Enantioselective cycloadditions catalyzed by face resolved arene chromium carbonyl complexes

Article abstract of DOI:10.1016/S0957-4166(98)00200-6

A new class of readily accessible enantioselective catalysts has been developed, and examined in the Diels-Alder cycloaddition of methacrolein. Analysis of potential transition state influences provides an insight for future modification and refinement.

Full text of DOI:10.1016/S0957-4166(98)00200-6

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 9 (1998) 2023–2026
Enantioselective cycloadditions catalyzed by face resolved arene
chromium carbonyl complexes
Graham B. Jones ∗ and Mustafa Guzel
Laboratory of Medicinal Chemistry, Department of Chemistry, Clemson University, Clemson, SC 29634-1905, USA
Received 15 April 1998; accepted 7 May 1998
Abstract
A new class of readily accessible enantioselective catalysts has been developed, and examined in the Diels–Alder
cycloaddition of methacrolein. Analysis of potential transition state influences provides an insight for future
modification and refinement. © 1998 Elsevier Science Ltd. All rights reserved.
The rapid evolution of enantioselective Diels–Alder catalysts has resulted in many systems capable of
mediating these cycloadditions with extremely high selectivity.1 Particularly impressive are dual point
binding catalysts, wherein conjugated substrates engage in primary coordination to a Lewis acidic site
via a carbonyl group of the dienophile, with secondary interaction achieved via overlap of the dienophile
vinyl group with an arene moiety of the catalyst. These secondary interactions range from π-shielding
effects to attractive π-stacking interactions and have been described in a number of systems.2 Pertinent
examples include dichloroborane 1,3 oxazoborolidine 2,4 and acyloxyboronate 3,5 each depicted as 1:1
complexes with a coordinated dienophile. Additional interactions of the substrate formyl H atom with
proximal lone pairs of oxygen atoms of the catalyst have also been suggested in the case of 2 and 3,
effectively establishing triple point binding catalyst–substrate assemblies.6
While tuning of the primary Lewis acidic σ coordination sites of such catalysts is usually accomplished
via metal ligand variation, modulation of the aryl–substrate vinyl π-shielding/π-stacking interactions
is not generally possible without drastically changing the catalyst architecture. Based on previous
experience with chiral arene chromium tricarbonyl complexes,7–9 we became interested in empowering
∗
Corresponding author. E-mail: graham@clemson.edu
0957-4166/98/$19.00 © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00200-6

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the planar chirality of these complexes to direct face selective cycloaddition reactions.10 Electronic
interactions between the substrate and arene could in principle be modulated by appropriate selection of
ligand combinations about chromium to render the arene either π-basic or π-acidic.9,11 To provide proof
of principal, m-disubstituted arene diol complexes were selected since they; (i) can be accessed from
readily available precursors, (ii) possess requisite planar chirality, (iii) asymmetry can be introduced
via versatile asymmetric dihydroxylation technology and (iv) the m-substituent should not present a
significant steric entity to metallocycles derived from these diols, allowing the effects of the metal
complex to be highlighted more effectively.10 Accordingly, m-anisaldehyde was subjected to olefination
followed by Sharpless dihydroxylation to give S-diol 5 in >99% e.e. (Scheme 1).12 Complexation at this
point using conventional conditions8 gave a moderate yield of a 1:1 mixture of diastereomers 6 and 7,
which were separable using chromatographic methods.13 Protection of the hydroxyl functions in the form
of ketal 8 followed by complexation gave a higher yield of complex 9, but in a ratio of 5:1 in favor of the
S,S-complex confirmed on deprotection to give 6. The identity of facial diastereomers 6/7 was established
via oxidative cleavage to give the known aldehydes 10.14
Scheme 1. Preparation and stereochemical assignment of catalyst precursors
The diols were then exposed to a variety of Lewis acids, and the corresponding metallocycles/chelates
examined in the catalytic enantioselective cycloaddition of 2-methacrolein with cyclopentadiene, using
catalysts derived from 5 as controls. Though exo-preference was observed with every Lewis acid
combination examined, R enantiomeric cycloaddition product 11 was favored with both the boron

G. B. Jones, M. Guzel / Tetrahedron: Asymmetry 9 (1998) 2023–2026
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and titanium metallocycles and the S-enantiomer 12 predominated with the aluminum metallocyles
(Scheme 2, Table 1).
Scheme 2. Metallodioxolane catalyzed [4+2] cycloadditions
A key feature of these catalysts is the geometric flexibility of the Lewis acidic metal center. Boronates
were in general less selective than the aluminates, and within this class, aluminates capable of forming
bona fide metallocyles [entries 8–11] less discriminating than the dihaloaluminates [entries 12–15]. As
noted above, the coordinative geometry of the metal center itself also has a profound effect on the
product enantiomer distribution. Though selectivity is modest (<65% e.e.), catalysts derived from 6 are
routinely superior to 7 which are in turn superior to uncomplexed analogs 5. However, since the same
enantiomeric product predominates using either 6 or 7 it is suggestive that the entire arene metal–carbonyl
appendage is functioning as a stand alone stereodirective element, a function of its planar chirality.
Ongoing investigations, using mixed ligand arene chromium carbonyl complexes of this class15,16 are
designed to delineate the relative importance of; (i) π–π interactions between the catalyst aryl group and
methacrolein vinyl group,17,18 (ii) formyl substrate–catalyst hydrogen bonds6 and (iii) the Lewis basicity
of the chiral sec-alcohol function.
In summary, a new family of enantioselective catalysts has been developed, utilizing the planar
chirality of m-disubstituted arene chromium carbonyl complexes. The ready accessibility of the catalysts,
and the potential for both refinement and application in a number of catalytic processes renders their study
an important objective.
Table 1
Enantioselective cycloaddition of 2-methacrolein using diol catalystsa

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Acknowledgements
We thank the GHS, Elsa U. Pardee Foundation and the Donors of the Petroleum Research Fund
(Administered by the American Chemical Society) for financial support of this work (28706-AC1).
References
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1
13. Key data: (6) H NMR (300 MHz, CDCl3) δ 6.92 (s, 1H), 5.58 (t, 1H, J 9 Hz), 5.42 (s, 1H), 5.09 (s, 1H), 5.05 (s, 1H),
4.79 (s, 1H), 4.53 (s, 1H), and 3.70 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 232.2, 128.3, 113.8, 94.9, 83.8, 82.9, 72.8, 67.8,
55.7; (7) 1H (300 MHz, CDCl3) δ 6.94 (s, 1H), 5.53 (t, 1H, J 6 Hz), 5.41 (s, 1H), 5.12 (s, 1H), 4.81 (s, 1H), 4.29 (s, 1H),
4.18 (s, 1H), and 3.79 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 233.1, 127.8, 113.1, 94.7, 83.8, 82.7, 70.4, 68.6, and 55.6.
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