It is shown, in the case ofthe diketone 2, that chromatography with achiral phases of a non-racemic mixture of enantiomers can furnish fractions which differ in enantiomeric excess. Such chromatography may, therefore, be used to further enrich a sample in one enantiomer. By thc same token, chromatography is not a generally safe method for the purification of the product of an enantio-differentiating process, if the enantiomeric excess of a purified portion of that product is taken to be a measure of the efficiency of the process. The described effect represents an enantiomer differentiation induced solely by an alredy existing enantiomeric excess during chromatography. It thus belongs to a class of effects where the relative amounts of two enantiomers induce an observable difference between them. Such effects are called EE effects. The coinmon principle underlying EE effects is explained by a simple symmetry argument. Since EE effects can also occur during reactions with achiral reagents, further transformations of an enantionier-enriched product may furnish false information on its enantiomeric excess.

Polymer Bound Cinchona Alkaloids as Catalysts in the Michael Reaction SummaryThree insoluble chiral polymers (6, 7 and 8) were prepared by functionalization of copoly(styrene -2% divinyl benzene) followed by reaction with quinine (9) or dihydrocupreine (10). Their utility as catalysts, in the reaction between methyl indane-1 -one-2-carboxylate (13) and 3-butene-2-one (14) was studied. Table 2 (runs 2-6 and 8) shows that the Michael-adduct 15 was formed in good chemical but low optical yields, independent of the chiral polymer used. These results are compared with those of the Michael reactions in the presence of the monomeric bases quinine (9), 0-acetyl-quinine (11) and eucipine (12) (runs 1, 7 and 9).

A total synthesis of betalainc pigments (6) is tlcecribcd. Thc key intermediate is betalamic acid in the form of its dimethyl cstcr scmicarbaeone (9), which was transformocl with tproline (16) into indicaxanthine dimethyl estcr (5). with L-cydodopa methyl estcr (17) into betanidinc trimethyl ester (3) and by hydrolysis of the latter into betanidinc (2). Betalainc (6) sind die in gewissenCcnttospernicn [I I und in Pilzen 1.21 vorkommcnden stickstoffhaltigen wasserlijslichen Farbstoffe. Dam gehoren die violetten Betacyme (Beispiel: Randenfarbstoff Betanin (1)) urid die gclbcn Hetaxanthine (Beispiel: Kaktusfarbstoff Indicaxdnthin (4)). AlIe Retahine (6) sind Immoniurnsalzc der in einigen Yflanzen ebenfalk nachgcwicsericn 31 Setalamins2ure (7), deren IXmethylester (8) und Dimethylester-semic,rb~~on (9) auch aus Betalainen (6) gewonnen werden konnten 1. 41 IS]. -.-.. --7) 2) Aus der gcplanten llissertation von K. llsvmasam ; als Mjtteilurig an rlcr I.lcrbstvr~rs.zrainlung dcr Schwcizerischen Chemischcn Gcsellschaft voin 3. Oktober 1975 in Aarau angekundigt. Stipendiat dcs Fonds aur Untevstidtzu?ag von Uokiwandsn uuf dam Gebiete der Chamie.Summary. [-Oxo-cr,/?-cnoncs react with lithium dimethylcuprate to give cyclic aldols such as hydroxydecalonc 1 arid hydroxyspiro14.51decanonc 2 in a rcgio-and stercospecific manner. This ncw reaction, a combination 01 conjugate methyl addition to a,,&enoncs with dirccted intramolecular aldolisatim, is suggested to proceed via either (:noate anions, such as 8 and 11, or radical anions, such as 9 A 10 and 12 13, as intermcdiates.Recently we 121 and others L341 have shown that metal enolates resulting from the conjugate addition of metal alkyls to ac,/h.msdturated ketones are valuable intermediates for intermolecular aldol condensations (Scheme 1).

(10 nil) and a 35% aqueous formaldehyde solution (7 ml). The mixture was poured into water, inade alkaline with 5~ NaOH and extracted with CHC13. Thc organic layer was dried, evaporated to dryness and the crude base converted t o its naphthalcne-l,5-disulfonate, yielding 6.9 g (69",) of 6b salt, m.p. 250-252". -C25HzsClN05S: C, H, N. ) -2,3,4,5-tctvahyydrn-l H-2-henzazepine (6 d) naphthalene-I, 5-disulfn~zate. Compound 5d was methylated to 6d, which was converted to its naphthalene-l,5-disulfonate as described for 6b, giving 79% of salt, m.p. 253-255". -C Z~H~~N O~S : ,1-[2-(4-Chlornphenyl)ethyZ] -7, S-dimethoxy-2-methyZ-2,3,4,5-tetrahydvn -7 I-I-2-benza:epine (6e) ~taflhtlzale~ze-I, 5-disulfonate. Compound 5 e was methylated to 6e, which was converted l o its naphthalene-l,5-disulfonate as described for 6b, giving 70% of salt, 1n.p. 233-236". -7-[3,4-Dimethoxyhenzyl)-7, 8-dillzethoxy-2-methyl-2,3,4,5-tetvahydro-l H-2-benaazefiine ( 6~) naplzthalene-l,5-disulfnlzate. The aniinc 5c (7.5 g, 21.0 mmol) was dissolved in 25 ml of ethanol, 40 ml of 35% aqueous solution of formaldehyde wcre added, and the solution was refluxcd for 1.5 h.The reaction mixture was then cooled to 0-5" and NaBHa (7,s g, 0.20 mol) was added in small portions. The mixture was allowed to warm up to RT. After addition of a large amount of water, the mixture was extracted with CHC13. The organic layer was dricd, evaporated to dryncss and the residual oil converted to its naphthalene-1,5-disulfonate as for 5b, giving 5.4 g (780/,) of 6c salt, m.p. 233-235'. -C Z~H~~N O~S :C, H, N. 2,3,10,7 7-Tetvametlznxy-5,6,7,7a,8,13-hexahydvo-isoqui~zolo[3,2-a]-Z-henzazepine ( 7 ) .Theaminc 5 c (7.5 g, 21 mmol) was dissolved in Z N HCl (75 ml) and a 35: aqueous formaldehyde solution (40 ml) was added. The mixture was refluxed for 1.5 h, then cooled and madc alkaline with 2 w NaOH. The compound was extracted with CHC13. The organic extract was dried, evaporated to dryness and the residue recrystallized from CHCl3/petrolcum ether, giving 4.7 g (6196) Preparation of dihydro-, tetrahydro-and hexahydro-chelidamic-acid derivatives. -Summavy. Three methods for the preparation of 4-0~0-2,6-piperidine-dicarboxylic acid (3) and derivatives, required as a synthon for betalaine pigments, were explored.

1. Einleitung. ~ Im Zusammenhang mit unserer Synthese von 17-Decarboxybetanidin (A) durch Pyridin-Ringoffnung [ 11 haben wir auf lhnliche Weise auch einige Modellsubstanzen mit dem charakteristischen Chromophor der Betalaine (der roten und gelben Farbstoffe gewisser Centrospermen Pflanzen [2]) hergestellt. Unter den Produkten ist das Betenamin (B), das Ring-Geriist des roten Riibenfarbstoffs (Randenfarbstoffs) Betanin (C), und einige offenkettige gelbe und rote 1,7-Diazaheptamethinium-Systeme'), speziell auch solche mit terminalen sekundiiren Aminosluren. Fur die Pyridin-Ringoffnungen beniitzten wir sowohl die Methode von Zincke und Konig [4] als auch die photolytische Methode von Freytug und Neudert [ 5 ] . 2. Betenamin-perchlorat (5). ~ Schutzen der NH,-Gruppe von 4-(2-Amino-ethy1)pyridin (1) [6] fuhrte zum Trifluoracetamid 2a (78 %) und zum tert-Butoxycarbamat 2b (nicht isoliert), welche mil l-Chlor-2,4-dinitrobenzol in die Salze 3a (nicht isoliert) ') Fur eine Erklarung dieser Benennung von delokalisierten n-Systemen s. [3]. HELVETICA CHIMICA ACTA ~ Vol. 69 (1986) Schema I 1589 ( d l = 110 = 513-403 nm) [S]. Der UV/VIS-spektroskopisch gemessene pK-Wert des Betenamin-perchlorats (5; pK, = 11,68) liegt um mehr als 3 Einheiten hoher als derjenige des Neobetenamins (6; pK, = 8,36 [7]), ein Effekt, der schon im Vergleich von Betanidintrimethylester-hydrochlorid (pK, 3 7) mit Neobetanidin-trimethylester-hydrochlorid (pK, = 33) zutage getreten war [S]. Erwartungsgemass sinkt die Basizitat eines 1,7-Diaza-RZ 6 R ' -R 2 = H 7 R' = OCH,. Rz = COOCH, ,)Systematischer Name und Numerierung im Exper. Teil

Total Synthesis of BetalainesSummary cis-4-0~0-2,6-piperidinedicarboxylic acid dimethyl ester (10) was transformed (44%) into the semicarbazone of 2,3-dihydrobetalamic acid dimethyl ester (13/14) by a modified Horner-W i t t i g reagent 12. Oxidation of 13/14 afforded 41 YO of a mixture of stereoisomers of betalamic-acid-dimethyl-ester semicarbazone (4), key intermediate for the synthesis of betalaine pigments. The utility of 4 in this respect was demonstrated on a small scale by its conversion to the dimethyl ester of indicaxanthine (9, 11%) and to the trimethyl ester of betanidine (7, 87%). Hydrolysis of 7 gave betanidine (6).We further describe the synthesis of the trimethyl ester of an oxidized form of betalamic acid (20/21) as well as model condensation reactions on the carbonyl group of cyclohexanone, cis-4-0~0-2,6-diphenylpiperidine (23) and its N-formyl derivative 27.Reaction of 4-0x0-1,2,3,4-tetrahydro-2,6-pyridinedicarboxylic-acid dimethyl ester (40) with acetic anhydride or with triethyloxonium tetrafluoroborate resulted in 0-acylation or in 0-alkylation along with dehydrogenative aromatization to yield the derivatives 39 or 42, respectively, of chelidamic acid.

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