Alkylidene carbene

Insertions into tertiary C—H bonds can be carried out with moderate yields. Among other less common reactions improved by the use of PTC-generated CCI2 are the carbylamine synthesis (RNH2 — R NC) (33). Alkylidene carbene (R2C=C ) and alkenyUdene carbene (R2C=C=C ) adducts have also been prepared (34,35). 

Feldman reported a route to dihydropyrroles, pyrroles, and indoles via the reaction of sulfonamide anions with alkynyliodonium triflates <96JOC5440>. Thus, upon nucleophilic addition of the anion of 91 to the p-carbon of the alkynyliodonium salt, the alkylidene carbene 92 is generated which can the undergo C-H insertion to the desired product 93. 

The Lewis-like picture suggests20 that saturated metal alkylidenes (carbenes) H M=CH2 of special stability should correspond to duodectet-rule-conforming... 

Alkylidene carbenes (isopropylidene [150] cyclohexylidene [150-152] cyclopentylidene [150] cyclopropylethylidene and dicyclopropylmethylidene carbenes [153] and alkenylalkylidene carbenes (Me,C=C=C [154-159] adamantylvinylidene carbene [160] MeCH=CH.CH=C [161] react in good yield... 

Stang etal. (94JA93) have developed another alkynyliodonium salt mediated approach for the synthesis of y-lactams including bicyclic systems containing the pyrrole moiety. This method is based on the formation of 2-cyclopentenones 114 via intramolecular 1,5-carbon-hydrogen insertion reactions of [/3-(p-toluenesulfonyl)alkylidene]carbenes 113 derived from Michael addition of sodium p-toluenesulfinate to /3-ketoethynyl(phenyl) iodonium triflates 112 (Scheme 32). Replacing 112 by j8-amidoethynyl (phenyl)iodonium triflates 115-119 provides various y-lactams as outlined in Eqs. (26)-(30). 

The treatment of the 2-methyl- 1-propenylbismuthonium salt with KOf-Bu in the presence of excess styrene gives alkylidenecyclopropanes in good yield (Scheme 7). The para substituent effect on the relative reactivity is very small, indicating that a free alkylidene carbene is generated as the active species. In this case, the alkylidene carbene is trapped by the styrene in solution. 

C-H insertion of an alkylidene carbene intermediate, which was generated via the Michael addition of a sulfinate anion to the acetylenic p-carbon. In MeOH,... 

Alkylidenes (alkylidene carbenes) are valence isomers of alkynes. They have been prepared by alkyne pyrolysis, by homologation of ketones, and by generation of alkenyl anions bearing oc-leaving groups. Generated by any of these means, an alkylidene will insert intramolecularly into a remote C- H bond to form a new C—C bond and thus a cyclopentene. A concerted two-electron process, this reaction proceeds with retention of absolute configuration at the C - H site. 

This reaction apparently proceeds by way of the normal phosphonate condensation product, the diazoalkylidene, which then spontaneously loses nitrogen to form the transient alkylidene car-bene. Careful work showed that, after statistical corrections were applied, the reactivity of a C-H bond toward insertion was approximately 0.003 for primary C-H bonds (methyl), 1.0 for secondary C-H bonds (methylene), 7.5 for benzylic (methylene) C-H bonds and 18.6 for tertiary C-H bonds. These relative reactivities are very similar to those previously observed for intramolecular C-H insertion by an alkylidene carbenoid generated from a vinyl bromide27. It was shown subsequently that the alkylidene carbene insertion reaction proceeds with retention of absolute configuration28. Using this approach, (l )-3-dimethyl-3-phenyl-l-cyclopentene and (i )-4-methyl-4-phenyl-2-cyclohexcnonc were prepared in high enantiomeric purity. 

Scheme 1.3.18 Asymmetric synthesis of monocyclic 2,3-dihydrofurans via O—Si bond insertion of alkylidene carbenes.

The methylation of sulfoximines 45 with Me30BF4 proceeded readily and gave the corresponding cyclic aminosulfoxonium salts 46 in quantitative yields. Upon treatment with LiN(H)t-Bu first at-78 °C and then at room temperature, salts 46 delivered the enantio- and diastereomerically pure bicyclic 2,3-dihydrofurans 50 cleanly in high overall yields. It is proposed that the reactions of the aminosulfoxonium salts 40 and 46 with the lithium amide at low temperatures afford the vinyl aminosulfoxonium ylides 41 and 47, respectively. These alkylidene carbenoids eliminate sulfinamide 35 at higher temperatures with formation of the alkylidene carbenes 42 and 48, respectively. Subsequently, the alkylidene... 

An N-methyl aniline works equally well. The reaction may be proceeding by way of a coordinated alkylidene carbene. 

Preparation of group 15 alkenyl(triphenyl)onium (P, As, Sb) tetrafluorobo-rates and group 16 alkenyl(diphenyl)onium (S, Se, Te) tetrafluoroborates involves the base-induced reductive a-elimination, followed by nucleophilic trapping of the resulting free alkylidene carbenes with group 15 and 16 element-centered nucleophiles [Eq. (97)] [173]. 

Both the lack of regioselectivity observed for the intramolecular insertion of alkylidene carbenes derived from (E)- and (Z)-A -iodanes 108 and the high degree of stereo convergence of the olefin geometry of vinylsulfonium salts indicate the intermediacy of the free alkylidene carbene [Eq. (99)] [53,172]. 

Strong bases like alkyllithiums or drastic reaction conditions are required to generate carbenic species from vinyl halides, thus precluding the presence of many functional groups in the substrate. The vinyl-A3-iodane method produces free alkylidene carbenes under mild conditions, making the reaction compatible with a variety of functional groups. 

Nucleophiles that undergo vinylic SN2 reaction involve sulfides, selenides [178], carboxylic acids [179], amides [180],thioamides [181],andphosphorose-lenoates [Eq. (102)] [182]. All of these reactions proceed with exclusive inversion of configuration. These nucleophiles are only weakly basic or non-basic. More basic nucleophiles would result in a facile a-elimination of vinyl-A3-iodanes generating alkylidene carbenes instead of the vinylic SN2 reaction. 

As shown above, insertion of alkylidene carbenes is highly regioselective. However, when the normal 1,5-C-H insertion pathway is blocked, 1,4- or 1,6-C-H insertion takes place [Eq. (109)]. Thus, the cyclobutene 121 [192] and the six-membered enol ether 123 [193] were obtained in modest yields. Intramolecular insertion into carbon-carbon double bond provides a method for synthesis of cyclopenten-annulated dihydropyrrole 124, which results from homolytic scission of a methylenecyclopropane intermediate [194]. 

Similarly, ethynylation of / -dicarbonyl enolates via the tandem Michael-car-bene rearrangement (MCR) pathway occurs smoothly by the reaction with the parent ethynyl-A3-iodane 128. High migratory aptitude of a-hydrogens of alkylidene carbenes is responsible for this facile ethynylation [199]. 

When migratory aptitudes of a-substituents of alkylidene carbenes are relatively poor, the MCI pathway competes with the MCR reaction. Reaction of the alkynyliodane with benzenesulfinate anion in water leads to a mixture of the MCI and the MCR products, because of a moderate migratory aptitude of aryl-sulfonylgroups [Eq. (114)] [170]. 

The cyclopentene annulations can also occur in the reactions of alkynyliodo-nium salts with nitrogen- and sulfur nucleophiles (Scheme 61). Specifically, azi-docyclopentene 155 is formed upon treatment of octynyliodonium tosylate 154 with sodium azide in dichloromethane [123]. The reaction of alkynyliodonium salt 156 with sodium toluenesulfinate results in the formation of substituted indene 157 via alkylidene carbene aromatic C-H bond insertion [124]. 

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