Alcohols protection-deprotection

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

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-... 

Finally, achiral phosphonium salts have been applied as Lewis acid catalysts in some other reactions. The examples will be listed here but not discussed in more detail. Phosphonium salts have been used as catalysts for the A,A-dimethylation of primary aromatic amines with methyl alkyl carbonates giving the products in good yields [123]. In addition acetonyltriphenylphosphonium bromide has been found to be a catalyst for the cyclotrimerization of aldehydes [124] and for the protection/ deprotection of alcohols with alkyl vinyl ethers [125, 126]. Since the pK of the salt is 6.6 [127-130], the authors proposed that, next to the activation of the phosphonium center, a Brpnsted acid catalyzed pathway is possible. 

Functionalizing C-5 of 2,4-oxazolidinediones is generally accomplished by alkylation or Knovenagel reaction (Schemes 6.66-6.69). For example, treating 251 (R = H, Ri = Me) with 3 equiv of LDA followed by two equivalents of a protected bromo alcohol and deprotection with dilute hydrochloric acid gave the... 

This enantioselective preparation of allylic alcohols has been applied to the synthesis of the side chain of prostaglandins . The addition to functionalized aldehydes, such as 483, allows the synthesis of C2-symmetrical 1,4-diols, such as 484, with excellent diastereoselectivity and enantioselectivity . An extension of this method allows the synthesis of C3-symmetrical dioF . Aldol-type products result from the catalytic enantioselective addition of functionalized dialkylzincs to 3-TIPSO-substituted aldehydes, such as 485, followed by a protection-deprotection and oxidation sequence affording 486 in 70% yield and 91% ee (Scheme 118) . The addition to a-alkoxyaldehydes provides a... 

Notes This alcohol protecting is easily attached and readily removed by Lewis acids such as zinc bromide and titanium tetrachloride. Phenols can be protected (reaction of the sodium salt with MEMC1) and deprotected with TFA. More easily removed than the MOM group. 

The sensitivity of some alcohol protecting groups to the acidic conditions of Jones oxidation allow the operation of one-pot reactions, in which deprotection of alcohols is followed by in situ oxidation to ketones. Some interesting synthetic applications of this principle are listed bellow ... 

Dicarboxypyridinium chlorochromate (2,6-DCPCC)392 possesses an acidic character that allows the in situ deprotection and oxidation of alcohols, protected as tetrahydropyranyl and trimethylsilyl ethers. 2,2 -Bipyridinium chlorochromate (BPCC)393 contains a ligand that complexes efficiently with the reduced chromium species, generated during the oxidation of alcohols, allowing for a substantial simplification of the work-ups. For this reason, it enjoys a popularity among chlorochromates surpassed by only PCC. 

Nafion-H has been shown to be effective in a variety of protection-deprotection reactions including (9-trialkylsilylation of alcohols, phenols, and carboxylic acids, as well as the preparation and methanolysis of tetrahydropyranyl (THP) ethers.672 However, when compared, for example, with HBF4-silica or Nafion nanocomposites,... 

Transesterifications. Use of titanates for transesterification has been described in the patent literature for some time and has now been recommended for research purposes by Seebach et al. In the presence of catalytic amounts of a tetraalkyl titanate, esters undergo transesterification with the alcohol solvent. Acyl-protected alcohols are deprotected in the process, but a wide variety of functional groups are unaffected, such as C=0, OH, OSi(CH3)2C(CH3)3, acetonide, lactam. One advantage is that completely dry alcohols are not required. 

Base-catalyzed condensation of cyanothioacetamide with ethyl / -(ethoxy-methylene)acetoacetate furnished (127), which was quantitatively 5-methylated to yield (128). Ester reduction and alcohol protection generated (129), which was oxidized to the corresponding sulphone with mcpba. Guanidine cycli-zation to (130) and deprotection then afforded (131), identical in all respects with material prepared by the previously described ring-transformation reaction. 

The combined catalyst of Sc(OTf)3 and distannoxane gives the one-treatment process. Namely, in the reaction of ro-hydroxy alkanal, one-pot aldehyde allylation and acetylation of a primary alcohol are achieved without protection/ deprotection procedures. The unwanted acetylation of a secondary homoallyl alcohol by Sc(OTf)3 is suppressed by hybridization with distannoxane (Equation (46)).151... 

The second part deals with the grafting of amines or alcohols with protection/ deprotection methods and the third one presents the grafting of alkenes bearing free hydroxyl or acid functions. Finally, a table summarizing all experiments is also presented. 

Alcohol protection. Primary and secondary hydroxyl groups are esterified by 1 in the presence of pyridine (71-92% yield). The usual selectivity for acylation of primary versus secondary hydroxyl functions obtains. The resulting 2-di-bromomethylbenzoates 2 are deprotected under neutral conditions by silver perchlorate mediated hydrolysis to 2-formylbenzoate esters 3 (2,6-lutidine or 2,4,6-collidine is added to maintain a virtually neutral reaction medium). Addition of morpholine then leads to rapid dcacylation with release of the alcohol in high yield... 

Epoxidadon of (Z)-vinyl sulfone, which is available from the Peterson olefination of (S)-O-pentylideneglyceraldehyde and phenyl trimethylsilylmethyl sulfone in three steps (40% overall yield), with f-BuOOH/t-BuOK in THE gives epoxy sulfone (eq 2). Deprotection of the ketal group and recrystallization affords an optically pure epoxy diol, which is then treated with sodium periodate followed by sodium borohydride to give an alcohol. Protection of the resulting alcohol as its silyl ether yields l/ ,25)-l-phenylsulfonyl-2- [ fcrf-butyldiphenyl)silyl]oxymethyl oxirane ). Its enantiomer is available in the same manner starting from / )-isopropylideneglyceraldehyde. ... 

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