A New Cysteine-Derived Ligand as Catalyst for the Addition of Diethylzinc to Aldehydes: The Importance of a ‘Free’ Sulfide Site for Enantioselectivity

Abstract

New chiral sulfides and disulfides were synthesized from readily available and inexpensive cysteine by straightforward methods in order to elucidate the relative importance of the various donor atoms (N, O, S) available in free or alkylated form resulting in covalent or dative bonds to the metal, respectively. Their application in the addition of diethylzinc to aldehydes provides secondary alcohols with up to 99% ee, and S-configuration, when catalytic amounts of disulfide ligands with the ability to form an S-Zn bond were used. In contrast to this, benzyl alcohols with the opposite absolute configuration R could be achieved, albeit with decreased yield and enantioselectivity, by the use of alkylated sulfide ligands.

Key words

cysteine - disulfide - chiral ligands - dialkylzinc - asymmetric synthesis

References

• 1 Gawley RE. Aube J. Principles of Asymmetric Synthesis   Pergamon; London: 1996. 
• 2 Seyden-Penne J. Chiral Auxiliaries and Ligands in Asymmetric Synthesis   Wiley; New York: 1995. 
• 3 Noyori R. Asymmetric Catalysis in Organic Synthesis   Wiley; New York: 1994. 
• 4 Noyori R. Kitamura M. Angew. Chem., Int. Ed. Engl.  1991,  30:  49 ; Angew. Chem. 1991, 103, 34
• 5 Kitamura M. Okada S. Suga S. Noyori R. J. Am. Chem. Soc.  1989,  111:  4028 
• 6 Yamakawa M. Noyori R. J. Am. Chem. Soc.  1995,  117:  6327 
• 7 Kitamura M. Suga S. Oka H. Noyori R. J. Am. Chem. Soc.  1998,  120:  9800 
• 8 Kitamura M. Yamakawa M. Oka H. Suga S. Noyori R. Chem.-Eur. J.  1996,  2:  1173 
• 9 Kitamura M. Oka H. Noyori R. Tetrahedron  1999,  55:  3605 
• 10 Bolm C. Hildebrand JP. Muniz K. Hermanns N. Angew. Chem. Int. Ed.  2001,  40:  3284 ; Angew. Chem. 2001, 113, 3284
• 11 Rudolph J. Rasmussen T. Bolm C. Norrby P.-O. Angew. Chem. Int. Ed.  2003,  42:  3002 ; Angew. Chem. 2003, 115, 3110
• 12 Bolm C. Hermanns N. Hildebrand JP. Muñiz K. Angew. Chem. Int. Ed.  2000,  39:  3465 ; Angew. Chem. 2000, 112, 3607
• 13 Bolm C. Schlingloff G. Harms K. Chem. Ber.  1992,  125:  1191 
• 14 Bringmann G. Breuning M. Tetrahedron: Asymmetry  1998,  9:  667 
• 15 Cho BT. Chun YS. Tetrahedron: Asymmetry  1998,  9:  1489 
• 16 Hulst R. Heres H. Fitzpatrick K. Peper NCMW. Kellogg RM. Tetrahedron: Asymmetry  1996,  9:  2755 
• 17 Fitzpatrick K. Hulst R. Kellogg RM. Tetrahedron: Asymmetry  1995,  6:  1861 
• 18 Hof RP. Poelert MA. Peper NCMW. Kellogg RM. Tetrahedron: Asymmetry  1994,  5:  31 
• 19 Rijnberg E. Hovestad NJ. Kleij AW. Jastrzebski JTBH. Boersma J. Janssen MD. Spek AL. van Kroten G. Organometallics  1997,  16:  2847 
• 20 Rijnberg E. Jastrzebski JTBH. Janssen MD. Boersma J. van Koten G. Tetrahedron Lett.  1994,  35:  6521 
• 21 Kang J. Lee JW. Kim JI. J. Chem. Soc., Chem. Commun.  1994,  2009 
• 22 Kang J. Kim DS. Kim JI. Synlett  1994,  842 
• 23 Gibson CL. Tetrahedron: Asymmetry  1999,  10:  1551 
• 24 Fulton DA. Gibson CL. Tetrahedron Lett.  1997,  38:  2019 
• 25 Gibson CL. Chem. Commun.  1996,  645 
• 26 Anderson JC. Cubbon R. Harding M. James DS. Tetrahedron: Asymmetry  1998,  9:  3461 
• 27 Anderson JC. Harding M. Chem. Commun.  1998,  393 
• 28 Kossenjans M. Pennemann H. Martens J. Juanes O. Rodrigues-Ubis JC. Brunet E. Tetrahedron: Asymmetry  1998,  9:  4123 
• 29 Kossenjans M. Soeberdt M. Wallbaum S. Harms K. Martens J. Aurich HG. J. Chem. Soc., Perkin Trans. 1  1999,  2353 
• 30 Juanes O. Rodriguez-Ubis JC. Brunet E. Pennemann H. Kossejans M. Martens J. Eur. J. Org. Chem.  1999,  3323 
• 31 Kossejans M. Martens J. Tetrahedron: Asymmetry  1998,  9:  1409 
• 32 Trentmann W. Mehler T. Martens J. Tetrahedron: Asymmetry  1997,  12:  2033 
• 33 Cho BT. Chun YS. Synth. Commun.  1999,  29:  521 
• 34 Huang HL. Lin YC. Chen SF. Wang CLJ. Liu LT. Tetrahedron: Asymmetry  1996,  7:  3067 
• 35 Nakano H. Kumagai N. Matsuzaki H. Kabuto C. Hongo H. Tetrahedron: Asymmetry  1997,  8:  1391 
• 36 Braga AL. Appelt HR. Schneider PH. Silveira CC. Wessjohann LA. Tetrahedron: Asymmetry  1999,  10:  1733 
• 37 Braga AL. Appelt HR. Schneider PH. Rodrigues OED. Silveira CC. Wessjohann LA. Tetrahedron  2001,  57:  3291 
• 38 Braga AL. Appelt HR. Silveira CC. Wessjohann LA. Schneider PH. Tetrahedron  2002,  58:  10413 
• 39a Braga AL. Silva S. Lüdtke DS. Drekener R. Silveira CC. Rocha JB. Wessjohann LA. Tetrahedron Lett.  2002,  43:  7329 
• 39b Braga AL. Paixão MV. Lüdtke DS. Silveira CC. Rodrigues OED. Org. Lett.  2003,  5:  2635 
• 40 Schrekker HS. Schneider PH. Wessjohann LA. Silveira CC. Braga AL. Eur. J. Org. Chem.  2004,  2715 
• 41 Braga AL. Rubim RM. Schrekker HS. Wessjohann LA. de Bolster MWG. Zeni G. Sehnem JA. Tetrahedron: Asymmetry  2003,  14:  3291 
• 42 Gelinsky M. Vogler R. Vahrenkamp H. Inorg. Chim. Acta  2003,  334:  230 
• 43 Gockel P. Vogler R. Gelinsky M. Meißner A. Albrich H. Vahrenkamp H. Inorg. Chim. Acta  2001,  323:  16 
• 44a Confalone PN. Pizzolato G. Baggiolini EG. Lollar D. Uskoković MR. J. Am. Chem. Soc.  1977,  99:  7020 
• 44b McKennon MJ. Meyers AI. J. Org. Chem.  1993,  58:  3568 
• 45 Casey M. Smith MP. Synlett  2003,  102 
• 47 Soai K. Ookawa A. Ogawa K. Kaba T. J. Chem. Soc., Chem. Commun.  1987,  467 
• 48 Eilers J. Wilken J. Tetrahedron: Asymmetry  1996,  7:  2343 
• 49 Masdeu-Bulstó AM. Diégues M. Martin E. Gómez M. Coord. Chem. Rev.  2003,  242:  159 

46

We thank a referee for pointing out the likely possibility of a transition state with 6-membered S/O-zinc-coordination to ligand 2. This explanation is based on the importance of a free sulfide site and its strength for primary binding. Would thioether-binding be sufficiently stable as sole first coordination point, ligands 5 and 6 should give stereoinduction with opposing signs of rotation. This was not observed.