Oxonium ylide

Allylic ethers and acetals can react with carbenoid reagents to generate oxonium ylides that undergo [2,3]-sigmatropic shifts.224... 

In addition to cyclopropane 145 and the expected [2,3] rearrangement product 143 of an intermediary oxonium ylide, a formal [1,2] rearrangement product 144 and small amounts of ethyl alkoxyacetate 146 are obtained in certain cases. Comparable results were obtained when starting with dimethyl diazomalonate. Rh2(CF3COO)4 displayed an efficiency similar to Rh2(OAc)4, whereas reduced yields did not recommend the use of Rh6(CO)16 and several copper catalysts. Raising the reaction temperature had a deleterious effect on total product yield, as had... 

Assuming a reactive oxonium ylide 147 (or its metalated form) as the central intermediate in the above transformations, the symmetry-allowed [2,3] rearrangement would account for all or part of 148. The symmetry-forbidden [1,2] rearrangement product 150 could result from a dissociative process such as 147 - 149. Both as a radical pair and an ion pair, 149 would be stabilized by the respective substituents recombination would produce both [1,2] and additional [2,3] rearrangement product. Furthermore, the ROH-insertion product 146 could arise from 149. For the allyl halide reactions, the [1,2] pathway was envisaged as occurring via allyl metal complexes (Scheme 24) rather than an ion or radical pair such as 149. The remarkable dependence of the yield of [1,2] product 150 on the allyl acetal substituents seems, however, to justify a metal-free precursor with an allyl cation or allyl radical moiety. 

The dominant role of the traditional copper catalysts, generally used under heterogeneous conditions, has not been challenged as yet. Only a few reports shed light on the efficiency of alternative catalysts. Copper(II) triflate allows high-yield intramolecular cyclopropanation of y,8-unsaturated diazoketone 182160) it is superior to CuS04 (53 % yield 192 ) or Rh2(OAc)4160). The solvent is crucial for an efficient conversion If the reaction is carried out in ether, the solvent competes with the double bond for the electrophilic metal carbene to give 184, presumably via an oxonium ylide intermediate. 

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. 

The assumption that 339 arises from the oxonium ylide by a proton transfer process is supported by the reversed product ratio obtained in the reaction with ethanol in the presence of diazabicyclo[4.3.0]non-5-ene (DBN)-... 

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 ). 

As shown in Scheme 3.88, an initially formed Rh-carbene species reacted with 169 to give either 172 or an oxonium ylide, 173. The latter underwent a [2,3]sigma-tropic rearrangement to form the allene 171 (Scheme 3.88). 

The intramolecular addition of acylcarbene complexes to alkynes is a general method for the generation of electrophilic vinylcarbene complexes. These reactive intermediates can undergo inter- or intramolecular cyclopropanation reactions [1066 -1068], C-H bond insertions [1061,1068-1070], sulfonium and oxonium ylide formation [1071], carbonyl ylide formation [1067,1069,1071], carbene dimerization [1066], and other reactions characteristic of electrophilic carbene complexes. 

Several examples have been reported for furanone formation by intramolecular C-H insertion of electrophilic carbene complexes [1006,1148] (Table 4.7). Yields can, however, be low with some substrates, possibly as a result of several potential side-reactions. Oxonium ylide formation and hydride abstraction, in particular, [1090,1149-1152] (see Section 4.2.9) seem to compete efficiently with the formation of some types of furanones. 

Fig. 4.11. Generation and transformations of oxonium ylides from electrophilic carbene complexes.

Ethers can react with electrophilic carbene complexes to yield oxonium ylides, which usually undergo either elimination reactions or 1,2-alkyl shifts to yield products of a formal carbene C-O bond insertion (Figure 4.11) [1020,1255-1259]. 

If chiral catalysts are used to generate the intermediate oxonium ylides, non-racemic C-O bond insertion products can be obtained [1265,1266]. Reactions of electrophilic carbene complexes with ethers can also lead to the formation of radical-derived products [1135,1259], an observation consistent with a homolysis-recombination mechanism for 1,2-alkyl shifts. Carbene C-H insertion and hydride abstraction can efficiently compete with oxonium ylide formation. Unlike free car-benes [1267,1268] acceptor-substituted carbene complexes react intermolecularly with aliphatic ethers, mainly yielding products resulting from C-H insertion into the oxygen-bound methylene groups [1071,1093]. 

Examples of reactions which presumably involve oxonium ylides are listed in Table 4.19. 

Experimental Procedure 4.2.6. Oxonium Ylide Formation and 2,3-Sigmatropic Rearrangement Ethyl 2,5-Dimethoxy-4-pentenoate [1264]... 

Fig. 4.12. Synthesis of non-racemic griseofulvin based on intramolecular oxonium ylide formation [1262],...

In reactions involving sulfonium ylides fewer side-reactions than with oxonium ylides are usually observed. This is probably because of the stabilization of the former by dtt-pK interaction this is not possible with oxonium ylides. 

Most recently, we have investigated the use of iterative oxonium ylide [1,2]- or [2,31-shifts as a convenient approach to the polypyran domains often found in the marine polyether ladder toxins (Scheme 18.8) [21]. Initial studies indicated that [l,2]-shifts of O-benzyl oxonium ylides such as 19 a or 19 b were inefficient. Alternative metallocarbene processes including C-H insertion and dimerization were found to predominate in these cases, again suggesting that carbene-ylide equilibration may occur [21b]. On the rationale that concerted [2,3]-shifts of the corresponding O-allyl oxonium ylides might occur more readily, the allyl ethers 19 c, 19 d were then examined. These examples were much more effective, especially in conjunction with the optimized catalyst Cu(tfacac)2 [21a]. However, rhodium(II) triphenylacetate (Rh2(tpa)4) [22] was found to... 

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