Towards Optically Pure Mono- and Difluorinated Amino Acids: Common Methodology­ Based on (R)-2,3-O-Isopropylideneglyceraldehyde

Abstract

The stereocontrolled synthesis of N-protected (2S,3R)-2-amino-3-fluoroundecanoic and (3R)-3-amino-2,2-difluoroundecanoic acids, as representative examples, from commercially available optically pure (R)-2,3-O-isopropylideneglyceraldehyde is described. Key steps involve the Mitsunobu reaction for the introduction of amino function, and incorporation of fluorine atom(s) by the fluorinating agent, morpholinotrifluorosulfurane.

Key words

nucleophilic fluorination - 1,2-diols - the Mitsunobu reaction - protecting group - fluorine-containing amino acids

References

• 1a Welch JT. Eswarakhrishnan S. In Fluorine in Bioorganic Chemistry   Wiley; New York: 1991. 
• 1b Organofluorine Compounds in Medicinal Chemistry and Biomedical Applications   Filler R. Kobayashi Y. Yagupolskii LM. Elsevier; Amsterdam: 1993. 
• 1c Biomedical Frontiers of Fluorine Chemistry   Ojima I. McCarty JR. Welch JT. American Chemical Society; Washington: 1996. 
• 2 Sewald N. Burger K. In Fluorine-Containing Amino Acids   Kukhar VP. Soloshonok VA. Wiley; New York: 1995. 
• 3a Abeles RH. Maycock AL. Acc. Chem. Res.  1976,  9:  313 
• 3b Kollonitsh J. Israel J. Chem.  1978,  17:  53 
• 3c Hageman JJM. Wanner MJ. Koomen GJ. Pandit UK. J. Med. Chem.  1977,  20:  1677 
• 4a Soloshonok VA. Svedas VA. Kukhar VP. Kirilenko AG. Rybakova AV. Solodenko VA. Fokina NA. Kogut OV. Galaev IYu. Kozlova EV. Shishkina IP. Galushko SV. Synlett  1993,  339 
• 4b Soloshonok VA. Kirilenko AG. Fokina NA. Shishkina IP. Galushko SV. Kukhar VP. Svedas VA. Kozlova EV. Tetrahedron: Asymmetry  1994,  6:  1119 
• 4c Soloshonok VA. Kirilenko AG. Fokina NA. Kukhar VP. Galushko SV. Svedas VA. Resnati G. Tetrahedron: Asymmetry  1994,  7:  1225 
• 4d Soloshonok VA. Fokina NA. Rybakova AV. Shishkina IP. Galushko SV. Sorochinsky AE. Kukhar VP. Savchenko MV. Svedas VA. Tetrahedron: Asymmetry  1995,  7:  1601 
• 5 Fokina NA. Kornilov AM. Kukhar VP. J. Fluorine Chem.  2001,  111:  69 
• 6 Kolb M. Barth J. Heydt J.-G. Jung MJ. J. Med. Chem.  1987,  30:  267 
• 7 Bey P. Ducep JB. Schirlin D. Tetrahedron Lett.  1984,  25:  5657 
• 8 Bravo P. Cavicchio G. Crucianelli M. Poggiali A. Zanda M. Tetrahedron: Asymmetry  1997,  16:  2811 
• 9a Kornilov AM. Sorochinsky AE. Kukhar VP. Tetrahedron: Asymmetry  1994,  6:  1015 
• 9b Kornilov AM. Kulik IB. Sorochinsky AE. Kukhar VP. Tetrahedron: Asymmetry  1995,  14:  199 
• 9c Kornilov AM. Kulik IB. Kukhar VP. Presented at 16th International Symposium - Fluorine Chemistry   Durham, England: 2000. ; Abstr. Nr. 2P-92
• 10a Schmid CR. Bradley DA. Synthesis  1992,  587 
• 10b Earle MJ. Abdur-Rashid A. Priestley ND. J. Org. Chem.  1996,  61:  5697 
• 10c Jurczak J. Pikul S. Bauer T. Tetrahedron  1986,  42:  447 
• 11 Hanessian S. Total Synthesis of Natural Products: The ‘Chiron’ Approach   Pergamon; Oxford: 1983. 
• 12a Middleton WJ. Mange KC. J. Fluorine Chem.  1989,  43:  405 
• 12b Messina PA. Mange KC. Middleton WJ. J. Fluorine Chem.  1989,  42:  137 
• 13a Leroy J. Hebert E. Wakselman C. J. Org. Chem.  1979,  19:  3406 
• 13b Kusumoto T. Ogino K. Sato K. Hiyama T. Takehara S. Nakamura K. Chem. Lett.  1993,  1243 
• 13c Card PJ. Reddy GS. J. Org. Chem.  1983,  48:  4734 
• 13d Jonge S. Overmeire I. Calenberg S. Hendrix C. Busson R. Keukeleire D. Herdewijn P. Eur. J. Org. Chem.  2000,  3177 
• 13e Avent AG. Bowler AN. Doyle PM. Marchand CM. Young DW. Tetrahedron Lett.  1992,  11:  1509 
• 14 Middleton WJ. J. Org. Chem.  1975,  40:  574 
• 15 Hudlizky M. Org. React.  1988,  35:  513 
• 16 Martin SF. Dodge JA. Tetrahedron Lett.  1991,  26:  3017 
• 17 Hughes DL. Org. React.  1992,  39:  42 
• 18 Mancuso AJ. Swern D. Synthesis  1981,  165 
• 19 Lal GS. Pez GP. Pesaresi RJ. Prozonic FM. Cheng H. J. Org. Chem.  1999,  64:  7048 
• 20 Markovskij LN. Pashinnik VE. Kirsanov AV. Synthesis  1973,  787 
• 21 Jackson DY. Synth. Commun.  1988,  4:  337