Nitrogen deprotection

Methoxy-5-(177-pyrrol-2-yl)-2-thienyl]-177-pyrrole 621 was also prepared by a cross-coupling reaction, Stille reaction in this case, between A -SEM-2-(trimethylstannyl)-l/7-pyrrole 620 and 2,5-dibromo-3-methoxythiophene in the presence of a Pd catalyst, followed by nitrogen deprotection (Scheme 126) <1997CM2876>. If Negishi coupling is applied, the main reaction product is, in this case, A -SEM-2,2 -dipyrrole, and the desired compound can be isolated only in trace amount. 

Allylsilane 59 was obtained by initial reaction of the succinimide 55 with the corresponding Grig-nard alkylsilane and a subsequent simple sequence of reactions. This allylsilane was readily cyclized in formic acid at room temperature to 60, which was subjected to a Wacker oxidation (Tsuji 1984) to afford the dihydroanatoxin-a derivative 28. The nitrogen deprotection step with iodotrimethylsilane (Melching et al. 1986) funushedthe ( )-dihydroanatoxin-a, which was reprotected with oc according to the previously discussed Rapoport methodology (Sardina et al. 1989) to furnish the racemic ( )-anatoxin-a. The overall yield of this synthesis was 7% from the succinimide. 

The aldehyde was then converted to a carboxylic acid via a Pinnick oxidation. Further elaboration to generate acyl telluride 185 was achieved by initial activation of the acid as a mixed anhydride using isobutyl chloro-formate under basic conditions. Nucleophilic displacement with sodium phenyl telluride, generated in situ from borohydride reduction of diphenyl ditelluride, completed the transformation. With acyl telluride 185 in hand, nitrogen deprotection employing TFA, followed by a reductive amination with aldehyde 186 furnished alkyne 187, which was envisioned to be a substrate for radical cyclization (Scheme 19). 

Model studies have demonstrated that the approach of Mariano and his coworkers does indeed permit rapid construction of the pentacyclic yohimbine skeleton (Scheme 129) (41, 42). For example, Diels-Alder reaction of dihydropyridine 193 with methyl vinyl ketone (194) afforded isoquinuclidene 195 which was sequentially ketalized, the nitrogen deprotected, and trypto-phylated to yield the model substrate 196. Treatment of 196 with t-butyl propiolate effected the crucial zwitterionic amino-Claisen rearrangement to efficiently provide the hexahydroisoquinoline 197 having the crucial cis-DE-ring fusion in place. Treatment of 197 under the Wenkert cyclization condi-... 

The exocychc nitrogens on cytosine and the purine bases must be protected during the synthesis. The search is ongoing for protecting groups that are subject to fewer side reactions and that can be removed more easily in the final deprotection step (34). 

HCl, Et20, 6 h, 83-88% yield.Acidic deprotection of the BOC group could not be achieved with complete selectivity in the presence of an MTM ester. The trityl and NFS (2-nitrophenylsulfenyl) groups were the preferred nitrogen protective groups. 

This group was developed to minimize the problem of nitrogen allylation during the deprotection step, because deprotection proceeds with /3-hydride elimination. The derivative is stable to TFA and 6 N HCl. ... 

Synthesis of the title compound is representative of a number of syntheses of nonaromatic nitrogen heterocycles via Pd(Ill-catalyzed amination of olefins. These tosylated enamines are not readily available by standard synthetic methods, and show potential for further functionalization of the heterocycle. The saturated amine can be synthesized from the title compound by hydrogenation of the double bond followed by photolytic deprotection. ... 

Finally, we tried to deprotect the amide nitrogen of the obtained pyridi-nones upon reflirx in neat trifluoroacetic acid (TFA) for 18 h [ 116]. Products were isolated in 73% and 79% yield, respectively. In contrast, upon microwave irradiation at 120 °C for only 20 min, a (1 2) TFA/DCM mixture sufficed to deprotect the pyridinones (isolated yields 75% and 73% respectively). Surprisingly, deprotection with either refluxing neat TFA (18 h) or microwave irradiation in neat TFA with a catalytic amount of methanesulfonic acid (20 min) did not work for dihydrofuropyridinone. 

Deprotection of the pMB group from 20 proceeded smoothly in TFA to provide the drug candidate 2. The isolation conditions of a suitable crystal form of 2 for development were optimized later since we had to change the protective group of the nitrogen of 4 for the subsequent asymmetric addition reaction. 

The removal of carbobenzyloxy (Cbz or Z) groups from amines or alcohols is of high interest in the fine chemicals, agricultural and pharmaceutical industry. Palladium on activated carbon is the catalyst of choice for these deprotection reactions. Nitrogen containing modifiers are known to influence the selectivity for certain deprotection reactions. In this paper we show the rate accelerating effect of certain N-containing modifiers on the deprotection of carbobenzyloxy protected amino acids in the presence of palladium on activated carbon catalysts. The experiments show that certain modifiers like pyridine and ethylenediamine increase the reaction rate and therefore shorten the reaction times compared to non-modified palladium catalysts. Triethylamine does not have an influence on the rate of deprotection. 

Two amino acid stereoisomers protected by benzyloxycarbonyl groups were deprotected in different ways. One isomer was hydrogenolyzed on 5% Pd/C (0.05 mol Pd/mol) in AcOEt-MeOH for 16 hours at ambient pressure and temperature. The other isomer was dissolved in MeOH, and cyclohexene (10 mol/mol) was added under nitrogen followed by 5% Pd/C (0.18 mol Pd/mol). The temperature was immediately raised to reflux, and stirring was continued for 7 minutes (Scheme 4.60).266... 

Pivalate deprotection of 102 provided primary alcohol 103. Oxidation attempts to form the aldehyde or carboxylic acid (104) were again not successful, even with the nitrogen as part of the indolizidine ring (rather than before as the imine, for 87 —> 88). The nitrogen still affected our ability to oxidize the remote alcohol... 

Reactions where the reduction of a functionalized nitrogen, or the deprotection of an amine group, start a domino process with the sequential formation of the two rings of the indolizidine system, find many examples in the literature. A recent one is provided by the synthesis of (—)-indolizidine 223AB <20040L1493> (Scheme 10). 

---