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Synthesis 2001(13): 2040-2054
DOI: 10.1055/s-2001-17704
FEATUREARTICLE
© Georg Thieme Verlag Stuttgart · New York

Diastereoselective Transformation of Arenes into Highly Enantiomerically Enriched Substituted Cyclohexadienes

Gérald Bernardinelli, Sandra Gillet, E. Peter Kündig*, Ronggang Liu, Alberto Ripa, Lionel Saudan
Department of Organic Chemistry, University of Geneva, 30 Quai Ernest Ansermet, CH-1211 Geneva 4, Switzerland
e-Mail: Peter.Kundig@chiorg.unige.ch; Fax: +41(22)3287396;
Further Information

Publication History

Received 1 June 2001
Publication Date:
10 August 2004 (online)

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Abstract

Sequential addition of a C-nucleophile and a C-electrophile to enantiomerically pure arene tricarbonyl chromium complexes 3a,b, 6, and 8b, containing aryl bound chiral oxazoline, SAMP-hydrazone and chiral imine auxiliaries affording substituted cyclohexadienes. C-Nucleophiles included alkyl-, vinyl-, and phenyl-lithium reagents. C-Electrophiles included methyl iodide, allyl bromide, benzyl bromide, and propargyl bromides. The 1,3-cylohexadienes were obtained with a 1,5,6-substitution pattern. The results are consistent with a diastereoselective exo-nucleophilic addition to an ortho position of the complexed arene, followed by addition of the electrophile to the metal center. With allyl, ben-zyl, and propargyl groups, direct reductive elimination then yielded trans-5,6-substituted products. With methyl iodide, reductive elimination was preceded by CO insertion and acetyl cyclohexadienes were formed exclusively whose in situ deprotonation/alkylation gave products in which three C-substituents had been added across an arene double bond with complete regio- and stereocontrol. The two path-ways reflect migratory aptitude to carbonylation. An X-ray structure determination of the phenyl oxazoline complex 3a allowed a rationalization of observed diastereoselectivity. Asymmetric induction was very high with the oxazoline and the SAMP-hydrazone complexes (>90% de) whereas the chiral benzaldehyde imine complex 8b afforded the substituted diene aldehydes in moderate enantiomeric purity (34-58% ee). Changing the reaction medium from THF to toluene in reactions with 8b resulted in products of the opposite chirality.

Key words

diastereoselective dearomatization - cyclohexadiene - arene Cr(CO)3 complexes - imine - oxazoline - SAMP-hydrazone

15

Diastereoselective meta nucleophile addition/protonation reactions have been carried out with chiral Cr(CO)3 bound aryl ethers. See refs. 7 and 8.

22

In the absence of the Cr(CO)3 group, phenyl oxazolines react with n-BuLi to give products arising from ortho-arene lithiation. See ref 21.

25

Crystal structure determination of 3a: Cr(CO)3(C12H15NO), Mr = 325.3; µ = 0.782 mm-1, dx = 1.451 g.cm-3, monoclinic, P21, Z = 4, a = 11.0923(10), b = 11.2412(7), c = 12.0144(12)Å, β = 96.471(11)°, V = 1488.5(2)Å3, yellow prism 0.10 x 0.20 x 0.26. Cell dimensions and intensities were measured at 200 K on a Stoe IPDS diffractometer with graphite-monochromated Mo Kα radiation (λ = 0.71069 Å). 22868 measured reflections, 7125 unique reflections of which 3728 were observables (|Fo| > 4 σ (Fo)); Rint for equivalent reflections 0.069. Data were corrected for absorption (T min, max = 0.8492, 0.9441). Full-matrix least-squares refinement based on F using weight of 1/[σ2(Fo)+ 0.0003(Fo)2] gave final values R = 0.032, wR2 = 0.032 and Flack parameter x = 0.02(5). Hydrogen atoms were placed in calculated positions.

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Crystallographic data (excluding structure factors) have been deposited to the Cambridge Crystallographic Data Base (deposition No. CCDC163963, CCDC163964 for 3a and 6 respectively). Copies of the data can be obtained free of charge on application to the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: Int. + 44(1223)336-033; e-mail: deposit@ccdc.cam.ac.uk).

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Crystal structure determination of 6: Cr(CO)3(C13H18N2O), Mr = 354.3; µ = 0.689 mm-1, dx = 1.415 g.cm-3, monoclinic, P21, Z = 4, a = 10.229(2), b = 13.276(2), c = 12.267(3)Å, β = 92.973(6)°, V = 1663.6(6)Å3, yellow prism 0.11 0.24 0.24. Cell dimensions and intensities were measured at room temperature on a Philips PW1100 diffractometer with graphite-monochromated Mo Kα]radiation (λ = 0.71069 Å). Two reference reflections measured every 60 min showed variation of about 10%; all intensities were corrected for this drift. -10 < h <10; 0 < k < 14; 0 < l < 12 and all anti-reflections; 4522 measured reflections, 4194 unique reflections of which 3155 were observables (|Fo| > 4 σ (Fo)); Rint for equivalent reflections 0.031. Data were corrected for absorption (T min, max = 0.8814, 0.9245). Full-matrix least-squares refinement based on F using weight of 1/[σ2(Fo)+ 0.0003(Fo)2] gave final values R = 0.050, wR2 = 0.047 and Flack parameter x = 0.02(6). Hydrogen atoms were placed in calculated positions. The methoxymethyl substituant of the anti-conformer is disordered. Two disordered fragments have been refined with population parameters of 0.70 and 0.30 for C12b-O1b-C13b and C12b’-O1b’-C13b’ respectively. The partial decomposition of the crystal during data collection and the presence of the disorder, led to relatively large uncertainties in the final coordinates.