Selective protection of primary alcohols

Selective protection of primary alcohols. Selective protection of primary hydroxyl groups of carbohydrates is possible by reaction of this chlorosilane and polyvinylpyridine in CH2CI, or THF in the presence of HMPT. Amberlite A-26 in the F form is recommended for desilylation. 

Selective protection of primary alcohols. Two recent syntheses of warburganal (1) required selective monoprotection of a primary diol. In both cases success was... 

Olefin 104 was then subjected to a Sharpless asymmetric dihydroxylation which proceeded with moderate diastereoselectivity, leading to an inseparable mixture of the diols 105a and 105b (d.r. 71 29) (Scheme 29). Fortunately, when the mixture of 105a and 105b was submitted to the following three-step sequence, for example, selective protection of primary alcohol, mesylation, and then cyclization, the major isomer 106a could be isolated in pure form. Two further deprotection steps were necessary to provide the hyacinthacine Bi 3 in 45.5% overall yield and 13 steps from lactam 101. In paraUel,... 

Protecting groups, including very labile ones, withstand the action of Collins reagent. The very labile primary TMS ethers are transformed into the corresponding aldehydes.103 As secondary and tertiary TMS ethers resist the action of Collins reagent, a protocol involving per-silylation followed by Collins oxidation allows the selective oxidation of primary alcohols in the presence of secondary ones.104... 

Selective Oxidations of Secondary Alcohols via Protection of Primary Alcohols... 

UButylmethoxyphenylsilyl ethers (r-BMPSi ethers). In DMF in the presence of NfCjHj), this bromosilane reacts with primary, secondary, and tertiary alcohols to form silyl ethers in good yield, and also with some enolizable ketones to form enol silyl acetals. Selective silylation of primary alcohols is possible by use of CHjClj as solvent. The hydrolytic stability of these ethers is intermediate between that of t-butyldimethylsilyl ethers and that of t-butyidiphenylsilyl ethers. The most useful feature of this new protecting group is the selective cleavage by fluoride ion in the presence of other silyl ethers. 

Protection of primary alcohols. This trityl bromide in the presence of AgNO, m DMF reacts selectively with the primary hydroxyl group of carbohydrates and nucleosides. The CPTr ether group is stable to aqueous pyridine and 80% acetic acid, but is selectively cleaved by hydrazine in pyridine-acetic acid. This protecting group is useful in the synthesis of oligoribonucleotides. 

This reagent selectively protects a primary alcohol in the presence of a secondary alcohol. ... 

Trimethylsilylation. Primary, allylic, benzylic secondary, hindered secondary, tertiary alcohols, and phenols are efficiently converted into the corresponding trimethylsilyl ethers when treated with neat TMSA and, when necessary, in the presence of a catalytic amount of tetrabutylammonium bromide (TBABr) in over 91% yields. This reaction can be also used to achieve selective protection of primary and secondary alcohols in the presence of tertiary ones. 

Protection of Alcohols.—The acylation of alcohols by polymers (48) of 3-acyl-2-oxazolone has been reported using fluoride ion as the catalyst, selective acylation of primary alcohols in the presence of secondary alcohols has been observed. Transesterification, mediated by titanium alkoxides, has been investigated and shown to be a selective, mild, and inexpensive technique for example, for the deacylation of alcohols. ... 

Since a secondary alcohol is oxidized in preference to a primary alcohol by Ph3C BF,i , this reaction results in selective protection of a primary alcohol. 

The trimethoxy derivative is too labile for most applications, but the mono and diderivatives have been used extensively in the preparation of oligonucleotides and oligonucleosides. The monomethoxy derivative has been used for the selective protection of a primary allylic alcohol over a secondary allylic alcohol (MMTr, Pyr, -10°). ... 

The reactivity of various steroid alcohols decreases in the order primary > secondary (equatorial) > secondary (axial) > tertiary. The only systematic investigation relating to the selective protection of steroidal hydroxyl functions has been carried out with the cathylate (ethyl carbonate) group. Since only equatorial hydroxyl groups form cathylates this ester has been used as a diagnostic tool to elucidate the configuration of secondary alcohols. 

HCOOH, 60°, 1 h, 93% yield. This method can be used to protect selectively only the primary alcohol of a pyranoside. ... 

Selective protection of the primary alcohol gave 138 (P=TBDMS), which was then esterified with ( )-3-hexenoic acid to produce the key intermediate 139 for cyclization. Ireland ester-enolate Claisen rearrangement and hydrolysis produced a protected hydroxyacid, which, after reduction of the acid and deprotection of the alcohol, yielded meso diol 128 more quickly and efficiently than in the previous synthesis. The meso diol was then converted to the racemate of the lactol pheromone 130 as previously described. 

The preparation of 1 started with the addition of lithiated 4 to the enantiomcrically-pure epoxide 5, which was prepared from the racemate using the Jacobsen protocol. Reduction followed by selective protection of the primary alcohol gave the monosilyl ether, which was further protected with MOM chloride to give 7. Pd-mediated oxidation to the methyl ketone followed by condensation with the Horner-Emmons reagent gave the unsaturated ester 8 as an inconsequential mixture of geometric isomers. Oxidation then set the stage for the crucial cyclization. 

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