E-silyl ketene acetal

Z-silyl ketene acetal syn isomer E-silyl ketene acetal... 

A number of factors other than the solvent can affect the stereoselectivity of deprotonation of esters, such as the acid-base ratio and the nature of the base. But selective formation of (E)-silyl ketene acetals from esters remains a problem, particularly since they are more reactive than the (Z)-isomers. 

The major products obtained from these reactions together with a detailed discussion of the factors that influence the formation of Z- and E-silyl ketene acetals may be found in Ireland, R.E., Wipf, P. and Armstrong, J.D. (1991). /. Am. Chem. Soc., 56, 650.]... 

B ( enamine ) C ( enol ether ) D ( silyl enol ether ) E ( silyl ketene acetal )... 

Reaction of (E)-silyl ketene acetals with benzaldehyde involves using Yb triflate as catalyst and the reaction scheme is shown below [159]. 

The formation of an ester enolate with LDA in THF can proceed via the two closed six-membered transition states A and B. The steric interaction between the methyl group of 15 and the isopropyl group of LDA disfavors transition state B. Thus, the E-qsXqv enolate is formed selectively, which is subsequently converted to the corresponding E-silyl ketene acetal 16 using TMSCl. 

Ireland demonstrated that the anti 2,3-dimethyl pentenoic acid isomer could be obtained either by rearrangement of the -silyl ketene acetal of -crotyl propionate or with the Z-silyl ketene acetal of the Z-crotyl propionate at comparable levels of diastereoselectivity (Scheme 4.16) [1]. The analogous results for the syn pentenoic acid can be obtained using the Z-silyl ketene acetal of silyl ketene acetal with Z-crotyl propionate. The diastereoselectivities varied from 5 1 to 8 1. Since the allyl silyl ketene acetals are achiral, the products are of course racemic. 

In their total synthesis of (-i-)-ophiobolin in 1989, Kishi et al. found that treatment of a cyclopentenyl ester under the typical Ireland conditions gave principally C-silylated ester [63]. Heating of a C-silyl ester (prepared by acylation using a C-silyl acyl chloride) at 230 °C resulted in a 1,3-Brook rearrangement followed by an Ireland-Claisen rearrangement to give the desired product as a 6 1 ratio of isomers at C2 of the pentenoic acid (Scheme 4.63). The major product could have arisen through either a chair transition state of the Z-sUyl ketene acetal or a boat transition state of the E-silyl ketene acetal. 

Lewis acid promoted condensation of silyl ketene acetals (ester enolate equiv.) with aldehydes proceeds via "open" transition state to give anti aldols starting from either E- or Z- enolates. 

Hepatite Virus NS3/4A having the pyrrolidine-5,5-trans-lactam skeleton [83], starting from (R)- and (S)-methionine, respectively. The key step is the addition of the proper silyl ketene acetal to an iminium ion, e.g., that generated by treatment of the intermediate 177 with boron trifluoride, which provided the adduct 178 with better diastereoselectivity than other Lewis acids. Inhibitors of hepatitis C virus NS3/4A were efficiently prepared by a similar route from (S)-methionine [83]. The addition of indole to a chiral (z-amino iminium ion was a completely diastereoselective step in a reported synthesis of tilivalline, a natural molecule which displays strong cytotoxicity towards mouse leukemia L 1210 [84]. 

This and similar catalysts are effective with silyl ketene acetals and silyl thioketene acetals.155 One of the examples is the tridentate pyridine-BOX-type catalyst 18. The reactivity of this catalyst has been explored using a- and (3-oxy substituted aldehydes.154 a-Benzyloxyacetaldehyde was highly enantioselective and the a-trimethylsilyoxy derivative was weakly so (56% e.e.). Nonchelating aldehydes such as benzaldehyde and 3-phenylpropanal gave racemic product. 3-Benzyloxypropanal also gave racemic product, indicating that the (i-oxy aldehydes do not chelate with this catalyst. 

The silyl ketene acetal rearrangement can also be carried out by reaction of the ester with a silyl triflate and tertiary amine, without formation of the ester enolate. Optimum results are obtained with bulky silyl triflates and amines, e.g., f-butyldimethylsilyl triflate and (V-methyl-Af, /V-dicyclohcxylaminc. Under these conditions the reaction is stereoselective for the Z-silyl ketene acetal and the stereochemistry of the allylic double bond determines the syn or anti configuration of the product.243... 

It was found that benzaldehyde reacts with E and Z configured silyl ketene acetals to furnish identical aldol products [93] with high enantioselectivity. Neither diastere-oselectivity nor enantioselectivity were affected by double bond geometry of the silyl ketene acetal. This is an evidence for an acyclic transition state (Scheme 27). 

Control of the side reactions is achieved through two factors (1) reversible complexation of the anionic propagating species XXVII by the silyl ketene acetal polymer chain ends XXVI maintains the concentration of the anionic propagating species at a low concentration and (2) the bulky counterion W+ (e.g., tetra-ra-huty I ammonium, tris(dimethylamino)sulfonium) decreases the reactivity of the anionic propagating centers toward the terminating side reactions. 

Similar results were obtained when diphenylnitrenium ion was trapped with various silylenol ethers and silyl ketene acetals (e.g., 116). In these experiments, a distribution of N-(117), p- (118), and o- (119) adducts were generated (Fig. 13.55). The ortho adducts underwent a cyclization reaction, producing an indolone derivative. 

This reaction, also, has been performed diastereoselectively.461 Allylic silanes R.2C=CHCH2SiMe3 can be used instead of silyl enol ethers (the Sakurai reaction). 462 Similarly, silyl ketene acetals, e.g., 56, give 8-keto esters, in MeN02 as solvent, for example,463... 

The addition of acetate-derived, achiral lithium enolates to monoprotected a-amino aldehydes is controlled by chelation, and leads to a modest stereochemical preference in favor of the 3,4-syn configuration (Table 1, entry a). 18 The formation of the 3, A-syn-product is enhanced by the use of acetate-derived silyl ketene acetals and the addition of titanium(IV) chloride or tin(IV) chloride to the reaction mixture (Table 1, entries b and c). 22-23 The same enolates add stereoselectively to A2 A-dibenzyl a-amino aldehydes but with diastereomeric ratios in favor of the Felkin-Ahn 3,4-anti-product (Table 1, compare entries a and d, and b and f). 22-24 Reverse stereocontrol is observed in the presence of a Lewis acid such as tita-nium(IV) chloride, but the yield is low (Table 1, entry e). 24 ... 

When catalyzed by the Cu(II) complexes 81-83, the addition of either E- or Z-thiopropion-ate-derived silyl ketene acetals afford adducts displaying 86 14-97 3 simple diastereoselectiv-... 

The use of aryl-A3-iodanes for C-heteroatom bond formation at the a-carbon atoms of ketones and / -dicarbonyl compounds, and related transformations of silyl enol ethers and silyl ketene acetals, has been exhaustively summarized in recent reviews (Scheme 27) [5,8]. Reactions of this type are especially useful for the introduction of oxygen ligands (e. g., L2 = OH, OR, OCOR, 0S02R, OPO(OR)2), and have been extensively utilized for the synthesis of a-sulfonyl-oxy ketones and a-hydroxy dimethyl ketals. 

Silyl ketene acetals from esters.1 Ireland has examined various factors in the enolization and silylation of ethyl propionate (1) as a model system. As expected from previous work (6, 276-277), use of LDA (1 equiv.) in THF at —78 -+ 25° results mainly in (E)-2, formed from the (Z)-enolate. The stereoselectivity is markedly affected by the solvent. Addition of TMEDA results in a 60 40 ratio of (Z)- and (E)-2 and lowers the yield significantly. Use of THF/23% HMPA provides (Z)- and (E)-2 in the ratio of 85 15 with no decrease in yield. This system has been widely used for (E)-selective lithium enolate formation from esters and ketones. Highest stereoselectivity is observed by addition of DMPU, recently introduced as a noncar-... 

The geometry of the double bonds in the Claisen substrate determines the stereochemistry around the newly-formed carbon-carbon single bond in the product. For example (E)- and (Z)-silyl ketene acetals produce diastereoisomeric products as illustrated in Figure Si3.11. 

The observed rc-face differentiation of the electrophilic animation process was rationalized by the authors [14b]. NMR Nuclear Overhauser experiments agree with the ( -configuration of the O-silyl ketene acetals 35 and with a j-yn-periplanar disposition of the C -OSi and C2-Ha bonds. Electrophiles E+ , such as Lewis acids-co-ordinated DTBAD, attack 35 preferentially from the less hindered C(a)-Si (back) face (Scheme 17). 

Fig. 11.43. Claisen-Ireland rearrangement of two O-allyl-O-silyl ketene acetals. 7ran.v-sclective synthesis of disubstituted and E-selective synthesis of trisubstituted alkenes.

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