Ferf-Butyl ethers groups

In peptide synthesis functional groups in the amino acid side chains are often protected with acid-labile protecting groups (Section 4.5.3). The tripeptide in Figure 4.35 contains, for example, a serine ferf-butyl ether and an L-lysine e-protected as an O-tert-butyl carbamate. In the standard strategy of synthesizing oligopeptides from the C- to the N-terminus (cf. Section 6.4.3) the C-terminus is either connected to the acid-labile... 

Many functional groups are stable under conditions for the alkylation of pseudoephedrine glycinamide enolates, including aryl benzenesulfonate esters (eq 18), rert-butyl carbamate and rerf-butyl carbonate groups (eq 19), tert-butyldimethylsilyl ethers, benzyl ethers, ferf-butyl ethers, methoxymethyl ethers, and alkyl chlorides. The stereochemistry of the alkylation reactions of pseudoephedrine glycinamide and pseudoephedrine sarcosinamide is the same as that observed in alkylations of simple A(-acyl derivatives of pseudoephedrine. 

Ethers with a tertiary, benzylic, or allylic group cleave by an S>jl or Ei mechanism because these substrates can produce stable intermediate carbocations. T hese reactions are often fast and take place at moderate temperatures. ferf-Butyl ethers, for example, react by an El mechanism on treatment with trifluoroacetic acid at 0 °C. WeTl see in Section 26.7 that the reaction is often used in the laboratory synthesis of peptides. 

Protection of hydroxyl and carboxyl groups as ferf-butyl ethers and esters... 

FIGURE 3.22 Protection (A) of carboxyl groups of amino acids as ferf-butyl esters,58 (B) of carboxyl groups of /V-substituted amino acids as fert-butyl esters,61 and (C) of phenolic and sulfhydryl groups as ethers. The amino acid esters are isolated as the hydrochlorides. 

The protection of a hydroxyl group as a ferf-butyl trimethylsilyl ether is one of the most important and useful reaction in organic synthesis because of its stability towards basic and mild acidic conditions [144]. The importance of any protecting group depends on how easily it can be installed and removed. 

The Dervan group discovered that addition of ferf-butyl hypochlorite to a solution of l-amino-2,2,6,6-tetramethylpiperidine and triethylamine in ether at —78 °C produces triethylammonium chloride as an insoluble white precipitate and an intense purple solution. The purple coloration, which is stable for hours at —78 °C, fades in minutes at 0 °C and was assigned to the 1,1-diazene 64. " " " ... 

Peroxy esters 67 were prepared in situ by the reaction of phosphonochloridate and ferf-butyl hydroperoxide in diethyl ether. The peroxy ester 67 (R = Ph) is stable for several days at 5 °C in diethyl ether. Most peroxyphosphates 67 with an RO group other than ferf-butylperoxy are unstable even for short periods264. This synthetic method was successfully applied for synthesis of ring peroxyphosphates 70 and 71 as colorless oils. They are very unstable and decompose at 25 °C to yield polymeric products and volatile side products264. 

Enaminoketoesters were reacted with benzyl chloroformiate in the presence of sodium hydride to furnish the /V-protected enaminoketoesters. The reduction of the carbonyl group with NaBkLt in methanol was followed by transformation of the derived hydroxyl group into the corresponding ferf-butyl dimethylsilyl ether by... 

In an exciting new challenge the Bristol-Myers-Squibb group carried out an ACP on a 100-kg scale with a chiral Ru Pybox catalyst, especially in two-phase media of water and ferf-butyl methyl ether (Scheme 5) [35]. The operations produced good yields and enantioselectivity,but separation was difficult. Similarly, Wurz and Charette [36] demonstrated ACP in aqueous media by using Ru, Rh, and Co catalysts including an O-H insertion reaction of carbenes. 

B-Bromocatecholborane cleaves MEM and MOM ethers at comparable rates and fm-butoxycarbonyl, benzyloxycarbonyl, /erf-butyl ethers, benzyl ethers, and TBS ethers are usually compatible,462 but not always. At a late stage in Boger s synthesis of Vancomycin, a MEM group was cleaved from a complex, multifunctional intermediate, but an tf-ferf-butoxycarbonyl was also cleaved and had to be restored in a separate step.169... 

---