TBDPS protecting group

Synthesis of Nitriles from Amides. Aryl carboxamides and other electron-rich amides could be converted to the corresponding nitriles in good yields by treatment with Ag20 and EtI in benzene at reflux (eq 23). This technique is typically compatible with acid-labile moieties or protecting groups (TBDPS, isopropy-lidene). Although this technique was found to be very efficient for the transformation of electron-rich carboxamides, simple aliphatic amides are rarely suitable for this purpose. 

Rozner published a synthesis of 3, 5 -C-branched nucleosides and used the addition of protected propargyl alcohol to an a-siloxyaldehyde to control absolute stereochemistry at C2 [25], He noted that use of the bulky trityl and TBDPS protecting groups were essential for the reaction. In this respect the corresponding product could be isolated in only low yield (>10%) when changing to MOM-pro-tected propargyl alcohol and TBS-protected oxyaldehyde (Eq. 20). 

The synthetic potential of silyl ethers as protecting groups for hydroxyls is based on the fact that they can be easily introduced and cleaved under mild conditions and their relative stability can be tuned by varying the substituents on silicon. In carbohydrate chemistry, the tert-butyl-dimethylsilyl (TBDMS), terl-butyldiphenylsilyl (TBDPS) and triethyl-silyl (TES) ethers are the most often applied silicon-based protecting groups (Scheme 2.9).23... 

FIGURE 10.1 Some monosaccharide building blocks used in the assembly of (a) HA, (b) CS, and (c) heparin/HS showing the array of protecting groups. All, allyl Bn, benzyl Bz, benzoyl Fmoc, 9-fluorenylmethoxycarbonyl Lev, levulinyl NAP, 2-naphthylmethyl PBB, p-bromobenzyl Phth, phthaloyl PMB, / -methoxybenzyl PMP, p-methoxyphenyl TBDPS, ferf-butyldiphenylsilyl TBS, ferf-butyldimethylsilyl TCA, trichloroacetyl TDS, dimethylthexylsilyl Tol, 4-tolyl. 

However, a protecting group is useful only if it can be introduced and removed in high yield without affecting the rest of the molecule and if it can survive a wide range of conditions in the course of the synthesis. The extreme steric bulk of the f-butyldiphenylsilyl (TBDPS) group makes it useful for selective protection of unhindered primary alcohols in the presence of secondary alcohols. 

The most stable common silyl protecting group (triisopropylsilyl or TIPS) has three branched alkyl substituents to protect the central silicon from attack by nucleophiles which would lead to cleavage. All three hindered silyl groups (TBDMS, TBDPS, and TIPS) have excellent stability but can still be removed with fluoride. 

The TES group is the most labile of the common silyl protecting groups, apart from TMS, and can usually be removed in the presence of TBS, triisopropylsilyl (TIPS) and rerf-butyldiphenylsijyl (TBDPS) groups. Selective deprotection of a TES ether using aqueous trifluoroaoetic acid left two TBS ethers and two TIPS ethers intact in the Merck synthesis of the immunosuppressant FK-506 [Scheme 4.19].22 Weaker acids such as H2O-HOAC-THF (3 5 11) at room temperature,33 HF pyridine24 and pyridinium p-toluenesulfonate [Scheme 4.2Q]23 can accomplish similar transformations. 

We invoke 7c-stacking of the alkene with a phenyl moiety on the silicon protecting group (since this high degree of selectivity was only observed for TBDPS and not with TBS), in the precursor to explain this remarkable selectivity (Figure 1). Lewis acid induced reduction of the epoxide with sodium cyanoborohydride led regioselectively to the 1,3-diol (11) the hydride attacks the more substituted position via an S 2 mechanism. ... 

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