Albert Loffet

New allyl group acceptors for palladium catalyzed removal of allylic protections and transacylation of allyl carbamates

Abstract Allyl carboxylates, carbamates and phenoxides may be cleaved or transacylated in the presence of palladium catalyst and either phenyltrihydrosilane or N-methyl-N-(trimethylsilyl)-trifluoroacetamide. These reactions are totally compatible with the presence of Boc and, as far as phenyltrihydrosilane is concerned, Fmoc protections.

On the use of silylated nucleophiles in the palladium catalysed deprotection of allylic carboxylates and carbamates

Abstract Palladium catalysts and silylamines, used together with a silylating electrophile (trimethylsilyl acetate), allow the deprotection of allyl carbamates under very mild and selective conditions.

Synthesis of chiral N-protected α-amino aldehydes by reduction of N-protected N-carboxyanhydrides (UNCAs)

A facile one step synthesis of a wide variety of N-protected (Boc, Z, Fmoc) α-amino aldehydes under mild conditions is described. Pure N-protected (Boc, Z, Fmoc) α-amino aldehydes were obtained in high yields by reduction of N-protected (Z, Boc, Fmoc)-N-carboxyanhydrides (UNCAs) with equivalent amounts of lithium tris(tertbutoxy)aluminium hydride [LiAlH(O-t-Bu)3] or lithium tris[(3-ethyl-3-pentyl)oxy]aluminium hydride (LTEPA) in THF as solvent. The reaction is simple, rapid and proceeds without detectable racemization.

Synthesis of chiral urethane N-alkoxycarbonyl tetramic acids from urethane N-carboxyanhydrides (UNCAs)

Abstract The synthesis of chiral N-protected tetramic acid derivatives which are important precursors of β-hydroxy γ-amino acid under mild conditions is described. Reaction of urethane-N-carboxyanhydrides (UNCAs) with Meldrums acid in the presence of a tertiary amine, followed by subsequent cyclisation produced tetramic acid derivatives. This procedure is applicable to Boc-, Fmoc- and Z- N-carboxyanhydrides.

Diastereoselective alkylation of sultam-derived amino acid aldimines preparation of Cα-methylated amino acids

Abstract Alkylation of Schiff bases 2 derived from 4-chlorobenzaldehyde and sultam-derived amino acids 1 gave crystalline diastereomers 3 which after deprotection and re-crystallization, if necessary, afforded in good yield enantiomerically pure Cα′-methylated amino acid (ex: αMePhe, αMeLeu, αMeMet).

Synthesis of chiral N-protected β-amino alcohols by the use of UNCAs

Abstract A facile synthesis of a wide variety of N-protected β-amino alcohol derivatives under mild conditions is described. N-urethane protected amino acid N-carboxyanhydrides (UNCAs) were used as starting material and reduced into the corresponding alcohols with the appropriate hydride, sodium borohydride. The reaction is simple, unexpensive, easily scaled up, and proceeds without observable racemization.

Allylic protection of thiols and cysteine: I: The allyloxycarbonylaminomethyl group

Abstract S-allyloxycarbonylaminomethyl derivatives of thiols in general and cysteine in particular are readily deprotected by palladium catalysed hydrostannolysis with tributyltin hydride in the presence of acetic acid. They are perfectly stable in the basic conditions (piperidine/DMF) of Fmoc group removal but tend to decompose, albeit slowly, in the acidic conditions ( TFA CH 2 Cl 2 ) of t-Bu and Boc groups removal.

ON THE ALLYL PROTECTION OF THE IMIDAZOLE RING OF HISTIDINE

Abstract The regiospecific synthesis of the N ( π )-allyl and the N ( τ )-allyl derivatives of N ( α )- tert -butoxycarbonyl-histidine is described. The DCC-mediated coupling of N ( α )- tert -butoxycarbonyl- N ( π )-allyl-(L)-histidine with (L)-prolinamide, used as a test reaction to probe the extent of racemization during coupling processes, was found to occur with good ( ca . 97%) conservation of enantiomeric purity. Three methods have been devised, all of them based on catalytic palladium π-allyl chemistry, for the selective removal under mild conditions of the N -imidazolic allyl groups. Finally it is shown that the allyl group at N(τ)-position may be used as a temporary protection in the synthesis of N(π)-substituted derivatives of histidine.

Synthesis of N-protected γ-amino-β-keto-esters from urethane N-carboxyanhydrides (UNCAs)

Abstract N-protected γ-amino-β-keto-esters were synthesized from the corresponding N-protected N-carboxyanhydride (UNCAs) by reaction with the lithium enolate of ethyl acetate in good yields. These compounds are precursors of statine derivatives.

Synthesis of pyrrolidine-2,4-diones from urethane N-carboxyanhydrides (UNCAs)

In the presence of a base in aprotic medium, UNCAs lead to N-urethane protected-3,5-dialkyl-3-amino pyrrolidine-2,4-diones as racemic cis/trans mixtures. Consequently the choice of the base should be carefully considered to optimize yields and avoid side products when UNCAs are used in peptide synthesis.