TBDMS protection

The tert-butyldimethylsilyl (TBDMS) protection of 50 gave a silyl ether... 

The synthesis in Scheme 13.47 was also based on use of a chiral auxiliary and provided the TBDMS-protected derivative of P-D lactone in the course of synthesis of the macrolide portion of the antibiotic 10-deoxymethymycin. The relative stereochemistry at C(2)-C(3) was obtained by addition of the dibutylboron enolate of an A-propanoyl oxazolidinone. The addition occurs with syn anti-Felkin stereochemistry. 

As shown in Figure 4.2, protection of the hydroxy group also played an important role in the yield of the coupling. For instance, coupling of iodoaniline 28 with 40d (Rj = TBDMS) gave 41d (R, = TBDMS, 77%) as compared to 56% yield with 36 (Rj = H). The C, O-bis-TBDMS-protected butynol 40c provided an 18% higher yield than the C-mono-TBDMS butynol 40e, 78% and 60%, respectively. 

Analogous derivative 338, lacking the TBDMS protection in the polyol side chain, when treated with DMAD in acetonitrile provides a mixture of unstable products, which after acetylation yields products 339-341. On the other hand, the same compound treated with DMAD in the presence of PTSA in boiling benzene gives a mixture of isomeric products 342 and 343 in a 4 1 ratio (Scheme 50) <2002T1199>. 

The same research group also showed that the r-butyldimethylsilyl (TBDMS)-protected 4-substitued 4,5-dihydro-l,2,4-oxadiazol-5-one 192 afforded the alcohol 193 on treatment with ethanolic HC1. Mesylation and treatment of the intermediate with sodium iodide gave the iodofluoroalkenyl-substituted 4,5-dihydro-l,2,4-oxadiazol-5-one 194 (Scheme 26) <2004T10907>. 

Other than classical H and 13C NMR spectra which have been reported for these compounds, no detailed studies have appeared in the literature. One X-ray crystal analysis of the TBDMS-protected alcohol analog of acid 368 has been carried out for structural proof. 

Primary and secondary alcohols were selectively oxidized to the corresponding aldehydes and ketones, respectively, by using Oxone in the presence of a catalytic amount of TEMPO (2,2,6,6-tetramethyl-l-oxypiperidinyl). This reaction has been proved to be a highly selective and efficient oxidation reaction, where a catalytic amount of TEMPO plays an important role. Thus TBDMS protected benzyl alcohols were oxidized selectively to benzaldehydes in 81% yield, without affecting the TBDMS moiety. 

Alai/r[(Z)-CF=C]-Pro containing N, 0-diacylhydroxamic acid type protease inhibitors have been prepared as shown in Scheme 18 [63,64], The synthesis is based upon the use of fert-butyl-a-fluoro-trimethylsilylacetate in a variation of the Peterson olefination procedure to construct the necessary functionalized fluoroolefin. Treatment of 51 with 4 equiv. of lithium diisopropylamide (LDA) and 6equiv. of chlorotri-methylsilane at 78°C formed 52 in 71% yield. The key step is the Peterson olefination reaction of the TBDMS-protected 2-(hydroxymethyl)cyclopentanone (53) with tert-butyl-a-fluoro-a-trimethylsilylacetate (52). The fluoroolefin product was obtained as a mixture of (Z) (E) isomers (54). Separation of the double-bond isomers by column chromatography provided (Z) isomer (54) in 43% yield. Further... 

The problem of the rather moderate yields of ene-adducts 177 was solved when the more robust TBDMS protecting group was employed. Using reagent 180 instead of 171, a smooth ene-reaction occurred, affording the silyl enol ethers 181 in improved yields (Scheme 13.63). 

The authors elaborated an innovative synthesis of the Taxane core based on an intramolecular Diels-Alder reaction as the key step. The TBDMS-protected cylohexenone-derived alcohol was converted into the corresponding nitrile intermediate in five steps by known synthetic manipulations (Scheme 43), mainly based on transmetallation protocols. The diene handle for the Diels-Alder reaction was then introduced following a simple but highly efficient four-step procedure. The dienophile for the cycloaddition, the terminal acetylene moiety, was incorporated via lithiation chemistry to furnish the substrate for the intramolecular Diels-Alder cyclization (Scheme 43). 

The reactions of titanated 133 and 134 with (R) and (5) TBDMS-protected lactaldehyde [MeCH(OTBDMS)CHO] are also highly diastereoselective. Very high levels of diastereoselectivity (> 98%) were observed when the facial selectivity of the allylic sulfoximine anion matched that of the chiral aldehyde (the matched case).86,87 In the mismatched cases the diastereoselectivities were less but still... 

In the total synthesis of wailupemycin B, the 1,3-dioxocin 301, upon acid hydrolysis, gave the t-butyldimethylsilyl (TBDMS)-protected dihydro wailupemycin B 302 (Equation 32) <2003AGE4685>. 

Renaud and coworkers have also recently found that related TBDMS-protected B-alkylboronate esters are suitable radical (see Radicals) precursors for conjugate addition to activated olefins such as methyl acrylate (equation 12). Catalyzed hydroborations gave the 1,3-addition products with regioselectivity opposite to those obtained in uncatalyzed reactions. 

The reaction is buffered by NaHCOj to prevent hydrolysis of the TBDMS protecting group by the acid produced in the course of the reaction. 

Monaharan has developed a versatile synthetic route for the synthesis of 2 -0-[(N, iV-dimethylamino)-oxyethyl] modified purine and pyrimidine nucleoside phosphoramidites (63a-d) to be used as antisense oligonucleotide building blocks. In the syntheses of the purine-based analogues, the (iV, N-dimethylamino)-oxyethyl group was introduced via a 2 -allyloxy nucleoside intermediate, while the pyrimidine-based nucleosides were obtained from the TBDMS-protected 2,2 -anhydro-5-methyluridine via ring opening reaction in the presence of borane and ethylene glycol. The aminoxy derivatives were... 

The most systematically investigated acyl anion equivalents have been the IMS ethers of aromatic and heteroaromatic aldehyde cyanohydrins, TBDMS-protected cyanohydrins, - benzoyl-protected cyanohydrins, alkoxycaibonyl-protected cyanohydrins, THP-protected cyanohydrins, ethoxyethyl-protect cyanohydrins, a-(dialkylamino)nitriles, cyanophosphates, diethyl l-(trimethylsiloxy)-phenyimethyl phosphonate and dithioacetals. Deprotonation di these masked acyl anions under the action of strong basie, usually LDA, followed by treatment with a wide varies of electrophiles is of great synthetic value. If the electrophUe is another aldehyde, a-hydroxy ketones or benzoins are formed. More recently, the acyl caibanion equivalents formed by electroreduction of oxazolium salts were found to be useful for the formation of ketones, aldehydes or a-hydroxy ketones (Scheme 4). a-Methoxyvinyl-lithium also can act as an acyl anion equivalent and can be used for the formation of a-hydroxy ketones, a-diketones, ketones, y-diketones and silyl ketones. - - ... 

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