Boc-deprotection

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 irradiation of films prepared from 1% triphenylsulfonium salts in poly(4-t-butoxycarbonyloxystyrene) with lithographically useful doses of 254 nm light generates acid which is less than 0.1% of the t-BOC groups. The efficiency of the photochemistry is several times less than the efficiency of acid generation from triphenylsulfonium salts in solution. The catalytic chain is about 1000 for the t-BOC deprotection step at 100°C. This implies that catalyst diffusion during postbake is on the order of 50A... 

KM Sivanandiaih, VV Suresh Babu, SC Shrankarama. Solid-phase synthesis of oxytocin using iodotrichlorosilane as Boc deprotecting reagent. Int J Pept Prot Res 45, 377, 1995. 

Hulme et al. describes the use of a convertible isonitrile for the generation of a ketopiperazine library (Scheme 12) [32]. Using a mono-A -Boc diamine 68 in the classical Ugi reaction followed by Boc deprotection and base-facilitated cyclization (3 steps, 1 pot) afforded the ketopiperazine 72 in relatively high yields. 

The use of benzimidazolone derivatives 4, prepared from the anilides 3, for the thioacylation of peptides (Scheme 4) have also been reported, 27 and three thioamide analogues of tuftsin were prepared. Due to the acid lability of thioamides, Boc deprotection with SnCl4 represents a mild alternative for N-terminal extension.12 ... 

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. 

The tetravalent lysinyl core peptide was synthesized as described previously 130 Briefly, the synthesis of the first level of carrier core to form Boc-Lys(Boc)-Ala-OCH2-PAM-resin was achieved using a fourfold excess of Boc-Lys(Boc)-OH DCHA salt with BOP in CH2C12. The second level of lysine was generated by the same protocol. After Boc deprotection, tetravalent chloroacetyl moieties were introduced to the core peptide by using a tenfold excess of chloroacetic acid via DIC/HOBt activation. The tetravalent (chloroacetyl)lysinyl core peptide was cleaved from the resin by HF/PhOMe (9 1) and finally purified by RP-HPLC. MALDI-MS m/z [M + H]+ calcd, 780.5 found, 780.5 [M+Na —H]+ calcd, 802.5 found, 802.3. 

Cyclic amide 100 was iV-Boc deprotected and coupled with the tripeptide 102 (Scheme 20) t47l subsequent diaryl ether formation led to an 8 1 mixture of (P)- and (M)-104 with the natural D-O-E isomer predominating. This stands in contrast to the Nicolaou process (Section 16.7.2), in which the unnatural isomer predominated at this step. Removal of protecting groups led to vancomycin aglycon (105). 

In a very significant development, the parent 277-azepine 85 was prepared for the first time (Scheme 10) <1995AGE1469>. A ring construction was adopted involving A-BOC deprotection of 84 followed by treatment with strong base to afford 85 after intramolecular imine formation and base-induced elimination of acetate. While the yield was only 1%, the azepine was sufficiently stable at 25 °C for 48 h to allow for H and 13C NMR spectroscopic characterization. 

An extension of the above work to fV-BOC deprotection of the amino ketones 86 gave the optically active 277-azepines 87 (e.g., 87, R1 = Me, Rz = Me 56%). Ready isomerization of 87 by a [1,5]-H shift to the corresponding 377-azepines was observed when the former were left in solution in organic solvents at 25 °C or on warming in CHCI3 solution (Equation 10) <1996T10883>. 

Golebiowski et al. reported the solid-phase [92] and the solution-phase [93] syntheses of bycyclic diketopiperazines which were of great interest because their conformation was similar to the type-1 /i-turn motif. A Merrifield hydroxymethyl resin was esterified with a-N-Boc-fi-N-Fmoc-L-diaminopropionic acid and then mono-deprotected at the />-N with piperidine. Ugi-4CR of the resulting resin-bound amine gave the resin-bound adducts 168. Subsequent N-Boc deprotection and intramolecular N-alkylation afforded the ketopiperazines 169. The diketopiperazines 170 were formed via N-Boc amino acid coupling followed by N-Boc deprotection... 

Step 1 Selective cleavage of the -Bu ester (analogous to Boc deprotection). 

Monotrifluoroacetylated diaminopyrazole was first reacted with the free Kemp s triacid to produce the imide, followed by N-Boc protection and amide-coupling with a m-substituted aniline derivative. Final Boc-deprotection occurred on the chromatography column leading directly to the new receptor modules. The recognition site X was chosen to be ethyl as a neutral reference, acetyl for polar side-chains, nitro for electron-rich aromatic residues and carboxylate for basic amino acids (Figure 2.4.4). 

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