Ethers, triethylsilyl removal

You will note that the oxygen atoms attached to carbons 5 and 12 in 43 reside in proximity to the C-9 ketone carbonyl. Under sufficiently acidic conditions, it is conceivable that removal of the triethylsilyl protecting groups would be attended by a thermodynamically controlled spiroketalization reaction.30 Indeed, after hydro-genolysis of the C-26 benzyl ether in 43, subjection of the organic residue to the action of para-toluenesulfonic acid in a mixture of methylene chloride, ether, and water accomplishes the desired processes outlined above and provides monensin methyl ester. Finally, saponification of the methyl ester with aqueous sodium hydroxide in methanol furnishes the sodium salt of (+)-monensin [(+)-1], Still s elegant synthesis of monensin is now complete.13... 

The completion of the total synthesis only requires a few deprotection steps. It was gratifying to find that the final deprotections could be conducted smoothly and without compromising the newly introduced and potentially labile trisulfide residue. In particular, exposure of intermediate 101 to the action of HF pyridine results in the cleavage of all five triethylsilyl ethers, providing 102 in 90% yield (Scheme 23). Finally, hydrolytic cleavage of the ethylene ketal with aqueous para-toluenesulfonic acid in THF, followed by removal of the FMOC protecting group with diethylamine furnishes calicheamicin y (1) (see Scheme 24). Synthetic calicheami-cin y, produced in this manner, exhibited physical and spectroscopic properties identical to those of an authentic sample. 

Trimethylsilylation has been accomplished with a large number of reagents most of which are commercially available. The cheapest (chlorotrimethylsilane) and the most reactive (trimethylsilyl triflate) rapidly silylate hydroxyl groups in the presence of a suitable base such as pyridine, triethylamine, i-Pr2NEt, imidazole, or DBU but an aqueous workup is required to ensure complete removal of the resultant amine hydrochloride or triflate whence hydrolysis of the nascent TMS ether may occur. In some cases the insoluble salt may be removed by filtration without aqueous workup. A wide range of solvents can be used for the reaction such as dichloromethane, acetonitrile, THF, or DMF. Care must be taken with trimethylsilyl triflate (TMSOTf) since it will convert aldehydes and ketones to the corresponding enol silanes and it will open epoxides in a reaction that has preparative significance [Scheme 4.6]. Similar transformations can be accomplished with tert-butyldimelhylsilyl triflate (TBSOTf) or triethylsilyl triflate (TESOTf). ... 

Condensation of 37 with the JK-ring carboxylic acid 38 under the Yam-aguchi conditions provided ester 39 in high yield (Scheme 4). After selective removal of the triethylsilyl (TES) ether, the resultant alcohol was converted to the allylstannane by the standard procedure. DIBALH reduction of the ester followed by in situ esterification with chloroacetic anhydride/DMAP/pyridine delivered of-chloroacetoxy ether 40. Intramolecular cyclization of 40 with magnesium bromide etherate in acetonitrile afforded the desired product 41 as a single stereoisomer in 82% yield. RCM reaction of 41 using 18 pro-... 

The pseudohexasaccharide 61 was constracted via glycosylation of 55 with tetramannoside 56 in the presence of TMSOTf in 71% yield (Scheme 12.9). Selective removal of the triethylsilyl ether with TBAF uncovered the C6 position of GlcN. 1 H-tetrazole-catalyzed esterification with phosphonic dichloride 59, followed by methanolysis gave the corresponding phosphonic diester. Staudinger reduction... 

Another common method for alcohol protection is reaction with RjSiCl to give a silyl ether. Reaction conditions usually involve RjSiCl, with 4-dimethylaminopyridine (DMAP) as the base. Both the ease of preparation of the silyl ether and the stability of the protected species depend on the nature of the R groups. Trimethylsilyl ethers (ROTMS) are very labile and readily removed with water and dilute acid. The triethylsilyl group (ROTES) is a little more robust but may be removed with fluoride ion (the use of fluoride to cleave silyl groups reflects the strength of the Si-F bond). r-BuMejSiCl (TBDMSCl) reacts selectively with... 

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