Alkenes carbonyl ylides

The parallel ability of oxiranes to undergo ring opening to carbonyl ylides was first noted in the case of tetracyanooxirane (68T2551), but such reactions have not been widely exploited. The addition to alkenes, leading to formation of tetrahydrofurans, is stereospecific (Scheme... 

The application of 1,3-dipolar cycloaddition processes to the synthesis of substituted tetrahydrofurans has been investigated, starting from epoxides and alkenes under microwave irradiation. The epoxide 85 was rapidly converted into carbonyl ylide 86 that behaved as a 1,3-dipole toward various alkenes, leading to quantitative yields of tetrahydrofuran derivatives 87 (Scheme 30). The reactions were performed in toluene within 40 min instead of 40 h under classical conditions, without significantly altering the selectivi-ties [64]. 

Nonstabilized carbonyl ylides (41) prepared by reaction of a-iodosilyl ethers with Smlj, can be trapped with various alkenes, alkynes and allenes to form furans of type 42, 43, and 44... 

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... 

Diels-Alder reaction of the 1,3,4-oxadiazole with the pendant olefin and loss of N2, the C2-C3 7t bond participates in a subsequent 1,3-dipolar cycloaddition with the carbonyl ylide to generate complex polycycles such as 45 as single diastereomers with up to six new stereocenters. That the cascade reaction is initiated by a Diels-Alder reaction with the alkene rather than with the indole is supported by the lack of reaction even under forcing conditions with substrate 46, in which a Diels-Alder reaction with the indole C2-C3 n bond would be required [26a]. 

Finally, it is important to mention that there are other related publications in which porphyrin macrocycles are not directly used as dipolarophiles but are transformed into new derivatives that can react with carbonyl ylides via ACE (alkene cyclobutene epoxide) reactions. This idea arose in 1997, when Russell and co-workers found that fused ester-activated cyclobutene epoxides 86 can be ring-opened to give carbonyl ylides 87, and that these can be trapped stereospecifically by ring-strained alicyclic dipolarophiles, such as 2,5-norbomadiene, to form hetero-bridged norbomanes 88 in good yields, through ACE transformations (Scheme 31) <97CC1023>. 

Fig. 4.14. Preparation of polycyclic compounds by intramolecular 1,3-dipolar cycloaddition of carbonyl ylides to alkenes 11301].

In more recent work, Chiu and co-workers [167, 168] have reported an intramolecular 1,3-dipolar cycloaddition approach toward the pseudolaric acids 85, in which the di-polarophile is an unactivated 1,1-disubstituted alkene. Hence, treatment of the diazo ketone 86 with catalytic Rh2(OAc)4 furnished a mixture of tricyclic products 87 and 88 in nearly equal proportions (Scheme 19.13). The synthesis of 2-pyridones [169] and their application to the ipalbidine core [170] has been described. The pentacyclic skeleton of the aspidosperma alkaloids was prepared via the cycloaddition of a push-pull carbonyl ylide [171]. The dehydrovindorosine alkaloids 89 have also been investigated, in which the a-diazo-/ -ketoester 90 undergoes a facile cycloaddition to furnish 91 in... 

Epoxide 96 was prepared such that photolytic conversion to the carbonyl ylide could be followed by an intramolecular cycloaddition with the tethered pendant olefin. However, photolysis of epoxide 96 led only to the formation of the regio-isomer 97 and the aldehyde 98 with no evidence of the corresponding cycloadduct. It was presumed that 97 arose from the ylide by thermal recyclization to the epoxide while 98 could form through the loss of a carbene from the ylide. The failure of the tethered alkene to undergo cycloaddition may have resulted from a poor trajectory for the cycloaddition. An extended analogue (99) allowed greater flexibility for the dipolarophile to adopt any number of conformations. Photolysis of epoxide 99 did lead to formation of the macrocyclic adduct 100, albeit in modest yields. 

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... 

Intramolecular ylide formation with the lactone carbonyl oxygen (53) in 145 provided a carbonyl ylide 146 that was trapped with Al-phenyl maleimide to give cycloadduct 147. Likewise (54), carbonyl yhde 149, derived from ester 148, suffers intramolecular cycloaddition with the tethered alkene to deliver acetal 150 in 87% yield. An enantioselective version of this process has also been described (Scheme 4.33). 

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... 

Padwa and Prein (105,106) applied chiral, but racemic, isomiinchnone dipoles in diastereoselective 1,3-dipolar cycloadditions. The carbonyl ylide related isomiinch-none derivative rac-70 was obtained from the rhodium-catalyzed cyclization of diazo-derivative rac-69 (Scheme 12.24) (105). The reactions of the in situ formed dipole with a series of alkenes was described and in particular the reaction with maleic acid derivatives 71a-c gave rise to reaction with high selectivities. The tetracyclic products 72a-c were all obtained in good yield with high endo/ exo and diastereofacial selectivities. In another paper by the same authors, the reactions of racemic isomilnchnones having an exo-cyclic chirality was described (106). 

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). 

Open-chain Carbonyl Ylide-Alkene Cyclizations 1161... 

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. 

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