Chemoselective alcohol-protecting group

Clean removal of trityl ether groups from O-isopropylidenated furanoses by using NaHS04-Si02 was previously described by Das et al.116 and afforded the corresponding alcohols at room temperature. The chemoselective deprotection was accomplished in yields above 91% within 2-2.5 h, leaving other protective-groups intact (Scheme 27). 

The sulfone moiety was reductively removed and the TBS ether was cleaved chemoselectively in the presence of a TPS ether to afford a primary alcohol (Scheme 13). The alcohol was transformed into the corresponding bromide that served as alkylating agent for the deprotonated ethyl 2-(di-ethylphosphono)propionate. Bromination and phosphonate alkylation were performed in a one-pot procedure [33]. The TPS protecting group was removed and the alcohol was then oxidized to afford the aldehyde 68 [42]. An intramolecular HWE reaction under Masamune-Roush conditions provided a macrocycle as a mixture of double bond isomers [43]. The ElZ isomers were separated after the reduction of the a, -unsaturated ester to the allylic alcohol 84. Deprotection of the tertiary alcohol and protection of the prima-... 

The parent 2(3/i/)-oxazolone moiety functions as a bifunctional leaving group when carboxyl groups are activated for acylations and condensations, similar to other five- and six-membered heterocycles such as imidazole, triazole, and 2-pyridinethiol. The excellent leaving ability of a 2(3//)-oxazolone moiety has led to the development of versatile reagents. Thus, 3-acyl- and 3-alkoxycarbonyl-2(3//)-oxazolones serve as ready-to-use -type agents for the regioselective and chemoselective N-protection of amino alcohols, amino phenols and polyamines. 

Protecting groups have been mentioned occasionally in previous chapters in this chapter the ideas behind their use are systematically presented and a collection of protecting groups suitable for a range of functional groups is tabulated. Protection allows us to overcome simple problems of chemoselectivity. It is easy to reduce the keto-ester I to the alcohol 2 with a nucleophilic reagent such as NaBHU that attacks only the more electrophilic ketone. 

N- and O-benzyl groups are among the most useful protective groups in synthetic organic chemistry and the method of choice for their removal is catalytic hydrogenolysis [37]. Recently the most important reaction conditions were identified [38] Usually 5-20% Pd/C the best solvents are alcoholic solvents or acetic acid acids promote debenzylation, whereas amines can both promote and hinder hydrogenolysis. Chemoselectivity can mainly be influenced by modifying the classical Pd/C catalysts. 

The most important protecting groups for alcohols are ethers and mixed acetals. The proper choice of the protecting group is crucial if chemoselectivity is desired. 

Deprotection of Amines and Ethers. Catalytic NIS in MeOH has been shown to be a chemoselective catalyst for the deprotection of alkyl TBDMS ethers selectively over phenyl TBDMS ethers. A method for the deprotection of dibenzylamino groups selectively to either the monobenzylamine or directly to the amine has also been developed. In the case of carbohydrates containing multiple protecting groups, as in eq 24, NIS in the presence of TEMPO provided the monobenzylamine in excellent yield. Excess NIS under slightly modified conditions could be used to afford the amine in modest yield. The process is not restricted to carbohydrates but does require the presence of a nearby alcohol or alkoxy substituent to work, as for the amine in eq 25. It should also be noted that the benzyloxy group in this example remained intact. 

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