Silylative aldehyde

Lueking et al. (1999) arrayed recombinant proteins on NC membranes and screened them with different antibodies. Joos and coworkers (2000) printed down autoantigens onto NC membranes and compared performance relative to silylated (aldehyde) and PLL glass slides. Protein arrays could be stored at room temperature for a month without significant loss in activity. Huang (2001) hand spotted down IgC species and antibodies directed toward various cytokines onto membranes. The properties of various commercial membranes were assessed in terms of absorption, background, and sensitivity levels based upon detection by enhanced chemiluminescence (ECL). 

Seong (2002) compared silylated (aldehyde) and silanated (amine and epoxy) compounds from several commercial sources to the performance of an antigen (IgG) microarray. In addition, the efficiency of phosphate-buffered saline (PBS) (pH 7.4) and carbonate (pH 9.6) printing buffers were compared. While the various slides and surface chemistries showed differences in their binding isotherms, they ultimately reached similar levels of saturation. Silylated (aldehyde) slides showed comparable loading in both buffer systems. Apparently, tethering of antibody to the surface by Schiff s base formation of the surface aldehyde and lysine residues on the protein was applicable over a broad pH. However, carbonate buffer increased binding of proteins on silanated surfaces. 

The a-silyl aldehydes can serve as vinyl cation equivalents in reactions with (irignard or alkyllithium reagents (equation II). 

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. 

A /3-hydroxysilane, like the one shown in Figure 4.38 (top, left), can be prepared stereo-selectively (e.g., via the Cram-selective reduction of an a-silylated ketone according to the reactions in Figure 8.9 or via the Cram-selective addition of organometallic compounds to a-silylated aldehydes similar to what is shown in Table 8.3). These compounds undergo a stereoselective anft -elimination in the presence of add and a stereoselective syn-elimination in the presence of a base (Figure 4.38). Both reactions are referred to as Peterson olefination. The stereochemical flexibility of the Peterson elimination is unmatched by any other HetVHet2 elimination discussed in this section. 

Chiral a-Silyl Aldehydes and Ketones 6 General Procedure27 ... 

The alkylation of SAMP/RAMP hydrazones with heteroelectrophiles leads to enantiomerically pure a-silyl aldehydes and ketones (eq 15), a-sulfenyl aldehydes and ketones (eq 16), and a-hydroxy aldehydes and ketones (eq 17). ... 

Epoxysilanes are converted by strong bases to silyl aldehydes and ketones. ... 

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]). 

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. 

The bis-trimethylsilyl ethers of stereoisomeric 5,7-undecanediol 78 (as well as the free diols) give upon chemical ionization (protonation with QH9) MH+ ions, which show two major processes (reaction 41). One corresponds to a Grob-type fragmentation 05-cleavage) of the ion 79 (formed by loss of Me3SiOH from protonated 78) to yield the silylated aldehyde 80. The second major reaction path involves loss of CH4 from MH+, followed by cyclization of the intermediate 81 (siloxy transfer) to 82 and ft-cleavage (loss of 1-hexene) to generate 8467. This reaction sequence, in which a centrally located structural unit rather than a peripheral one is eliminated, is rarely observed under chemical ionization and deserves further study. 

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 carbon skeleton of 13-bromoretinaldehyde (465) was synthesized by a Wittig reaction of the C15 salt (10) with the silylated aldehyde (462) (Motto et aL, 1980). The resulting mixture of the isomeric acetylenes (463) was de-protected and oxidized with manganese(IV) oxide to give the extremely unstable Cj9 acetylenic aldehyde (464). Finally, (464) was subjected to an addition reaction with hydrogen bromide to give the bromoaldehyde (465), which likewise is very unstable. 

An unusual case of cyclopropanol formation from a hemiacetal of a jS-silyl aldehyde is ascribed to an enhanced reactivity of the silicon, due to an appropriately placed oxyanion generated from the hemiacetal." ... 

Hudrlik and Kulkarni have shown that a-t-butyldimethylsilyl aldehydes serve as vinyl cation equivalents for the synthesis of /3,y-unsaturated ketones (and esters). Addition of lithium enolates to the a-silyl aldehydes is highly erythro-selective, enabling products of either E- or Z-geometry to be obtained (Scheme 58). In a related process, phenylselenoacetaldehyde has been used to transform ketones into the corresponding a-vinylketones (Scheme 59) phenyl-selenoacetone enables a- isopropenylation of ketones in an analogous fashion. ... 

Kulkarni have now reported a potentially general method for the preparation of a-t-butyldimethylsilyl aldehydes by hydrolysis of the a-silyl imines (Scheme 34). These silyl aldehydes serve as stereoselective vinyl cation... 

Synthesis of Siloxybutylated Aldehydes and Ketones. During the course of their investigations on the enantioselective synthesis of a-silylated aldehydes and ketones (see below), Enders et al. observed that lithiated S AMP-/RAMP- or S ADP-hydrazones reacted with the solvent tetrahydrofuran at —78 °C in the presence of various trialkylsilyl trifluoromethanesulfonates, such as TDSOTf, to give high yields of a-siloxybutylated hydrazones (eq 17). The hydrazones were oxidatively cleaved by ozone at —78 °C to afford a-trialkylsiloxybutylated aldehydes and ketones in excellent yields and enantiomeric purities (>95% ee, 81%). 

The carbonyl compound can also contain additional functionality. Thus, treatment of an a,fi- poxy ketone with excess lithium reagent (1) provides the allyl alcohol (2) (eq 2). The use of an a-phenyl selenoaldehyde as electrophile allows either an allyl selenide or a /3-silyl aldehyde to be obtained, depending upon the reaction conditions used with the hydroxysilane (eq 3). With a,/8-unsaturated ketones, the lithium reagent (1) adds in the 1,2-sense the Grignard analog can provide 1,4-addition. The cuprate derived from (1) undergoes the expected reactions for this class of compounds, such as 1,4-addition. ... 

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]. 

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