Allyl ethers deprotection

Curious about these strained products, we wondered if more rigid starting structure could be used for the Adler-Becker/Diels-Alder sequence (Scheme 10). We decided to see if chromanones could be substituted with benzofuian stractures. SUylation of resorcinol 44 was followed by bromination and cyclizatiOTi to form benzofuran 46. As shown previously, triahylatiOTi and allyl ether deprotection yielded ketone 47, which was subsequently reduced to the benzylic alcohol however, this required much harsher conditions than those in the chromanone series (LiAlHj vs. NaBHj). Although less efficient than the chromanone derivative, the Adler-Becker oxidation proceeded to provide epoxy benzofuranone 48... 

Silyl-derived linker 36 was prepared in three steps from a silyl ether of serine and incorporated for Fmoc/tBu-based assembly of protected gly-copeptide blocks (Scheme 11) [42]. The a-carboxylic acid function of serine was protected as an allyl ester. Deprotection by a Pd(0) catalyst in the presence of dimedone liberated the carboxylic acid in order for subsequent... 

RhCl(PPh3)3 is an effective catalyst for the deprotection of allyl ethers in the presence of l,4-diazabicyclo[2.2.2]oc-tane (DABCO) (Equation (20)).74 75 The role of the base is to prevent hydrolysis of prop-l-enyl ether to propanal, which poisons the catalyst. 

Allylic amination is important for the solid-phase organic synthesis.15 The solid-phase allylic aminations are devised into the G-N bond formation on solid support and the deprotection of allyl ethers. As a novel deprotection method, the palladium-catalyzed cyclization-cleavage strategy was reported by Brown et al. (Equation (4)).15a,15b The solid-phase synthesis of several pyrrolidines 70 was achieved by using palladium-catalyzed nucleophilic cleavage of allylic linkages of 69. 

Scheme 85 Cleavage of an aryl allyl ether for deprotection of a phenol.

The cationic complex [Ni(bpy)3](BF4)2 is a good catalyst for the electroreductive cleavage of the C—O (allyl) bond of allyl ethers, affording parent alcohols or phenols. The Ni(II)-catalyzed electroreductive deprotection of allyl ethers is found to proceed in a DMF-Bu4NBp4-(Mg) system. For... 

Allyl carbonates can be cleaved by nucleophiles under palladium(O) catalysis. Allyl carbonates have been proposed for side-chain protection of serine and threonine, and their stability under conditions of /VT moc or /V-Boc deprotection has been demonstrated [107]. Prolonged treatment with nucleophiles (e.g., 20% piperidine in DMF, 24 h) can, however, lead to deprotection of Alloc-protected phenols [108,109]. Carbohydrates [110], tyrosine derivatives [107], and other phenols have been protected as allyl ethers, and deprotection could be achieved by palladium-mediated allylic substitution (Entry 9, Table 7.8). 9-Fluorenyl carbonates have been used as protected intermediates for the solid-phase synthesis of oligosaccharides [111]. Deprotection was achieved by treatment with NEt3/DCM (8 2) at room temperature. 

Allyl ethers are also formed under PTC conditions (see Expt 5.73). These ethers are stable under moderately acidic and basic conditions. Deprotection is achieved by treatment with potassium t-butoxide in dimethyl sulphoxide, which results in rearrangement to the corresponding prop-l -enyl ether, followed by reaction with a mercury(n) chloride/mercury(n) oxide reagent mixture.78... 

An alternative deprotection method, which proceeds without prior isomerisation, involves heating under reflux the allyl ether in aqueous methanol with palladium/activated charcoal in the presence of toluene-p-sulphonic acid.79... 

Jacquinet and Sinay [231] synthesised the trisaccharide (341) considered to be the possible determinant of the Lewis c (Lec) antigen. Condensation of (322) with compounds (343), both prepared via the allyl ethers (342), in the presence of bromide ion gave the trisaccharides (344) in 85 % yield in both cases. Deprotection of these gave (341). 

Alcohols are protected as allyl ethers, which are difficult to cleave with the Pd catalyst and deprotected by other methods [149]. Alcohols are conveniently converted to allyl carbonates 334 by treatment with allyl chloroformate (333). The allyl carbonates are deprotected using HCO2H [150], and HSnBu3 [151]. This method is called the AOC (allyloxycarbonyl) method. Phenols are protected as allyl phenyl ethers, which can be cleaved with HSnBu3 [152]. 

One protecting method for ketones and aldehydes is the formation of oximes, but sometimes further protection of the oximes is required. For this purpose, the oximes can be protected as the allyl ethers 335, which are deprotected by the Pd-catalysed hydrogenolysis with HCO2H Et3N in boiling dioxane under mild conditions without attacking the acetal group in 335 [153],... 

On the other hand, an allyl ether can also be considered a protected alcohol that is liberated by Pd(0)-catalyzed allylation for further catalytic transformation. As an excellent example for sequential homobimetallic catalysis, Gabriele and coworkers [85] just recently disclosed a Pd(0)-catalyzed deprotection-Pd(II)-catalyzed heterocyclization of allyloxyaryl propargylic alcohols 97 to provide benzofurans 98 in excellent yields (Scheme 33). 

Allyl ethers of phenols can be deprotected in a single step by trapping the ic-allyl palladium intermediates with either reducing agents or soft nucleophiles. 

Interception of the ji-allyl palladium intermediate with soft nucleophiles such as morpholine and dimedone is attractive on the grounds of efficacy, economy, safety and scope. Deprotection of a phenol allyl ether in a synthesis of the antibiotic Vancomycin demonstrates that aryl iodides and chlorides remain intact [Scheme 4.227],429... 

Ally) ethers are selectively cleaved with titanium(lV) isopropoxide and commercially available Grignard reagents like /i-butyl- or cyclohexylmagnesium chloride [Scheme 4.229].432 Neither benzylidene acetals nor more highly substituted allylic ethers suffer under the reaction conditions. A mechanism for the reaction implicates formation of the titanacyclopropane intermediate 229.1 as the first step. Ligand exchange with an unsubstituted allyl ether affords intermediate 229.2. -Elimination to the allyltitanium(lV) alkoxide 2293 followed by hydrolysis returns the deprotected alcohol. The reaction closely resembles an earlier method based on zirconium.433... 

Olefin isomerization catalyzed by ruthenium alkylidene complexes can be applied to the deprotection of allyl ethers, allyl amines, and synthesis of cyclic enol ethers by the sequential reaction of RCM and olefin isomerization. Treatment of 70 with allyl ether affords corresponding vinyl ether, which is subsequently converted into alcohol with an aqueous HCl solution (Eq. 12.37) [44]. In contrast, the allylic chain was substituted at the Cl position, and allyl ether 94 was converted to the corresponding homoallylic 95 (Eq. 12.38). The corresponding enamines were formed by the reaction of 70 with allylamines [44, 45]. Selective deprotection of the allylamines in the presence of allyl ethers by 69 has been observed (Eq. 12.39), which is comparable with the Jt-allyl palladium deallylation methodology. This selectivity was attributed to the ability of the lone pair of the nitrogen atom to conjugate with a new double bond of the enamine intermediate. 

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