Enol ethers reaction with carbonyl compounds

Using chiral catalysts, not only various enantioselective Mukaiyama and vinylogous Mukaiyama aldol reactions have been developed but also asymmetric reactions of a,a-difluoro silyl enol ethers (1) with carbonyl compounds have been reported ... 

Silyl enol ethers, Reaction of carbonyl compounds with in situ generated BrSi(CH3)3 and triethylamine results mainly in the thermodynamic silyl ether, usually the (Z)-isomer. 

Allylation andaldol reaction. Diallylstannane and silyl enol ethers condense with carbonyl compounds to furnish homoallylic alcohols and p-hydroxy ketones, respectively. A mixture of HjO, EtOH, and toluene is a suitable reaction medium as CufOTflj is stable in water. 

Silyl enol ethers undergo reaction with carbonyl compounds promoted by Lewis acids, but especially titanium tetrachloride. The reaction is thought to proceed via a titanium chelate which inhibits the reverse aldol process and the regiochemical integrity of the starting silyl enol ether is retained (Scheme 102).373... 

Mukaiyama found that Lewis acids can induce silyl enol ethers to attack carbonyl compounds, producing aldol-like products.22 The reaction proceeds usually at -78 °C without selfcondensation and other Lewis acids such as TiCl4 or SnCI4 are commonly used. The requisite silyl enol ether 27 was prepared by treatment of ketone 13 with lithium hexamethyl disilazide (LiHMDS) and trapping the kinetic enolate with chlorotrimethylsilane. When the silyl enol ether 27 was mixed with aldehyde 14 in the presence of BF3-OEt2 a condensation occurred via transition state 28 to produce the product 29 with loss of chlorotrimethylsilane. The induced stereochemistry in Mukaiyama reactions using methylketones and a, -chiral aldehydes as substrates... 

As discussed in Section 2.3.3.1, enol stannyl ethers react with carbonyl compounds readily without the need for catalysts. However, catalytic amounts of AgBp4 and h have bron found to improve considerably the yield of the condensation of the tin(II) enol ether (159) with the azetidinone (93). The use of a catalytic amount of PdCl2[P(o-MeC6H4)3]2 improves the yield of the reactions between enol stannyl(IV) ethers and aldehydes. ... 

Aldol condensation. Silyl enol ethers react with carbonyl acceptors to give )3-siloxy ketones and esters. As BiX, is also a catalyst for the replacement of /3-siloxy groups, prolonged reaction times can be applied to prepare /3-halo carbonyl compounds directly. The reaction is enhanced by ultrasound. 

Reaction with ei,fi-Unsaturated Sulfoxides. The reaction of TMSI with a, -unsaturated sulfoxides in chloroform at ambient temperature is a mild, efficient, and general method for the preparation of carbonyl compounds (eq 63). The proposed reaction mechanism is shown in eq 63. Formation of a strong oxygen-silicon bond is followed by reduction of the sulfur function and oxidation of iodide to iodine, the latter precipitating in chloroform. The trimethylsiloxy anion attacks the unsaturated carbon linked to the sulfur function, which leaves the substrate, allowing the formation of the sUyl enol ether species. Finally, hydrolysis converts the silyl enol ether into the carbonyl compound. ... 

Treatment of methoxymethyltrimethylsilane with BuTi in THF gives methoxy-(trimethylsilyl)methyllithium, and its subsequent reactions with carbonyl compounds have been reported to afford the adducts, a-methoxy-j8-hydroxyalkylsilanes 58 (Scheme 2.38). Although the initial adducts do not undergo elimination of a silyl group in situ, the corresponding enol ethers 59 are formed upon treating... 

Silyl(methoxy)benzotriazol-l-ylmethane 62 is lithiated with BuLi to give the corresponding anion, which undergoes Peterson reactions with carbonyl compounds (Scheme 2.40) [100, 101]. The products, l-(l-methoxy-l-alkenyl)benzotriazoles 63, are synthetically equivalent to an acylbenzotriazole synthon in which the carbonyl group is masked as an enol ether [102, 103]. Transformation of the alkenyl ethers into carboxyhc acids is readily achieved by treatment with zinc bromide and hydrochloric add in refluxing 1,4-dioxane [104]. 

The crossed aldol reaction of silyl enol ethers with carbonyl compounds (Mukaiyama-aldol) was studied by Lubineau and co-workers... 

Still another possibility in the base-catalyzed reactions of carbonyl compounds is alkylation or similar reaction at the oxygen atom. This is the predominant reaction of phenoxide ion, of course, but for enolates with less resonance stabilization it is exceptional and requires special conditions. Even phenolates react at carbon when the reagent is carbon dioxide, but this may be due merely to the instability of the alternative carbonic half ester. The association of enolate ions with a proton is evidently not very different from the association with metallic cations. Although the equilibrium mixture is about 92 % ketone, the sodium derivative of acetoacetic ester reacts with acetic acid in cold petroleum ether to give the enol. The Perkin ring closure reaction, which depends on C-alkylation, gives the alternative O-alkylation only when it is applied to the synthesis of a four membered ring ... 

Besides the allylation reactions, imines can also undergo enol silyl ether addition as with carbonyl compounds. Carbon-carbon bond formation involving the addition of resonance-stabilized nucleophiles such as enols and enolates or enol ethers to iminium salt or imine can be referred to as a Mannich reaction, and this is one of the most important classes of reactions in organic synthesis.104... 

An interesting novel coupling reaction of allenes with carbonyl compounds mediated by a lanthanide metal species was reported recently [80], The samarium(II) iodide-mediated reaction of various ketones or aldehydes 153 with methoxyallene (56) afforded exclusively y-addition products 4-hydroxy-l-enol ethers 154 in moderate to good yields with low cis/trans selectivity (Scheme 14.39). 

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