Ether Lewis acid catalyzed

The Lewis acid-catalyzed reaction of nitrone 21 with ethyl vinyl ether 22 (Scheme 8.8) was also investigated for BH3 and AlMe3 coordinated to 21 [32]. The presence of BH3 decreases the activation energy for the formation of 23 by 3.1 and 4.5 kcal mol to 9.6 kcal mol for the exoselective reaction and 11.6 kcal-mol for the endo-selective reaction, respectively, while the activation energy for the formation of 24 increases by >1.4 kcal mol , compared to those for the uncatalyzed reaction. The transition-state structure for the BH3-exo-selective 1,3-dipolar cycloaddition reaction of nitrone 21 with ethyl vinyl ether 22 is shown in Fig. 8.19. 

For example, using (/ )-5-trimethylsilyl-2-cyclohexenone as the chiral Michael acceptor, optically active m // .v-3.5-disubstituied cyclohexanones 1 are obtained via a Lewis acid catalyzed addition of silylenol ethers or ketene acetals. 

The Lewis acid catalyzed reactions of silyl enol ethers with nitroalkenes have been reviewed, however the diastereoselectivity of these reactions has not been addressed17. 

Optically active norbornene derivatives [26] have been prepared by cycloaddition of hexachlorocyclopentadiene with /-menthylacrylate and /-menthylallyl-ether (Equation 2.9). Low levels of enantiomeric excess have been obtained in the thermal processes, whereas Lewis acid catalyzed reactions (BF3, BBr3, AICI3, SnCU, DCM, 40-80 °C) gave better results. 

Synthesis of highly functionalized 3,4-dihydro-2H-pyrans by high-pressure Lewis-acid-catalyzed cycloaddition of enol ethers and a,/i-unsaturated aldehydes [83]... 

The Mukaiyama aldol reaction refers to Lewis acid-catalyzed aldol addition reactions of silyl enol ethers, silyl ketene acetals, and similar enolate equivalents,48 Silyl enol ethers are not sufficiently nucleophilic to react directly with aldehydes or ketones. However, Lewis acids cause reaction to occur by coordination at the carbonyl oxygen, activating the carbonyl group to nucleophilic attack. 

Nitroalkenes are also reactive Michael acceptors under Lewis acid-catalyzed conditions. Titanium tetrachloride or stannic tetrachloride can induce addition of silyl enol ethers. The initial adduct is trapped in a cyclic form by trimethylsilylation.316 Hydrolysis of this intermediate regenerates the carbonyl group and also converts the ad-nitro group to a carbonyl.317... 

Asymmetric Lewis-Acid Catalyzed. Another important advance in aqueous Mukaiyama aldol reaction is the recent success of asymmetric catalysis.283 In aqueous ethanol, Kobayashi and co-workers achieved asymmetric inductions by using Cu(OTf)2/chiral >A(oxazoline) ligand,284 Pb(OTf)2/chiral crown ether,285 and Ln(OTf)3/chiral Mv-pyridino-18-crown-6 (Eq. 8.105).286... 

Nitrone 1,3-DC reactions are still the most general approach to isoxazolidines. The stereocontrol is usually achieved by the use of chiral nitrones and/or dipolarophiles, but new interesting achievements on Lewis acid catalyzed cycloadditions are also frequently reported. Tris(6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanatedionate) europium(III) [Eu(fod)3] selectively activated the Z-isomer of C-alkoxycarbonyl nitrone 75 existing as an E,Z-equilibrium mixture by forming the (Z)-75-Eu(fod)3 complex. (Z)-75-Eu(fod)3 reacted with electron-rich dipolarophiles such as vinyl ethers to give the trans-adducts with excellent diastereoselectivity <06T12227>. 

Judging from these findings, the mechanism of Lewis acid catalysis in water (for example, aldol reactions of aldehydes with silyl enol ethers) can be assumed to be as follows. When metal compounds are added to water, the metals dissodate and hydration occurs immediatdy. At this stage, the intramolecular and intermolecular exchange reactions of water molecules frequently occur. If an aldehyde exists in the system, there is a chance that it will coordinate to the metal cations instead of the water molecules and the aldehyde is then activated. A silyl enol ether attacks this adivated aldehyde to produce the aldol adduct. According to this mechanism, it is expected that many Lewis acid-catalyzed reactions should be successful in aqueous solutions. Although the precise activity as Lewis acids in aqueous media cannot be predicted quantitatively... 

Lewis acid-catalyzed ene reactions proceed between allenyl sulfides, e.g. 330, and aldehydes 329 to afford cis-trans mixtures of 1,3-butadienes 331 (Scheme 8.90) [168, 175b], Similar ene reactions observed with imines such as 332 provide the corresponding allylamines [168,177]. It was also found that the ene reaction of 1-silylated allenyl sulfide 333 with various aldehydes (or acetals) furnishes a,/l-unsaturatcd acyl compounds such as 334 and 335 under BF3-etherate catalysis [175b]. 

Lewis acid-catalyzed aldol condensation of aldehyde and silyl enol ether. 

Lewis acid-catalyzed Michael addition of silyl enol ether to a,P-unsaturated system. 

Shackelford and co-workers studied the 1,2-addition of 2,2-dinitropropanol, 2,2,2-trinitroethanol, and 2-fluoro-2,2-dinitroethanol across the double bonds of vinyl ethers. These reactions are Lewis acid catalyzed because of the weak nucleophilic character of alcohols which contain two or three electron-withdrawing groups on the carbon p to the hydroxy functionality. Base catalysis is precluded since alkaline conditions lead to deformylation with the formation of formaldehyde and the nitronate salt. 

Liu et al. 43) prepared chiral BINOL ligands bearing dendritic Frechet-type polybenzyl ether wedges ((J )-41-(J )-44), which were assessed in enantioselective Lewis acid-catalyzed addition of Et2Zn to benzaldehyde. 

Dithioketals, especially the cyclic dithiolanes and dithianes, are also useful carbonyl-protecting groups. These can be formed from the corresponding dithiols by Lewis acid-catalyzed reactions. The catalysts that are used include BF3, Mg(03SCF3)2, Zn(03SCF3)2, and LaCl3.100 S-Trimethylsilyl ethers of thiols and dithiols also react with ketones to form dithioketals.101... 

Kociehski s group assembled the 3-lactone segment utilizing a Lewis acid-catalyzed [2 + 2] cycloaddition strategy. In the presence of a catalytic amount of boron trifluoride etherate, the [2 + 2] cycloaddition between aldehyde 28 and trimethylsilylketene 29 took place rapidly and cleanly to give a mixture of diastereomers of P-lactone 30. After a delicate desilylation and a flash chromatography, the desired diastereomer 31 was obtained in 55% yield. 

SCHEME 120. Lewis acid-catalyzed asymmetric aldol-type reaction of enol silyl ethers. 

The Lewis acid-catalyzed reaction of the endoperoxide of 1-methoxycarbonylpyrrole with enol ethers presents an interesting route to 2-alkylpyrroles (Scheme 30) (79TL3477, 80H(14)102>. In the case of the reaction with l-(trimethylsilyloxy)buta-l,3-diene, the reaction provides a viable route to indole, which, with only slight modification, can also be employed in the synthesis of 4-substituted indoles <8lH(l6)959>. The endoperoxide reacts with 1-methylpyrrole to produce the l,l -disubstituted 2,2 -bipyrrole in low yield. 

At this point, consideration was next accorded to proper introduction of the pair of substituents as in 34. As expected, the regiocontrolled introduction of a methyl group proved not to be problematic, and lithium diisopropylamide came to be favored as the base. The p isomer 29 predominted by a factor of 5 1 over the a isomer for the usual steric reasons (Scheme 5). To reach silyl enol ether 31, it was most efficient and practical to react the 29/30 mixture with chlorotrimethylsilane under thermodynamic conditions. This step proved to be critical, as it allowed for implementation of the Lewis acid-catalyzed acetylation of 31 under conditions where the benzyloxy substituent was inert. Equally convenient was the option to transform the modest levels of enol acetate produced competitively back to starting ketone by saponification with methanolic potassium hydroxide. 

The use of silyl enol ethers as an enolate equivalent in Lewis acid-catalyzed aldol additions. The trimethylsilyl group is thought of as a sterically demanding hydrogen equivalent that activates the enol and traps the aldol hydroxyl. 

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