Preparation of Metal-Free Corrin Derivatives via A ! B Ring Closure. Complexationo fthe Corrin Chromophore withMetal Ions, and Some Properties of the Ligandsi nC orrin ComplexesIn 1965, J. I. Toohey [11],w orking in the laboratoryo fH. A. Baker at Berkeley,i solated Co-free natural corrinoids from photosynthesizingb acteria. This discovery,t ogether with the challenge to prepare and to study corrin complexes containing also metal ions other than those of transition metals, led to the quest for as ynthesis of metal-freec orrin ligands.H erein, we describe how this goal was achieved in 1968 in the heptamethyl series through adaptation of the sulfide contractionmethodology (cf.P art VI of this series)t ot he problemo fa chieving an A/B-secocorrin ! corrin cyclization within a non-robust Zn II complex. Most prominent among our studies of the properties of the metal-free corrin ligands are the complexations with various metal ions.W ealso describe experiments on the introduction of Me groups into the meso-positions of dicyano-Co 2,2,7,7,12,, i.e., experiments carried out as model study for corresponding methylations tepsi nt he finals tage of the Harvard/ETH vitamin B 12 project.Chapter A: A ! B Ring Closure by Sulfide Contraction via Oxidative Coupling:S ynthesiso frac-Chloro-zink(II)-15-cyano-1,2,2,7, 7, 12,12-heptamethylcorrinate [3][5] [6]. Thec hapter describes the adaptation of the sulfide contraction C,C-condensation method (cf.P art VI of this series)t ot he A/B-secocorrin ! corrin-cyclizationstep in the synthesiso faZ n II -corrin complex. Corrin complexes of non-transition metals such as Zn are non-robust in the sense that the metal ion can be removed without destruction of the corrin ligand. Thes earch for optimal reaction conditions of the C,C-bondforming sulfide-contraction step required extensivee xperimentation and led to observations that turned out to be essential for the application of the A ! B macroring-closure method in the synthesis of vitamin B 12 . Chapter B: Preparationand Properties of Salts of rac-15-Cyano-1,2,2,7,7,12,12-heptamethylcorrinium Cations [3][5][6]. Azidolytic decomplexation of aZ n II -heptamethyl-corrin complex led to the first Helv eticaChimica Acta -V ol. 98 (2015)1845 2015 Verlag Helvetica Chimica Acta AG,Z ürich 1 ) Teile I und IV vgl. [1] und [2]. Der Teil V umfasst Ergebnisse aus den Promotionsarbeiten von A. Fischli [3] (1964 -1967), vgl. Fussnote 1i n[ 2], E.-L. Winnacker [4] (1964 -1968) und H.-U.B laser [5] (1967 -1970), sowie aus Postdoktoratsarbeiten von D. Bormann (1966, J. Schossig ( ) und N. Hashimoto (1970). Ein Te il der hier beschriebenenE rgebnisse war Gegenstand vorläufiger Mitteilungen[ 6-8] und Vorträge[ 9] [10].synthesis of ac orrin as metal-free N-protonated corrinium salt. Metal ions were introducedi nto the corrinium ligand to form aw ide variety of robust and non-robust corrin complexes.I mportantly,t he neutral form of the synthetic corrin ligand prefers to exist in as ensitive tautomeric form, featuring a second NH group and an olefinic bond in an e...

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Summary. Sulfoncs, prepared from conjugated arylsulfonyl ylicls and allylic halides, eliminatc corresponding aryl su~Iitlatcs with forrnatiun ot con jugdfcd polyencs. Using this method p-carotene (8) has been synthesized. Zur Herstcllung dcs bditigten Dichlorids 6 wurde vom entsprechcnden Dialdchyd 4 ausgegangen, der rnit Nntriumborhydrid in 2-Propmol/Tetrahydrofuran zum allylischen Dialkohol 5 in 88proz. Ausbeute reduziert wurde. In diesem, ebenfalls kristallinen Zwischcnprodukt konnte die all-trans-Konfiguration mittels SC-NMR. emittelt werdcn, wie weiter unten ausfiihrlicher diskutiert wird. Der Dialkohol 5 1) Vgl. auch [6]. 2)Vgl. auch [6] [7]. a) 15,15'-Dehydro-9,9', lO,l0'-tctrahydro-9,9'-bis(phenylsulfonyl)-~-caro.tin. 4)6)

A chiral economic synthesis of (R)-and (S)-muscone using the cyclofragmentation of epoxysulfones SummaryStarting with isobutyric acid (2) and using a microbiological oxidation with pseudomonas putida (S)-8-hydroxy-iso-butyric acid (3) has been prepared. Oxidation of 12 with peracid produced a mixture of the two epoxy-sulfones 13 and 14 (cf. scheme 6). The olefin-derivative 24 was oxidized to the corresponding mixture of 25 and 26. A one pot cyclofragmentation (cJ [4] and scheme 6) produced a mixture of (E)-and (Z)-3-methylcyclopentadec-4-en-1-one (13+ 14 --f 15+ 16, 25+ 26 --f 27

SummaryHydrogen bonds as presented in Figure 2 cannot account for the enantioselective attack of cob (1)alamin (4 (I)) or heptamethyl cob (1)yrinate (5 (I)) on one of the two enantiotopic faces of the substrates. The attack of the strongly nucleophilic 3d,z orbital is preferentially directed to the re-side of the starting materials with (2)-configuration and leads, after the highly stereoselective reductive cleavage of the Co,C bond, to saturated products with (9-configuration in varying enantiomeric excesses (see Schemes 1,3 and Table I).1. Introduction. -The enantioselective reduction of the a,P-unsaturated ester 1 using cob (1)alamin (4 (I); see Schemes 1 and 2 ) has been published in two earlier communications in these series (21 [3]. The product was shown to be the corresponding saturated ester 3 with (S)-configuration at the chiral center showing enantiomeric excesses of 16.2-23.8% depending on the reaction conditions applied. The formation of alkylcobalamins by a nucleophilic attack of cob (1) It is therefore reasonable to expect intermediate alkylcobalamins during this overall reduction of a double bond. It has been shown in an earlier paper [l] that the reductive cleavage of a Co,C bond follows 97% retention of configuration at the C-atom using zinc as electron source in aqueous acetic acid. The mechanistic pathway followed in this enantioselective reduction can therefore be outlined as shown in Scheme 1. Cob (1)alamin (4 (I)) attacks the electrophilic C-atom in position 3 of 1 with the lobe of the 3d,~orbital on the P-side of the catalyst2). This attack

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Cob(1)alamin as Catalyst 4. Communication. Reduction of a$-Unsaturated Nitriles SummaryUsing catalytic amounts of cob (1)alamin and an excess of metallic zinc as source of electrons 1-naphthonitril (5) has been reduced to (1-naphl.hyl)methylamin (6) and in small amounts to (1-naphthy1)methanol (7) and (1,2,3,4-tetrahydro-lnaphthy1)methanol (8) ( 5 % h, CH,COOH/H,O; s. Scheme 3). Starting from cyclododecylideneacetonitrile (15) similar conditions (68 h, CH3CO~OH/H20) produced the amines 16-19 as well as the nitrogen free saturated aldehyde 20, the corresponding allylic alcohol 21 and the saturated derivative 22 (s. Scheme 6). It is deduced that the first attack of cob(1)alamin on an a,B-unsaturated nitrile might occur on both the nitrile dipole as well as on the carbon atom in P-position. Cob(1)alamin in aqueous acetic acid saturates the isolated double bonds in allylic alcohols and amines. In a slow reaction the two different aromatic rings of (1 -naphthyl)methanol (7) have been reduced giving the corresponding tetrahydronaplithalene derivatives 8 and 12, and in one case the production of the octahydroderivative 14 has been observed in a low yield (s. Scheme 5).In einer fruheren Untersuchung dieser Reihe wurde gezeigt, dass mit katalytischen Mengen Cob (1)alamin (vgl. Schema I) a , p-ungesattigte Nitrile reduziert werden konnten [ 11. Dabei fie1 auf, dass bei (2)-I-Cyclododecencarbonitril (1; vgl. Schema 2) zuerst in einer schnellen vorgelagerten Reduktion') die Doppelbindung abgesattigt wurde und anschliessend in einer langsameren Umsetzung*) das gesattigte Nitril3, uber ein entsprechendes Imin3), unter den wasserig sauren Bedingungen zum gesattigten Aldehyd 4 reduziert wurde. Dabei stellte sich die Frage, ob generell durch Cob (1)alamin u , P-ungesattigte Nitrile zuerst in P-Stellung und erst anschliessend am Nitril-dipol angegriffen werden. 3)Vgl. [2].

Unter kstimmten GC.-Bcdingungen (z.B. 2 m, 20% C-20-M*, 85"-ZOO') erschien die analysenreine Substanz in Form zweier dicht benachbarter, anniihernd glcich grosscr Pike und girb auch damit des Vorliegcn cines (~/E)-Stereoiaomerengeinisches zu crkcnnen. 1,ZTERATURVERZE'lCH NI S [l] M . Schlosser, U. SiAaub. B. Spakic' L % G.Summary. Using a meso-compound which is asymmetrically substituted with a chiral moiety 8s an intermediate, prostaglandins have becn synthesizcd. Sincc the undesired enantiomer is readily recycled, this approach leads to a synthcsis with high c h i d efficiency. In addition it is possible to prepare both enantionwric configurdions of prostaglandins by simply altcring thc sequence of reactions. This concept should be generally useful in thc synthesis of optically activc molecules. I. Ehnleitung. -Wnseren synthetischen Arbciten zur Offnung eines neuen Zugangs zu den Prostaglandinen [I] war das Postulat der totalen Umsetzung des achiralen Ausgangsmaterials zum gewiinsch ten optiscli aktiven Produkt zugrunde gelegt. Von den moglichen Wegen wurcle derjenige iiber einc asymmetrische Synthesc bereits von anderer Seite xealisiert [Z]; unscr Ziel war der Aufbau einer racemischen Zwischenstufe rnit anschliessendcr Racernatspaltung und Ruckfuhrung des unerwiinschten Enantiomeren. weden, Die Reduktion des kristallinen An'hydrids 3 rnit Natrium-bis-B-mcthoxy-HLLVETICA CRIMICA ACTA -Vol. 58, Fa%. 2 (1975) -Nr. 67 567 Schema 3 t ~~hoxy-alurniniumhydrid (REDAL) lieferte die gcwiinschte kristalline meso-Verbindung 4 in guter Ausbeute. Zur asymmetrischen Acylierung wurde die krist a l h e msso-Verbindung 4 , (vgl. Schema 5) zunachs t mit Phosgen in Toluol LU einem siehengliedrigen, cyclivchen Carbonat I) umgesetzt, das sehr leicht bei Raumtemperatur mit nattirlichem Iso-bornylamin3) ([aJzT* = -42,9", G 3 ; 0,96, EtOH) zum Diastereomerenpaar 5a und 5b geoff net werden konnte. Durch einc frdktionnierte Kristallisation mit Essigester konnten die beiden Diastereomeren 5a und 5b gctrennt werden, wobei das Uiastereomere Sa = -56,2", c = I 1,0, EtOH) in ZU-U% Ausbeute, bezogen auf die Gcsamtmenge dieses Diastereomeren irn Ausgmgsgemisch, isoliert wurde. Die Mutterlaugc, in der sich mchr vom unerwiinsdhten Diastereomeren 5b befand, m i t e rnit l) Diem wurde in der Toluollbung mittels X . / M S . eindcutig nachgcwiewn. *) Hergestellt aua natllrlichem Csmpheroxim durch katalytieche Reduktion mit Pd/C in Mc-than01 bei 90" und YO Atii. _-_---568 HBLWTICA CHIMICA ACTA --Vol. 58, Fasc. 2 (1975) -Nr. 67 Schema 5 \ I \ 1 Kaliumhydroxid verseift. Ilabei wurde dic krjstdline meso-Verbindung 4 in 75-80proz. Ausbcute regeneriert. IXese Hydrolyse erlaubt cine wcitgehende Recyclisicrung des uncrwiinschten Dimtereomeren 5b. Auf diese Weisc wird os m6glicti, bci maxirnalen Ausbeut.cn der chiral asymmctrischen Acylierung , der Diastercomerentrennung und der Recyclisierung, das gcsamte Ausgangsrnaterial zu eitiem eitizigcn Diastcrcomeren (hicr 5 a) umzusetzen.3. Beweis der abaoluten Konfiguration des Hydroxy-urethans 5a. -Urn die