Home
  >  
Section 11
  >  
Chapter 10,215

Asymmetric synthesis of alpha,alpha-difluoro-beta-amino acid derivatives from enantiomerically pure N-tert-butylsulfinimines

Staas, D.D.; Savage, K.L.; Homnick, C.F.; Tsou, N.N.; Ball, R.G.

Journal of Organic Chemistry 67(23): 8276-8279

2002

ISSN/ISBN: 0022-3263
PMID: 12423170
Accession: 010214883
Download citation:  
Text
  |  
BibTeX
  |  
RIS
Addition of the Reformatsky reagent derived from ethyl bromodifluoroacetate to alkyl- and aryl-substituted N-tert-butylsulfinimines furnishes beta-tert-butylsulfinamyl-beta-substituted alpha,alpha-difluoroproponiates in diastereomeric ratios ranging from 80:20 to 95:5. The diastereomers are easily separated and the enantiomerically pure, protected beta-amino esters are readily transformed to the corresponding acid, amide, and amine derivatives as useful synthons for medicinal chemistry targets.

PDF emailed within 1 workday: $29.90




Related References

Satoh, T.; Fukuda, Y. 2003: A new synthesis of enantiomerically pure alpha- and beta-amino acid derivatives using aziridinyl anions Tetrahedron 59(49): 9803-9810, 1 December
Vidal, A.; Nefzi, A.; Houghten, R.A. 2002: Solid phase synthesis of alpha,alpha-difluoro-beta-amino acid derivatives by Reformatsky reaction Abstracts of Papers American Chemical Society 223(1-2): ORGN 234
Boutin, R.H.; Rapoport, H. 1986: Alpha amino acid derivatives as chiral educts for asymmetric products synthesis of sphingosine from alpha' amino alpha beta ynones Journal of Organic Chemistry 51(26): 5320-5327
Kazmierski, W.M.; Hruby, V.J. 1991: Asymmetric synthesis of topographically constrained amino acids synthesis of the optically pure isomers of alpha beta dimethylphenylalanine and alpha beta dimethyl 1 2 3 4 tetrahydroisoquinoline 3 carboxylic acid Tetrahedron Letters 32(41): 5769-5772
Yang; Foster; Stephenson; Brown; Roberts 2000: Asymmetric wolff rearrangement reactions with alpha-alkylated-alpha-diazoketones: stereoselective synthesis of alpha-substituted-beta-amino acid derivatives Organic Letters 2(14): 2177-2179
Cheguillaume, A.; Lacroix, S.; Marchand-Brynaert, J. 2003: A practical synthesis of 2,2-difluoro-3-amino-propanoic acid (alpha,alpha-difluoro-beta-alanine) Tetrahedron Letters 44(11): 2375-2377
Hvidt, T.; Szarek, W.A.; Maclean, D.B. 1988: Synthesis of enantiomerically pure beta amino alpha methylene gamma butyrolactones by way of ozonolysis of aromatic alpha amino acids Canadian Journal of Chemistry 66(4): 779-782
Soloshonok, V.A.; Ohkura, H.; Sorochinsky, A.; Voloshin, N.; Markovsky, A.; Belik, M.; Yamazaki, T. 2002: Convenient, large-scale asymmetric synthesis of beta-aryl-substituted alpha,alpha-difluoro-beta-amino acids Tetrahedron Letters 43(31): 5445-5448, 29 July
Yamagishi, T.; Suemune, K.; Yokomatsu, T.; Shibuya, S. 2002: Asymmetric synthesis of beta-amino-alpha-hydroxyphosphinic acid derivatives through hydrophosphinylation of alpha-amino aldehydes Tetrahedron 58(13): 2577-2583, 25 March
Ghosez, Leon; Yang, Gaoqiang; Cagnon, Jos-Renato; Le-Bideau, Franck; Marchand-Brynaert, Jacqueline 2004: Synthesis of enantiomerically pure alpha-amino-beta-hydroxycyclobutanone derivatives and their transformations into polyfunctional three- and five-membered ring compounds Tetrahedron 60(35): 7591-7606
Sorochinsky, A.; Voloshin, N.; Markovsky, A.; Belik, M.; Yasuda, N.; Uekusa, H.; Ono, T.; Berbasov, D.O.; Soloshonok, V.A. 2003: Convenient asymmetric synthesis of beta-substituted alpha,alpha-difluoro-beta-amino acids via Reformatsky reaction between Davis' N-sulfinylimines and ethyl bromodifluoroacetate Journal of Organic Chemistry 68(19): 7448-7454
Tang, X.; Soloshonok, V.A.; Hruby, V.J. 2001: Asymmetric synthesis of alpha,beta-disubstituted-alpha-amino acids via direct alkylation of chiral amino acid derivatives with racemic sec-alkyl bromides Abstracts of Papers American Chemical Society 221(1-2): ORGN 16
Abellan, T.; Mancheno, B.; Najera, C.; Sansano, J., M. 2001: Asymmetric synthesis of alpha-amino acids from alpha,beta-(Z)-didehydroamino acid derivatives with 1,2,3,6-tetrahydropyrazin-2-one structure Tetrahedron 57(30): 6627-6640
Hung, M.-H.; Long, L.; Yang, Z.-Y. 2004: New and efficient syntheses of alpha-iodo-alpha,alpha-difluoro- and beta-iodo-alpha,alpha,beta,beta-tetrafluorocarboxylic acid derivatives as useful building blocks for making functional fluoro compounds Journal of Organic Chemistry 69(1): 198-201
Wade, T.N.; Kheribet, R. 1980: New convenient synthesis of .beta.,.beta.-difluoro amines and .beta.,.beta.-difluoro-.alpha.-amino acid alkyl esters by the addition of hydrogen fluoride on 1-azirines The Journal of Organic Chemistry 45(26): 5333-5335
Chen, X.; Zhu, Y.; Qiao, Z.; Xie, M.; Lin, L.; Liu, X.; Feng, X. 2010: Efficient synthesis of beta-hydroxy-alpha-amino acid derivatives via direct catalytic asymmetric aldol reaction of alpha-isothiocyanato imide with aldehydes Chemistry 16(33): 10124-10129
García Ruano, J.. L..; Fernández, I..; del Prado Catalina, M..; Hermoso, J.. A..; Sanz-Aparicio, J..; Martínez-Ripoll, M.. 1998: Enantiomerically Pure alpha-Alkylidene beta-Amino Esters from Asymmetric Addition of Metal Dienolates to N-Sulfinylimines Journal of Organic Chemistry 63(21): 7157-7161
Moody, H.M.; Kaptein, B.; Broxterman, Q.B.; Boesten, W.H.J.; Kamphuis, J. 1994: Synthesis of enantiomerically pure 2,2-disubstituted-2-amino-ethanols by dissolving metal reduction of alpha,alpha-disubstituted amino acid amides Tetrahedron Letters 35(11): 1777-1780
Matsushita, M.; Maeda, H.; Kodama, M. 1998: Asymmetric synthesis of alpha,alpha-disubstituted alpha-amino acid derivatives using MABR promoted rearrangement Tetrahedron Letters 39(22): 3749-3752
Palomo, C.; Ganboa, I.; Odriozola, B.; Linden, A. 1997: Synthesis of - and -tert leucine enabling direct coupling with alpha-amino acid esters via beta-lactam-derived alpha-amino acid N-carboxy anhydrides Tetrahedron Letters 38(17): 3093-3096