Remote protecting group

Model studies aimed at the synthesis of Calyculin discovered a subtle effect of a remote protecting group on the stereoselectivity of an epoxidation reaction [Scheme 1,46], 79 Treatment of the unprotected diol derivative 46.1 with potassium carbonate, benzonitrile and hydrogen peroxide gave a diastereoisomeric mixture of epoxides 46.2a,b (3 1) in favour of 46.2a. However, the same reaction performed on the terf-butyldiphenylsilyl ether 463 both increased the selectivity (1 18) and inverted its sense now 46 4b was the major product. 

Perhaps the best studied instance of stereospecificity in a glycosylation reaction that can be related to remote protecting groups is the -directing effect of 4,6-alkyl... 

Kalikanda, J., and Li, Z. (2011). Study of the Stereoselectivity of 2-Azido-2-deoxygalactosyl Donors Remote Protecting Group Effects and Temperature Dependency. J. Org. Chem., 76(13), 5207-5218. 

Keywords Directing effect. Electron-withdrawing protecting groups, Glycosylation, Remote participation. Remote protecting group... 

There are some other remote protecting groups which are not the usual electron-withdrawing groups, but they still deactivate glycosyl donors 4,6-benzyUdene acetal, 3,4-cyclohexylidene diacetal (cyclohexane-1,2-diacetal CD A), dispiroketal (dispoke), and butane diacetal (BDA) (Fig. 2). 

Tomono S, Kusumi S, Takahashi D, Toshima K. Armed-disarmed effect of remote protecting groups on the glycosylation reaction of 2,3-dideoxyglycosyl donors. Tetrahedron Lett. 2011 52 2399-2403. 

The 1,4,5-oxadiazepine 63 was transformed into 65 by a four-step reaction sequence (1) cleavage of both /-butoxycarbonyl (BOC) and the lactone, (2) acylation of the remote amino group with 2-(trimethylsilyl)ethyloxy-carbonyl chloride (TeocCl), (3) protection of the alcohol functionality with a silyl group, and (4) ester hydrolysis (Scheme 10) C1998AGE2995, 2001CEJ41>. 

The covalent C-B bonds of organoboronic acids and esters are very inert to ionic and radical reactions, thus allowing functionalization of remote sites other than the B-G bond (Equations (94)-(97)). Bulky diols such as pinacol have been used as the protecting group of B(OH)2 because of their high stability to nucleophiles and water and silica gel in amination of 316,474 hydroboration-amination of 317,475 Wittig reaction of 3 18,476 and oxidation-alkylation of 319.477... 

Alcohols protected as methyl ethers can be retrieved by reaction with tribromo-borane. Activation of the methyl ether by co-ordination of the Lewis acidic tri-bromoborane followed by nucleophilic cleavage of the O—Me bond (with concomitant formation of bromomethane) is typical behaviour. However, the cleavage took a different course with 39.1 [Scheme L39] instead of the O—Me bond being cleaved, the alternative C—O bond cleaved owing to participation of the remote acetoxy group.72 The formation of bromide 39.4 with retention of configuration is circumstantial evidence implicating dioxonium ion intermediate 393. 

The ease of hydrolysis can vary enormously in some cases hydrolysis is so easy that inadvertent loss of the protecting group during chromatography becomes a nuisance (such as acetals of a, f3-unsaturated ketones). On the other hand acetals may be so robust that forcing conditions (mineral acid and heat) are required. For example, substrates that contain a basic amino function — even if it is remote — can be quite resistant to hydrolysis, because protonation first takes place at the more basic amino function,18 The resultant positive charge repels the second Q-protonation required to set in motion the hydrolysis. An acid-catalysed hydrolysis of a basic acetal that required refluxing with 6 M HC1 in acetone for 6-10 h19 is illustrated in Scheme 2,3, Perhaps the mildest conditions employ pyridinium p-toluenesulfonate (PPTS, pKa 5.2) in methanol or aqueous acetone exemplified by the transacetalisation reaction taken from a synthesis of the vacuolar H+-ATPase inhibitor Bafilomycin Ai [Scheme 2.4, 20... 

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