Ethers, enol reaction with carbenes

Intermolecular [4C+2S] cycloaddition reactions where the diene moiety is contained in the carbene complex are less frequent than the [4S+2C] cycloadditions summarised in the previous section. However, 2-butadienylcarbene complexes, generated by a [2+2]/cyclobutene ring opening sequence, undergo Diels-Alder reactions with typical dienophiles [34,35] (Scheme 59). Also, Wulff et al. have described the application of pyranylidene complexes, obtained by a [3+3] cycloaddition reaction (see Sect. 2.8.1), in the inverse-electron-demand Diels-Alder reaction with enol ethers and enamines [87a]. Later, this strategy was applied to the synthesis of steroid-like ring skeletons [87b] (Scheme 59). 

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. 

Very few pericyclic reactions of carbene complexes have been studied that are not in the cycloaddition class. The two examples that are known involve ene reactions and Claisen rearrangements. Both of these reactions have been recently studied and thus future developments in this area are anticipated. Ene reactions have been observed in the the reactions of alkynyl carbene complexes and enol ethers, where a competition can exist with [2 + 2] cycloadditions. Ene products are the major components firom the reaction of silyl enol ethers and [2 + 2] cycloadducts are normally the exclusive products with alkyl enol ethers (Section 9.2.2.1). As indicated in equation (7), methyl cyclohexenyl ether gives the [2 -t- 2] adduct (84a) as the major product along with a minor amount of the ene product (83a). The t-butyldimethylsilyl enol ether of cyclohexanone gives the ene product 9 1 over the [2 + 2] cycloadduct. The reason for this effect of silicon is not known at this time but if the reaction is stepwise, this result is one that would be expected on the basis of the silicon-stabilizing effect on the P-oxonium ion. 

The catalytic activity of low-valent ruthenium species in carbene-transfer reactions is only beginning to emerge. The ruthenium(O) cluster RujCCO), catalyzed formation of ethyl 2-butyloxycyclopropane-l-carboxylate from ethyl diazoacetate and butyl vinyl ether (65 °C, excess of alkene, 0.5 mol% of catalyst yield 65%), but seems not to have been further utilized. The ruthenacarborane clusters 6 and 7 as well as the polymeric diacetatotetracarbonyl-diruthenium (8) have catalytic activity comparable to that of rhodium(II) carboxylates for the cyclopropanation of simple alkenes, cycloalkenes, 1,3-dienes, enol ethers, and styrene with diazoacetic esters. Catalyst 8 also proved exceptionally suitable for the cyclopropanation using a-diazo-a-trialkylsilylacetic esters. ... 

D.ii. Addition to Aromatic Derivatives. Aromatic compounds also react with carbenes, but ring expansion usually follows the initial cyclopropanation. In a typical example, 2-methoxynaphthalene (373) reacted with dichlorocarbene to give 374, and subsequent ring expansion gave 375, 99 which is a general reaction of enol ethers, which give either unsaturated acetals or unsaturated carbonyls. oo... 

An interesting study reports carbene additions to the androstane enol ether (139). Addition of dibromo- and dichloro-carbene gave the D-homo-a-halo-genoenones (140a) and (140b), respectively. The Simmons-Smith reaction on (139) afforded the l6a,17a-cyclopropyl steroid (141). Whereas treatment of (141) with acid provided the D-homo-derivative (142), reaction with iodine, followed by... 

Parham, W. E., and S. H. Groen Reaction of Enol Ethers with Carbenes, VI. Allylic Rearrangements of Sulfur Ylides. J. Org. Chem. 30, 728 (1965). 

Philip Kocienski published an elegant synthesis of racemic olean. The starting material is the THP ether of 4,4-dibromobutanol. In spite of the acid-sensitivity of the acetal, the formation of a carbene complex with titanium tetrachloride and zinc can be achieved. Its reaction with a corresponding ester leads to an enol ether, which cyclises to olean under acidic conditions. [217]... 

In contrast with polarized C—C double bonds (Michael acceptors), the unfunctionalized alkenes are usually regarded as unsuitable acceptor for Stetter reaction [45]. In 2006, She and co-workers reported an carbene-catalyzed alkylation of aldehydes (Scheme 7.26). Mechanically, this reaction may involve the generation of enol ether by elimination of tosylate, followed by intramolecular Stetter reaction. This hypothesis was then demonstrated by the following work of the corresponding reaction with the prepared enol ether [46]. 

The second example is a rhodium(II)-catalysed decomposition of an a-diazo ketone (71). This interaction generated a metal-bound carbene that appears to undergo CH-insertion when tethered to thiophenes the product (72) was an aromatic tricycle. The direct CH-insertion mechanism is probably excluded by the reaction of (73). Treatment of (73) with a rhodium catalyst gave rise to a bicyclic system (75) with a pendant ketene group. The ketene appears to have migrated the authors suggested a mechanism via ketene (74), being formed by nucleophilic attack of the enol ether on the electrophilic carbene. ... 

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