Tert enol ether

A related tert-butylation procedure in which the silyl enol ether is added to a mixture of titanium tetrachloride and tert-butyl chloride gives rise to distinctly lower yields. This is also the case if the tertiary halide is added to a mixture of silyl enol ether and titanium tetrachloride. ... 

Diels-Alder cycloaddition of 5-bromo-2-pyrone with the electron-rich tert-butyldi-methylsilyl (TBS) enol ether of acetaldehyde, using superheated dichloromethane as solvent, has been investigated by Joullie and coworkers (Scheme 6.90) [188]. While the reaction in a sealed tube at 95 °C required 5 days to reach completion, the anticipated oxabicyclo[2.2.2]octenone core was obtained within 6 h by microwave irradiation at 100 °C. The endo adduct was obtained as the main product. Similar results and selectivities were also obtained with a more elaborate bis-olefin, although the desired product was obtained in diminished yield. Related cydoaddition reactions involving 2-pyrones have been discussed in Section 2.5.3 (see Scheme 2.4) [189]. 

Caubere et al. [63, 64] treated 32a with sodium amide-sodium tert-butoxide (NaNH2-NaOtBu) in tetrahydrofuran (THF) in the presence of secondary amines and obtained enamines. Analogously, the corresponding thioenol ethers were formed from 32a and sodium amide-sodium thiolate in the presence or absence of NaOtBu. It was shown, however, that cyclohexyne rather than 6 is the decisive intermediate en route to the enamines as well as the thioenol ethers [63b, 64], As already mentioned above, the enol ether 41 arises inter alia from 32b and KOtBu in DMSO. The best yield (47%) was obtained in refluxing THF (Scheme 6.11) [60],... 

In addition to the tert-butyl enol ethers mentioned above (15% yield), the action of KOtBu on l-iodo-4-methylcyclohexene in DM SO furnished the dimers 85 and tri-mers of 81 in 30 and -25% yield (Scheme 6.24). As in the case of 6 (see Scheme 6.10), the formation of oligomers of 81 was completely suppressed on performance of this reaction in the presence of (tBu)2NO, whereas theenol ethers (86 and its 5-methyl isomer, with the former originating in part and the latter totally from 4-methylcydohex-yne) were observed as in the reaction in the absence of the stable radical. Instead of the dimers 85 and the trimers of 81, a mixture of the hydroxylamine derivatives 87 was isolated in 38% yield. These findings indicate that 81 has no diradical character, in contrast to its immediate dimer 84, which is hence trapped quantitatively by (tBu)2NO [61]. 

Inspired by the previous results, Leighton et al. reported the enantioselective [3 + 2] acylhydrazone-enol ether cycloaddition reaction by employing the same pseudoephedrine-based chiral silane. The pyrazohdine product was obtained in 61% yield with 6 1 dr and 77% ee in 24 h. The use of tert-butyl vinyl ether led to an improvement in both diastereoselectivity and enantioselectivity as shown in Scheme 34 [108]. 

The required 1-oxa-l,3-diene precursor was synthesized according to the synthesis design (Scheme 8). Cycloadditon with enol ether furnished exclusively the endo-isomer. Raney nickel treatment in refluxing ethanol yielded in one step the desired tetrahydropyran derivative in a favorable 6 1 cis/trans ratio. Transformation into the lactone and ring closure with potassium tert.-butoxide afforded (+)-ramulosin. 

The reaction has broad scope 5-, 6-, and 7-membered ring metallated enol ethers participate equally well as do organocuprates derived from MeLi, PhLi, sec-BuLi, tert-BuLi, MejSnLi, and PhMejSiLi among others. The reaction also works with Grignard reagents. Some examples are given in the Table. 

Substituted cyclohexanones, bearing a methyl, isopropyl, tert-butyl or phenyl group, give, on deprotonation with various chiral lithium amides in the presence of chlorotrimethylsilane (internal quench), the corresponding chiral enol ethers with moderate to apparently high enantioselec-tivity and in good yield (see Table 2)13,14,24> 29 36,37,55. Similar enantioselectivities are obtained with the external quench " technique when deprotonation is carried out in the presence of added lithium chloride (see Table 2, entries 5, 10, and 30)593. 

Diethyl [(2-tetrahydropyranyloxy)methyl]phosphonate is useful in the Wlttig-Horner synthesis of enol ethers, which are intermediates in one-carbon homologations of carbonyl compounds. This procedure is an adaptation of a general method for making dialkyl hydroxymethylphosphonates. An 0-tetra-hydropyranyl derivative also has been made from dibutyl hydroxymethyl -phosphonate, and diethyl hydroxymethylphosphonate has been O-silylated with tert-butylchiorodimethylsilane and imidazole. Another useful congener in this series has been prepared by an Arbuzov reaction of methoxyethoxymethyl (HEM) chloride and triethyl phosphite. 

The ketone is added to a large excess of a strong base at low temperature, usually LDA in THF at -78 °C. The more acidic and less sterically hindered proton is removed in a kineti-cally controlled reaction. The equilibrium with a thermodynamically more stable enolate (generally the one which is more stabilized by substituents) is only reached very slowly (H.O. House, 1977), and the kinetic enolates may be trapped and isolated as silyl enol ethers (J.K. Rasmussen, 1977 H.O. House, 1969). If, on the other hand, a weak acid is added to the solution, e.g. an excess of the non-ionized ketone or a non-nucleophilic alcohol such as tert-butanol, then the tautomeric enolate is preferentially formed (stabilized mostly by hyperconjugation effects). The rate of approach to equilibrium is particularly slow with lithium as the counterion and much faster with potassium or sodium. 

Use of the preformed Z-silyl enol ether 18 results in quite substantial anti/syn selectivity (19 20 up to 20 1), with enantiomeric purity of the anti adducts reaching 99%. The chiral PT-catalyst 12 (Schemes 4.6 and 4.7) proved just as efficient in the conjugate addition of the N-benzhydrylidene glycine tert-butyl ester (22, Scheme 4.8) to acrylonitrile, affording the Michael adduct 23 in 85% yield and 91% ee [10]. This primary product was converted in three steps to L-ornithine [10]. The O-allylated cinchonidine derivative 21 was used in the conjugate addition of 22 to methyl acrylate, ethyl vinyl ketone, and cydohexenone (Scheme 4.8) [12]. The Michael-adducts 24-26 were obtained with high enantiomeric excess and, for cydohexenone as acceptor, with a remarkable (25 1) ratio of diastereomers (26, Scheme 4.8). In the last examples solid (base)-liquid (reactants) phase-transfer was applied. 

Reactions of trimethylsilyl enol ethers with diazo ketones give cyclopropanes contaminated by ring opened compounds 60,61). Use of the more stable tert-BuMe2Si-derivatives or of Rh2 (0Ac)4 as a catalyst might eventually improve the situation. O-Silylated ketene acetals and O.S-ketene acetals, respectively, did not provide products with cyclopropane structure 61 ... 

Jin and Fuchs reported that vinyl sulfones, using basic phase-transfer catalyst conditions, were regiospecifically alkylated at the a-position.78 No P-elimination products were observed in systems capable of undergoing anion-promoted P-elimi-nation. He also reported that y-methoxy vinyl sulfones 116 can be converted to the corresponding substituted enones 119 using this protocol (Scheme 32).79 On reaction with tert-butyllithium, 116 is converted to the y-methoxy allylsulfonyl anion 117, which was regiospecifically trapped by a variety of electrophiles to provide the enol ether 118. On hydrolysis the -substituted enone 119 was obtained. 

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