Asymmetric hydrogenolysis of racemic 3-substitued-3-hydroxy-isoindolin-1-ones employing SPINOL-derived chiral phosphoric acid

doi:10.1016/j.tetlet.2018.03.030

Tetrahedron Letters

Volume 59, Issue 16, 18 April 2018, Pages 1592-1595

https://doi.org/10.1016/j.tetlet.2018.03.030 Get rights and content

Highlights

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Employing SPINOL-derived phosphoric acid as catalyst.
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Using a high steric demand Hantzsch ester as the hydrogen source.
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The corresponding products 3-aryl-3-hydroxyisoindolin-1-ones are obtained in good yields and up to 93% enantioselectivities.

Abstract

The asymmetric hydrogenolysis of racemic 3-substitued-3-hydroxyisoindolin-1-ones has been developed employing SPINOL-derived phosphoric acid and a high steric demand Hantzsch ester as the hydrogen source. The corresponding products are obtained in good yields and up to 93% enantioselectivities.

Graphical abstract

Introduction

The isoindolinone ring system is substructure of numerous bioactive molecules, pharmaceuticals and natural products.¹ Among the known strategies for the construction of isoindolinones, hydrogenolysis² of racemic tertiary alcohols is one of the most important methods in organic synthesis. In general, most of the hydrogenolysis reactions were processed in the presence of a transition-metal complex³ or acid⁴ to obtain the corresponding racemic product. Although the synthesis of racemic 3-substituted isoindolinones has been thoroughly explored,⁵ in contrast to the great progress made in asymmetric synthesis within few decades, the methodology for the asymmetric synthesis of 3-substituted isoindolinones with high enantioselectivity has been rarely explored. Only a few asymmetric ways to optically active isoindolinones synthesis have been described, mainly get good results by using (1) chiral auxiliaries,⁶ (2) organocatalytic approaches,⁷ or (3) other catalytic asymmetric processes (intramolecular aminocarbonylation,⁸ asymmetric Diels–Alder reaction,⁹ C–H Activation¹⁰ etc.¹¹).

Only a handful of reports focused on the organocatalytic asymmetric hydrogenolysis for the generation of 3-substituted-3-hydroxyisoindolin-1-ones. In 2012, Zhou¹² disclosed an enantio-selective hydrogenolysis of 3-alkyl-3-hydroxyisoindolin-1-ones to produce cyclic N-carbonyl chiral amines in modest to excellent enantioselectivities. In 2013, Jia¹³ reported the use of BINOL-derived chiral phosphoric acid in the enantioselective hydrogenolysis of racemic 3-aryl-3-hydroxyisoindolin-1-ones catalyzed with benzothiazoline as the hydride source. However, the extension of the 3-aryl substituted substrate to form highly enantioenriched cyclic diaryl methylamine was not very successful in both cases mentioned above (Fig. 1).

Inspired by previous works, and also in conjunction with our ongoing interest in asymmetric catalysis,¹⁴ we present herein a SPINOL-derived chiral phosphoric acid catalyzed enantioselective hydrogenolysis of 3-substituted-3-hydroxyisoindolin-1-ones 1 with Hantzsch ester as stoichiometric hydride source. Moreover, we mainly focused on 3-aryl substituted substrates 1.

Section snippets

Results and discussion

We started our investigations with evaluation of representative chiral phosphoric acids 4 for the hydrogenolysis of the 3-hydroxy-3-phenylisoindolin-1-one 1a at room temperature. Initial tests were not very promising, the desired products 2a were mostly obtained in good yields and low to moderate enantioselectivities (Table 1, entries 1–7). Then, different substituted Hantzsch esters 3 were tested (Table 1, entries 5–7), and it clearly showed that HEH 3d gave the best enantioselectivity of 90%.

Conclusion

In summary, we have successfully developed a highly efficient SPINOL-derived chiral phosphoric acid catalyzed hydrogenolysis of various 3-substitued-3-hydroxy-isoindolin-1-ones. The chiral phosphoric acids based on SPINOL backbone were found to be effective to access the corresponding 3-substitued-isoindolin-1-ones with good yields and enantioselectivities. To our knowledge, the present study is by far among the best in the asymmetric hydrogenolysis of racemic 3-aryl-3-hydroxy-isoindolin-1-ones

Acknowledgments

We sincerely thank the “Hundred Talents Program” of Harbin Institute of Technology (HIT), the “Fundamental Research Funds for the Central University” (HIT.BRETIV.201502), the NSFC (21202027), the NCET (NCET-12-0145), and the “Technology Foundation for Selected Overseas Chinese Scholar” of Ministry of Human Resources and Social Security of China (MOHRSS) for funding.

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Asymmetric hydrogenolysis of racemic 3-substitued-3-hydroxy-isoindolin-1-ones employing SPINOL-derived chiral phosphoric acid

Highlights

Abstract

Graphical abstract

Introduction

Section snippets

Results and discussion

Conclusion

Acknowledgments

J Am Chem Soc

J Org Chem

Angew Chem Int Ed

J Org Chem

Org Process Res Dev

J Med Chem

Org Lett

Angew Chem, Int Ed

Angew Chem Int Ed

Angew Chem, Int Ed

Org Lett

ACS Catal

Handbook of Organopalladium Chemistry for Organic Synthesis

Tetrahedron Lett

Tetrahedron Lett

Chem Eur J

Org Lett

Science

Chem Eur J

Chem Eur J

Adv Synth Catal

J Org Chem

Synlett

ACS Catal

Bioorg Med Chem Lett

Tetrahedron Lett

Synthetic Commun

Org Biomol Chem

Adv Synth Catal

New J Chem

Org Lett

Chem Commun

J Org Chem