Reactions with Enol Ethers

The situation with inverting enzymes is less clear-cut, probably because the catalytic base is further removed and the nucleophilic water molecule stands between it and C2. Nonetheless, various p-amylases (probably GH 14) transferred a hydron to the p face of maltal ° proton inventory studies showed that the solvent isotope effects [up to qJ- gj ere due to the transfer of a 

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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). 

Whereas metal-catalyzed decomposition of simple diazoketones in the presence of ketene acetals yields dihydrofurans 121,124,134), cyclopropanes usually result from reaction with enol ethers, enol acetates and silyl enol ethers, just as with unactivated alkenes 13). l-Acyl-2-alkoxycyclopropanes were thus obtained by copper-catalyzed reactions between diazoacetone and enol ethers 79 105,135), enol acetates 79,135 and... 

In a remarkable cycloaddition, 1,2-oxazines have been prepared from polystyrene-bound acrylates by reaction with enol ethers and nitroalkenes under high-pressure (Entry 4, Table 15.34). 

The reaction with enol ethers, enamines, and electron-rich alkenes, without allylic hydrogens of proper orientation, to yield 1,2-dioxetanes... 

This three-component reaction as the key step of this synthesis is called a domino-Knoevenagel-hetero-Diels-Alder reaction. Domino reactions are defined as processes of two or more bond forming reactions in which a subsequent transformation takes place by virtue of the functionalities introduced in a former transformation.2,16 The tetrahydrocarbolinaldehyde 11 first reacts in a Knoevenagel type condensation with Meldrum s acid 14 and ethyleneammonium diacetate 41 as the catalyst to oxabutadiene 44 which then undergoes a Diels-Alder reaction with enol ether 13. 

The reactivity of 47/-benzopyran-4-ones in Diels-Alder reactions is well documented <1987T3075>, and recently high asymmetric induction has been achieved in the reaction of 3-alkoxycarbonyl-substituted chromones with chiral auxiliaries and Danishefsky s diene <1991JOC2058>. It should be noted that 3-formylchromones can react as heterodienes in the stereoselective inverse electron Diels-Alder reaction with enol ethers <1994T11755> to provide a route to pyrano[4,3-A][l]benzopyrans a heterocyclic nucleus which occurs naturally in the fungal metabolite fulvic acid <1984CC1565>. The thermal Diels-Alder reaction of 477-pyran-4-one 405 in the presence of an excess of Danishefsky s diene 404 provided cycloadduct 406 (Equation 32) <1996H(43)745>. 

Recrystallization from water/acetone (even at a basic pH) causes some hydrolysis of the acetal. (2,2-Diethoxyethyl)cobalamin, like all alkyl cobalamins, is light sensitive in solution in addition, and unlike most other alkylcobalamins, it is add sensitive, decomposing to both (formylmethyl)cobalamin and aqua-cobalamin.2 The formation of other alkylcobalamins and cobaloximes by reaction with enol ethers has been described.2... 

There have been a number of unsuccessful attempts to trap 1,4-zwitterionic intermediates, - but there have also been some reported successes. At best, then, such trapping experiments are not uniformly diagnostic for zwitterionic intermediates. truns-Propenyl ethyl ether reacts with TONE in ethanol solvent at 25 C to give product (140). " The normal [2 + 2] adduct (139) gives this same product when allowed to react in ethanol, but at a slower rate. Just how fast this solvolysis might take place under the conditions of the cycloaddition reaction, with enol ether and TCNE present, is not clear. Acetone does not interfere with the addition of ethyl vinyl ether to TCNE, but the adduct (141) is converted over one week at room temperature to the six-membered ring product (142), which may be postulated as being derived from ci ture of a 1,4-zwitterionic intermediate in equilibrium with the cyclobutane structure. Alternatively, since acetone like ethanol is known to react with TCNE, it may be a case of acid-catalyzed solvent-assisted solvolysis. 

Reactions with Enol Ethers, Silylenol Ethers and Enamines... 

Ethyl diazoacetate (228 mg, 2.0 mmol) was added at a controlled rate over a 6-8 h period to a stirred mixture of the alkene (20.0 mmol) or diene (10.0 mmol) and the catalyst (0.01 -0,02 mmol) under and ordinarily at 25 C. For copper(I) triflate catalyzed reactions with enol ethers, the diazo ester dissolved in the enol ether w as added to copper(II) triflate in EtjO in order to minimize polymerization of the enol ether. Alkenes were generally purified by distillation prior to their use. The initial solubility of the transition metal compound was dependent on the alkene employed, and, with the exception of Rhg(CO)jg, bis(acetylacetonato)copper(II), and copper bronze, homogeneous solutions were obtained prior to or immediately after the initial addition of ethyl diazoacetate. 1 h after addition was complete, EtjO was added, the resulting solution was washed twice with sat. aq NaHC03 dried (MgSOJ. EtjO and excess alkene were distilled under reduced pressure. The desired cyclopropanes were obtained either by fractional bulb-to-bulb distillation or by preparative GC (Table 8). 

The carbenoid reaction between a-diazo ketones and simple alkenes or styrenes leads to acylcyclopropanes. (For the enantioselective cyclopropanation of styrene with 2-diazo-5,5-dimethylcyclohexane-l,3-dione, see Section 1.2.1.2.4.2.6.3.2.). With ketene acetals, 2,3-dihyd-rofurans are obtained. In contrast, l-acyl-2-oxycyclopropanes or 2-oxy-2,3-dihydrofurans can be formed in reactions with enol ethers and enol acetates the result depends strongly on the substitution pattern of both reaction partners.Whereas simple diazo ketones usually lead to cyclopropanes (Table 15), 3-diazo-2-oxopropanoates and 2-diazo-l,3-dicarbonyl compounds, such as 2-diazoacetoacetates, 3-diazopentane-2,4-dione, and 2-diazo-5,5-dimethylcy-clohexane-1,3-dione, yield 2,3-dihydrofurans and occasionally acyclic structural isomers thereof when reacted with these electron-rich oxy-substituted alkenes. 

The Knoevenagel products of sufficiently reactive acyclic as well as cyclic 1,3-dicarbonyls can act as oxadienes in hetero Diels-Alder reactions with enol ethers and enamines. Alkenes may be used as dieno-philes if the reaction is performed in an intramolecular mode. The cycloadditions of ethyl vinyl ether... 

The relative reactivities of acetals and orthoesters in Lewis acid catalyzed reactions with enol ethers have been investigated. For BF3-OEt2-catalyzed reactions with methyl vinyl ether, the following order has been found saturated acetals < methyl orthoformate < benzaldehyde acetals < a,p-unsaturated acetals. ... 

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