Ylides from carbenoids

For a monograph, see Johnson Ylid Chemistry, Academic Press New York. 1966. For reviews, sec Morris. Surv. Prog. Chem. 1983, 10, 189-257 Hudson Chem. Br. 1971, 7, 287-294 Lowe Chem. Ind. (London) 1970, 1070-1079. For a review on the formation of ylides from the reaction of carbenes and carbenoids with heteroatom lone pairs, see Padwa Hornbuckle Chem. Rev. 1991, 91, 263-309. 

Other reactions. /3-Lactams, such as 182, were prepared in moderate to good yields by [2,3]-rearrangement of ammonium ylides produced by the reaction of copper carbenoids tethered to allylic amines (Scheme 77) <2001J(P1)3312>. The catalyst of choice in the generation of carbenoid/ylide from a-diazoketone precursor is copper(n) acetylacetonate. 

An enantioselective synthesis of the CE ring system has also been described from S -prolinol. The key step in this approach was an intramolecular generation and rearrangement of the spiro-fused bicyclic ylide from a copper carbenoid [76] (see Scheme 15b). 

Generation of iminium ylides from carbenes and carbenoids and their synthetic application 05UK183. 

In contrast to ethyl diazoacetate, diethyl diazomalonate reacts with allyl bromide in the presence of Rh2(OAc)4 to give the ylide-derived diester favored by far over the cyclopropane (at 60 °C 93 7 ratio). This finding bespeaks the greater electrophilic selectivity of the carbenoid derived from ethyl diazomalonate. For reasons unknown, this property is not expressed, however, in the reaction with allyl chloride, as the carbenoids from both ethyl diazoacetate and diethyl diazomalonate exhibit a similarly high preference for cyclopropanation. 

Whereas pyrrole was reported not to give N/H insertion by ketocarbenoids, such a reaction mode does occur with imidazole Copper-catalyzed decomposition of ethyl diazoacetate at 80 °C in the presence of imidazole gives ethyl imidazol- 1-ylacetate exclusively (93 %) small amounts of a C-alkylated imidazole were obtained additionally under purely thermal conditions 244). N/H insertion also takes place at benzimidazole 245 a). The reaction is thought to begin with formation of an N3-ylide, followed by N1 - C proton transfer leading to the formal N/H insertion product. Diazomalonic raters behave analogously however, they suffer complete or partial dealkoxycarbonylation under the reaction conditions 244) (Scheme 34). N-alkylation of imidazole and benzimidazole by the carbenoids derived from co-diazoacetophenone and 2-(diazoacetyl)naphthalene has also been reported 245 b>. 

Concerning the mechanism of O/H insertion, direct carbenoid insertion, oxonium ylide and proton transfer processes have been discussed 7). A recent contribution to this issue is furnished by the Cu(acac)2- or Rh2(OAc)4-catalyzed reaction of benz-hydryl 6-diazopenicillanate 237) with various alcohols, from which 6a-alkoxypenicil-lanates 339 and tetrahydro-l,4-thiazepines 340 resulted324. Formation of 340 is rationalized best by assuming an oxonium ylide intermediate 338 which then rearranges as shown in the formula scheme. Such an assumption is justified by the observation of thiazepine derivatives in reactions which involved deprotonation at C-6 of 6p-aminopenicillanates 325,326). It is possible that the oxonium ylide is the common intermediate for both 339 and 340. 

Intramolecular oxonium ylide formation is assumed to initialize the copper-catalyzed transformation of a, (3-epoxy diazomethyl ketones 341 to olefins 342 in the presence of an alcohol 333 . The reaction may be described as an intramolecular oxygen transfer from the epoxide ring to the carbenoid carbon atom, yielding a p,y-unsaturated a-ketoaldehyde which is then acetalized. A detailed reaction mechanism has been proposed. In some cases, the oxonium-ylide pathway gives rise to additional products when the reaction is catalyzed by copper powder. If, on the other hand, diazoketones of type 341 are heated in the presence of olefins (e.g. styrene, cyclohexene, cyclopen-tene, but not isopropenyl acetate or 2,3-dimethyl-2-butene) and palladium(II) acetate, intermolecular cyclopropanation rather than oxonium ylide derived chemistry takes place 334 ). 

Interaction of an electrophilic carbene or carbenoid with R—S—R compounds often results in the formation of sulfonium ylides. If the carbene substituents are suited to effectively stabilize a negative charge, these ylides are likely to be isolable otherwiese, their intermediary occurence may become evident from products of further transformation. Ando 152 b) has given an informative review on sulfonium ylide chemistry, including their formation by photochemical or copper-catalyzed decomposition of diazocarbonyl compounds. More recent examples, including the generation and reactions of ylides obtained by metal-catalyzed decomposition of diazo compounds in the presence of thiophenes (Sect. 4.2), allyl sulfides and allyl dithioketals (Sect. 2.3.4) have already been presented. 

The homologation of selenoesters 379 with diazomethane in the presence of Cu or Cul to give a-selenoketones is thought not to involve a carbenoid pathway and an Se-ylide intermediate but rather a tetrahedral species resulting from nucleophilic attack of CH2N2 at the carbonyl carbon atom. The role of the catalyst is seen in facilitating nucleophilic attack at C=0 by complexation at the selenium atom. 

Dipoles can also be generated from rearrangements that take place after the formation of an initial rhodium carbenoid product ]40, 70, 71]. One example of this type of transmutation, also known as a dipole cascade process, involves the formation of an azomethine ylide via the initial formation of a carbonyl ylide [72]. This process was... 

Some years later, the first stable thiocarbonyl ylides 9 and 10 were prepared by the reaction of thiourea with cyano-substituted oxiranes (19,20) or by addition of Rh-di(tosyl)carbenoid to benzo-l,2-dithiole-3-thione (21), respectively. Enhanced stability and the low reactivity of 9 and 10, which enables their isolation in crystalline form, results from the push-pull substitution at the two termini [cf. also (22)]. Another class of stable thiocarbonyl ylides that are also able to afford [3 + 2]-cycloaddition products are the mesoionic 1,3-dithiole-4-ones of type 11 (23,24). 

Suga et al. (197) reported the first stereocontrolled 1,3-dipolar cycloaddition reactions of carbonyl ylides with electron-deficient alkenes using a Lewis acid catalyst. Carbonyl ylides are highly reactive 1,3-dipoles and cannot be isolated. They are mainly generated through transition metal carbenoid intermediates derived in situ from diazo precursors by treatment with a transition metal catalyst. When methyl o-(diazoacetyl)benzoate is treated with A-methylmaleimide at reflux... 

Saito et al. <1995S87> described a new method for the synthesis of heterocycle-fused[c]thiophenes via reaction of aryl heteroaryl thioketones with the carbene precursors. Heteroaromatic thioketones A react with carbenoids generated from bis(arylsulfonyl)diazomethanes or phenyliodonium bis(phenylsulfonyl)methylides to give heterocycle-fused[f]thiophenes B. The reaction involves the ring closure of the intermediary thiocarbonyl ylides, followed by restorative aromatization via the elimination of a sulfenic acid (Equation 11). 

Schlosser670 proposed an equivalent mechanism at the phosphorane 64 stage, formed from the corresponding ylide and not from the phosphonium salt the driving force for the migration comes from the carbenoid nature of the carbon in the a-position to the phosphorus. This is consistent with the anionotropic nature of the migration. The mechanism is corroborated by a similar migration from the ylide 65670 (reaction 198). 

A carbenoid-type mechanism with free or surface-bound species formed by a elimination from methanol promoted by the strong electrostatic field of zeolites was proposed first.433,456,457 Hydrocarbons then can be formed by the polymerization of methyl carbene, or by the insertion of a surface carbene (8) into a C-O bond453-455,458,459 (Scheme 3.2, route a). If surface methoxyl or methyloxonium species are also present, they may participate in methylation of carbene454,455,460,461 depicted here as a surface ylide (9) (Scheme 3.2, route b). A concerted mechanism with simultaneous a elimination and sp3 insertion into methanol or dimethyl ether was also suggested 433,454,457... 

The comparison of thiophene with thioethers on the one hand and with enol thioethers on the other, in regard to its behaviour towards conventional electrophiles, has been made in Section 3.02.2.3. Attack on carbon is the predominant mode of reaction (Section 3.14.2.4) reaction at sulfur is relatively rare (Section 3.14.2.5). Carbenes are known to act as electrophiles attack at both carbon and sulfur of thiophene has been reported. The carbene generated from diazomalonic ester by rhodium(II) catalysis attacks the sulfur atom of thiophene, resulting in an ylide. It has also been shown that the carbenoid species derived by thermolysis of such an ylide functions as an electrophile, attacking the a-carbon of a second molecule of thiophene (Section 3.14.2.9). Singlet nitrene is electrophilic. However, in contrast to carbenes, it invariably attacks only the carbon atom (Section 3.14.2.9). 

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