P-Silyl aldehydes

Regioselective hydroformylation. The rhodium-catalyzed hydroformylation of (Z)-f-butyldiphenylsilylalkenes is an excellent route to p-silyl aldehydes (equation I). A bulky silyl group is essential for this regiocontrol. 

Chiral P-Silyl Aldehydes as Precursors of Chiral P-Hydroxy Acids and Chiral 1 -Diols... 

The one-pot synthesis sequence of metallation, silylation, metallation, and alkylation of allyl-SMP 1 generates almost enantiopure (R)-P-silyl aldehydes 6. These aldehydes 6 are oxidized... 

The copper salt (or copper complex) reacts with Me2PhSi-B(Pin) to deliver the corresponding L-Cu(l)-silane. In parallel, the chiral amine forms the iminium intermediate V with the a,p-unsaturated aldehyde. Next, the catalytic cycles merge and the L-Cu-silane complex stereoselectively reacts with the chiral iminium intermediate V via a possible intermediate W to form a C-Si bond in intermediate X. Subsequent hydrolysis of iminium ion X gives the corresponding P-silyl aldehyde product as weU as regenerate the Cu(I)-silane and the chiral catalyst L37 [115]. 

Hydroformylations of (Z)-silyl olefins such as 422 furnish the P-silyl aldehydes 423 with high regioselectivity if the silyl group is bulky enough (TBDPS) (Scheme 3.81). Unfortunately, no diastereoselection was observed when a stere-ogenic carbinol center was present (entries 5-8 in Table 3.3) [132]. 

Epoxy Silyl Ether MABR P-Siloxy Aldehyde Yield (%)... 

However, formation of this bond through the conjugate addition of a soft sulfur nucleophile to a,P-unsaturated aldehydes is efficiently catalysed using iminium ion catalysis [116], Using diarylprolinol silyl ether 55 the addition of a series of sulfur based nucleophiles to a variety of a,P-unsaturated aldehydes was shown to be effective (73-87% yield 89-97% ee). The products were isolated as their p-hydroxy sulfide derivatives 73 after in situ reduction of the products (Scheme 33). 

Simultaneous publication of the iminium ion catalysed hydrophosphination of a,p-unsaturated aldehydes by Melchiorre and Cordova showed diarylprolinol silyl ether 55 was effective in the conjugate addition of diphenylphosphine 74 [117, 118], Direct transformation of the products allowed for one-pot methods for the preparation of P-phosphine alcohols 75 (72-85% yield 90-98% ee), P-phosphine oxide acids 76 (65% yield 92% ee) and 3-amino phosphines 77 (71% yield 87% ee) (Scheme 34). These reports represent the first examples of the addition of P-centred nucleophiles and the resulting highly functionalised products may well have further use in asymmetric catalysis. 

MacMillan reported a short and effective synthesis of spiculisporic acid which elegantly exemplified his Mukaiyama-Michael addition of silyloxyfurans to a,P-unsatu-rated aldehydes [88], Robichaud and Tremblay augmented this in a formal synthesis of compactin [224], Within this report it was shown that low enantioselectivities were obtained in the conjugate addition to aCTolein. Use of p-silyl acrolein 177 circumvented this and gave butenohde 178 in 95% yield and 82% ee. Conversion of adduct 178 to the decaUn (179) in eight steps resulted in a formal synthesis (Scheme 71). 

As an extension of this highly enantioselective Michael addition of silyl nitronates with a, p-unsaturated aldehydes, the reactions with cyclic a,p-unsaturated ketones as a Michael acceptor were also tested (Scheme 9.15). Cyclohexenone and cyclohepte-none were employed as a useful Michael acceptor with various silyl nitronates in the presence of catalyst (R,R)-6c, and gave the corresponding enol silyl ethers 28 with excellent stereoselectivities [30]. 

Thiosalicylaldehydes afford chiral thiochromene-3-carbaldehydes 39 on reaction with a,P-unsaturated aldehydes catalysed by a chiral pyrrolidine silyl ether. Initial activation of the enal triggers sequential Michael and aldol reactions and dehydration completes the highly enantioselective synthesis <06JA10354, 06TL8547>. In a similar manner, cyclic enones afford cycloalkanone[ ]thiochromenes <06TL8679>. 

High 1,3- and 1,4-asymmetric induction is possible in addition reactions to chiral P-alkoxy aldehydes. The reaction with allylsilanes catalyzed by TiC shows high diastcr-eofacial selectivity (equation II). Essentially only one. vv -adduct of two possible dias-tereomers is obtained in reactions with silyl enol ethers (equation III). 

Such p-silyl enolate intermediates also react with aldehydes with high diastereoselectivity with respect to both new chiral centers being created, the relative stereochemistry in the aldol reaction being dependent upon the original geometry of the enolate double bond (Scheme 13). This aldol reaction has... 

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. 

Conjugate addition of 1 to a,p-unsaturated esters, ketones, or aldehydes followed by reaction with an alkyl iodide (or bromide) proceeds by stereoselective attack anti to the silyl group, apparently because of electronic effects. Protonation of the p-silyl enolate of 5 proceeds in the same sense to give the opposite diaster-eomer (Chart I). 

Rhodium cationic and zwitteiionic complexes proved to be superior catalysts for the hydroformylation of vinylsilanes, producing either a- or ff-silyl aldehydes depending on the reaction conditions [162], On the other hand, carbonylation of vinylsilanes in the reaction related to hydrocarboxylation and hydroesterification afforded P- and a-silyl esters in high yields (eq. (14) [163]). 

A high level of 1,3-asymmetric induction was achieved by the assistance of a Lewis acid. Complexa-tion of a P-alkoxy aldehyde with TiCU followed by addition of Bu2Zn, allylsilane or silyl enol ethers at -78 C results in chelation-controlled products in >85% selectivities (Scheme 12). > Even a considerable level of 1,4-asymmetric induction is observed with the MeiZn-TiCU system (equation 33). ... 

Metallation of the bis(silyl) derivadve (166) generates a symmetrical carbanion (167), which also reacts stereoselectively with aldehydes to produce anti p-silyl alcohol derivatives (168), which undergo base-catalyzed elimination reactions to generate the (,E)I(Z) diene system (169 Scheme 74). ... 

Normally stable sulfonyl ylide 46 reacts with benzaldehyde derivatives under the influence of microwave irradiation to produce a,fl-unsaturated sulfones. P-Silylated olefins are obtained from the corresponding aldehydes or ketones and [Ph3PCH3]I."... 

In turn, a,p-unsaturated aldehydes or ketones (326, 329) can be enoHzed by Huenig s base before being trapped by support-bound silyl chlorides. The resulting support link is very labile and a ketone is released from the support upon treatment with TFA [312]. Some examples of these Diels-Alder reactions can be seen in Scheme 69. 

Corey, Enders and Bock were among the first to describe the utility of lithium dimethylhydrazone anions for crossed aldol reactions. In the reaction shown in equation (14), an azaallyllithium reagent derived from an aldehyde dimethylhydrazone was first silylated with trimethylsilyl chloride to yield a silyl aldehyde dimethylhydrazone. Subsequent lithiation using lithium diethylamide at -20 C for 1 h generated the silylated azaallyllithium reagent (29). Subsequent addition of one equivalent of an aldehyde or ketone at -78 C and warming to -20 C then yielded the product a,p-unsaturated aldehyde dimethylhydrazone in yields of 85-95%. Hydrolysis produced the unsaturated aldehyde in 75% overall yield. 

Additions of enol silanes to p-alkoxy aldehyde (85 equation 25) are reported in Table 17. High selectivity (chelation control) was obtained with TiCU via complex (78 entries 1, 2). The same preference for isomers (86) and (87) was obtained with BF3 via complex (80), which simulates chelation. The influence of chelation on simple stereoselection is also evident in the reactions of achiral aldehydes (90) and (92) with silyl enol ethers (Z)-(91) and ( )-(93), which are usually moderately anti selective in their reactions with aldehydes incapable of chelation high syn selectivity was obtained irrespective of the enol ether geometry (equations 26 and 27). - ... 

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