Amines reaction with diazoalkanes

Muller has explored enantioselective C-H insertion using optically active rhodium complexes, NsN=IPh as the oxidant, and indane 7 as a test substrate (Scheme 17.8) [35]. Chiral rhodium catalysts have been described by several groups and enjoy extensive application for asymmetric reactions with diazoalkanes ]46—48]. In C-H amination experiments, Pirrung s binaphthyl phosphate-derived rhodium system was found to afford the highest enantiomeric excess (31%) of the product sulfonamide 8 (20equiv indane 7, 71% yield). 

Substituted 1,4-diazooxides rect with secondary aliphatic amine to give the corresfxjnding triazene (diazoamino compounds) in high yield, while the products with primary amine are surprisingly unstable and deompose by a radical mechanism. Reactions with diazoalkanes yield asymmetrical azine 29 (15) in the case of 1,4-diazooxide, and cyclic benzoxadiazines 30 with 1,2-diazooxides (16) . 

Compared to diazonium salts, diazo compounds are generally much less reactive towards nucleophiles than towards electrophiles. As a result of this azo coupling reactions of diazo compounds are the exception rather than the rule. Electron withdrawing substituents on the diazo carbon increase the reactivity towards nucleophiles. Consequently the ability to undergo azo coupling reactions increases from diazomethane to diazocarbonyl- and 2-diazo-l, 3-dicarbonyl compounds. Among the earliest reactions known were those with cyanide and sulfite ions Tertiary phosphines, as opposed to amines, can form stable addition complexes with diazoalkanes probably due to the ability of phosphorus to stabilize the betaine with its empty d orbitals (6). 

A significant advance in the study of cyclopropanones resulted from studies by the Turro and the de Boer groups on the formation of cyclopropanones in solution by the reaction of ketenes with diazoalkanes. These investigators found that it is possible to store the parent ketone only for short periods at low temperature because of its unusual reactivity and propensity for polymerization. Subsequent work has shown that cyclopropanone seems to show chemical behavior similar to that of ketene. Thus, it is attacked by nucleophilic species such as water, alcohol and amines and reacts rapidly with itself to form... 

The reaction is especially suited to the generation of optically active diazonium ions with specifically oriented counter-ions. In this respect it has possibilities which are absent for the reaction of diazoalkanes with acids and the deamination of aliphatic amines. However, in carrying out stereochemical studies, great care must be exercised to avoid spurious results, since the transient formation of a diazoalkane, either by loss of a proton from the diazonium ion or by what is probably a concerted elimination reaction of the diazoester, can lead to racemisation of the alkyl function and loss of asymmetry in the anion. Moreover, the diazoester is liable to nucleophilic displacement, for example by an acid molecule formed from already rearranged nitrosoamide, and this can lead to inverted product. 

Table 2-1 shows ten types of synthetic process. Methods 1 and 2 are based on aliphatic amines, 3-5 on derivatives of carbonyl compounds, 6 on hydrocarbons with a relatively acidic CH proton, and 7-9 are reactions of diazoalkanes obtained by one of the types 1-6. Reaction 10 involves a diazo ketone, which can be obtained by reaction 9, the first step of the Arndt-Eistert synthesis. 

The discovery of stable alkenediazonium salts by Bott initiated some investigations on the reactivity of these compounds, e.g., with the hexachloroantimonate of the 2,2-diethoxyethene-l-diazonium ion (9.100). Saalfrank and Ackermann (1981a, 1981 b) reported that 9.100 reacts with primary amines to give l/f-l,2,3-triazoles. This process might be the result of an initial A-azo-coupling reaction with the amine (characteristic of diazonium salts) with subsequent cyclization of the resulting triazene, or result from attack of the amine at the C()ff)-atom with formation of a diazoalkane that cyclizes (9-45). 

Reaction of sulfonyl halides with tertiary amines and diazoalkanes... 

The best known example of the treatment of a primary aliphatic amine with nitrous acid involves the reaction of esters of glycine hydrochloride with sodium nitrite to form esters of diazoacetic acid. This reaction is carried out at low temperatures and under such reaction conditions that any IV-nitroso primary amine which might have been formed is immediately converted to the diazoacetate [15, 16]. Treatment of 1-methyl-2,2,2-trifluoroethylamine hydrochloride, another primary amine, with sodium nitrite in an aqueous system also evidently leads to the corresponding diazoalkane [17]. 

The three-, four-and five-membered cyclic sulfones have some interesting reactions. Three-membered ring sulfones, called thiirane-1,1-dioxides or episulfones, can be prepared by reaction of a diazoalkane, e.g. (160), with sulfur dioxide (Scheme 63). The reaction affords a mixture of the cis-episulfone (161) and trans-episulfone (162), and both isomers can be isolated by fractional crystallisation at low temperature. Another method of preparation of episulfones is by treatment of a diazoalkane with a sulfonyl chloride (containing a-hydrogen atoms) and a tertiary amine (Scheme 64). Both these syntheses involve the formation of the highly reactive sulfene intermediate (163) (see Chapter 7, p. 114) episulfones on warming eliminate sulfur dioxide to form the alkene (164) as indicated in Scheme 64.7... 

Allyl sulfides and allyl amines. Rhodium-catalyzed decomposition of ethyl diazoacetate in the presence of these allyl compounds generates products 136 and 137, respectively, derived from [2,3] rearrangement of an S- or N-ylide intermediate, besides small amounts of carbene dimers No cyclopropane and no product resulting from the ylide by [1,2] rearrangement were detected. Besides RhjfOAc) and Rhg(CO)i6, the rhodium(I) catalysts [(cod)RhCl]2 and [(CO)2RhCl]2 were found to behave similarly, but yields with the only allyl amine tested, CH =CH—CH NMe, were distinctly lower with the latter two catalysts. Reaction temperatures are higher than usually needed in rhodium-promoted diazoalkane decomposition, which is certainly due to competition between the diazo compound and the allylic hetero-... 

Azide synthesis (2, 415). In the definitive paper3 describing the conversion of primary amines into azides by a diazo transfer reaction, methyllithium is preferred to methylmagnesium chloride as the base. The reaction has been extended to hydrazones. Thus, when the hydrazones of benzophenone, fluorenone, and acetophenone are treated with methylmagnesium chloride and then with tosyl azide, the corresponding diazoalkanes are obtained in about 20% yield. 

Pathway B is closely related to A if the C(a) —bond is sufficiently strong, the amine residue R-N will be protonated and it will remain within the rest of the diazoalkane. If there is no H-atom at C()8), no diazoalkane can be formed. The intermediate alkyldiazonium zwitterion 2.169 will lose N2, and the carbocation will be solvolyzed or it will form rearranged products that are of no immediate interest in the context of the present section. With very few exceptions, we will discuss the chemistry of azide additions only for reactions leading to diazo compounds. 

The deamination of aliphatic amines is occasionally effected through reaction of the amine with an alkyl nitrite in a non-polar solventPrimary carbinamines apparently react in this system via diazoalkanes (see section (3), path (b)). Triazenes (RN2NHR) and free radicals are also possible intermediates that must be considered for deaminations in non-polar solvents. The reaction of amines with nitrosonium salts in aromatic solvents is probably a closely related process . Through the use of alkyl nitrites in nonpolar solvents, it has been shown recently that certain vinyl amines yield products that probably stem from carbene intermediates (equation 165) ° . 

Also of interest in the preparation of diazoalkanes are the di-azotization of primary amines with activating substituents in the a-position, reaction of hydrazine or hydrazides with dichlorocarbene, diazo-group transfer reactions, the oxidation of hydrazones, and condensation reactions of active methylene compounds. 

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