Ketene silyl acetals, aldol reactions, selective

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. 

Analogous with the previous results of enol silyl ethers of ketones, nonsubstituted ketene silyl acetals are found to exhibit lower levels of stereoregulation, while the propionate-derived ketene silyl acetals display a high level of asymmetric induction. The reactions with aliphatic aldehydes, however, resulted in a slight reduction in optical and chemical yields. With phenyl ester-derived ketene silyl acetals, syn adducts predominate, but the selectivities are moderate in most cases in comparison with the reactions of ketone-derived silyl enol ethers. Exceptions are a,p-unsaturated aldehydes, which revealed excellent diastereo- and enantioselectivities. The observed syn selectivity and re-face attack of nucleophiles on the carbonyl carbon of aldehydes are consistent with the aforementioned aldol reactions of ketone-derived enol silyl ethers. 

The reaction of /3-chiral aldehydes with ketene silyl acetals gives both syn and anti aldols in similar yields without Cram selectivity (Eq. 55) [43d],... 

A pair-selective aldol reaction proved to be possible and is illustrated in Eq. (25) from the four starting materials, only two products were obtained [100], This clearly indicates that the coupling of the ketene silyl acetal and acetophenone and that of the enol silyl ether and benzaldehyde dimethylacetal are very favorable paths, whereas the reactions of other combinations are not. A similar phenomenon is illustrated by Eq. (26) [100]. 

Aldol-type reactions. The condensation between an aldehyde and a ketene silyl acetal proceeds in CH2CI2 with LiC104 as catalyst at —30°C. iy/i-Selectivity is observed when o-oxyaldehydes are used as reaction partners. 

Aldol reactions. Asymmetric aldol reactions of ketene silyl acetals with catalytic systems consisting of Sn(OTf)2, a chiral diamine, and SnO or Bu2Sn(OAc)2 are very efficient." It is interesting that slight changes in the structure of the chiral diamine ligand (derived from proline) can have opposite effects on the enantio-selectivity."... 

Aldol condensation. The reaction of A-protected a-amino aldehydes with ketene silyl acetals is jy/i-selective in the presence of (/-PrO)2TiCl2. (V,(V-Disubsti-tuted amides and thioamides behave similarly, although the less acidic Lewis acid (i-PrO)3TiCl is used as catalyst. ... 

Optically active syn and anti diol units can be easily prepared by the asymmetric aldol reaction of aldehydes with silyl enolates (4) and (5), respectively, under the influence of chiral tin(II) Lewis acid (6). Diastereofacial selectivities are controlled simply by choosing the protective group of the ct-alkoxy part of ketene silyl acetals (eqs 2 and 3). 

Lewis acid promoted reactions of silicon enolates, /.e., silyl enol ethers and ketene silyl acetals with various electrophiles have yielded a wealth of novel and selective synthetic methods. This combination of reagents has been used in the past to perform such reactions as aldol-condensations with aldehydes and acetals, imine-condensations, conjugate additions to a,P-enones, alkylations, electrophilic aminations, and Diels-Alder/cyclocondensations. Our own interest in this field has involved the use of titanium tetrachloride to promote the reaction of ketene silyl acetals with non-activated imines as an efficient route to P-lactams. This reaction has been applied to the asymmetric synthesis of P-lactams via a chiral imine-titanium tetrachloride template. We have also found that both ketene silyl acetals and vinylketene silyl acetals oxidativelly dimerize or cross-couple, in the presence of titanium tetrachloride to conveniently yield various diesters . Our present study concerns reactions of vinylketene silyl acetals with non-activated imines and vinylimines promoted by titanium and zirconium tetrachlorides. 

Besides their application in asymmetric alkylation, sultams can also be used as good chiral auxiliaries for asymmetric aldol reactions, and a / -product can be obtained with good selectivity. As can be seen in Scheme 3-14, reaction of the propionates derived from chiral auxiliary R -OH with LICA in THF affords the lithium enolates. Subsequent reaction with TBSC1 furnishes the 0-silyl ketene acetals 31, 33, and 35 with good yields.31 Upon reaction with TiCU complexes of an aldehyde, product /i-hydroxy carboxylates 32, 34, and 36 are obtained with high diastereoselectivity and good yield. Products from direct aldol reaction of the lithium enolate without conversion to the corresponding silyl ethers show no stereoselectivity.32... 

A catalytic enantio- and diastereo-selective aldol reaction of ketones with ketene (g) silyl acetals, H2C=C(OTMS)-OMe, gives fair to good yields and ee.129 With further substitution of the vinyl function, the reaction is diastereoselective, up to 97%. A highly developed catalyst/promoter protocol is employed a copper fluoride complex is combined with a Taniaphos auxiliary (a chiral ferrocenyldiphosphine), plus (EtO)3SiF. Evidence for the formation of species (EtO)4 SiF (n > 2) as active... 

Aldol Reactions of Ester Derivatives. The Titanium(IV) C/tlor/dc-catalyzed addition of aldehydes to 0-silyl ketene acetals derived from acetate and propionate esters proceeds with high stereoselectivity. Formation of the silyl ketene acetal was found to be essential for high diastereoselectivity. Treatment of the silyl ketene acetal, derived from deprotonation of the acetate ester with LICA in THF and silyl trapping, with a corresponding aldehyde in the presence of TiCU (1.1 equiv) afforded the addition products in 93 7 diastereoselectivity and moderate yield (51-67%). Similarly, the propionate ester provides the anti-aldol product in high antilsyn selectivity (14 1) and facial selectivity (eq 4). 

The use of CAB as a chiral reagent seems to be more effective for this reaction, which proceeds faster and with higher yields and enantiomeric excess. Kiyooka et al. first described the use of various chiral oxaborolidines, derived from sulfonamides of a-amino acids and borane, in the course of the selective aldol reaction between silyl ketene acetals and aldehydes (Eq. 47) [43a]. Stereoselectivity and yields were relatively high. 

C2-symmetric bis(oxazolinyl)pyridine (pybox)-Cu (II) complex 27 has been shown to catalyze highly enantioselective Mukaiyaraa aldol reactions between (benzyloxy)acetaldehyde and silyl ketene acetals by Evans and co-workers as exemplified in Scheme 1-9 [38]. Here, the requirement for a chelating substituent on the aldehyde partner is critical to catalyst selectivity, as a-(terl-butyldimethylsil-oxy)acetaldehyde gave lower enantioselectivity (56% ee). In addition, P-(benzyl-oxy)propionaldehyde provided the racemic product, indicating a strict requirement for a five-membered catalyst-substrate chelate. 

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