Sensitive protecting groups

TsOH, DMF, Mc2C(OMe)2, 24 h. This method has become one of the most popular methods for the preparation of acetonides. It generally gives high yields and is compatible with acid-sensitive protective groups such as the TBDMS group. 

These base-sensitive protective groups were introduced from the chloroformate or azidoformate. They are more sensitive to base than is the Fmoc group. Cleavage times with 0.2 mL of piperidine to 0.1 mmole of urethane in 5 mL of CHCL at It occur as follows Climoc, <10 min Bimoc, <14 h Fmoc, 18 h. °... 

Soares AMS, Costa SPG, Gonfalves MST (2010) 2-Oxo-2//-benzol/i bcnzopyran as a new light sensitive protecting group for neurotransmitter amino acids. Amino Acids, doi 10.1007/ s00726-009-0383-z... 

FIGURE 2.14 Peptide-bond formation from chlorides of A-alkoxycarbonylamino acids. N-9-Fluorenylmethoxycarbonylamino-acid chlorides.41 The base is NaHCO, Na2C03, or a tertiary amine. The reaction is carried out in a one- or two-phase system. The latter is used to try to suppress formation of the 2-alkoxy-5(4//)-oxazolone that is generated by the action of the base on the acid chloride. The method is applicable primarily to Fmoc-amino-acid derivatives that do not have acid-sensitive protecting groups on their side chains. 

Ester formation is the main and most efficient means of protecting carboxylic acids. The protection of a carboxylic acid as an amide is infrequent, as its removal normally requires drastic conditions. Most of the work concerned with the use of light-sensitive protecting-groups for carboxylic acids is in peptide synthesis. Carboxylic acids are protected as photosensitive esters, including ester linkages to polymer supports or as (difficult to prepare) photosensitive amides. Many of these techniques may be readily applied to sugar acids. 

The photosolvolysis of 3-nitrophenyl esters is the first example of the use of a light-sensitive protecting-group that has appeared in the literature. 3-Nitrophenyl and the more-sensitive 3,5-dinitrophenyl phosphoric esters undergo photohydrolysis (mercury lamp) to a phosphoric derivative and the corresponding nitrophenol an example of a synthetic application is presented in Scheme 30. 

Compound 2 is a nonacidic fluorinating agent that has found application for the fluorination of sugars with acid-sensitive protection groups.42,43... 

The development of light-sensitive protective groups began in the early 1960s [129-131] and led to the identification of several functionalities that could be selectively cleaved under UV irradiation (for a review, see [132]). Some of these protective groups, such as 2-nitrobenzyl esters, carbonates, or carbamates [131,133-135], benzoin [136-139], and other phenacyl esters [140] were also found to be useful as photocleavable linkers. 

The peptide-bond-forming steps are repeated as many times as needed to build up the desired sequence. Ultimately, the peptide chain is removed from the resin, usually with HBr in anhydrous trifluoroethanoic acid, CF3C02H, or with anhydrous HF. This treatment also removes the other acid-sensitive protecting groups. 

Only very acid-sensitive protecting groups are hydrolyzed under the conditions of the Jones oxidation. When free alcohols result from the hydrolysis of very acid-sensitive protecting groups, they are in situ oxidized to ketones or carboxylic acids. 

The Parikh-Doering oxidation provides a very high regioselectivity for the oxidation of alcohols. Oxidation-sensitive functionalities, like indoles,99a,c sulfides,109 and selenides 110 as well as oxidation-sensitive protecting groups, like dithioacetals,111 PMB104 and dimethoxybenzyl ethers109b, do not react. 

In spite of the slightly acidic nature of IBX,5 no interference is observed from very acid-sensitive protecting groups, such as TMS ethers105 or THP ethers.99a... 

Oxidation-sensitive protecting groups, such as PMB ethers,106 resist the action of IBX under the experimental conditions used for the oxidation of alcohols. 

As Fetizon s oxidation is carried out under neutral conditions, acid-and base-sensitive protecting groups resist its action. The oxidation-sensitive p-methoxybenzyl (PMB) protecting group resists the action of Fetizon s reagent.12... 

DDQ oxidations are made under almost neutral conditions. Therefore, both base- and acid-sensitive protecting groups and functionalities need not be altered in the presence of DDQ. During DDQ oxidations, the corresponding hydroquinone is generated, which possesses a slight acidity that normally does not cause any interference. However, some acid-catalyzed isomerization of an acetal was observed on a prolonged oxidation with DDQ.108... 

Tosyl chloride 361 can be applied similarly (entry 23) [404], Here the best cobalt complex was dependent on the structure of the starting olefin. For terminal alkenes 2 mol% of the (salen)Co complex 357a was preferred. Secondary alkyl chlorides were obtained with complete regioselectivity in 73-94% yield, while the catalyst derived from Co(BF4)2 and /V-salicylidene diphenylglycinate 353 proved to be better for the hydrochlorination of 1,1-disubstituted olefins (entry 22). Tertiary alkyl chlorides 362 were obtained in 67-96% yield. The reaction conditions are mild so that acid- and base-sensitive protecting groups are compatible. 

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