Deprotection of allyl esters

The Baran group has reported an unusual deprotection of allyl esters in micro-wave-superheated water. A diallyl ester structurally related to the sceptrin natural products (see Scheme 6.87) was cleanly deprotected at 200 °C within 5 min (Scheme 6.168) [181]. Other standard deprotection transformations carried out under microwave conditions, specifically N-detosylations [317], trimethylsilyl (TMS) removal [318, 319], and N-tert-butoxycarbonyl (Boc) deprotection [231], are summarized in Scheme 6.169. 

The reaction of tert-butyl esters with Et3SiH/TFA results in the reductive deprotection of the ester and formation of isobutane. The yields of the isobutane are not recorded, but the acids are obtained nearly quantitatively (Eq. 150).307 In a similar manner, the lactone shown in Eq. 151 is converted into the acid in good yield.308 In like manner, the reductive deprotection of allyl esters provides the carboxylic acids in high yields.270... 

The Pd(0)-catalyzed displacement of allylic acetates (297) with various nucleophiles via the allylic Pd(II) complex (298) is a well-established procedure (Scheme 114). Through attack of electrons (+2e ) in place of nucleophiles, (298) is expected to undergo a reductive cleavage providing allylic carbanions (299) and the acetate anion along with Pd(0) complexes. The latter can then be captured by various electrophiles (polarity inversion. Scheme 114) leading to (300) [434]. This procedure is useful for the deprotection of allyl esters under neutral conditions. Recently, a mechanistic study of the Pd-catalyzed reaction of allylic acetate (297), using carbonyl compounds as an electrophile, has been reported [435]. 

The electroreduction procedure can also be used effectively for the deprotection of allyl esters. Palladium(0)catalyzed electroreductive cleavage of allylic esters has been performed in an MeCN—Et4NOTs—(Pt/Pb) system in the presence of Pd(0)—... 

Allyl alk-2-ynoates can be readily converted into alk-2-ynoic acids by reaction with morpholine as the nucleophilic scavenger and Pd2(dba>3 as catalyst together with l, 3-diphenylphosphtnopropane as associated ligand, thereby enabling deprotection of allyl esters of 2,2,3,3-tetradehydro-PGE derivatives [Scheme 6.64]. 

Following a first report by Kunz and WaldmannP l secondary amines such as diethylamine, piperidine, and in particular the less basic morpholineP l have been extensively used for the deprotection of allyl esters. As the allylammonium species formed in this process (Scheme 14) may also behave as an allyl donor towards palladium zerovalent complexes, the use of an excess of scavenger is highly recommended in order to totally displace the equilibrium towards deprotection. Secondary amines can also be used in the deprotection of allyl carbamates. Here again an excess of scavenger is necessary to avoid kineticaUy competitive allylation of the liberated amine. 

Scheme 5 Deprotection of Allyl Esters by Allyl Transfer in the Presence of Pd(0) Catalyst...

The full impact of Pd-catalysed deprotection of allyl esters was first appreciated by Jeffrey and McCombie who showed that an allyl ester could be deprotected to the potassium salt of the corresponding carboxylic acid under Pd catalysis — a transformation that is particularly valuable for acid-sensitive substrates. In the example shown in [Scheme 6.57], the displacement of the exchange equilibrium over to the desired product was assured by employing the sodium salt of 2-ethyl-hexanoate, which is soluble in most common solvents except hydrocarbons. ... 

Deprotection of allyl ester in 467 with HC02H/Et3N was highly chemoselec-tive. In the coexistence of a 2,4-enyne system in 467, at first 7r-allylpalladium carboxylate 468, formed from the allyl ester, attacked the triple bond to form the butenolide 469 without reacting with formate. Hydrogenolysis with formate took place only at the final step to afford 470 chemoselectively. Also, the alkenyloxirane group, which is allylic epoxide, stayed intact [175],... 

The last class of nucleophiles used to scavenge the n-allylpalladium intermediate is that of sulfur nucleophiles. 2-Thiobenzoic acid has been used as a water-soluble scavenger of 7r-allylpalladium complexes in allyl carbamate deprotections. More recently, aryl sulfinic acids have been demonstrated to very effectively serve as nucleophiles in the Pd-mediated deprotection of allyl esters, carbamates, amines, and ethers. This reagent appears to afford substantially bettCT reactivity than most other classes of nucleophiles. 

Deprotection of allyl esters has been accomplished using Pd(PPh3)4 or Pd(PPh3)2Cl2 in conjunction with dimedone, 2-ethylhexanoic acid, BusSuH, PhSiHj.f ... 

B.vi.a. Deprotection ofAllyl Esters. The deprotection of allyl esters under palladium catalysis has frequently been employed in various syntheses of pharmaceutically... 

Scheme 19. Deprotection of allyl esters on solid support (recent examples).

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