Ethers alcohol protecting group

Butyl ethers can be prepared from a variety of alcohols, including allylic alcohols. The ethers are stable to most reagents except strong acids. The /-butyl ether is probably one of the more underused alcohol protective groups, considering its stability, ease and efficiency of introduction, and ease of cleavage. 

Silyl Ethers as Protective Groups for Alcohols. Oxidative Deprotection and Stability Under Alcohol Oxidation Conditions, Muzart. J. Synthesis. 1993, 11... 

C tert-Butyl Ethers by Alktlation of alcohols. Protecting Groups... 

Like Still s reagent, tributyl[(methoxymethoxy)methyl)etannane incorporates an alcohol protective group that can be conveniently unmasked under mild acidic conditions. However, an advantageous feature of this MOM ether derivative is that, in contrast to Still s reagent, it is achiral. In many applications the introduction of an additional chiral center into synthetic intermediates is undesirable because of the complications associated with the manipulation, analysis, and purification of diastereomeric mixtures. 

The methylthiomethyl (MTM) group is a related alcohol-protecting group. There are several methods for introducing the MTM group. Alkylation of an alcoholate by methylthiomethyl chloride is efficient if catalyzed by iodide ion.9 Alcohols are also converted to MTM ethers by reaction with dimethyl sulfoxide in the presence of acetic acid and acetic anhydride10 or with benzoyl peroxide and dimethyl sulfide.11 The latter two methods involve the generation of the methylthiomethylium ion by ionization of an acyloxysulfonium ion (Pummerer reaction). 

Notes This is often used as a protecting group for alcohols, where it is observed that primary alcohols form more readily than secondary hydroxy groups, which in turn are more reactive than tertiary alcohols. As with most benzylic ethers, this protecting group can be removed by hydrogenolysis over Pd or by metal-ammonia reduction.1 Examples ... 

Brook, M.A., Balduzzi, S., Mohamed, M. and Gottardo, C. (1999) The photolytic and hydrolytic lability of sisyl (Si(SiMe3)3) ethers, an alcohol protecting group. Tetrahedron, 55, 10027—10040. 

Zert-Butyldiphenylsilyl (TBDPS) protection is one of the most popular alcohol protective groups. It is more stable than other silyl ethers under acidic conditions. 

The initial research efforts focused on the preparation of the precursor, the omegar-r-butyldimethylsilyloxyalkyl halide, from the corresponding haloalcohol and /-butyldimethylsilyl chloride. The t-butyldimethylsilyl moiety was originally introduced as an alcohol protecting group by Corey. In this procedure, 1.2 equivalents of t-butyldimethylsilyl chloride and 2.5 equivalents of imidazole, as the acid acceptor, were utilized. The solvent employed was N,N-dimethylformamide. These reaction conditions afforded the desired product in excellent yield. However, the cost of the excess reagents, their subsequent removal, the utilization of an expensive, hydroscopic solvent, and an aqueous workup were not very practical from a commercial perspective. Since its inception in 1972, a variety of other procedures have been described for the preparation of t-butyldimethylsilyl ethers. These procedures typically require solvents that are expensive, difficult to recycle, or environmentally unfriendly. Furthermore, traces of some of these solvents, such as methylene chloride, in the precursor would be incompatible with lithium metal in the subsequent lithiation step. 

---