Enol silyl ethers regioselectivity

Hintz, S. Frolich, R. and Mattay, J. (1996) PET-oxidative cyclization of unsaturated silyl enol ethers. Regioselective control by solvent effects. Tetrahedron Letters, 37, 7349-7352. 

Regioselectivity of formation of enamines Lithium enolates and silyl enol ethers Regioselective Aldol Reactions... 

The Q -(methyldiphenylsilyl) ketones isomerize to the corresponding silyl enol ether regioselectively simply by mild thermolysis at about 150 °C (eq 6). This reaction can also be done in a stereoselective fashion to give the (Z)-enol silyl ether when the thermolysis is carried out in acetonitrile (eq 7). ... 

Another preparative method for the enone 554 is the reaction of the enol acetate 553 with allyl methyl carbonate using a bimetallic catalyst of Pd and Tin methoxide[354,358]. The enone formation is competitive with the allylation reaction (see Section 2.4.1). MeCN as a solvent and a low Pd to ligand ratio favor enone formation. Two regioisomeric steroidal dienones, 558 and 559, are prepared regioselectively from the respective dienol acetates 556 and 557 formed from the steroidal a, /3-unsaturated ketone 555. Enone formation from both silyl enol ethers and enol acetates proceeds via 7r-allylpalladium enolates as common intermediates. 

Rhodium-catalysed addition (10) of hydridosilanes (Chapter 17) to a/3-unsaturated carbonyl compounds can be performed regioselectively, to afford either the product of 1,2-addition, or, perhaps more usefully, that of 1,4-addition, i.e. the corresponding silyl enol ether this latter process is an excellent method for the regiospecific generation of silyl enol ethers. Of all catalyst systems investigated, tris(triphenylphosphine)rhodium(l) chloride proved to be the best. 

The reactions with a combination of (DHQ)2-PHAL [or (DHQD)2-PHAL] and /V-halosulfo-namides can be successfully applied to trans-olefins. Especially when the substrates are a,j3-unsaturated esters, high regioselectivity as well as good enantioselectivity is realized (Scheme 55).210,211 The use of an /V-halosulfonamide bearing a smaller A-substituent increases the enantioselectivity.211 n-Propanol/water (1 1) is the solvent of choice. Aminohydroxylation of silyl enol ethers has been successfully performed with DHQD-CL or (DHQD)2-PYR, to give the corresponding a-amino ketones.212... 

The reaction is applicable to acyclic and cyclic enol ethers and to various (3-dicarbonyl compounds, but fails with silyl enol ethers and simple 1,2-disubstituted alkenes. When applicable, this route to furans is useful because the yields and regioselectivity are consistently satisfactory. The paper includes a preparation of the reagent by reaction of Mn(NO,)3 with Ac20 at 100° to give Mn,0(0Ac)7 H0Ac in 60% yield. 

A straightforward method for aldolizing unsymmetrical ketones on the more hindered side involves the use of catalytic titanium(lV) chloride in toluene at room temperature. For examples using acyclic and cyclic ketones, and linear, branched, and aromatic aldehydes, the regioselectivity varied from 7 1 to >99 1, while the symanti ratios were moderate to good, and yields were in the range 62-91%. In contrast to other methods, base is not required, and the ketone can be used as is (i.e. the silyl enol ether is not required). 

Mattay et al. examined the regioselective and stereoselective cyclization of unsaturated silyl enol ethers by photoinduced electron transfer using DCA and DCN as sensitizers. Thereby the regiochemistry (6-endo versus 5-exo) of the cyclization could be controlled because in the absence of a nucleophile, like an alcohol, the cyclization of the siloxy radical cation is dominant, whereas the presence of a nucleophile favors the reaction pathway via the corresponding a-keto radical. The resulting stereoselective cis ring juncture is due to a favored reactive chair like conformer with the substituents pseudoaxial arranged (Scheme 27) [36,37]. 

Scheme 27 Regioselective and stereoselective cyclization of unsaturated silyl enol ethers.

Fully conjugated species are somewhat rare in the 1,2-thiazine class of heterocycles. These molecules are comprised of two separate subclasses, the first of which includes the highly reactive 1,2-thiazinylium salts. Although these salts, such as 27, have in some cases been isolated, they readily react regioselectively at C-6 with a variety of nucleophiles including sodium alkoxides 76, silyl enol ethers 77, sodium malonates 78, and sodium thiophenoxide 79 (Scheme 10) <2001T8965>. 

F-Teda BF4 (6) is very effective for the fluorination of a wide variety of organic substrates steroidal enol acetates (Table 7)92 and silyl enol ethers, certain carbanions, mildly activated aromatic compounds, and sulfides bearing oc-H atoms.73,75,76,77,84,88 90 The products are obtained with good yields and regioselectivity under very mild reaction conditions (Table 8). 

Ureidoaikylation1 of silyl enol ethers. The group — CH2N(CH3)COOR can be introduced regioselectively by reaction of silyl enol ethers with chloromethyl-carbamates under the influence of TiCl4.7 Examples ... 

A photochemical reaction of the silyl enol ether of acetophenone and benzaldehyde provided the 2,3-diphenyl-3-trimethylsilyloxyoxetane (13) with excellent regioselectivity (> 95 5) and diaster-eoselectivity (> 95 5) (91TL7037). In this example, the diastereoselection was explained by anti-approach of the two phenyl groups during the carbon-carbon bond forming step from the diradical intermediate (Scheme 7). 

Very good yields, mild conditions, regioselectivity, versatility in the choice of the two reacting species (easy access to thermodynamic versus kinetic silyl enol ethers as well as to the required a-chloroalkyl phenyl sulfides) give to these sequences a particularly wide scope. Neopentylation is one illustration of their utility [325]. 

C-Carboxylation of enolates.1 Carboxylation of potassium enolates generated from silyl enol ethers is not regioselective because of extensive enolate equilibration. Regiospecific C-carboxylation of lithium enolates is possible with carbonyl sulfide in place of carbon dioxide. The product is isolated as the thiol methyl ester. If simple esters are desired, transesterification can be effected with Hg(OAc)2 (8, 444). Carboxylation of ketones in this way in the presence of NaH and DMSO is not satisfactory because of competing alkylation of the enolate.2 Example ... 

Reaction of diphenyl(fluoro)-A3-iodane with silyl enol ethers in THF results in a regioselective a-phenylation [Eq. (74)] [131]. 

Using other hypervalent iodine compounds or different reagent combinations, various functional groups can be introduced in the a-position of ketones. a-Tosylations of ketones can be achieved directly using [hydroxy(tosyloxy)-iodo]benzene 6. The major drawback is the low regioselectivity observed in these reactions, although the a-tosylation of silyl enol ethers circumvents this problem. In the last few years some efforts have been done in the synthesis of chiral hypervalent iodine compounds [48, 53-55,113-117], but only a few of them have been used successfully in stereoselective synthesis. With chiral derivatives of type 59 it is possible to a-tosylate propiophenone with about 40% ee [56,118,119]. 

Also, the [4+2] benzannulation of enyne 154 with diyne 155 proceeds chemo- and regioselectively to afford 156 [66], A similar reaction of enyne silyl enol ether 157 with the diyne offers a good synthetic route to polysubstituted phenols 159 via 158 [67]. In this reaction enol silyl ethers having the (E) configuration as shown in 157 give satisfactory results. 

Scheme 7.9 Regioselective formation of oxetanes derived from silyl enol ethers and allylic silanes.

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