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BINOL and Derivatives
BINOL and its derivatives are one of the most widely used types of ligands in asymmetric synthesis; being utilized in a variety of reactions including——Diels-Alder, carbonyl addition and reduction, Michael addition, and a variety of other reactions. Although great success has been achieved using the BINOL-catalyzed system, other C2-symmetric diol ligands have also attracted some attention. These include the arch-shaped biaryl ligands developed by Wulff and coworkers. Both arch 3,3'-biphenol (VAPOL) and arch 2,2'-binaphthol (VANOL) have proved to be excellent ligands for catalyzing asymmetric Diels-Alder, imineraldehyde, and aziridinylation reactions (Figure 1).1?Recently, a phosphate derivative of VAPOL was shown to be an effective chiral Br?nsted acid catalyst. In many of the examples shown herein, the archival biaryl group has higher yields and induction rates than using the BINOL ligand in the same reaction.
Figure 1.
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Asymmetric Diels-Alder reactions
In the very early days, catalysts generated from Et2AlCl and VAPOL were shown to be an effective catalyst for the asymmetric Diels-Alder reaction.2?As shown in Scheme 1, the cycloaddition reaction of acrolein with cyclopentadiene in the presence of VAPOL-derived catalysts allows high conversion of exo isomers and excellent stereoselectivity at very high optical purity. Similar reactions over BINOL-derived catalysts gave high yields of cyclic compounds with very low ee% values (13-41%).
Scheme 1.
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Asymmetric aziridination reactions
Aziridines are an important part of organic synthesis because they enable easy access to amines, amino alcohols, diamines, and other useful nitrogen-containing molecules. Many of the present-day methods for the preparation of chiral aziridines rely on chiral pools. Recently, the Wulff group has developed a robust catalytic asymmetric aziridination reaction that provides optically active aziridines in high yields and selectivity. The reaction relies on the addition of purchasable ethyl diazoacetate (EDA) to diphenylmethylimine in the presence of an arylboronic ester catalyst prepared from an archival aryl ligand and B(OPh)3.3?This aziridination reaction showed excellent selectivity for the cis-isomer and high ee% values were obtained. The resulting benzoyl-protected aziridines underwent a variety of reactions including: deprotection, reductive ring opening or alkylation reactions (Scheme 2, Table 1). The asymmetric synthesis of the leukocyte integrin LFA-1 antagonist, BIRT-377, utilized an azide/alkylation methodology, which provided the glycolide urea target in excellent overall yields.
Scheme 2.
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Table 1.
The rapid synthesis of the antimicrobial agent (-)-chloramphenicol utilized an asymmetric azide reaction and subsequent nucleophilic ring opening of the aziridine with dichloroacetic acid and subsequent acyl migration (Scheme 3, Table 2). Both VANOL and VAPOL afforded higher yields and stereoselectivities than the BINOL-derived catalysts.
Scheme 3.
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Table 2.
(* The product is the enantiomer of the shown aziridine)
Asymmetric hydroxyl aldehyde reaction
The asymmetric imine hydroxylaldehyde reaction can also be catalyzed by arch-associated aryl-derived catalysts, providing an important approach for the synthesis of chiral β-amino esters. Addition of methylsilyl vinyl ketone acetal to aryl imines in the presence of Zr-VANOL or Zr-VAPOL catalysts promotes highly asymmetric induction reactions and yields excellent yields (Scheme 4, Table 3). Importantly, both catalysts exhibited significantly higher levels of induction than similar BINOL-derived catalysts.4
Scheme 4.
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Table 3.
Chiral BR?NSTED acid
Antilla and colleagues demonstrated that the VAPOL hydrogen phosphate salt is a useful chiral Br?nsted acid catalyst when adding sulfonamides to Boc-activated aryl imines (Scheme 5).5?The resulting N,N-acetalized amine products were obtained in high yields as well as with impressive enantiomeric purity. The same reaction utilizing a BINOL-derived Br?nsted acid catalyst gave excellent yields (95%) but with poorer chiral control (<5% ee). A variety of sulfonamides and aryl imines can be active in the imide amidation reaction, and the resulting protected acetal amines are storage-resistant compounds.
Scheme 5.
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References
1. Bao?J,?Wulff?WD,?Dominy?JB,?Fumo?MJ,?Grant?EB,?Rob?AC,?Whitcomb?MC,?Yeung?S,?Ostrander?RL,?Rheingold?AL.?1996.?Synthesis, Resolution, and Determination of Absolute Configuration of a Vaulted 2,2’-Binaphthol and a Vaulted 3,3’-Biphenanthrol (VAPOL).?J. Am. Chem. Soc..?118(14): 3392-3405.?https://doi.org/10.1021/ja952018t
2.?(a) Bao?J,?Wulff?WD,?Rheingold?AL.?1993.?Vaulted biaryls as chiral ligands for asymmetric catalytic Diels-Alder reactions.?J. Am. Chem. Soc..?115(9): 3814-3815.?https://doi.org/10.1021/ja00062a073
(b) J?B,?W. D?W.?1995.?Angew. Chem., Int. Ed. 2000, 39, 4518.?Tetrahedron Lett.. 36, 3321.
(c) D. P. et al?H.?1997.?J. Am. Chem. Soc.?119, 10551.
3.?(a) J. C?A,?W. D?W.?1991.?J. Am. Chem. Soc.. 121, 5099.
(b) J. C?A,?W. D?W.?2000.?Angew. Chem., Int. Ed. 2000, 39, 4518.
(c) A. P. et al.?P.?2005.?Org. Lett. 2005, 7, 2201..?Org. Lett?7, 2201.
4.?S. et al.?X.?2001.?Angew. Chem., Int. Ed. .40, 2271.?https://doi.org/10.1002/1521-3757(20010618)113:12<2331::AID-ANGE2331>3.0.CO;2-P
5. Rowland?GB,?Zhang?H,?Rowland?EB,?Chennamadhavuni?S,?Wang?Y,?Antilla?JC.?2005.?Br?nsted Acid-Catalyzed Imine Amidation.?J. Am. Chem. Soc..?127(45):15696-15697.?https://doi.org/10.1021/ja0533085
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