Carbonyl ylides, cycloaddition alkynes

Dihydrofurans are valuable synthetic compounds. Nevertheless, little is known about intramolecular cycloaddition of carbonyl ylides to alkynes. In one example, alkynyl pyran-4-one (233) was cyclized to dihydrofuran (234 Scheme 69).128 Possibly this reaction proceeds via an oxidopyrylium ylide intermediate as shown. 

It is well known that di- and tetrahydrofurans can be obtained by inter- and intramolecular 1,3-dipolar cycloaddition reactions of carbonyl ylides with alkynes and alkenes. This methodology has also been shown to be of value in the preparation of a furanophane <92TL57>. 

A type of 1,3-dipole that has received considerable recent interest is the carbonyl ylide. One method for its formation makes use of carbenoid chemistry (see Section 4.2). Cyclization of an electrophiUc rhodium carbenoid onto a nearby carbonyl group provides access to the carbonyl ylide. Cycloaddition with an alkyne or alkene dipolarophile then gives the dihydro- or tetrahydrofuran product. For example, the carbonyl ylide 235, formed from the diazo compound 234 and rhodium(II) acetate, reacts with dimethyl acetylenedicarboxylate to give the bridged dihydrofuran 236 (3.148). 

Interaction of a carbonyl group with an electrophilic metal carbene would be expected to lead to a carbonyl ylide. In fact, such compounds have been isolated in recent years 14) the strategy comprises intramolecular generation of a carbonyl ylide whose substituent pattern guarantees efficient stabilization of the dipolar electronic structure. The highly reactive 1,3-dipolar species are usually characterized by [3 + 2] cycloaddition to alkynes and activated alkenes. Furthermore, cycloaddition to ketones and aldehydes has been reported for l-methoxy-2-benzopyrylium-4-olate 286, which was generated by Cu(acac)2-catalyzed decomposition of o-methoxycarbonyl-m-diazoacetophenone 285 2681... 

Ester derivatives are also capable of forming carbonyl ylides and can undergo traditional cycloaddition with activated alkenes and alkynes and can even undergo reactions with heterodipolarophiles. Padwa was able to generate ester derived... 

Friedrichsen and co-workers (133) approached substituted benzotropolones from an aromatic substituted carbonyl ylide with a tethered alkyne as the intramolecular dipolarophUe (Scheme 4.67). Starting from an aromatic anhydride, Friedrichsen was able to make the tethered alkyne via addition of either pentyn-ol or hexyn-ol, then transform the recovered benzoic acid to the a-diazocarbonyl cycloaddition precursor. Addition of rhodium acetate resulted in the tandem formation of cyclic carbonyl ylide followed by cycloaddition of the tethered alkyne producing the tricyclic constrained ether 252. Addition of BF3 OEt2 opened the ether bridge, forming the benzotropylium ion, which subsequently rearranged to form the tricyclic benzotropolone (253). 

Use orbital interaction theory to develop the orbitals of the 2-oxaallyl system, R2C— —CR2, also known as a carbonyl ylide. Show why 2-oxaallyl readily reacts with alkenes and alkyne in a 4 + 2 cycloaddition reaction (an example may be found in El-Saidi, M. Kassam, K. Pole, D. L. Tadey, T. Warkentin, J., J. Am. Chem. Soc., 1992, 114, 8751-8752). 

In recent years there has been a growing interest in the use of carbonyl ylides as 1,3-dipoles for total synthesis.127-130 Their dipolar cycloaddition to alkenic, alkynic and hetero multiple bonded dipolaro-philes has been well documented.6 Methods for the generation of carbonyl ylides include the thermal and photochemical opening of oxiranes,131 the thermal fragmentation of certain heterocyclic structures such as A3-l,3,4-oxadiazolines (141) or l,3-dioxolan-4-ones132-134 (142) and the reaction of carbenes or car-benoids with carbonyl derivatives.133-138 Formation of a carbonyl ylide by attack of a rhodium carbenoid... 

Linn and Benson discovered in 1963 the ability of tetracyanoethylene oxide (145) to react with alkenes and alkynes at elevated temperatures in [3 + 2] cycloadditions.139 The kinetics of the reaction of (145) with styrene revealed that the formation of (147) is preceded by a first-order step consisting of the electrocyclic ring opening to the carbonyl ylide (146 Scheme 33). 

Transition-metal mediated carbene transfer from 205 to benzaldehyde generates carbonyl ylides 211 which are transformed into oxiranes 216 by 1,3-cyclization, into tetrahydrofurans 212, 213 or dihydrofurans 214 by [3 + 2] cycloaddition with electron-deficient alkenes or alkynes, and 1,3-dioxolanes 215 by [3 + 2] cycloaddition with excess carbonyl compound120 (equation 67). Related carbonyl ylide reactions have been performed with crotonaldehyde, acetone and cyclohexanone (equation 68). However, the ylide generated from cyclohexanone could not be trapped with dimethyl fumarate. Rather, the enol ether 217, probably formed by 1,4-proton shift in the ylide intermediate, was isolated in low yield120. In this respect, the carbene transfer reaction with 205 is not different from that with ethyl diazoacetate121, whereas a close analogy to diazomalonates is observed for the other carbonyl ylide reactions. 

Anhydro-4-hydroxyoxazoIium hydroxides, such as compound (231), behave as carbonyl ylides (232) in cycloaddition reactions, yielding bicyclic adducts with alkenes and carbonyl compounds (Scheme 24). The adducts produced by combination with alkynes fragment spontaneously in a retro-Diels-Alder reaction, giving furans (equation 57). The formation of a furan by the action of DMAD on the 4(5//)-oxazolone (233) shows that the latter exists in equilibrium with the mesoionic tautomer (234 equation 58) (79JOC626). 

While most of the initial studies have involved the transition metal-catalyzed decomposition of a-carbonyl diazo compounds and have been reviewed [3-51], it appears appropriate to highlight again some milestones of these transformations, since polycyclic structures could be nicely assembled from acyclic precursors in a single step. Two main reactivities of metalo carbenoids derived from a-carbonyl diazo precursors, namely addition to a C - C insaturation (olefin or alkyne) and formation of a ylid (carbonyl or onium), have been the source of fruitful cascades. Both of these are illustrated in Scheme 27 [52]. The two diazo ketone functions present in the same substrate 57 and under the action of the same catalyst react in two distinct ways. The initially formed carbenoid adds to a pending olefin to form a bi-cyclop. 1.0] intermediate 58 that subsequently cyclizes to produce a carbonyl ylide 59, that is further trapped intramolecularly in a [3 + 2] cycloaddition. The overall process gives birth to a highly complex pentacyclic structure 60. 

The carbonyl ylides are trapped in a [2-1-3]-cycloaddition with activated alkenes or alkynes. For example, the reaction of the a-chloro ether 3.56 with cesium fluoride (CsF) in the presence of dimethyl fumarate gives only the trans cycloaddition product 3.57, while the reaction with dimethyl maleate gives exclusively the cis-isomer 3.58 (Scheme 3.24). 

In the course of our study on the preparation and [3-1-2] cycloadditions of silyl-protected 1,3-dipoles [581] we succeeded in generating carbonyl ylides 156 by CsF-pro-moted 1,3-eliminationofchloromethyl a-trimethylsilylbenzyl ethers (Scheme 10.223) [582]. The carbonyl ylides react smoothly with a variety of alkenes, alkynes, allenes, and heterodipolarophiles to give five-membered cyclic ethers in good to high yields. 

Another type of multicomponent [2 + 2+1] cycloaddition is achieved with diazo carbonyl compounds in the presence of rhodium or copper catalysts. Reaction with additional carbonyl groups within the substrate gives carbonyl ylides. These, as formal 1,3-dipoles, can undergo [3 + 2] cycloaddition with alkenes or alkynes to form heterocyclic ring systems,7 83... 

Rhodium(II)-catalyzed reactions between diazosulfones and aldehydes yielded an entry to carbonyl ylides, which underwent inter- and intra-molecular cyclization reactions with dipolarophiles, such as alkynes and alkenes, to afford tetrasubstituted furans in modest to good yields <01SL646>. The rhodium(ll) acetate catalyzed reaction of 3-diazobenzopyran-2,4(3 -dione with terminal alkynes provided a mixture of 2-substituted furo[3,2-c]coumarin and furo[2,3-f ]coumarin, presumably through a formal [3+2] cycloaddition reaction <01S735>. Furo[3,2-c]coumarins were also produced from 4-hydroxycoumarins and a-haloketones via a tandem 0-alkylation-cyclization procedure <01TL3503>... 

Cycloaddition reactions, [3 + 2] or [2 + 2] depending on L, of TpRe(CO)(L) (f/ -furan) complexes have been reported. The electrophilic alkene tetracyano-ethylene (TCNE) and the alkyne dimethylacetylenedicarboxylate (DMAD) were used as dienophiles. For L = PMcs and BuNC, 1,3-dipolar cycloaddition of TCNE to / -furan gives [3 + 2] products via a carbonyl ylide (Scheme 47). Addition of... 

The formation of 5-membered ring carbonyl ylides from a 5-keto fimc-tionality was shown to undergo the intramolecular [3+2]-cycloaddition with alkenes or alkynes. An illustrative example [79] is the reaction of acyclic diazo ketone 71 with a catalytic quantity of rhodiiun(ll) acetate at room temperature to afford the polycyclic adduct 72 in 50% yield with complete diastereoselectivity (Scheme 21). This example shows that the intramolecular cycloadditions of 5-membered ring carbonyl ylide can take place across the unactivated 1-hexenyl zr-bond. 

One recent example of applying this process was reported by Johnson et al. for the preparation of furan derivatives (Scheme 16.12) [19]. This reaction involved the rhodium(II)-catalyzed intermolecular generation of carbonyl ylides A or B from diazosulfone (18) and aldehydes 19 or 21, respectively. The 1,3-dipolar cycloaddition of the resulting carbonyl ylides with an intramolecular tethered alkyne moiety or dimethyl acetylenedicarboxylate (DMAD, an intermolecular process), followed by elimination of phenylsulfinic acid, could access furan derivatives. 

Recently, metal-containing carbonyl ylides have attracted much attention as a class of powerful dipoles for 1,3-dipolar cycloaddition reactions to assemble heterocyclic compounds, which was first reported by Iwasawa et al. in 2001 [20]. The in situ generation of metal-containing carbonyl ylides involves the electrophilic activation of an alkyne by a transition metal toward nucleophilic attack of the carbonyl group. One representative example for the synthesis of naphthalene derivatives is shown in... 

Scheme 16.13 [21]. When a mixture of o-ethynylbenoates (or o-ethynylbenzothioate) 23 and vinyl ethers 24 was treated with PtCb (10 mol %) in toluene at room temperature, a wide range of naphthalene derivatives (25) were obtained in good yields. It was proposed that electrophilic activation of the alkyne motif of 23 by PtCl2 and the successive nucleophilic addition of the carbonyl group to the alkyne might generate platinum-containing carbonyl ylides A and B. Successive 1,3-dipolar cycloaddition, 1,2-alkyl migration, and aromatization would afford the desired products.

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