Protective groups assisted-removal

Three selective methods to remove protective groups are receiving much attention assisted, electrolytic, and photolytic removal. Four examples illustrate assisted removal of a protective group. A stable allyl group can be converted to a labile vinyl ether group (eq. 4) a /3-haloethoxy (eq. 5) or a /3-silylethoxy (eq. 6) derivative is cleaved by attack at the /3-substituent and a stable o-nitro-phenyl derivative can be reduced to the o-amino compound, which undergoes cleavage by nucleophilic displacement (eq. 7) ° ... 

The design of new protective groups that are cleaved by assisted removal is a challenging and rewarding undertaking. 

The SEM ester was used to protect a carboxyl group where DCC-mediated esterification caused destruction of the substrate. It was formed from the acid and SEM chloride (THF, 0°, 80% yield) and was removed solvolytically. The ease of removal in this case was attributed to anchimeric assistance by the phosphate group. Normally SEM groups are cleaved by treatment with fluoride ion. Note that in this case the SEM group is removed considerably faster than the phenyl groups from the phosphate. ... 

The base hydrolysis under harsh conditions very often brings about undesired cleavage of phosphates. In contrast, removal of an o- orp-chlorophenyl protecting group by lV ,iV, iV, /V -tetramethylguanidinium ryn-p-nitrobenzaldoxymate (NBO) (108 equation 65) or syn-pyridin-2-aldoxymate (PAO) (109) is achievable at room temperature and no side reaction occurs. The 8-quinolyl phosphate (110 equation 66) is also hydrolyzed under mild conditions with the assistance of a stoichiometric amount of ZnCb or CuCb salt. ... 

Three selective methods to remove protective groups have received attention assisted, electrolytic, and photolytic removal. Four examples illustrate assisted removal of a protective group. A stable allyl group can be converted to a labile vinyl... 

The following derivatives represent protective groups that contain an auxilliary functionality, which when chemically modified, results in intramolecular, assisted cleavage, thus increasing the rate of cleavage over simple basic hydrolysis. In general, this allows for their removal in the presence of other esters that would normally be cleaved using conventional hydrolytic methods. 

Removal of the protecting group with fluoride provides diol 439. At the diol stage, the syn anti mixture can be easily separated by chromatography. Acetonide formation followed by mercury-assisted hydrolysis of the dithioacetal group furnishes the desired threose 440. 

The (1-deuterated) diastereomers 135 are accessible via deuteration and TMEDA-assisted removal of the remaining proton [Eq. (38)] [79]. In other words, the extraordinarily high kinetic H/D isotope effect permits the utilization of deuterium as a protecting group against deprotonation. 

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