Carbonyl deprotection

The notion of enol silyl ethers (ESE) as electron donors was first provided by Gassman and Bottorff,34 who showed that selective (carbonyl) deprotection can be readily achieved in the presence of an alkyl silyl ether group via an electron-transfer activation (e.g., equation 9). 

Under the conditions of electrochemical carbonyl deprotection, some strained cyclic systems like 2-, 2,2-, and... 

The Cheng group at Chugai Pharma reported a very efficient synthesis of A5-2-oxopiperazines 116 as constrained dipeptidomimetics either in solution or in the solid phase by an Ugi-4CR reaction starting from aminoacetaldeyde diethyl acetal, followed by carbonyl deprotection and cydization to give 116 (Scheme 2.42) [73]. 

The Ugi-4CR between cyclic ketones, primary amine hydrochlorides, potassium thiocyanate (or selenocyanate), and 2,2-diethoxyethyl isocyanide [91] afforded the spiro 2-thio-(or seleno)hydantoin-4-imines 166. On heating in acetic acid, compounds 166 underwent carbonyl deprotection and cyclization to spiro imidazo[l,5-ajimidazoles 167 (Scheme 2.60). 

Scheme 2.60. Imidazo[l,5-o]imidazoles via Ugi-4CR/carbonyl deprotection/cyclization.

Additionally, primary amides and ketoamides were synthesized in good yields via a more traditional carbonylation-deprotection sequence in the presence of Pd(OAc)2/2PPh3 (Scheme 2.13) [134]. Initially, aryl iodides were reacted with ferf-butylamine under 1 bar of CO. When the reaction proceeded at 60 °C, ketoamides resulting from double carbonylation were mainly produced, whereas formation of the amides was favored at 100 °C. The desired primary amides were produced after heating the previous isolated products with one equivalent of tert-butyldimethylsilyl triflate (TBDMSOTf) in toluene at 100 °C. 

Scheme 11.18) [39]. The five-step sequence (cycloaddition, oxidation, ester hydrolysis, carbonyl deprotection, decarboxylation) required for the transformation of chromium carbene chelate 50 into the benzyl-protected rolipram precursor has been performed tvithout isolation of any intermediates after the final debenzyla-tion (-I-)-rolipram 51 is obtained in lotv overall yield. 

In this series of amides, hydrolysis or aminolysis of a simple ester, cleavage of a silyl groups a cis/trans isomerization, or reduction of a quinone to a hydro-quinone exposes an alcohol that then induces deprotection by intramolecular addition to the amide carbonyl. 

Acylation of the monosubstituted piperazine, 99 (obtainable by the protection-deprotection scheme outlined above), with cinnamoyl chloride gives the corresponding amide (100). Reduction of the carbonyl by means of lithium aluminum hydride affords cinnarizine (101). ... 

The homology between 22 and 21 is obviously very close. After lithium aluminum hydride reduction of the ethoxycarbonyl function in 22, oxidation of the resultant primary alcohol with PCC furnishes aldehyde 34. Subjection of 34 to sequential carbonyl addition, oxidation, and deprotection reactions then provides ketone 21 (31% overall yield from (—)-33). By virtue of its symmetry, the dextrorotatory monobenzyl ether, (/ )-(+)-33, can also be converted to compound 21, with the same absolute configuration as that derived from (S)-(-)-33, by using a synthetic route that differs only slightly from the one already described. 

The procedure involves C-alkylation of an a-sulfonyl carbanion derived from 245 with alkyl halides or carbonyl compounds, followed by cleavage of the cyclopropanols 247 produced by deprotection of the hydroxy group of 246 to give (E)-substituted aldehydes141. 

The regeneration of carbonyl compounds from 1,3-dithianes can be achieved using potassium hydrogen persulfate, Oxone , supported on wet alumina <96SL767> and by periodic acid under non-aqueous conditions <96TL4331>. The deprotection of benzyl substituted 1,3-dithianes can be achieved using the one electron oxidant [Fe(phen)3](PF6)3 <96SL315>. 

Enantiopure N,N -hnked oligoureas were originally described in 1995 by Burgess and coworkers as novel peptide backbone mimetics [271, 272]. Several synthetic approaches have been reported, all of which involve sequential acylation and amine deprotection cycles using appropriately protected carbonyl synthons [83, 271, 272, 274, 286-288]. Although elongation can be performed in solution, most of the synthetic procedures are elaborated on solid supports starting from Rink s... 

The carbonyl group can be deprotected by acid-catalyzed hydrolysis by the general mechanism for acetal hydrolysis (see Part A, Section 7.1). A number of Lewis acids have also been used to remove acetal protective groups. Hydrolysis is promoted by LiBF4 in acetonitrile.249 Bismuth triflate promotes hydrolysis of dimethoxy, diethoxy, and dioxolane acetals.250 The dimethyl and diethyl acetals are cleaved by 0.1-1.0 mol % of catalyst in aqueous THF at room temperature, whereas dioxolanes require reflux. Bismuth nitrate also catalyzes acetal hydrolysis.251... 

A similar series of reactions was performed by Paulsen and Hdlck141 for the preparation of the T-antigenic, unprotected, amino acid-disaccha-rides 200 and 201, starting from the 4,6-0-benzylidene-N-(benzyloxy-carbonyl) benzyl esters 198 and 199, respectively, by condensation with 110 in the presence of mercury dicyanide-mercury dichloride and molecular sieves 4A, and deprotection of the product. Sinay and co-workers148 also reported the synthesis of hexa-O-acetyl derivatives of 200 and 201 by application of the sequence of azido-nitration-bromination. 

To complete the synthesis of nakiterpiosin (1), we first deprotected 52 and then coupled it to 51 under the previously described carbonylative conditions (Scheme 2.6). Photolysis of 64 readily provided the desired annulation product. 

Deprotection of 2,2-disubstituted-l,3-dithiolanes to give carbonyl compounds can be achieved using Oxone with KBr in aq. MeCN <06TL8559> and a review of silylated heterocycles as formyl anion equivalents includes reference to 64 <06CC4881>. A method for transformation of propargylic dithiolanes 43 into tetrasubstituted furans has been reported <06SL1209> and Michael addition of enolates to the chiral dithiolane dioxide 65 takes place... 

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