Deprotection alcohols

A second convergent synthesis of haliclamine A (64) was achieved in a stepwise sequence from cyclopropyl(thiophen-2-yl)methanone (76) (Scheme 7) [37]. The protected thiophene 77 was condensed with formyl-piperidine to give 78, suitable for a Wittig olefination with 79. After desulfurization of the product 80, the deprotected alcohol 82 was subjected to homoallylic rearrangement using MesSiBr in the presence of ZnBr2. The re-... 

Flynn et al., also described the synthesis of the fused indoles [73]. The o-iodotrifluoroacetanilide 110 was coupled to aryl alkyne 111 under Sono-gashira conditions followed by subsequent reaction with aryl iodide, 107 with gaseous carbon dioxide produced the fused indole 158. Lewis acid dealkylation with aluminum trichloride produced the deprotected alcohol 159. 

Methyl ethers are stable to acidic and basic conditions, and oxidising or reducing reagents. Deprotection to regenerate the alcohol is difficult (see Section 9.6.10, p. 1254) a convenient mild procedure uses iodotrimethylsilane in chloroform solution at room temperature.768 The alkyl methyl ether under these conditions gives the alkyl silyl ether and methyl iodide the former on treatment with methanol gives the deprotected alcohol. 

Procedures for deprotection of THP-ethers. Use of methanolic hydrochloric acid. The THP-ether (0.2 mol) was dissolved in methanol (200ml) and concentrated hydrochloric acid (30 ml), and the mixture heated under reflux for 2 hours. After cooling, the solution was neutralised by the addition of an excess of sodium hydrogen carbonate, diluted with ether (200 ml), filtered and the ether evaporated. The residue was dissolved in ether, washed twice with water, dried and evaporated. The deprotected alcohol was distilled under reduced pressure. 

Among a wide range of other applications, the combination of alumina-supported reactions and microwave irradiation was successfully applied to the cleavage of esters, a commonly used strategy to deprotect alcoholic groups in multi-step organic synthesis. Deacylation of alcoholic and phenolic ac-... 

Treatment of naphtho[2,l- ][l,5]oxazocine 464 with HF yielded the deprotected alcohol 465 (95%), which was subsequently oxidized under Swern conditions to give the oxo-butyl 1,5-oxazocine 466 (96%). Reaction of the latter with 4-[(.y)-2-methylsulfinylphenyl]piperidine in presence of NaBH4 under standard reductive animation, afforded the oxazocine 467 (72%) (Scheme 93) <2004BMC2653>. 

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... 

Another hybrid protecting group is the p-[(trimethylsilyl)ethoxy]methoxy benzyl (p-SEM-benzyl) ether354 Phenolate anions generated by treatment of p-SEM-benzyl ethers with TBAF in DMF at 80 °C eliminate to give the deprotected alcohol as illustrated in Scheme 4.303 p-SEM-benzyl ethers are compatible with many of the standard manipulations in oligosaccharide synthesis and they arc orthogonal to benzyl and p-methoxybenzyl ethers. 

The CuCli-CuO promoted hydrolysis is not solely limited to thioacetals—a variety of acetals are also deprotected [21]. Treatment of 26 with the copper catalysts in acetone-water afforded the spiroacetals 27 and 28 via concomitant hydrolysis of the thioacetal and benzylidene dioxy and ethoxyethyl acetals (Sch. 7) [22], Copper(II) chloride dihydrate has also been shown to hydrolyze a variety of acetals [23] and trityl groups can also be removed in the presence of copper sulfate in benzene to afford deprotected alcohols [24]. 

In the absence of protons the deprotection is complicated by nucleophilic attack of RO on the tosylate ester with formation of the ether, ROR [Eq. (60)]. This side reaction can be suppressed on addition of a proton donor, such as acetic acid. In that case aromatic radical anions cannot be used as catalyst and Ni(acacen) was used. The difference in yield of deprotected alcohol from direct and indirect reduction was insignificant [249]. 

The diester enantiomer (108) derived from ribonolactone, has been cyclized and decarboxylated to the bicyclic ketone (109) in 83% overall yield for the two steps (Scheme 38)." Similarly, the cyclopentanol diester (110) has been cyclized and decarboxylated to (111), separation of the two diastereomers being effected on the deprotected alcohols (Scheme 39)." Cyclization of (112) occurs regioselectively as expected to give (113) in 81% yield (equation 32)." The 9-azaprostaglandin skeleton has been formed through a combination of Michael and Dieckmann reactions." ... 

After the first electron transfer, a chemical reaction (here a scission) may occur only if the transition n -+ with formation of the arenesulphinate ion. This reaction was exploited for deprotecting alcohols and amines. 

Stepwise alkylation of the diester 364, obtained conventionally using the Michaelis-Arbuzov reaction, leads to 365, from which the 0-(2-trimethylsilylethyl) protecting group may be removed with HF in MeCN. A Peterson reaction on the deprotected alcohol 3 (R = prenyl) results in the formation of the unsaturated phosphonic diester 367(R = prenyl) ... 

Fluoride ions induce a fragmentation reaction of SEM ethers resulting in loss of fluorotrimethylsilane, ethylene, and formaldehyde to give the deprotected alcohol (see section 1.2.4). However, compared with deprotection of ordinary silyl ethers, the reaction requires rather protracted reaction times, higher temperatures, or the presence of HMPA [Scheme 4.294]. Different combinations of fluoride source and dipolar aprotic solvent have been used. Deprotection of a SEM ether in a synthesis of Galbanolide [Scheme 4.295] was accomplished with tetraethyiammonium fluoride in hot DMSO whereas Ireland used excess cesium fluoride in HMPA at 115 C for 20 h to delete the SEM ether that completed the synthesis of Monensin [Scheme 4.296]. Fluoride-induced cleavage of a SEM ether in HMPA at temperatures as low as 45 has been re-ported. ... 

Cleavage of acetals to esters (eq 88) as well as cleavage of THP ethers with Oxone on wet alumina has also been reported. THP ethers gave mainly the deprotected alcohols along with significant amounts of esterified products. 

Mechanism of Action. Under photolysis, acidic, and electron bombardment conditions, the transformation of o-nitrobenzyl alcohol or its derivatives involves an internal redox reaction sequence followed by liberation of the deprotected alcohol or amine (eq 1). Analogously, the photorearrangement of esters of o-NBA, obtained through its reaction with acid chlorides or anhydrides, also induces an internal redox reaction (eq 2). 

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