by one of the traditional copper catalysts resulted in formation of imidazoline derivatives via an intermediate azomethine ylide261). 

The outcome of the copper-catalyzed decomposition of a diazo compound in the presence of a 1,1-diarylmethanimine depends on the nature of the diazo compound. With diazodiphenylmethane, the N/H insertion product 281 and the isomeric imine... 

Although formally the product of 1,4-addition of the carbene to the ADC 4n unit, 1,3,4-oxadiazolines probably arise via initial nucleophilic attack of the diazo compound to give, after loss of N2, a dipolar intermediate. This intermediate azomethine imine can collapse directly to give the oxadiazoline,... 

In 2007, Maruoka et al. introduced chiral dicarboxylic acids consisting of two carboxylic acid functionalities and an axially chiral binaphthyl moiety. They applied this new class of chiral Brpnsted acid catalyst to the asymmetric alkylation of diazo compounds withA-Boc imines [91]. The preparation of the dicarboxylic acid catalysts bearing aryl groups at the 3,3 -positions of the binaphthyl scaffold follows a synthetic route, which has been developed earlier in the Maruoka laboratory [92]. 

Scheme 73 Fiiedel-Crafts-type alkylation of diazo compounds with A-Boc imines...

The [3 + 2] cycloaddition of diazo compounds to imines or nitriles is an alternative approach to the preparation of 1,2,3-triazoles and 1,2,3-triazolines. For reviews, see CHEC-I <84CHEC-I(5)7I7>. 

The preparation of thiiranes is most conveniently performed in solution. However, there are also protocols reported for reaction in the gas and solid phase. By using diazo and thiocarbonyl compounds in ether as solvent, both alkyl and aryl substituted thiiranes are accessible. As indicated earlier, aryl substituents destabilize the initially formed 2,5-dihydro-1,3,4-thiadiazole ring and, in general, thiiranes are readily obtained at low temperature (13,15,35). On the other hand, alkyl substituents, especially bulky ones, enhance the stability of the initial cycloadduct, and the formation of thiiranes requires elevated temperatures (36 1,88). Some examples of sterically crowded thiiranes prepared from thioketones and a macro-cyclic diazo compound have been published by Atzmiiller and Vbgtle (106). Diphenyldiazomethane reacts with (arylsulfonyl)isothiocyanates and this is followed by spontaneous N2 elimination to give thiirane-2-imines (60) (107,108). Under similar conditions, acyl-substituted isothiocyanates afforded 2 1-adducts 61 (109) (Scheme 5.23). It seems likely that the formation of 61 involves a thiirane intermediate analogous to 60, which subsequently reacts with a second equivalent... 

Thus in the N-silyl substituted series, 17 and 18, which rearrange thermally to the corresponding diazo compounds, the stability increases through the series R=Me, Ph, i-Pr. As discussed below, these compound undergo the usual cycloaddition and electrocyclization reactions of nitrile imines and are not simply overstabilized curiosities. The usefulness in synthesis of those with P—C bonds is probably limited since these bonds are not easily broken, but products derived from those with C—Si and C—B bonds (e.g., 21 and 22) should be capable of further... 

In principle, it would appear that the presence of bulky substituents R and E should kinetically favor the formation of nitrile imines. Lithium salts have been used for much of this work and it has been shown that this is generally the case [e.g., for 151 (X = S)] bulky electrophiles favor the nitrile imine (e.g., 153) while smaller analogues favor diazo compounds (e.g., 152). Reducing the size of the substituent on the diazo compound has a similar effect (e.g., 150 from 151) (X = lone pair). 

Stannyl diazo compounds are less reactive than their lithium analogues and, containing a bigger metal atom, strongly favor reaction at N to give nitrile imines (e.g., 155 from 154). The use of bis(trimethylstannyl)diazomethane (156) provides an easy one-step route to symmetrically substituted systems (e.g., 157). 

In an earlier survey of the cycloaddition chemistry of diazo compounds with imines (5), it was noted that diazoalkanes react particularly well with both electron-deficient acyclic and strained cyclic imines, such as 27/-azirines, producing... 

In contrast to the epoxides, preparative routes to the aziridines are fairly evenly split between the [C=N + C] and the [C=C + N] routes. Among contributions in the former category, aziridine carboxylate derivatives 110 can be prepared through the lanthanide-catalyzed reaction of imines with diazo compounds, such as ethyl diazoacetate (EDA). In this protocol, iV-benzyl aryl aldimines and imines derived from aromatic amines and hindered aliphatic aldehydes are appropriate substrates <99T12929>. An intramolecular variant of this reaction (e.g.. Ill —> 112) has also been reported <990L667>. 

Throughout this chapter, we have almost always ignored the role of the carbene precursor. Carbenes are generally made from diazo compounds, or from a variety of surrogate diazo compounds including diazirines, tosylhydrazone salts, and aziridyl imines, all of which probably decompose through nonisolable diazo compounds. Not surprisingly, it turns out that diazo compounds have a rich chemistry of their own, especially when irradiated. Moreover, that chemistry often closely resembles the reactions of carbenes. Much of intramolecular carbene chemistry is, in fact, diazo compound chemistry. 

Organic azides (RNS) are isoelectronic with diazo-compounds, and like them are yellow in colour. On irradiation azides lose nitrogen to produce monovalent nitrogen species, nitrenes lRN . In the absence of an addend, aliphatic nitrenes generally undergoa shift of hydrogen to give an imine (5.34), whereas aromatic nitrenes can dimerize to yield an azo-compound (S.3SI. 

Two general methods are available for the assembly of the sterically stabilized species 16-24, both starting from metallic derivatives of diazo compounds (147) (16). The latter have two nucleophilic centers and can, in principle, react with electrophiles at C giving the functionalized diazo compounds (148), or at N, which leads to the nitrile imines (149). 

The diazoacetonitrile-imine reaction may be considered complimentary to azide addition to cinnamonitriles because in the latter case only triazoline thermolysis products result.284 The reversed order of reactivity of the diazoacetonitrile to that of diazomethane implies an electrophilic attack on the imine and is explained in terms of a LUMOdi MC lonit[ile-HOMOin,int controlled interaction. Thus electron-rich enamines, which do not react with diazoalkanes, may be expected to react with electron-poor diazo compounds. 

Azide addition to open-chain vinyl ethers results in different thermolysis products, depending on the azide and the enol ether employed. In Scheme 180, when R = benzoyl or ethoxycarbonyl, R2 = OR1 and R3 = H, imino ethers are obtained by alkoxyl migration along with minor amounts of azir-idine.269 525 However, when R = Ph and the carbons are fully substituted, the imine (108) is obtained apparently from the reversibility of the imine-diazo compound addition (Section IV,B,2) (Scheme 181).270... 

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