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Bisoxazoline ligand

In chemistry, bisoxazoline ligands (BOX ligands for short) are chiral ligands based on an bis oxazoline skeleton and used in combination with a metal compound in asymmetric synthesis as a chiral catalyst ^[1]. Three frequently encountered such ligands are PyBOX, tBuBOX and PhBOX. BOX ligands exist as organic compounds with the organometallic complex formed in-situ or as pre-prepared metal complexes.

Bisoxazoline	R	Systematic name	CAS number	Melting point °C
PyBOX	phenyl	2,6-Bis[(4R)-4-phenyl-2-oxazolinyl]pyridine	128249-70-7	171-175
tBuBOX	tert-butyl	(S,S)-2,2′-Methylenebis(4-tert-butyl-2-oxazoline)	132098-54-5	51-53
PhBOX	phenyl	(S,S)-2,2-Bis(4-phenyl-2-oxazolin-2-yl)propane	131457-46-0	56-58
Representative bisoxazolines ^[2]

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Background

In 1968 Ryoji Noyori and William S. Knowles independently developed the first chiral ligands, with those of Knowles based on phosphorus and those of Noyori based on nitrogen. One advantage of chiral nitrogen-containing compounds is that they are cheaply available for instance from naturally occurring chiral amino acids. The Noyori ligand ^[3] is based on a reaction of salicylaldehyde with chiral methylbenzylamine to the imine followed by complexation with copper(II) acetate to the dinuclear copper complex. The cyclopropanation of styrene with ethyl diazoacetate results in a mixture of cis and trans isomers with a very modest enantiomeric excess of 6%.


Noyori ligand synthesis 1968		Noyori cyclopropanation 1968

In 1975 Aratani ^[4] used a similar ligand in the asymmetric cyclopropanation of another diene to the insecticide chrysanthemic acid. His ligand was derived from reaction of salicylaldehyde with a chiral amino alcohol (the latter synthesized from a Grignard reaction with an ester of chiral alanine).


Aratani ligand synthesis 1975		Aratani cyclopropanation 1975

In 1984 Brunner ^[5] started the development of nitrogen containing ligands because phosphine ligands tended to fail in enantioselective hydrosilylations which was the focus of many research groups. One 1984 study describes a nitrogen-nitrogen bidentate ligand with a pyridine group fused to a thiazolidine group.

In 1989 Brunner replaced the thiazolidine (difficult to control stereochemistry) by an oxazoline group ^[6] and demonstrated the new ligand in a monophenylation of a diol by the organobismuth compound triphenylbismuth diacetate.


Enantioselective hydrosilylation Brunner 1984. ^[7]		Enantioselective phenylation Brunner 1989

In the same year hydrosilylation was demonstrated with a closely related pyridine-oxazoline by Balavoine ^[8].

As a logical follow-up step, PyBOX with pyridine flanked by two oxazoline groups, was also introduced in 1989 by Nishiyama ^[9]. With three nitrogen atoms this ligand is tridentate with bite angle 158.7° in a complex with rhodium(III) chloride. The isobutyl derivate is synthesized in several steps starting from pyridine-2,5-dicarboxylic acid. The nitrogen fragment is easily obtained from naturallly occurring valine.


Enantioselective hydrosilylation Balavoine 1989		Enantioselective hydrosilylation Nishiyama 1989

BOX-type ligands based on malonate esters and chiral amino alcohols (obtained by reduction of the corresponding amino acids) were first described by in 1990 by Masamune ^[10] and in 1991 by David Evans. ^[11] ^[12]


PyBOX synthesis Nishiyama 1989		Bisoxazoline synthesis Evans 1991

As before, the ligands are obtained by reaction of an acid chloride with L-valinol (which is the reduced form of valine) followed by ring-closure to the acetal and an elimination reaction (facilitated by either thionyl chloride or tosyl chloride) to the oxazoline.

Both Masamune and Evans demonstrated their nearly identical BOX ligands in a cyclopropanation reaction via diazotation.


Bisoxazoline ligand in cyclopropanation Evans 1991 ^[13]		Bisoxazoline ligand in cyclopropanation Masamune 1990

Scope

Many organic reactions (not just hydrosilylations or cyclopropanations) are found to display enantioselectivity when performed in presence of a BOX ligand. The obvious targets are 100% enantiomeric excess (ee) with the use of as little as possible amounts of metal and ligand, usually between 0.01 equivalent and 0.1 equivalent. Selecting the ligand most suitable for a particular reaction is most often a process of trial and error.


Aldol addition ^[14]		Copper catalyzed nucleophilic addition of an alkyne to pyridinium chloride ^[15]


Friedel-Crafts alkylation at indole^[16]		Henry reaction ^[17]


Diels-Alder reaction resulting in verbenone synthesis ^[18] ^[19]		Copolymerization of cyclohexene oxide and carbon dioxide ^[20]

References

^ Bisoxazoline (BOX) Ligand-Metal Complexes: An Emerging Chiral Catalyst Ramkrishna Basak Synlett 2003, No. 8, 1223–1224 Article link
^ www.sigmaaldrich.com
^ Homogeneous catalysis in the decomposition of diazo compounds by copper chelates : Asymmetric carbenoid reactions Tetrahedron, Volume 24, Issue 9, 1968, Pages 3655-3669 H. Nozaki, H. Takaya, S. Moriuti and R. Noyori doi:10.1016/S0040-4020(01)91998-2
^ Asymmetric synthesis of chrysanthemic acid. An application of copper carbenoid reaction Tetrahedron Letters, Volume 16, Issue 21, 1975, Pages 1707-1710 T. Aratani, Y. Yoneyoshi and T. Nagase
^ Asymmetric syntheses. 20. Enantioselective hydrosilylation of ketones with [Rh(cod)Cl 2/thiazolidine catalysts Henri Brunner, Richard Becker, and Georg Riepl Organometallics; 1984; 3(9) pp 1354 - 1359; doi:10.1021/om00087a006
^ Asymmetric catalysis. 44. Enantioselective monophenylation of diols with cupric acetate/pyridinyloxazoline catalysts Henri Brunner, Uwe Obermann, and Peter Wimmer Organometallics; 1989; 8(3) pp 821 - 826; doi:10.1021/om00105a039
^ Substrate acetophenone, metal catalyst the Cyclooctadiene rhodium chloride dimer, hydride donor: diphenylsilyl hydride. The intermediate silyl ether is converted to the alcohol by protonation. The thiazolidine group is a diastereomeric pair due to epimerization at C2 but this does not affact the outcome of the reaction
^ Enantioselective hydrosilylation of acetophenone with rhodium / oxazolines catalysts Tetrahedron Letters, Volume 30, Issue 38, 1989, Pages 5141-5144 G. Balavoine, J. C. Clinet and I. Lellouche doi:10.1016/S0040-4039(01)93469-0
^ Chiral and C2-symmetrical bis(oxazolinylpyridine)rhodium(III) complexes: effective catalysts for asymmetric hydrosilylation of ketones Hisao Nishiyama, Hisao Sakaguchi, Takashi Nakamura, Mihoko Horihata, Manabu Kondo, and Kenji Itoh Organometallics; 1989; 8(3) pp 846 - 848; doi:10.1021/om00105a047 10.1021/om00105a047
^ Asymmetric catalytic cyclopropanation of olefins: bis-oxazoline copper complexes Tetrahedron Letters, Volume 31, Issue 42, 1990, Pages 6005-6008 Richard E. Lowenthal, Atsushi Abiko and Satoru Masamune doi:10.1016/S0040-4039(00)98014-6
^ Bis(oxazolines) as chiral ligands in metal-catalyzed asymmetric reactions. Catalytic, asymmetric cyclopropanation of olefins David A. Evans, Keith A. Woerpel, Mira M. Hinman, and Margaret M. Faul J. Am. Chem. Soc.; 1991; 113(2) pp 726 - 728; doi:10.1021/ja00002a080
^ Organic Syntheses, Vol. 83, p.97 (2006). Link
^ Asymmetric cyclopropanation of styrene with an diazo compound catalysed by copper(I) triflate / tBuBOX
^ C2-Symmetric Tin(II) Complexes as Chiral Lewis Acids. Catalytic Enantioselective Anti Aldol Additions of Enolsilanes to Glyoxylate and Pyruvate Esters Evans, D. A.; MacMillan, D. W. C.; Campos, K. R. J. Am. Chem. Soc.; (Communication); 1997; 119(44); 10859-10860. doi:10.1021/ja972547s 10.1021/ja972547s
^ Enantioselective Addition of Activated Terminal Alkynes to 1-Acylpyridinium Salts Catalyzed by Cu-Bis(oxazoline) Complexes Zhankui Sun, Shouyun Yu, Zuoding Ding, and Dawei Ma J. Am. Chem. Soc.; 2007; 129(30) pp 9300 - 9301; (Communication) doi:10.1021/ja0734849
^ Asymmetric Friedel-Crafts Alkylations of Indoles with Nitroalkenes Catalyzed by Zn(II)-Bisoxazoline Complexes Yi-Xia Jia, Shuo-Fei Zhu, Yun Yang, and Qi-Lin Zhou J. Org. Chem.; 2006; 71(1) pp 75 - 80; (Article) doi:10.1021/jo0516537
^ Catalytic asymmetric Henry reactions—a simple approach to optically active -nitro -hydroxy esters Christina Christensen, Karsten Juhl and Karl Anker Jørgensen Chem. Commun., 2001, 2222 - 2223, doi:10.1039/b105929g open access
^ Catalytic asymmetric Diels–Alder reactions of -thioacrylates for the preparation of norbornenone Varinder K. Aggarwal, Emma S. Anderson, D. Elfyn Jones, Kerstin B. Obierey, Robert Giles, Chem. Commun., 1998, (18),1985-1986 doi:10.1039/a805366i open access
^ the final conversion with diphenylphosphoryl azide involves a modified Curtius rearrangement
^ Enantiomerically-enriched organic reagents via polymer synthesis: enantioselective copolymerization of cycloalkene oxides and CO2 using homogeneous, zinc-based catalysts Ming Cheng, Nicholas A. Darling, Emil B. Lobkovsky and Geoffrey W. Coates Chem. Commun., 2000, 2007 - 2008, doi:10.1039/b005537i 10.1039/b005537i open access

Category: Organic chemistry

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Bisoxazoline_ligand". A list of authors is available in Wikipedia.