Silyl enol ethers chlorination

The overall sequence of cyclopropanation of a cyclic silyl enol ether, chlorination with FeCl3, and dehydrochlorination represents a very reliable one-carbon ring expansion method for cycloalkanomer (Table 11). 

The silatropic ene pathway, that is, direct silyl transfer from an silyl enol ether to an aldehyde, may be involved as a possible mechanism in the Mukaiyama aldol-type reaction. Indeed, ab initio calculations show that the silatropic ene pathway involving the cyclic (boat and chair) transition states for the BH3-promoted aldol reaction of the trihydrosilyl enol ether derived from acetaldehyde with formaldehyde is favored [60], Recently, we have reported the possible intervention of a silatropic ene pathway in the catalytic asymmetric aldol-type reaction of silyl enol ethers of thioesters [61 ]. Chlorine- and amine-containing products thus obtained are useful intermediates for the synthesis of carnitine and GABOB (Scheme 8C.26) [62],... 

The ( )/ (Z) substrate-dependent absolute stereochemistry and the steric influence of 5n-substituents on the enantioselectivity observed in these reactions suggest that the mechanism is essentially different from that of silyl enol ethers. Although the detailed stereochemical course has not been ascertained, it is possible that the protonation occurs via a two-chlorine-bridged intermediate between allyltrimethyltin and LBA. Keck et al. have reported that transmetalation between allyltributyltin and free... 

Ring expansion of the substituted bicyclo[4.1.0]heptanes 8, formed by addition of chloromethyl-carbene to silyl enol ethers, was accomplished almost equally effectively by refluxing in toluene, or by heating in methanol containing triethylamine. In each case, the crude mixture of cis- and /rani-7-chloro-7-methylbicyclo[4.1. Ojheptanes 8 was used, although it was observed that the traui-isomers, with the chlorine and trimethylsiloxy substituents tram to each other, rearranged more rapidly. 

Silyl enol ethers (CHj = CROSiMe3) react with cyanuryl chloride and replace only one chlorine with a carbon substituent (CH2COR R = cyclopropyl, 70 /o, R = Ph, 90 /o). Friedel-Crafts arylation <83KGS1125,92EUP497734>, the Ullmann reaction of 2-iodo-1,3,5-triazine to form 2,2 -bis-1,3,5-triazine <82NKK1425>, and a palladium-catalyzed cross-coupling reaction of 2-substituted 4,6-dichloro-... 

Nucleophilic displacement of chlorine, in a stepwise manner, from cyanuric chloride leads to triazines with heteroatom substituents (see Section 6.12.5.2.4) in symmetrical or unsymmetrical substitution patterns. New reactions for introduction of carbon nucleophiles are useful for the preparation of unsymmetrical 2,4,6-trisubstituted 1,3,5-triazines. The reaction of silyl enol ethers with cyanuric chloride replaces only one of the chlorine atoms and the remaining chlorines can be subjected to further nucleophilic substitution, but the ketone produced from the silyl enol ether reaction may need protection or transformation first. Palladium-catalyzed cross-coupling of 2-substituted 4,6-dichloro-l,3,5-triazine with phenylboronic acid gives 2,4-diaryl-6-substituted 1,3,5-triazines <93S33>. Cyanuric fluoride can be used in a similar manner to cyanuric chloride but has the added advantage of the reactions with aromatic amines, which react as carbon nucleophiles. New 2,4,6-trisubstituted 1,3,5-triazines are therefore available with aryl or heteroaryl and fluoro substituents (see Section 6.12.5.2.4). 

Activation of Se-arsanyl selenoestersf Chlorination renders arsanyl sele-noesters electrophilic, enabling them to react with silyl enol ethers to form Se-(/3-oxoalkyl) selenoesters. 

Siloxy-a-haloketones have been prepared with high anti-selectivity via a Mukaiyama aldol of super-silyl enol ethers, using the tris(trimethylsilyl)silyl (or TTMSS) group. Most cases involve chlorine, but fluorine works too, and one-pot sequential double-aldol versions deliver, 5-bis(super-silyl)oxy-a,y-dihaloketones with 0 control of four contiguous chiral centres. 

Diacetone-D-glucose has also served as auxiliary for synthesis of (S)-2-haloalk-anoic acids, 374. Silyl enol ethers 373 were brominated or chlorinated (NBS or NCS) with 75-96 % d.e., oxidative cleavage of the auxiliary then yielding the (S)-2-chloro- and (S)-2-bromoalkanoic acids (Scheme 59)." ... 

When electron-withdrawing substituents such as chlorine and fluorine are substituted on a silicon atom of silyl enol ethers and allylsilanes, the silicon center becomes Lewis acidic enough to activate carbonyls. Coordination of a Lewis base carbonyl to the silicon atom further enhances the Lewis acidity of the silicon center due to delocalization of a negative charge over ligands to allow diastereoselective allylation of aldehydes through a six-membered transition state involving a hexacoordinate silicate species (Scheme 3-112). " ... 

The effects of changing the alkoxy group of the acrylates 7 on the yields of reactions with the silyl enol ethers 4a-6a are summarized in Table 4.2. Unfortunately, the reaction of trimethylsilyl (TMS) enol ether 4a with methyl acrylate (7a) gave no desired product, because hydration of silyl enol ether occurred quickly (Table 4.2, entry 1). The reaction of ferf-butyldimethylsilyl (TBS) enol ether 5a with methyl acrylate (7a) afforded the diastereomeric cyclobutane trans-8a and cw-8a in 60 and 19% yields, respectively (entry 2). Further exploration demonstrated that incorporation of fluorine or chlorine in the alkoxy moiety led to enhanced yields... 

Yamamoto and co-workers have demonstrated the highly enantioselective stoichiometric chlorination of silyl enol ethers using a,a-dichloromalonic ester X8 as the halogen source in the presence of ZrCLt (Table 43.5 entry 1). Coordination of the Lewis acid (Z1CI4) to reagent X8 was crucial to generate a C2-symmetric environment where the selective chlorination occurs. Hajra et al. have reported on a similar stoichiometric enantioselective chlorination of... 

Hajra S, Bhowmick M, Maji B, Sinha D. Design and synthesis of chiral IV-chloroimidodicarbonates application to asymmetric chlorination of silyl enol ethers. J. Org. Chem. 2007 72(13) 4872 76. 

Enol silyl ethers can lead to a-chloro ketones on treatment with anhydrous copper(II) chloride in DMF or iron(lll) chloride in acetonitrile (equation 13, Table 1). The chlorination of (36 equation 14) proceeds through a cation radical intermediate formed by an electron-transfer process with metal halides. 

A BINAP-Pd complex brings about enantioselective 1,4-disilylation of a,3-unsaturated ketones with chlorinated disilanes, giving enol silyl ethers in 74-92% ee (eq 21). ... 

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