Catalytic Enantioselective Arylation of Aldehydes by Using Functionalized Grignard Reagents Generated from Aryl Bromides

Abstract

An efficient catalytic method has been developed for the enantioselective synthesis of functionalized diarylmethanols starting from aryl bromides and aldehydes. In the presence of (R)-3-(3,5-diphenylphenyl)BINOL (2 mol%) and titanium tetraisopropoxide, functionalized aryl Grignard reagents (FGArMgCl; FG = 3-F₃C, 4-F₃C, 3-Br, 3-CN, 4-CN), prepared in situ by treatment of the bromides with i-PrMgCl˙LiCl, undergo addition to aldehydes to give the corresponding functionalized diarylmethanols in high enantioselectivities.

Key words

aldehydes - arylation - asymmetric catalysis - magnesium - titanium

References and Notes

• Review:
• 1a Schmidt F. Stemmler RT. Rudolph J. Bolm C. Chem. Soc. Rev.  2006,  35:  454 
• 1b Paixão MW. Braga AL. Lüdtke DS. J. Braz. Chem. Soc.  2008,  19:  813 
• 2a Sakai M. Ueda M. Miyaura N. Angew. Chem. Int. Ed.  1998,  37:  3279 
• 2b Yamamoto Y. Kurihara K. Miyaura N. Angew. Chem. Int. Ed.  2009,  48:  4414 
• 2c Nishimura T. Kumamoto H. Nagaosa M. Hayashi T. Chem. Commun.  2009,  5713 
• 2d Morikawa S. Michigami K. Amii H. Org. Lett.  2010,  12:  2520 
• 2e Karthikeyan J. Jeganmohan M. Cheng C.-H. Chem. Eur. J.  2010,  16:  8989 ; and references cited therein
• 3a Bolm C. Rudolph J. J. Am. Chem. Soc.  2002,  124:  14850 
• 3b Schmidt F. Rudolph J. Bolm C. Adv. Synth. Catal.  2007,  349:  703 
• 3c Wang X.-B. Kodama K. Hirose T. Yang X.-F. Zhang G.-Y. Tetrahedron: Asymmetry  2010,  21:  75 
• 3d Wouters AD. Trossini GHG. Stefani HA. Lüdtke DS. Eur. J. Org. Chem.  2010,  2351 
• 3e Moro AV. Tiekink ERT. Zukerman-Schpector J. Lüdtke DS. Correia CRD. Eur. J. Org. Chem.  2010,  3696 ; and references cited therein
• 4a Shannon J. Bernier D. Rawson D. Woodward S. Chem. Commun.  2007,  3945 
• 4b Glynn D. Shannon J. Woodward S. Chem. Eur. J.  2010,  16:  1053 
• 5a Muramatsu Y. Harada T. Angew. Chem. Int. Ed.  2008,  47:  1088 
• 5b Muramatsu Y. Harada T. Chem. Eur. J.  2008,  14:  10560 
• 5c Muramatsu Y. Kanehira S. Tanigawa M. Miyawaki Y. Harada T. Bull. Chem. Soc. Jpn.  2010,  83:  19 
• 5d Nakagawa Y. Muramatsu Y. Harada T. Eur. J. Org. Chem.  2010,  6535 
• Review:
• 6a Knochel P. Dohle W. Gommermann N. Kneisel FF. Kopp F. Korn T. Sapountzis I. Vu VA. Angew. Chem. Int. Ed.  2003,  42:  4302 
• 6b Knochel P. Krasovskiy A. Sapountzis I. In Handbook of Functionalized Organometallics   Vol. 1:  Knochel P. Wiley-VCH; Weinheim: 2005.  p.109 
• 6c Hiriyakkanavar I. Baron O. Wagner AJ. Knochel P. Chem. Commun.  2006,  583 
• 7a Boymond L. Rottlander M. Cahiez G. Knochel P. Angew. Chem. Int. Ed.  1998,  37:  1701 
• 7b Krasovskiy A. Knochel P. Angew. Chem. Int. Ed.  2004,  43:  3333 
• 7c Shi L. Chu Y. Knochel P. Mayr H. J. Org. Chem.  2009,  74:  2760 
• 7d Piller FM. Metzger A. Schade M. Haag BA. Gavryushin A. Knochel P. Chem. Eur. J.  2009,  15:  7192 
• 8 Fillon H. Gosmini C. Périchon J. J. Am. Chem. Soc.  2003,  125:  3867 
• 9 Leazer JL. Cvetovich R. Tsay F.-R. Dolling U. Vickery T. Bachert D. J. Org. Chem.  2003,  68:  3695 
• 10 Welch JT. Eswarakrishnan S. Fluorine in Bioorganic Chemistry   John Wiley and Sons; New York: 1991.  p.246 

11

The mixed titanium reagent of 2-MeOC₆H₄MgBr and Ti(Oi-Pr)₄ also underwent nonenantioselective reaction to an aldehyde.^5c Intramolecular coordination of the ortho substituents to the titanium center might be responsible for the poor selectivities.