1. Development of privileged chiral spiro ligands and catalysts
Although a great number of chiral ligands as well as chiral catalysts have been reported in the past decades, only a handful of them rooted on a very few core structures can be regarded as truly successful as they demonstrate proficiency in a variety of mechanistically unrelated reactions. People named the chiral catalysts showing good enantioselectivity over a wide range of different reactions "privileged chiral catalysts", term coined by Jacobsen. The essential thing makes one catalyst to be "privileged" is the scaffold (core structure) it possessed. Chiral 1,1'-spirobiindane scaffold collect high rigidity, perfect C2 symmetric, simple chirality, and easy modification and represents one of the ideal chiral ligand backbones. Starting with easily available 1,1'-spirobiindane-7,7'-diol (SPINOL), more than one hundred chiral spiro ligands including diphosphines SDPs, bisoxazolines SpiroBOXs, amino-phosphines SpiroAP, phosphine-oxazolines SIPHOXs, diimines SIDIMs, and a wide range of monodentate phosphorous ligands SITCPs, ShiPs, FuPs, and SIPHOS, have been prepared through a single or multiple steps. Some of these ligands, such as SIPHOS, ShiPs, SDPs, SIPHOXs, and SpiroBOXs are now commercially available from Aldrich and Strem Co. The chiral spiro ligands have been applied in a variety of mechanistically unrelated reactions, such as hydrogenation, carbon–carbon bond formation, and carbon–heteroatom bond formation, and exhibit unique enantioselectivity and reactivity. The chiral spiro ligands have become one of the "privileged" chiral ligands.
2. Asymmetric hydrogenation
The transition metal-catalyzed asymmetric hydrogenation utilizing molecular hydrogen to reduce prochiral unsaturated bonds is one of the most efficient and atom-economic methods for the preparation of optically active compounds. The chiral spiro ligands including bidentate phosphines SDPs, phosphine-oxazolines SIPHOXs, amino-phosphines SpiroAP, and monodentate phosphorous ligands (SIPHOS and FuPs) exhibited high activity and excellent enantioselectivity in the asymmetric hydrogenations of functionalized olefins (including enamides, enamines, and α,β-unsaturated carboxylic acids), ketones, aldehydes, and imines.
2.1 Hydrogenation of enamides
Ref. Chem. Commun. 2002, 480–481.
Angew. Chem. Int. Ed. 2002, 41, 2348–2350.
J. Org. Chem. 2004, 69, 4648–4655.
J. Org. Chem. 2004, 69, 8157–8160.
2.2 Hydrogenation of enamines
Ref. J. Am. Chem. Soc. 2006, 128, 11774–11775.
J. Am. Chem. Soc. 2009, 131, 1366–1367.
Adv. Synth. Catal. 2009, 351, 3243–3250.
2.3 Hydrogenation of α,β-unsaturated acids
Ref. J. Am. Chem. Soc. 2008, 130, 8584–8585.
J. Am. Chem. Soc. 2010, 132, 1172–1179.
2.4 Hydrogenation of ketones
Ref. J. Am. Chem. Soc. 2003, 125, 4404–4405.
J. Am. Chem. Soc. 2010, 132, 4538–4539.
2.5 Hydrogenation of racemic α-substituted aldehydes and ketones via DKR
Ref. J. Org. Chem. 2005, 70, 2967–2973.
J. Am. Chem. Soc. 2007, 129, 1868–1869.
Angew. Chem. Int. Ed. 2007, 46, 7506–7508.
J. Am. Chem. Soc. 2009, 131, 4222–4223.
Adv. Synth. Catal. 2010, 352, 81–84.
2.6 Hydrogenation of imines
Ref. J. Am. Chem. Soc. 2006, 128, 12886–12891.
3. Asymmetric carbon-carbon bond-forming reaction
Transition metal-catalyzed asymmetric carbon-carbon bond-forming reaction is essential in modern organic synthesis. Chiral spiro monodentate and bidentate phosphorous ligands have been successfully used in various asymmetric carbon-carbon bond-forming reactions. In most of investigated reactions, the spiro ligands showed superior chiral inducements than the ligands with other backbones.
3.1 Rhodium-catalyzed asymmetric arylation reactions
Ref. Org. Lett. 2006, 8, 1479–1481.
Org. Lett. 2006, 8, 2567–2569.
Angew. Chem. Int. Ed. 2008, 47, 4351–4353.
3.2 Nickel-catalyzed three component coupling reaction
Ref. J. Am. Chem. Soc. 2007, 129, 2248–2249.
J. Am. Chem. Soc. 2008, 130, 14052–14053.
J. Am. Chem. Soc. 2010, 132, 10955–10957.
3.3 Nickel-catalyzed hydrovinylation reaction
Ref. J. Am. Chem. Soc. 2006, 128, 2780–2781.
3.4 Rhodium-catalyzed hydrosilylation/cyclization reaction
Ref. Angew. Chem. Int. Ed. 2007, 46, 1275–1277.
4. Asymmetric carbon-heteroatom bond-forming reaction
Because carbon–heteroatom (C–X) bonds are prevalent in organic compounds, the development of reliable and efficient methods for construction of such bonds is of highly practical value. Transition metal–catalyzed insertion of carbenes into heteroatom–hydrogen bonds (X–H, X = O, N, S, etc.) provides one of the most efficient approaches to the formation of C–X bonds. Remarkable advances have been made in the development of methodology for catalytic asymmetric diazo insertion into C–H bonds, but only limited success has been achieved for asymmetric diazo insertions into heteroatom–hydrogen bonds. By using chiral spiro bisoxazoline ligands SpiroBOXs and diimine ligands SIDIMs, a series of catalytic asymmetric insertion of α-diazoesters into N–H, O–H, S–H, and Si–H bonds was developed with high to excellent enantioselectivities.
Ref. J. Am. Chem. Soc. 2007, 129, 5834–5835.
J. Am. Chem. Soc. 2007, 129, 12616–12617.
Angew. Chem. Int. Ed. 2008, 47, 932–934.
Angew. Chem. Int. Ed. 2008, 47, 8496–8498.
Nature Chemistry. 2010, 2, 546−551.
5. Asymmetric synthesis of biologically active compounds
Various aforementioned catalytic procedures have been applied in the synthesis of biologically active compounds and natural products.
5.1 Synthesis of key intermediate of new blood pressure-lowering drug Aliskiren
Ref. J. Am. Chem. Soc. 2008, 130, 8584–8585.
5.2 Synthesis of key intermediate of rupintrivir, a rhinovirus protease inhibitor
Ref. J. Am. Chem. Soc. 2010, 132, 1172–1179.
5.3 Synthesis of key intermediate of active form of the anti-inflammatory loxoprofen.
Ref. J. Am. Chem. Soc. 2010, 132, 4538–4539.
5.4 Synthesis of leukotriene receptor antagonists BAY X 1005
Ref. J. Am. Chem. Soc. 2007, 129, 1868–1869.
5.5 Synthesis of highly selective κ-opioid agonist U-(-)-50488
Ref. Angew. Chem. Int. Ed. 2007, 46, 7506–7508.
5.6 Synthesis of isoquinoline alkaloid crispine A
Ref. J. Am. Chem. Soc. 2009, 131, 1366–1367.
5.7 Synthesis of natural product α- and β-conhydrine
Ref. Org. Lett. 2009, 11, 4994–4997.