Diazo compounds Diazomethane, cyclopropanation

Diazoalkane decomposition. Surprisingly, tetraphenylethylene is almost as efficient as various copper catalysts for decomposition of diazoalkanes to car-benoids. For example, diazomethane and cyclohexene in the presence of this catalyst react to form norcarane in 15 5% yield with copper catalysis the yield of norcarane is 24%. Cyclopropanations have been observed with this hydrocarbon catalyst with a variety of diazo compounds diazomethane, a-diazoacetophenone, and diazofluorene. Diphenyldiazomethane, however, is converted mainly into benzophenone azine, (C5H5)2C=NN=C(C6Hs)2. 

Whereas the utility of these methods has been amply documented, they are limited in the structures they can provide because of their dependence on the diazoacetate functionality and its unique chemical properties. Transfer of a simple, unsubstituted methylene would allow access to a more general subset of chiral cyclopropanes. However, attempts to utilize simple diazo compounds, such as diazomethane, have never approached the high selectivities observed with the related diazoacetates (Scheme 3.2) [4]. Traditional strategies involving rhodium [3a,c], copper [ 3b, 5] and palladium have yet to provide a solution to this synthetic problem. The most promising results to date involve the use of zinc carbenoids albeit with selectivities less than those obtained using the diazoacetates. 

The Lewis acid-Lewis base interaction outlined in Scheme 43 also explains the formation of alkylrhodium complexes 414 from iodorhodium(III) meso-tetraphenyl-porphyrin 409 and various diazo compounds (Scheme 42)398), It seems reasonable to assume that intermediates 418 or 419 (corresponding to 415 and 417 in Scheme 43) are trapped by an added nucleophile in the reaction with ethyl diazoacetate, and that similar intermediates, by proton loss, give rise to vinylrhodium complexes from ethyl 2-diazopropionate or dimethyl diazosuccinate. As the rhodium porphyrin 409 is also an efficient catalyst for cyclopropanation of olefins with ethyl diazoacetate 87,1°°), stj bene formation from aryl diazomethanes 358 and carbene insertion into aliphatic C—H bonds 287, intermediates 418 or 419 are likely to be part of the mechanistic scheme of these reactions, too. 

In 1986, Pfaltz et al. introduced a new type of pseudo C2-symmetrical copper-semicorrin complex (68) as the catalyst (Scheme 60).227 228 The complexes (68) are reduced in situ by the diazo compound or by pretreatment with phenylhydrazine to give monomeric Cu1 species (69), which catalyze cyclopropanation. Of the semicorrin complexes, complex (68a) (R = CMe2OH) showed the best enantioselectivity in the cyclopropanation of terminal and 1,2-disubstituted olefins.227,228,17 It is noteworthy that complex (68a) catalyzes cyclopropanation, using diazomethane as a carbene source, with good enantioselectivity (70-75% ee).17... 

Electron-withdrawing substituents generally increase diazo compounds stability toward decomposition. Dicarbonyl diazomethane, which bears two carbonyl groups flanking the diazomethane carbon, are more stable than diazo compounds with only one carbonyl substituent. In general, metal catalysed decomposition of dicarbonyl diazomethane requires higher temperature than does monocarbonyl substituted diazomethane. As indicated before, rhodium(II) carboxylates are the most active catalysts for diazo decomposition. With dicarbonyl diazomethane, the rhodium(II) carboxylate-promoted cyclopropanation process can also be carried out under ambient conditions to afford a high yield of products. 

Reactions of transition-metal coordinated olefins with diazo compounds as a route to cyclopropane products have not yet been rigorously established. Catalysts that should be effective in this pathway are those that are more susceptible to olefin coordination than to association with a diazo compound and also those whose coordinated alkene is sufficiently electrophilic to react with diazo compounds, especially diazomethane. Pd(II), Pt(II), and Co(II) compounds appear to be capable of olefin coordination-induced cyclopropanation reactions, but further investigations will be required to unravel this mechanistic possibility. 

Due to the electrophilic character of carbenes. they are not expected to easily react with electron-poor alkenes, and the only reported examples concern reactions with diazo compounds (i.e., diazomethane, diazofluorcnc. ethyl diazoacetate. and phenyldiazoniethane ). However, depending on the reaction conditions, carbenes arc not always the reactive species. Cyclopropanes are often obtained by decomposition of pyrazolines which arise from 1,3-dipolar cycloaddilion reactions (see Section 2.1.1.6.2.3.1.). Even when reactions are performed under irradiation, pyrazolines can be obtained as the result of a diradical addition. ... 

The available literature data support the assertion that the outcome of the methylene cycloadditions depends to a large extent on the ability of the olefin to be coordinated to the palladium center. In that respect, the mechanism of palladium-catalyzed cyclopropanation appears to differ significantly from that of rho-dium(ll)-catalyzed cyclopropanations. One advantage of using palladium catalysts with diazomethane is associated with the possibility of synthesizing polycyclopropane adducts, a topic of current interest (vide infra) which has no general satisfactory solution with other diazo compound/catalyst combinations. This point is exemplified below for the cyclopropanation of the esters of trans-polyunsaturated acids. Moreover, the reactivity of the double bonds depends both on their position in the linear hydrocarbon chain and on their configuration (eq. (f)). 

Monoaryldiazomethanes, readily prepared by a number of methods, are the carbene precursors most frequently used for the synthesis of arylcyclopropanes. When such diazo compounds are decomposed photochemically, thermally, or by using various transition-metal salts in the presence of an alkene, arylcyclopropanes are formed. The yield is often quite high, but in a number of cases cyclopropane formation has been hampered by competing reactions, of which, disregarding intramolecular reactions, azine formation, stilbene formation, and hydrogen abstraction followed by dimerization are the most predominant. Many aspects related to the use of diazomethane derivatives as carbene precursors have been thoroughly discussed by Wentrup. ... 

When diaryldiazomethanes are decomposed by means of a metal salt in the presence of an alkene, 1,1-diaryIcyclopropanes are formed (see also Section 1.2.1.2.4.2.6.3.). A number of salts are able to promote the decomposition of the diazo compounds,but whatever the salt is, the cyclopropane is generally afforded in moderate to low yield due to formation of significant quantities of ketazine and benzophenone derivatives. Thus, decomposition of diphenyl-diazomethane by copper(II) sulfate in butyl vinyl ether gave l-butoxy-2,2-diphenylcyclo-propane (1) in 17% yield, benzophenone azine (2) in 14% yield and benzophenone (3) in 11% yield. ... 

The success of this method is strongly dependent on the substituents on the starting diazo compound. Copper-catalyzed decomposition of various (alkyl)(dimethoxyphosphoryl)di-azomethane derivatives in benzene did not lead to the formation of cyclopropanes. In the same way, the photolysis of (benzyl)(dimethoxyphosphoryl)diazomethane or (benzoyl)(dimeth-oxyphosphoryl)diazomethane derivatives in benzene did not afford cyclopropane adducts, but alkenes or ketenes arising from migration of substituents. ... 

Phenyl(trimethylsilyl)carbene can be generated by gas-phase pyrolysis of phenyl(trimethyl-silyl)diazomethane (1) at 500 °C (see Houben-Weyl Vol. El9b, p 1427). An attempt to trap this carbene with 2,3-dimethylbuta-l,3-diene furnished cyclopropane 3 only in trace amounts besides products 2, 4, and 5. Cyclopropane 3 can be prepared independently and in better yield by photolyzing the diazo compound in the presence of the butadiene. Thermally induced ring expansion of 3 provides cyclopentene 4, a fact that explains the low yield found under pyrolysis conditions. 

Bis(diisopropylamino)phosphanyl(trimethylsilyl)diazomethane 6, easily available by treatment of chlorobis(diisopropylamino)phosphane with lithiated diazo(trimethylsilyl)methane, provides upon flash thermolysis at 250"C the so-called stable carbene 7.38,39,40 behaves partly as a nucleophilic carbene and reacts only with electron-deficient alkenes such as methyl propenoate or diethyl fumarate under cyclopropanation." In the former case only the Z-isomer 8 is formed. Cyclopropane 9 is thermally unstable and is, therefore, oxidized in situ at the phosphorus atom with elemental sulfur to provide cyclopropane 10, Cyclopropanes 8 and 9 are also generated from the diazo compound 6 and the appropriate alkene by photolysis." ... 

A number of diazo compounds are known to be decomposed by Zn(II), Co(II), Co(ni) and Rh(III) complexes of porphyrins (409) to give 1 1 and 1 2 adducts between the porphyrin and the formal carbene unit. Depending on the metal ion, different products may result (Scheme 42) Zinc octaethylporphyrin or meso-tetraphenylporphyrin yield N-alkylated porphyrins 410 with ethyl diazoacetate and ethyl 2-diazopropionate In the latter case, a homoporphyrin 411 is obtained additionally. Cu(I)-catalyzed decomposition of diazomethane or alkyl diazoacetates in the presence of zinc me.yo-tetraphenylporphyrin leads to cyclopropanation of a pyrrolic pp double bond, besides an N-alkylated product of type 410 The... 

The most versatile carbene precursors are a-diazocarbonyl compounds such as diazoacetic acid esters because they are readily prepared, easy to handle and much more stable than ordinary diazoalkanes [10,38]. Nevertheless, one should always be aware of the potential hazards of diazo compounds in general [39],but if the necessary precautions are taken, they can be safely handled even on an industrial scale [18]. The most frequently used reagent is commercially available ethyl diazoacetate. Besides a-diazocarbonyl reagents, diazomethane [40,41 ] and a y-diazoacrylate derivative [42] have been used in enantioselective Cu-cata-lyzed cyclopropanations but the scope of these reactions has not been studied systematically. It has been shown in certain cases that diazo compounds can be replaced by other carbene precursors such as iodonium ylides, sulfonium yUdes, or lithiated sulfones [8,43],but successful applications of these reagents in enantioselective Cu-catalyzed reactions have not been reported yet. 

Intramolecular cyclopropanations with unsaturated diazo ketones have also been reported. Furthermore, enantioselective cyclopropanation with diazomethane can be achieved in up to 75% ee. In detailed mechanistic discussions, a copper(I) species, complexed with only one semicorrin ligand, and formed by reduction and decomplcxation, is suggested as the catalytical-ly active species, cisjtrans Stereoselection and discrimination of enantiotopic alkene faces should take place within a copper-carbene-alkene complex25-54"56. According to these interpretations, cisjtrans selectivity is determined solely by the substituents of the alkene and of the diazo compound (especially the ester group in diazoacetates) and is independent of the chiral ligand structure (salicylaldimine or semicorrin)25. 

From Diazo Compounds. Addition of diazomethane or its substituted derivatives to double bonds is a standard approach for the preparation of cyclopropyl compounds. Pyrazolines may be intermediates in such reactions, but are often decomposed in situ without isolation. An example is the addition of diazomethane to the bis-ketal (92). The initially formed pyrazoline extrudes nitrogen at 450 C to give the cyclopropane (93 93%) which can be converted into the bis-aldehyde, or pyrolysed to ring-opened (94) and ring-expanded (95) products, ... 

Certain diazo compounds, however, do not require a transition-metal catalyst in order to react with carbon-carbon double bonds. Diazomethane itself acts as a 1,3-dipole and undergoes 1,3-dipolar additions with alkenes. The pyrazoline intermediate initially produced loses N2 to produce a cyclopropane ... 

Apart from routine applications to cyclopropane synthesis,the application of new catalysts to the decomposition of diazo-compounds has received considerable attention. The use of palladium acetate, originally reported in 1972 by Paulissen et o/., has been extended and applied to diazomethane and ethyl diazoacetate in the presence of aP-unsaturated carbonyl compounds. With a- and a-substituted aP-unsaturated ketones, stereospecific cis-addition occurs in excellent yields, but the catalyst proves to be ineffective with analogous trisubstituted olefins, as illustrated for the formation of (110) with diazomethane. The use of palladium chloride with the... 

By far the best source for 3a is (trimethylsilyl)diazomethane (19). It has already been mentioned that gas-phase pyrolysis of 19 alone yields products which are derived from intramolecular carbene reactions such as 1,3-C,H insertion and silylcarbene-to-silene rearrangement (see equation 20). Also, copyrolysis of 19 with alcohols or benzaldehyde allowed one to trap the silene but not the carbene 33 (see equation 5). Furthermore, solution photolysis of 19 in the presence of alcohols or amines did not give the X,H insertion products of the carbene but rather trapping products of the silene . On the other hand, photochemically generated carbene 3a did undergo some typical intermolec-ular carbene reactions such as cyclopropanation of alkenes (ethylene, frani-but-2-ene, but not 2,3-dimethylbut-2-ene, tetrafluoroethene and hexafluoropropene), and insertion into Si—H and methyl-C—H bonds (equation 39). The formal carbene dimer, trans-1,2-bis(trimethylsilyl)ethene, was a by-product in all photolyses in the presence of alkenes it is generally assumed that such carbene dimers result from reaction of the carbene with excess diazo compound. 

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