Ylides origination

Another example features a Heck-type 5-exo-trig cyclization of the aryl iodide 139 occurring at room temperature in dichloromethane (Scheme 22) [82], Azomethine ylides originating from imines 133 were used to trap the Heck product 140 in a subsequent 1,3-dipolar cycloaddition. The diastereomeric products 141 and 142 both derive from an endo attack of... 

The most attractive feature of the Wittig reaction is its regiospecificity. The location of the double bond is never in doubt. The double bond connects the carbon of the original C=0 group of the aldehyde or ketone and the negatively charged carbon of the ylide. 

The insertion of a carbene into a Z-H bond, where Z=C, Si, is generally referred to as an insertion reaction, whereas those occurring from Z=0,N are based on ylide chemistry [75]. These processes are unique to carbene chemistry and are facilitated by dirhodium(II) catalysts in preference to all others [1, 3,4]. The mechanism of this reaction involves simultaneous Z-H bond breaking, Z-car-bene C and carbene C-H bond formation, and the dissociation of the rhodium catalyst from the original carbene center [1]. 

Olefination Reactions Involving Phosphonium Ylides. The synthetic potential of phosphonium ylides was developed initially by G. Wittig and his associates at the University of Heidelberg. The reaction of a phosphonium ylide with an aldehyde or ketone introduces a carbon-carbon double bond in place of the carbonyl bond. The mechanism originally proposed involves an addition of the nucleophilic ylide carbon to the carbonyl group to form a dipolar intermediate (a betaine), followed by elimination of a phosphine oxide. The elimination is presumed to occur after formation of a four-membered oxaphosphetane intermediate. An alternative mechanism proposes direct formation of the oxaphosphetane by a cycloaddition reaction.236 There have been several computational studies that find the oxaphosphetane structure to be an intermediate.237 Oxaphosphetane intermediates have been observed by NMR studies at low temperature.238 Betaine intermediates have been observed only under special conditions that retard the cyclization and elimination steps.239... 

Intramolecular carbonyl ylide formation was also invoked to explain the formation of the AH-1,3-oxazin-5(6//)-ones 291a, b upon copper-catalyzed decomposition of diazoketones 290a, b 270 >. Oxapenam 292, obtained from 290b as a minor product, originates from an intermediary attack of the carbenic carbon at the sulfur atom. In fact, this pathway is followed exclusively if the C(Me, COOMe) group in 290b is replaced by a CH2 function (see Sect. 7.2). 

The reaction of carbenes with alcohols can proceed by various pathways, which are most readily distinguished if the divalent carbon is conjugated to a tt system (Scheme 5). Both the ylide mechanism (a) and concerted O-H insertion (b) introduce the alkoxy group at the originally divalent site. On the other hand, carbene protonation (c) gives rise to allylic cations, which will accept nucleophiles at C-l and C-3 to give mixtures of isomeric ethers. In the case of R1 = R2, deuterated alcohols will afford mixtures of isotopomers. 

Alkenes are scavengers that are able to differentiate between carbenes (cycloaddition) and carbocations (electrophilic addition). The reactions of phenyl-carbene (117) with equimolar mixtures of methanol and alkenes afforded phenylcyclopropanes (120) and benzyl methyl ether (121) as the major products (Scheme 24).51 Electrophilic addition of the benzyl cation (118) to alkenes, leading to 122 and 123 by way of 119, was a minor route (ca. 6%). Isobutene and enol ethers gave similar results. The overall contribution of 118 must be more than 6% as (part of) the ether 121 also originates from 118. Alcohols and enol ethers react with diarylcarbenium ions at about the same rates (ca. 109 M-1 s-1), somewhat faster than alkenes (ca. 108 M-1 s-1).52 By extrapolation, diffusion-controlled rates and indiscriminate reactions are expected for the free (solvated) benzyl cation (118). In support of this notion, the product distributions in Scheme 24 only respond slightly to the nature of the n bond (alkene vs. enol ether). The formation of free benzyl cations from phenylcarbene and methanol is thus estimated to be in the range of 10-15%. However, the major route to the benzyl ether 121, whether by ion-pair collapse or by way of an ylide, cannot be identified. 

The ylide rearrangement is a sigmatropic change of the order (3, 2) since the new o bond is two and one atoms away from the original position. 

Some transition metal complexes readily react with ylides to yield electrophilic carbene complexes. If these complexes can transfer the carbene to a given substrate in such a way that the original transition metal complex is regenerated then this complex can be used as a catalyst for the transformation of the ylide (carbene precursor) into carbene-derived products (Figure 3.35). 

Ether cleavage and further functionalization afforded the intermediate 268. The [5+2]-cycloaddition provided the hydroazulene 267 with the correct relative configuration at and C. Tracing back the synthesis of the pyryli-um ylide 266 leads to the astonishing realization that 2-methyl cyclopent-2-enone (90) was the original cyclic starting material and that the methyl as well as the isopropyl group were introduced by a sequence of cuprate addition and enolate alkylation (see Schemes 15, 31 and 36 for comparison). 

Sulfur ylides behave similarly to phosphorus ylides, but the final products are different. Figure 10-31 shows the mechanism for the prepciration of a sulfur ylide and the reaction of the sulfur ylide with a carbonyl group. Notice that the mechanism for the formation of the sulfur ylide is similar to the formation of a phosphorus ylide. However, the last step in the sulfur ylide mechanism is an internal S, 2 reaction, which eliminates the original thioether (dimethyl sulfide). The reaction of a sulfur ylide with a ketone yields epoxides, whereas the product of a phosphorus ylide with a ketone is an alkene. 

Especially reactive carbonyl compounds such as methyl pyruvate can be used to trap the carbonyl ylide component. For example, ozonolysis of cyclooctene in the presence of methyl pyruvate leads to G, which, when treated with triethylamine, is converted to H, in which the two carbons of the original double bond have been converted to different functionalities.148... 

Treatment of proline derivative 154 with rhodium acetate (57) originally led to ylide 155. However, this ylide (155) quickly rearranges to the more stable azomethine ylide 156, which undergoes cycloaddition with DMAD to give the unusual adduct 157. Intramolecular trapping experiments (58,59) have also been conducted (Scheme 4.35). 

Much of the initial synthetically useful carbonyl ylide work originated from the Ibata group. Exploiting simple disubstituted aromatic diazoketo-esters and structurally diverse dipolarophiles, Ibata and co-workers (64—70) prepared several different cycloadducts 167-169 through an intermolecular ylide cycloaddition (Scheme 4.38). 

The 1,3-dipolar addition of ylide 223 with various dipolarophilic alkenes to produce 224 after aromatization of the adducts was reported to proceed significantly more selectively in the presence of MnOz than in the original reaction where TPCD (tetrakis(pyridine) cobalt(II) dichromate) was used as the oxidant in which 224 were minor by-products <99JCR(S)552>. 

Irradiation of the pyridinium dicyanomethylide (324) in benzene gives the substituted pyrrole (325), by the postulated route shown (Scheme 242) which originates from the singlet excited ylide. 7,7-Dicyanoazanorcaradiene presumably arises by N—C bond fission in the triplet which produces a dicyanocarbene (of dubious multiplicity) which is trapped by the solvent benzene (67CR(C)(264)1307). Photolysis of the imino-ylide (326) in benzene (equation 200) follows the same pathways initially but the two products result from ring expansions,... 

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