Silylketene

Silylketenes as useful building blocks for heterocycles 99JHC1555. 

Silylketenes in formation of (3-lactones and (3-lactams 98JCS(P1)2105. Syntheses of (3-lactams, (3-lactones, and 1,3- and 1,4-diazetidinediones by pho-tochemically induced cycloaddition reactions of chromium carbene complexes with imines, aldehydes, and azo compounds 97T4105. 

An important variant is the rearrangement of silylketene acetals like 10 and 11 which are easily accessible from allyl esters 9. This so-called Ireland-Claisen rearrangement is a valuable carbon-carbon bond forming reaction that takes advantage of the fact that the reactants are first connected to each other by an ester linkage as in allyl esters 9, that are easy prepare. 

By employing optically active enol borinates instead of silylketene acetals, the Ireland-Claisen rearrangement has been further developed to an enantioselective... 

A confusing picture emerges from the stereochemical outcome of the Mukaiyama variation of the aldol addition. The titanium(IV) chloride mediated addition of silylketene acetals to isobutyraldehyde confirms this statement while there is a reasonable correlation between the predominance of the (/t)-silylkctenc acetal 2 over the (Z)-acetal, and the favored formation of the an/t -carboxylic ester over the. svn-product, the pure (Z)-diastereomer displays no syn selectivity26. 

I.3.4.2.2. Chiral Ulster Enolates, Silylketene Acetals, and Thioester Enolates... 

In general, chiral propanoates providing simple diastereoselectivity (in favor of yyn-aldols), combined with a reasonable degree of auxiliary-induced stereoselectivity, are rare. Numerous terpenoid- and carbohydrate-derived propionates do not display satisfactory syn selectivity60. Similarly, the titanium(IV) chloride promoted aldol addition of the following JV-metbylephe-drine derived silylketene acetal leads to the formation of the. mi-adduct in the moderate diastereomeric ratio of 78 22 (syn-adduct sum of the other stereoisomers)61. 

Camphor derived acetates 1 (Helmchen-type65) and 3 (Oppolzer-lype66) add to aldehydes in a stereoselective manner when the Mukaiyama variation via the corresponding silylketene acetals is undertaken. Careful optimization of the reaction conditions provides predominantly... 

Highly stereoselective formation of. syn-adducts (syn/anti. >95 < 5) results from the titanium(IV) chloride induced addition ofa-unsubsliluled enolsilanes, as well as of the a-dimethyl silylketene acetal, to 2-benzyloxypropanal3. 

Incomplete simple diastereoselectivity. combined in at least some cases with lower induced stereoselectivity, is also found in the addition of silylketene acetals 1-alkoxy-l-trirnethylsilyloxy-l-propene to 2-benzyloxypropanal3. On the other hand, a single diastereomeric adduct results from the tin(IV) chloride mediated addition of the following enolsilane to (S )-2-benzyloxypropanal12. 

The Mukaiyama variation of the aldol reaction also allows 1,3-induced chelation control. Thus, the reaction of the enolsilane or silylketene acetal with (5 )-3-benzyloxybutanal results in both cases in the predominant formation of the cwt/ -adduct (92 8 and 90 10), respectively14. 

The chelation-controlled addition of silylketene acetal, 1-phenoxy-l-trimethylsilyloxyethene, to enantiomerically pure (S)-2-dibenzylaminopropanaI is not easily accomplished. Although the predominant formation of one diastcrcomcr is possible (d.r. 95 5), the reaction is plagued by a low chemical yield9. 

The Lilanium(lV) chloride mediated reactions of the silylketene acetal, l-methoxy-2-methyI-l-trimethylsilyloxy-l-propene. with a-methylthioaldehydes afford predominantly adducts resulting from chelation control, besides minor amounts of the diastereomers10. 

The combination of the enantiomerically pure 7V-methylephedrine derived silylketene acetal l-[(l/ ,2S)-2-dimethylamino-1-phenylpropoxy]-l-triniethylsilyloxy-l-propene with the chiral aldehyde (,R)-3-benzyloxy-2-methylpropanal leads, after reduction with lithium aluminum hydride, to the formation of a single 1,3-pentanediol 9 ( matched pair ). 

In contrast, the reaction of the i. V)-aldehyde with this silylketene acetal gives the 1,3-pentane-diols in a 1.3 1 ratio ( mismatched pair )18. 

A matched pair combination of the above silylketene acetal and (/ ,if)-2,4-dimethyl-2-heptenal has been applied in a stereoselective synthesis of the C17-C25 fragment of zincophor-... 

The proline derived diamines 2 and 4 (vide supra) are also suitable chiral additives in enantiose-lective additions of a-unsubstituted enolates. Best results are obtained with the naphthyl derivative, as demonstrated in the tin(II) triflate mediated addition of the O-silylketene thio-acetal l-toT-butylthio-l-trimethylsilyloxyethane to aldehydes which delivers 3-hydroxythio esters in optical purities of up to 95% ee and chemical yields between 50 and 90 %24... 

The (acyloxy)borane complex 9, readily available from tartaric acid derivative 8, also catalyzes aldol additions of silyl enol ethers34 and silylketene acetals3 5 in an enantioselective manner. Thus,. u -ketones 10 and /Thydroxy esters 12 are available34, as well as a-unsubstituted ketones 1135. 

The predominant formation of ann -carboxylic esters and thioesters results when the additives 13 or 14 are used to mediate aldol additions of silylketene acetals derived from propionates and propanethioates37. The enantioselective addition of a-unsubstituted esters or thioesters is also feasible with the borane 1437. 

Q Chiral racemic y-alkyl-substituted enones the titanium(IV) chloride mediated addition of enol silanes and silylketene acetals to 7 shows high induced diastereoselection (diastereomeric ratios from 89 11 to more than 97 3) and the major isomer 8 results from addition of the enolsilane with ul topicity288. Re face attack on the S enantiomer of 7.)... 

Alternatively, the silylketene acetal R R C=C(OSiR3)OCH2CH=CHR is often used instead of 116. This rearrangement also proceeds at room temperature. By... 

Optimized rearrangement conditions in presence of excess silylketene acetal. Rearrangement in the presence of dihydropyrane, re-addition of PhSeOH. 

By analogy with aromatic nitro compounds, nitroolefins such as yS-nitrostyrene 1032 react with the O-silylketene acetal 1033 at -78 °C, in the presence of the selective Lewis acid MAD, in toluene, to give a 6.3 1 syn/anti mixture of the co-nitro ester 1034 and 94a [98] (Scheme 7.33). 

Silylation of the 2-qfclohexanone phenylsulfoxide 1213 with the O-silylketene-acetal 1214 in the presence of Znl2 gives 75% of the Sila-Pummerer product 1215, whereas the 2-cyclooctanone phenylsulfoxide 1216 affords a ca. 1 1 mixture of the Sila-Pummerer products 1217 and the olefin 1218 [31] (Scheme 8.12). 

HMDSO 7 [39]. With 20/DIPEA sulfoxide 1233 affords 76% of 1235 [40]. Analogous silylation of the S-oxide function in 1237 with the O-silylketene acetal 1214 and subsequent cyclization with ZnCl2 or Znl2 affords 1238, a precursor of thie-namycin [41-43] (Scheme 8.16). 

Cyclization of co-amidophenyl sulfoxides 1244 for n=l, 2, 3 with O-silylketene acetal 1214 affords 5-, 6-, and 7-membered lactams 1245 in 100, 54, and 57% yields, respectively, and [Me3CSi(Me)]20 94 a [47, 48], whereas cyclization of N-mefhyl-2-methylsulfenyl benzamide 1246 with silylketene acetal 1214 and Znl2 gives 85% 3-mefhyl-2,3-dihydro-l,3-benzofhiazine-4-one 1247 and [Me3CSi(Me)2]20 94a [48] (Scheme 8.18). 

Different rearrangements were observed in other cases. Thus, Maas22 reported that when photolyzed in benzene the polysilyldiazoketone 180 gave the isomeric ketene 181, the product of a Wolff rearrangement (a 1,2 carbon-to-carbon rearrangement) of the initially formed carbene 182 (Eq. 57). The isomeric bis-silylketene 183 was not observed, but the siloxa-tene 184 was also a product of the reaction. 

Table 3.24 C-C coupling of nitronates (356a-j) with silylketene acetal. (An-4-MeO-C6H4)...

With chiral enol species (/ )-silylketene acetal derived from (1 R,2S)-N-methyl ephedrine-O-propionate, both the aldehyde carbonyl and the ephedrine NMe2 group are expected to bind to TiCU, which usually chelates two electron-donating molecules to form ra-octahedral six-coordinated complexes.25 Conformational freedom is therefore reduced, and the C-C bond formation occurs on the six-coordinated metal in a highly stereoselective manner.18... 

The efficiency of catalysts 86-89 for the asymmetric aldol reaction of a series of nucleophiles toward benzyloxyacetaldehyde was studied. For example, compound 89c was found to be an excellent catalyst for the asymmetric aldol reaction of silylketene acetal derivatives of t-butyl thioacetate, ethyl thioacetate, and ethyl acetate with benzyloxyacetaldehyde. In the presence of 0.5 mol% of the catalyst, the asymmetric aldol reaction took place at —78°C in CH2C12, affording the respective /i-hydroxy esters with excellent enantioselectivity (Scheme 3-32). 

Catalyst 86a also catalyzed the enantioselective aldol reaction between a-keto esters and silylketene acetals or enolsilanes with high ee (ranging from 93% to 99%).58... 

Silylketene acetals and enolsilanes can also undergo conjugate addition to a,/ -unsaturated carbonyl derivatives. This reaction is referred to as the Mukaiyama-Michael addition and can also be used as a mild and versatile method for C-C bond formation. As shown in Scheme 8-34, in the presence of C2-symmetric Cu(II) Lewis acid 94, asymmetric conjugate addition proceeds readily, giving product with high yield and enantioselectivity.75... 

The utilization of copper complexes (47) based on bisisoxazolines allows various silyl enol ethers to be added to aldehydes and ketones which possess an adjacent heteroatom e.g. pyruvate esters. An example is shown is Scheme 43[126]. C2-Symmetric Cu(II) complexes have also been used as chiral Lewis acids for the catalysis of enantioselective Michael additions of silylketene acetals to alkylidene malonates[127]. 

D. A. Evans, P. H. Carter, E M. Carreira, J. A. Pmnet, A. B. Charette, M. Lautens Asymmetric Synthesis of Bryosta-tin 2 , Angew. Chem, Int. Ed. Engl. 1998,37,2354-2359. For methodological studies on asymmetric Cu-catalyzed aldol addition, see D. A. Evans, J. Murry, M. C. Koz-lowski C2-Symmetric Cu(II) Complexes as Chiral Lewis Adds. Catalytic Enantiosdective Aldol Additions of Silylketene Acetals to (Benzyloxy)acetaldehyde , J. Am Chem. Soc 1996,118,5814-5815. 

The third group4 used (1R,2S)-N methylephedrine as the chiral auxiliary. Thus the derived silylketene acetal (6) reacts with 1 in the presence of TiCl4 to give 7 in 45-70% yield with —90% stereoselectivity. The products are converted by TFA and LiOH to (R)-a-hydrazino acids (8), which are obtained in 5=98% ee after one crystallization. 

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