(PTC) C-alkylation of activated amino acids by alkyl halides

CherrieBaby · chouchou

Here are the rest of the articles on the synthesis of substituted alpha-amino acids via PTC alkylation of activated alpha-amino acids with alkyl halides. They are all PDFs.

A Catalytic Enantioselective Synthesis of alpha-Methyl Amino Acid Derivatives by Phase-Transfer Catalysis
Martin J. O'Donnell* and Shengde Wu
Tetrahedron: Asymmetry 1992, Vol. 3, No. 5, pp. 591-594
Abstract: Optically active alpha-methyl amino acid derivatives are prepared in up to 50% enantiomeric excess by phase-transfer catalytic alkylation of aldimine Schiff bases of alanine t-butyl ester.

http://rapidshare.de/files/983863/PTC-a-AminoAcid.Tetr.Asymetry.v3.pp591-4_1992_.pdf.html (PDF)

The Stereoselective Synthesis of alpha-Amino Acids by Phase-Transfer Catalysis
Martin J. O'Donnell,* William D. Bennett, and Shengde Wu
J. Am. Chem. Soc. 1989, v. 111, pp. 2353-2355

http://rapidshare.de/files/983818/PTC-a-AminoAcid.JACS.1989.v111.pp2353-5.pdf.html (PDF)

Synthesis of alpha-CH2-X Functionalized Tryptophan Methyl Ester
Dagmar Pettig, David C. Horwell
Synthesis, 1990 pp. 465-6
Abstract: A short and efficient synthesis of alpha-CH2-X functionalized tryptophan methyl ester (methyl 2-amino-3-(1H-indol-3-yl)propionate) is described, by alkylation of methyl 2-isocyano-3-(1H-indol-3-yl)propionate with a range of functionalized alkyl halides.

http://rapidshare.de/files/983888/PTC-a-AminoAcid.Synthesis.1990.pp465-6.pdf.html (PDF)

Preparation of Optically Pure alpha-Methyl-alpha-amino Acids via Alkylation of the Nickel(II) Schiff Base of (R,S)-Alanine with (S)-2-N-(N'-Benzylprolyl)aminobenzaldehyde.
Yuri N. Belokon', Nina I. Chernoglazova, Constantin A. Kochetkov, Natalia S. Garbalinskaya, and Vasili M. Belikov
J. Chem. Soc., Chem. Commun., 1985, pp. 171-2
Abstract: Chiral nickel(II) complexes of Ala with (S)-2-N-(N'-benzylprolyl)aminobenzaldehyde [(S)-bba] were alkylated with
alkyl halides and the diastereoisomeric complexes formed were separated on SiO2; their decomposition led to the
isolation of enantiomerically pure (R)- and (S)-alpha-alkyl-alpha-amino acids with recovery of the initial (S)-bba.

http://rapidshare.de/files/983839/PTC-a-AminoAcid.JCS.Chem.Communs.1985.pp171-2.pdf.html (PDF)

Acidities of Glycine Schiff Bases and Alkylation of Their Conjugate Bases
Martin J. O'Donnell, William D. Bennett, William A. Bruder, William N. Jacobsen, Keith Knuth, Brigitte LeClef, Robin L. Polt, Frederick G. Bordwell, Susan R. Mrozack, and Thomas A. Cripe
J. Am. Chem. Soc. 1988, v. 110, pp. 8520-8525
Abstract: Equilibrium acidities in Me2SO are reported for six ketimines of the type Ph2C=NCH(R)CO2Et and five aldimines, ArCH=NCH(R)CO2Et. Changing R in the ketimine from H to Ph increased the pKa by 2.2 units. This surprising acidity decrease for Ph substitution points to a substantial increase in steric effect, as do the increases in pKa of 3.8 and 4.2 units observed for the replacement of hydrogen by Me and PhCH2, respectively. Phase-transfer alkylation of the Ph2C=NCH2CO2Et ketimine gave over 90% of monoalkylate whereas, under similar conditions, the aldimine 4-ClC6H4CH=NCH2CO2Et gave a mixture of mono- and dialkylate. The difference is that the pKa of the monoalkylated aldimine is essentially the same as that of the parent, which leads to rapid equilibration with the parent anion and consequent dialkylation. The rates of alkylation in Me2SO of these parent and monoalkylated anions did not differ greatly, showing that the relative pKHAs of the parent acid and its monoalkyl derivative, rather than the relative rates of the mono- and dialkylation reactions, is the principal factor that determines the extent of the competition between monoalkylation and dialkylation.

http://rapidshare.de/files/983804/PTC-a-AminoAcid.JACS.1988.v110.pp8520-5.pdf.html (PDF)

Phase-Transfer Catalysis Offers Practical alpha-Amino Acids Synthesis
Ward Worthy
C&EN 1989, April 10, pp. 25-7 (Chemistry & Engineering News?)
Indiana chemists develop industrially attractive procedure that works at room temperature and uses low-cost reagents

http://rapidshare.de/files/983665/PTC-a-AminoAcid.CE_N.1989.April_10.pp25-27.pdf.html (PDF)

I have some earlier articles I haven't posted and an interesting later one that uses alkyl chloride (in a microwave) for the alkylation rather than alkyl bromide. These others are, generally, smaller. Not all of the articles I post will use PTC but all use strong base and C-alkylation.

Note that this is similar to the condenstion of benzaldehyde with alanine to give phenyl propanolamine except that the yields with these, above, procedures are better and the end product can be amphetamine rather PPA.