Silyl acetals

Silyl acetals have been investigated by Hutchinson and co-workers as tethers in radical cyclization reactions [78]. A number of commercially available dialkyldichlorosilanes were investigated as tether precursors although Pr2SiCl2 was found to be the most suit- 

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An Q-arylalkanoate is prepared by the reaction of aryl halide or triflate with the ketene silyl acetal 74 as an alkene component. However, the reaction is explained by transmetallation of Ph - Pd—Br with 74 to generate the Pd eno-late 75, which gives the a-arylalkanoate by reductive elimination[76]. 

Silyl enol ethers are other ketone or aldehyde enolate equivalents and react with allyl carbonate to give allyl ketones or aldehydes 13,300. The transme-tallation of the 7r-allylpalladium methoxide, formed from allyl alkyl carbonate, with the silyl enol ether 464 forms the palladium enolate 465, which undergoes reductive elimination to afford the allyl ketone or aldehyde 466. For this reaction, neither fluoride anion nor a Lewis acid is necessary for the activation of silyl enol ethers. The reaction also proceed.s with metallic Pd supported on silica by a special method[301j. The ketene silyl acetal 467 derived from esters or lactones also reacts with allyl carbonates, affording allylated esters or lactones by using dppe as a ligand[302]... 

Allylic acetates react with ketene silyl acetals. In this reaction, in addition to the allylated ester 468, the cyclopropane derivative 469. which is formed by the use of bidentate ligands, is obtained[303]. Formation of a cyclopropane derivative 471 has been observed by the stoichiometric reaction of the 7r-allylpal-... 

The reaction can be applied to the synthesis of q, /3-unsaturated esters and lactones by treatment of the ketene silyl acetal 551 with an allyl carbonate in boiling MeCN[356]. The preparation of the q,, 3-unsaturated lactone 552 by this method has been used in the total synthesis of lauthisan[357]. 

Group-Transfer Polymerization. Living polymerization of acrylic monomers has been carried out using ketene silyl acetals as initiators. This chemistry can be used to make random, block, or graft copolymers of polar monomers. The following scheme demonstrates the synthesis of a methyl methacrylate—lauryl methacrylate (MMA—LMA) AB block copolymer (38). LMA is CH2=C(CH2)COO(CH2) CH2. 

Another useful application of these Reformatsky reagents is their conversion to difluaraketene silyl acetals and subsequent reaction of these ketene silyl acetals with electrophiles [86, 89, 90] (equation 59)... 

This reaction can also be used for the preparation of ketene silyl acetals from tt/l-unsaturated esters, including simple acrylates (72) in geometrically defined cases, the (Z) isomer is produced stereoselectively (7) ... 

The 2+2 cycloadditions of benzyne to cis- and trani-propenyl ether gave cis- and fran -benzocyclobntanes as the main products, respectively [ 117,118], Stereospecific [2+2] cycloaddition reactions were observed between the benzyne species generated by the halogen-Uthium exchange reaction of ort/io-haloaryl triflates and the ketene silyl acetals (Scheme 23) [119],... 

Lewis acids such as TiCl4 and SnCl4 induce addition of both silyl enol ethers and ketene silyl acetals to aldehydes.49... 

Silyl acetals of thiol esters have also been studied. With TiCl4 as the Lewis acid, there is correspondence between the configuration of the silyl thioketene acetal and the adduct stereochemistry.314 L-Isomers show high anti selectivity, whereas Z-isomers are less selective. 

Montmorillonite K10 was also used for aldol the reaction in water.280 Hydrates of aldehydes such as glyoxylic acid can be used directly. Thermal treatment of K10 increased the catalytic activity. The catalytic activity is attributed to the structural features of K10 and its inherent Bronsted acidity. The aldol reactions of more reactive ketene silyl acetals with reactive aldehydes proceed smoothly in water to afford the corresponding aldol products in good yields (Eq. 8.104).281... 

Instead of using an aldehyde for trapping the primarily formed enolate, there are also a few examples which involve an imino acceptor in the second anionic step. The Collin group used a lanthanide iodide-mediated reaction of a ketene silyl acetal... 

Alkylation of ketene silyl acetals with nitroalkenes has several limitations such as modest yield, lack of generality, and inconveniently low reaction temperatures. Tucker and coworkers have found that sterically encumbered Lewis acids such as MAD give better results than other Lewis acids (Eq. 4.64).83... 

It was first observed that reactions of imines with ketene silyl acetals proceeded smoothly in the presence of 5mol.% Yb(OTf)3 to afford the corresponding /3-amino ester derivatives in moderate yields.50 However, Sc(OTf)3 was found to be a more active catalyst in this reaction. Benzoylhy-drazones also react with ketene silyl acetals in the presence of a catalytic amount of Sc(OTf)3 to afford the corresponding adducts in high yields (Scheme 11).51 In contrast, catalytic activation of benzoylhydrazones by use of a typical Lewis acid such as TiCl4, SnCl4, or BF3-OEt2, etc. is not effective. 

In aldol reactions, especially Mukaiyama aldol reactions, TiIV compounds are widely employed as efficient promoters. The reactions of aldehydes or ketones with reactive enolates, such as silyl enol ethers derived from ketones, proceed smoothly to afford /3-hydroxycarbonyl compounds in the presence of a stoichiometric amount of TiCl4 (Scheme 17).6, 66 Many examples have been reported in addition to silyl enol ethers derived from ketones, ketene silyl acetals derived from ester derivatives and vinyl ethers can also serve as enolate components.67-69... 

In SiCl4-mediated Mukaiyama-Michael reactions, an electron-transfer mechanism is proposed for the case in which ketene silyl acetals bearing less hindered silyl substituent are used as substrates.342-344 As shown in Scheme 82, ketene silyl acetals having more substituents at the /3-position are much more reactive. 

Pro-chiral pyridine A-oxides have also been used as substrates in asymmetric processes. Jprgensen and co-workers explored the catalytic asymmetric Mukaiyama aldol reaction between ketene silyl acetals 61 and pyridine A-oxide carboxaldehydes 62 <06CEJ3472>. The process is catalyzed by a copper(II)-bis(oxazoline) complex 63 which gave good yields and diastereoselectivities with up to 99% enantiomeric excess. 

Addition of Ketene Acetals and Enoles In recent years, much attention has been given to the synthesis of optically active nitrogen-containing compounds, with the key step being the highly stereoselective nucleophilic addition of ketene silyl acetals to nitrones (Scheme 2.174). Similar to nitrone cyanations, in ketene silyl acetal reactions one observes an accelerating effect with thiourea derivatives (633). 

W-benzyl-TV-hydroxylamine)phenylmethyl]-3-hydroxybutanoate (398) (637). The absolute configuration (398) was determined as (aRfiS,yR) thus, diastere-oselective addition of ketene silyl acetals (397) to nitrone proceeds as anti-a, p-anti-p, y (Scheme 2.176). 

Addition of ketene silyl acetals to a,N-diarylnitrones, catalyzed by lanthanum trifloromethanesulfonate [lanthanide triflate, La(OTf)3], affords addition... 

Addition of ketene silyl acetals to aldehydes and ketones is also mediated by achiral palladium(ll) acetate-diphosphine complexes (Equation (109)).46S,46Sa Although the precise mechanism is still unclear, high catalytic activity may be ascribed to the intermediacy of palladium enolates. 

Chiral bis-phosphine acylplatinum complex 210 with a strong acid such as TfOH serves as an effective enantio-selective catalyst for aldol-type reactions of aldehydes with ketene silyl acetals (Equation (127)).486 The presence of water and oxygen in the catalyst preparation step is required to obtain the highly enantioselective catalyst. The intermediacy of a C-bound platinum enolate was suggested by IR and 31P NMR spectroscopies. 

Iwasawa and co-workers developed a facile method for the construction of polycyclic indole derivatives 190a and 190b by the tungsten(0)-catalyzed reaction of A-(2-(l-alkynyl)phenyl)imine 188 with the electron-rich alkenes 189a and 189b (Scheme 32).42b Photoirradiation of a mixture of imine 188 and ketene silyl acetal 189a with 10mol% of... 

In the synthesis of D-eryt/zro-sphingosine (78 without BOC protection), the key step is the asymmetric aldol reaction of trimethylsilylpropynal 75 with ke-tene silyl acetal 76 derived from a-benzyloxy acetate. The reaction was carried out with 20 mol% of tin(II) triflate chiral diamine and tin(II) oxide. Slow addition of substrates to the catalyst in propionitrile furnishes the desired aldol adduct 77 with high diastereo- and enantioselectivity (syn/anti = 97 3, 91% ee for syn). In the synthesis of protected phytosphingosine (80, OH and NH2 protected as OAc and NHAc, respectively), the asymmetric aldol reaction is again employed as the key step. As depicted in Scheme 3-27, the reaction between acrolein and ketene silyl aectal 76 proceeds smoothly, affording the desired product 80 with 96% diastereoselectivity [syn/anti = 98 2) and 96% ee for syn (Scheme 3-27).50... 

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