Elsevier

Tetrahedron

Volume 65, Issue 35, 29 August 2009, Pages 7277-7288
Tetrahedron

Chiral photochemistry in a confined space: torquoselective photoelectrocyclization of pyridones within an achiral hydrophobic capsule

On the occasion of 70th birthday V.R. dedicates this manuscript to his beloved mentor and teacher Professor R. S. H. Liu
https://doi.org/10.1016/j.tet.2009.01.110Get rights and content

Abstract

Chiral induction during the photoelectrocyclization of pyridones included within octa acid (OA) capsule has been established. Chiral induction is brought about by a chiral auxiliary appended to the reactive pyridone moiety. Importantly, the same chiral auxiliary while ineffective in acetonitrile solution is found to be effective within the confined space of OA capsule. The diastereomeric excess of 92% obtained here is comparable only to that in solid state. OA capsule, we believe, provides restriction to the rotational motions of the reactant pyridone and chiral auxiliary and thus places the chiral auxiliary in a selective conformation with respect to the reactive pyridone part. A correlation between the position of the methyl group on the pyridone ring and diastereoselectivity was noted. Structures of the host–guest complexes were examined by 1H NMR and the data were used to obtain preliminary information concerning the mechanism of chiral induction within the confined spaces of OA capsule.

Introduction

Chiral chemistry in confined spaces has attracted considerable attention during the last two decades.1 Although a number of elegant and efficient chiral induction strategies have evolved for thermal reactions, the short lifetimes of excited states have hampered the development of effective interaction between excited reactant and a chiral perturber thus slowing down similar progress with photoreactions. The chiral sources that have been employed to achieve stereoselectivity in photochemical reactions in solution include circularly polarized light, chiral-sensitizers, -solvents, -substituents, and -hosts.2, 3, 4, 5, 6 During the last two decades supramolecular approaches toward chiral photochemistry have attracted considerable attention. For example, use of chiral hosts such as cyclodextrins, proteins, and DNA to complex achiral reactant molecules in aqueous solution has resulted in low to moderate chiral induction in photoproducts, but significantly higher than in isotropic solvents.4

In comparison to solution, supramolecular approaches in the solid state have provided promising leads. Solid host–guest complexes of optically pure host and achiral guest molecules often resulted in quantitative chiral induction.7 The elegant technique of transformation of chiral crystals of achiral molecules into chiral photoproducts in 100% enantiomeric excess (ee) is noteworthy.8 Some achiral molecules that failed to crystallize in a chiral space group were forced to crystallize in a chiral space group by using an ionic or a co-valent chiral auxiliary and which upon subsequent irradiation yielded products with 100% diastereomeric excess (de).9 We have recently demonstrated the use of confined cavities of a zeolite and the resident charge compensating cations in inducing enantio- and diastereoselectivities in products of photoreactions such as geometric isomerization, hydrogen abstraction, and cyclization.10 Based on the literature, we believe that solid-state chiral photochemistry is more advanced than the solution counterpart and we should apply the solid-state concepts to solution chiral photochemistry. In this context the supramolecular approach in solution holds promise.

We had explored the use of chiral cyclodextrins as hosts for a number of unimolecular photoreactions toward developing a solution-based chiral induction strategy.11, 12, 13 The best ∼20% ee we could obtain in solution is largely due to cyclodextrin–guest complexes' poor solubility in water. The similarities in shape and size of cyclodextrins and the recently synthesized cavitand octa acid (OA) led us to explore OA's effectiveness in bringing about chiral induction in photoreactions. While the guest is only partially surrounded by cyclodextrin (as 1:1 guest@host complex), two molecules of OA self-assemble and encapsulate the guest (as either a 2:2 or a 1:2 guest@host capsule) (Fig. 1).14, 15 Thus the OA capsule provides a relatively ‘confined-solid-like’ reaction cavity resembling crystals and zeolites. Our experience with the latter two solid media suggested that the restriction provided by a closed tight enclosure would enhance the influence of a chiral auxiliary during a photoreaction. In this study this prediction has been realized with the guest pyridone systems 1ae, appended with the chiral auxiliary α-methylbenzyl amide (Scheme 1) in OA.16, 17, 18 The position of the methyl group on the pyridyl ring was changed with the hope that it would influence the orientation of the guest, and thereby the free space, within the OA cavity. Prior studies with molecules like 4,4′-dimethylstilbene and dibenzyl ketone (Fig. 2) that are comparable in dimension to 1ae assured us accommodation of these guests inside OA cavity. Binding properties of compounds 1ae with OA were examined by NMR spectroscopy prior to initiating the photochemical studies. Both NMR and photochemical results are presented in this report.

The probe molecules 1ae undergo concerted 4e disrotatory photocyclization in the excited singlet state. The mechanism of the photocyclization reaction is shown in Scheme 2. Planar achiral pyridone undergoes disrotatory cyclization (via two modes: in and out rotation) to yield the chiral 2-azabicyclo[2.2.0]hex-5-en-3-one. The products distinguished by the stereochemistry at the ring junction exist as enantiomers. Note that the planar reactant becomes bent (∼110°) in the product. In a homogeneous environment, the cyclization occurs by both modes of rotation with equal efficiency. In a supramolecular chiral assembly, the host could provide torquoselectivity during the disrotatory cyclization process thus possibly leading to chiral enrichment on the photocyclized product.19, 20, 21 Since the OA capsule is non-chiral, the photocyclization had to be influenced either through co-inclusion of a chiral inductor within the achiral capsule or through a chiral auxiliary co-valently linked to the reactant molecule. Our unsuccessful attempts at the former approach led us to explore the chiral auxiliary strategy that we had previously exploited in zeolites and crystals. This led us to investigate the photobehavior of pyridones 1ae within OA capsule. The results presented here highlight the influence of chiral auxiliary on the photocyclization when the reaction space is tightly controlled. Although the observed high de is remarkable we still do not fully understand the mechanics of the restricted space of the OA capsule in bringing about an interaction between the chiral auxiliary and the reaction center. We plan to continue to explore the origin and rules of chiral induction in photochemical reactions within the restricted space of OA capsule.

Section snippets

Preparation and characterization of 1ae@OA2 complexes

Methyl-substituted pyridones 1be were synthesized and their complexation behavior within OA was examined. The procedure for synthesis of these compounds is presented in the experimental section. Complexes of OA and pyridones 1ae were prepared using the following general procedure. A known volume of the guest from a stock solution in CD3CN was transferred to a sample vial. The solvent was evaporated in a stream of air. To the solid pyridone thus deposited in the vial, solution of OA in

Discussion

The results of photochemical reactions pose the following questions: (a) Why there is a difference in de between isotropic solution and OA capsule? (b) How does the position of the methyl on the pyridone ring control the extent of de? (c) How does the chiral communication occur between the chiral auxiliary and the reaction center within the OA capsule?

We have previously established that high chiral induction on a variety of photoreactions could be achieved within a zeolite, a medium where

Summary

We have achieved significant chiral induction (92%) during the photocyclization of pyridones within a hydrophobic capsule. Such high chiral induction in a hydrophobic capsule, to our knowledge, is unprecedented. Controlling free space and freedom of rotation are major factors in deciding the efficiency of chirality transfer between the chiral auxiliary and the reaction site. For instance, reactions in solid state yield better selectivity than in solution state due to the denser packing of

General methods

Host octa acid was synthesized and characterized using literature procedures. Synthesis of compounds 1ae using reported procedures is explained below. 1H NMR spectra were recorded using Bruker Avance 300, 400 or 500 MHz spectrometers at 298 K unless mentioned otherwise. Photoproducts of 1ae were separated by HPLC analysis using Rainin HPLC instrument fitted with Chiralcel AD column and hexane and 2-propanol as eluants.

(R)-2-Bromo-N-(1-phenylethyl)ethanamide

To a solution of bromoacetic acid (2.52 mmol, 1.1 equiv) in CHCl3, N-ethyl-N

Acknowledgements

V.R. greatly appreciates the continuous encouragement, penetrating discussions, and critical comments by Professor R. S. H. Liu to whom this paper is dedicated. V.R. thanks the National Science Foundation, USA for financial support (CHE-0213042 and CHE-0531802). C.L.D.G. and B.C.G. thank the National Institute of Health (RO1 GM074031) for financial support.

References and notes (30)

  • J. Shailaja et al.

    Tetrahedron Lett.

    (2002)
  • S. Koodanjeri et al.

    Tetrahedron Lett.

    (2002)
  • S. Koodanjeri et al.

    Tetrahedron

    (2000)
  • F. Toda et al.

    Tetrahedron Lett.

    (1988)
  • L.C. Wu et al.

    Tetrahedron Lett.

    (1997)
  • D. Place et al.

    Tetrahedron Lett.

    (1998)
  • Y. Inoue et al.

    Chiral Photochemistry

    (2004)
  • H. Rau
  • B. Grosch et al.
  • T. Wada et al.
  • N. Hoffmann et al.
  • Y. Inoue
  • F. Toda et al.
  • M. Sakamoto
  • J.R. Scheffer
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