Protection, phenols

Phenols protected as r-BuMe2Si ethers can be converted directly to methyl or benzyl ethers (Mel or BnBr, KF, DMF, rt, >90% yield). ... 

An isopropyl ether was developed as a phenol protective group that would be more stable to Lewis acids than an aryl benzyl ether. The isopropyl group has also been... 

A useful process for phenol protection and analysis is exemplified by tlie reaction of estrone with perfluorotoluene [72] (equation 8) The hydroxyl function replaces the 4 fluorme in high yield, and the hydroxyl may be deprotected in 87% yield on treatment with hydroxide... 

The TBDPS ether has been used for the monoprotection of a catechol (TBDPSCl, Im, DMF, 5 h, 83% yield) or simple phenol protection. It is cleaved with Bu4N F- (THF, 94% yield). ... 

A closely related reaction having the phenol protected with a trimethylsilyl group was also examined (Scheme 31) [45]. Unlike the earlier examples, the cyclization reaction resulting from this substrate did not require the presence of a mild acid. The anodic oxidation in methanol solvent with no acetic acid led to a 73% yield of the tricyclic product. In a nearly identical reaction, an anodic oxidation of the trimethylsilyl-protected substrate in the presence of 2,6-lutidine led to the cyclized product in a 60% yield. The use of the silyl group expanded the utility of the anodic C-C bond-forming reaction being studied by allowing for the use of neutral and basic conditions. Hence, it would appear that the cyclization reactions are compatible with the presence of both base and acid sensitive functionality. 

The lithiation of phenols protected as acetals—methoxymethyl acetals like 140 in particular—is especially valuable the second oxygen supplies a powerful coordination component to their directing effect (Scheme 69) The regioselective lithiation of 141 was used in the synthesis of the pterocarpans 4 -deoxycabenegrins A-I. 

The 4- and 6-positions of pyrrolo[2,3-3]pyridines can be substituted via palladium-catalyzed cross-coupling reactions with the 4- or 6-halo-substituted derivatives (Scheme 3) <2001SL609>. Nucleophilic displacement of the 4-substituent of 6-chloro-4-nitro- and 4,6-dichloro-pyrrolo[2,3-/ ]pyridines takes place with phenols. Protection of the pyrrole nitrogen with a /3-trimethylsilylethoxymethyl (SEM) group affords good yields of the aryl ethers (Equation 3) <2006TL2069>. 

A flask was charged with the step 2 product, the step 3 product, and /V-(3-dimcthyl-aminopropyl)-A -ethylcarbodiimide hydrochloride and then treated with boron tribromide dissolved in CH2CI2 to remove the phenol protecting group. 

A new alcohol and phenol protective group, the l-[(2-trimethylsilyl)ethoxy]ethyl moiety, readily introduced using 2-(trimethylsilyl)ethyl vinyl ether and catalytic pyridinium p-toluenesulfonate (PPTS), has been described76. Cleavage is achieved under near-neutral conditions using TBAF monohydrate (equation 16). 

SCHEME 3. Conditions that the phenol protecting group R must withstand... 

Aside from its summit position as a DMG (10, Scheme 3) the OCONEt2 provides versatile anionic aromatic chemistry anionic ortho-Fries rearrangement (9, Scheme 3) [11], a useful synthetic step by itself but also one that provides a path, after incipient phenol protection, to further DoM, resulting in a 1,2,3-sub-stituted aromatic derivative (9 —> 12, see also Scheme 13) [12] homo-ortho-Fries rearrangement to aryl acetamides (10 —> 11) providing a route to benzofura-nones which are difficult to prepare by Friedel-Crafts-based strategies [9] intra-... 

Directed remote metalation (DreM) of biaryl amides and O-carbamates, conceptually based on the complex-induced proximity effect (CIPE) [15] provides, especially in view of their link to transition metal-catalyzed cross coupling regimens [16], general and versatile routes to fluorenones (16 —> 15, Scheme 4) [5,17] and biaryl amides (16 —> 17) [18] whose features are overriding Friedel-Crafts reactivity and yield enhancement in comparison to Suzuki-Miyaura coupling routes for highly hindered biaryls, respectively. Additional features of the O-carbamate DreM result is potential further DoM of 17 with appropriate phenol protection and cyclization to dibenzopyranones [18]. 

Scheme 2.30 Influence of the phenol protecting group with catalyst Cl.

The benzannulation reaction further allows the concomitant generation of an axial and chiral plane in a single reaction step (Scheme 28) [68f]. The diastereomeric ratio of the benzannulation products depends on the protocol used for phenol protection. Thus, in situ protection gives the kinetic ratio of 74a 74b — 11 89, whereas a two-step benzannulation/ protection sequence results in thermodynamic control to give a ratio of 74a 74b >99 1. These results can be explained in terms of a possible or arrested rotation around the biaryl axis in the benzannulation product before protection to give either 74a or 74b. 

Phenacyl ethers, to protect phenols, 153 Phenacylsulfonamides, to prote ct amines, 385 Phenols, protection of, 143-170 as esters, 162-170 as ethers, 145-162 Reactivity Chart 4, 425-428 Phenothiazinyl-(10)-carbonyl derivatives, to protect amines, 346... 

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