Tandem Claisen-Diels-Alder reactions in synthesis. A facile approach to anthracyclines

Acid 8b is available in seven steps from ketone 1. Quinone 5 represents a useful intermediate for the synthesis of anthracyclines. Disciplines Chemistry | Environmental Chemistry | Inorganic Chemistry | Organic Chemistry | Other Chemistry | Polymer Chemistry Comments Reprinted (adapted) with permission from The Journal of Organic Chemistry, 50(10); 1782-1784. Doi: 10.1021/jo00210a052. Copyright 1985 American Chemical Society. This article is available at Iowa State University Digital Repository: http://lib.dr.iastate.edu/chem_pubs/714 1782 J. Org. Chem. 1985,50, 1782-1784 Table I. Asymmetric Hydrovinylation of Cyclohexa-1,3-diene Catalyzed by the Ni(COD)2-AlEt2Cl-AMPP Systema (AMPP Ligands PhzPN(CHs)CH*RCH20PPhz) 3-vinvlcvclohex-1-ene I starting amino acids AMPP ligands,b R [ a I z 6 D , deg (c 1.00, toluene) confignc T, "C optical yields: %ee (BS,SR)-threonine CHaCH*(OPPh,) (6) +227.5 S 40 85 +243.5 +248.5 +249 +250 (S)-phenylalanine PhCHz (7) -56.5 R (&alanine CH3 (8) -45 R (S)-valine i-Pr (9) -26.5 R (Rbphenylglycine P h (10) -12 R (5')-aspartic acid CHzCHzOPPhz (1 1) -75 R @)-glutamic acid (CHZ)zCH20PPh2 (12) -50 R -104.5 -139 -30 10 91 0 93 -20 93 -30 930 40 21 -5 39 -25 52 40 17 40 10 -5 11 -5 4 40 28 40 19 "An autoclave was successively charged with a pre-formed solution of AMPP ligands (0.4 mmol) and Ni(COD)2 (0.4 mmol) in toluene (5 mL), a solution of Et,AlCl (0.2 mL) in toluene (5 mL), and 1 (7 g, 87.5 mmol). Then, the autoclave was pressurized with a stoichiometric amount of ethylene. The reactions were monitored by ethylene consumption and were conducted to completion within 15 min at 40 "C. Under these conditions the selectivities in 2 approached 100%. 2 was purified by spinning column distillation. The reaction time a t -30 "C is 225 min. bAll compounds described here gave NMR (%, 'H, and 31P) spectra consistent with their structures. CSee text. Results were reproducible to within 0.5%. Duplicate experiments were run for each entry. Hydroboration12 of 13 gave quantitatively a mixture of the four diastereoisomeric alcohols 14-17. Optical yields were determined by GLC either on urethanes prepared from isopropyl isocyanate by using Konig's method13 (glass capillary column, 50 m, coated with XE-60-S-valine-S-aphenyl ethylamide, isotherm at 75 "C) or on urethanes from (+)-(R)-1-phenylethyl isocyanate (capillary column, 50 m, SE 52 isotherm at 160 "C). All optical yields evaluated by the two methods agreed within the experimental errors (i0.5%). Along hydrogenation and hydroboration reactions, the configuration of the asymmetric carbon in 2 was maintained, thus the S configuration of (+)-VCH has been deduced from the following reference compounds. (i) trans-(1S,2S)-2-Ethylcyclohexanol and trans-(1S,3S)-3-ethylcyclohexanol were prepared respectively from the corresponding racemic ketones by specific enzymatic reduction catalyzed by HLADH with recycling NADH.14 (ii) trans-(1R,3R)-3-Ethylcyclohexanol and cis-(lR,2S)-2-ethylcyclohexanol were obtained from a stereospecific esterification with lauric acid carried out in organic phase and catalyzed by a lipase15 (from the yeast Candida cyclindracea). Optical yields for the different AMPP are reported in Table I. Relative to the optical yield of 85% obtained at 40 "C from threophos (6), the other ligands AMPP, particularly 9 and 10, were much less enantioselective and, although AMPP ligands such as (S)-proliphos and D-ephos, obtained respectively from (S)-proline and D-ephedrine, have proved to be very effective toward asymmetric hydrogenatiod and hydroformylation,16 they were practically inefficient for reaction 1, as far as asymmetric induction (10) Brown, C. A.; Ahuja, V. K. J. Org. Chem. 1973, 38, 2226-2229. (11) For optically pure (+)-(R)-ethyl-3-cyclohex-l-ene an absolute rotation [O(]%D +77O (c 1.00, toluene) was evaluated. This value allows a reevaluation of the optical yield of 63% obtained in the asymmetric coupling reaction between allylphenyl ether and Grignard reagent. Consiglio, G.; Morandini, F.; Piccolo, 0. J. Chem. SOC., Chem. Commun. 1983,112-114. (12) Brown, H. C. "Organic Synthesis via Boranes"; Brown, H. C.; Wiley Interscience: New York, 1975; pp 25-26. (13) KBnig, W. A.; Francke, W.; Benecke, I. J. Chromatographr. 1982, 239,227-231. (14) Jones, J. B.; Beck, J. F. "Applications of Biochemical Systems in Organic Chemistry"; Jones, J. B., Sih, C. J., Perlman, D., Ed.; Wiley-Interscience: New York, 1976; Vol. X, Part I, p 297. (15) Langrand, G.; Secchi, M.; Baratti, F.; Buono, G.; Triantaphylides, C. Tetrahedron Lett., in press. (16) Lecorne, T.; Petit, F.; Mortreux, A.; Buono, G.; Peiffer, G.; Colloque National sur les oxydes de carbone, Ecully, France (1.9.84). is concerned. Potential tridentate ligand (2R,3R)-threophos (6) was one of the most effective ligands, giving quantitatively (+)-(S)-3-vinylcyclohex-l-ene. The extent of optical induction was readily upgraded to 93% ee by lowering the reaction temperature to 0 "C. Undoubtly, the antipode (2S,3S)-threophos would be able to produce (-)-(R)-3-vinylcyclohex-l-ene, with the same enantiomeric excess, so that this reaction could be a useful tool for production of chiral synthons; thus, we are preparing optically pure trans-perhydro-1-indanone from a Brown's annelation. " Registry No. 1,592-57-4; (S)-2,76152-63-1; (R)-2,95421-8&8; 3, 39994-75-7; 4, 2313-74-8; 5, 95421-89-9; 6, 95421-90-2; 7, 91662-87-2; 8, 95421-91-3; 9, 95421-92-4; 10, 90032-62-5; 11, 95421-93-5; 12, 95421-94-6; 13, 95421-95-7; 14, 95529-72-9; 15, 69854-63-3; 16,87759-26-0; 17,69854-64-4; Ni(COD),, 1295-35-8; EhAlCl, 96-10-6; CH2=CH2, 74-85-1; (2S,3R)-threonine, 72-19-5; (S)-phenylalanine, 63-91-2; (S)-alanine, 56-41-7; (S)-valine, 72-18-4; (R)-2-phenylglycine, 875-74-1; (S)-aspartic acid, 56-84-8; (S)glutamic acid, 56-86-0; (i)-2-ethylcyclohexanone, 64870-41-3; (f)-3-ethylcyclohexanone, 64847-85-4. (17) Brown, H. C.; Negishi, E. Chem. Commun. 1968, 594. Gerard Buono,* Chhan Siv Gilbert Peiffer, Christian Triantaphylides Laboratoire de l'Ecole Supgrieure de Chimie de Marseille et des Organophosphorgs, Universitg d'Aix-Marseille 111, Marseille Cedex 13, France Philippe Denis, Andre Mortreux, Francis Petit Laboratoire de Chimie Organique Appliquge U A CNRS 402, ENSC Lille BP 108 59652 Villeneuue D'Ascq, France Received December 28, 1984 Tandem Claisen-Diels-Alder Reactions in Synthesis. A Facile Approach to Anthracyclines Summary: Acid 8b is available in seven steps from ketone 1. Quinone 5 represents a useful intermediate for the synthesis of anthracyclines. Sir: The rearrangement of allyl phenyl ethers to o-allylphenols, termed the Claisen rearrangement,' has been less 0022-3263/85/1950-1782$01.50/0