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Notes: A conformationally directed Cyclization to the Octahydrophenanthridine System.The bicyclic precursors 5b and 8b are cyclized to the cis-fused phenanthridine derivative 6b without any detectable formation of the corresponding trans-derivative 7b. The conformational aspects of this stereoselective cyclization are discussed.

Notes: Using a meso-compound which is asymmetrically substituted with a chiral moiety as an intermediate, prostaglandins have been synthesized. Since the undesired enantiomer is readily recycled, this approach leads to a synthesis with high chiral efficiency. In addition it is possible to prepare both enantiomeric configurations of prostaglandins by simply altering the sequence of reactions. This concept should be generally useful in the synthesis of optically active molecules.

Notes: The alkylation of conjugated arylsulfonyl ylids, prepared from the corresponding allylic sulfones (2 or 8), and allylic halides bearing terminal carbonylgroups (3 or 4) leads to polyene sulfones which readily undergo spontaneous elimination of the corresponding aryl sulfinates. By this method two apocarotenoids (5 and 6) and torularhodin ethyl ester (9) have been prepared.

Notes: A chiral economic synthesis of (R)- and (S)-muscone using the cyclofragmentation of epoxysulfonesStarting with isobutyric acid (2) and using a microbiological oxidation with pseudomonas putida (S)-β-hydroxy-iso-butyric acid (3) has been prepared. From this /pseudosymmetrical: (see text) intermediate the two enantiomeric bromo derivatives 8 (R) and 20 (S) have been synthesized (cf. scheme 4) by altering the sequence of the reactions (cf. scheme 3). A Grignard reaction starting from the two bromo compounds 8 and 20 and from cyclododecanone 1 produced after hydrogenolysis the two enantiomeric dialcohols 9 and 21 (1 + 8 → 9, 1 + 20 → 21, cf. scheme 5). The subsequent transformations led to the two enantiomeric olefin derivatives 12 and 24. 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 (cf. [4] and scheme 6) produced a mixture of (E)- and (Z)-3-methylcyclopentadec-4-en-1-one (13 + 14 → 15 + 16, 25 + 26 → 27 + 28). The final hydrogenation led to natural (R)- and unnatural (S-muscone (3-methylcyclopentadecanone). The achiral starting material has been transformed to the desired optically active target products without loss of material with undesired absolute configuration. The authors used the notion of chiral economic synthesis to characterize synthetic sequences with the above mentioned features.

Notes: Cob(I)alamin as Catalyst. 5. Communication [1]. Enantioselective Reduction of α,β-Unsaturated Carbonyl DerivativesThe cob(I)alamin-catalyzed reduction of an α,β-unsaturated ethyl ester in aqueous acetic acid produced the (S)-configurated saturated derivative 2 with an enantiomeric excess of 21%. The starting material 1 is not reduced at pH = 7.0 in the presence of catalytic amounts of cob(I)alamin (see Scheme 2). It is shown that the attack of cob(I)alamin and not of cob(II)alamin, also present in Zn/CH3COOH/H2O, accounts for the enantioselective reduction observed. All the (Z)-configurated starting materials 1, 3, 5, 7, 9 and 11 have been transformed to the corresponding (S)-configurated saturated derivatives 2, 4, 6, 8, 10 and 12, respectively. The highest enantiomeric excess revealed to be present in the saturated product 12 (32,7%, S) derived from the (Z)-configurated methyl ketone 11 (see Scheme 3 and Table 1). The reduction of the (E)-configurated starting materials led mainly to racemic products. A saturated product having the (R)-configuration with a rather weak enantiomeric excess (5.9%) has been obtained starting from the (E)-configurated methyl ketone 23 (see Scheme 5 and Table 2). The allylic alcohols 16 and 24 have been reduced to the saturated racemic derivative 17.

Notes: Cob(I)alamin as Catalyst. 4. Communication. Reduction of α,β-Unsaturated NitrilesUsing catalytic amounts of cob (I)alamin and an excess of metallic zinc as source of electrons 1-naphthonitril (5) has been reduced to (1-naphthyl)methylamin (6) and in small amounts to (1-naphthyl)methanol (7) and (1,2,3,4-tetrahydro-1-naphthyl)methanol (8) (5 ½ h, CH3COOH/H2O; s. Scheme 3). Starting from cyclododecylideneacetonitrile (15) similar conditions (68 h, CH3COOH/H2O) 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 (I)alamin on an α,β-unsaturated nitrile might occur on both the nitrile dipole as well as on the carbon atom in β-position. Cob (I)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 tetrahydronaphthalene derivatives 8 and 12, and in one case the production of the octahydroderivative 14 has been observed in a low yield (s. Scheme 5).

Notes: Starting from the cyclopropanol 2, the isomeric cyclopropanol 4 and the β, γ-unsasturated aldehydes 7 and 8 have been produced by a cobalamin-dependant transformation. In traces, the two acetoxycyclopropanes 3 and 6, the saturated aldehydes 5 and 11 and the β,γ-unsaturated aldehyde 9 could be detected (cf. Structural Formulae and Table). Starting from 4 the same products in a rather similar distribution were obtained. The isomerization 2⇄4 as well as the transformations leading to 7,8, and 9 are shown to be mediated by cob(III)alamin (1(III)). The results are explained on the basis of rearranging Co-complexes. The migrations might be driven by the electrophilic nature of the central Co(d6)-atom.

Notes: A Synthesis of Vitamin A According to the Sulfone Method.Starting from β-ionyl phenyl sulfone 7 and an appropriate allylic chloride 10 retinol 14 has been prepared by a direct procedure. Subsequent acetylation and isomerization led to crystalline all-E-vitamin A acetate 16.

Notes: Cob(I)alamin as Catalyst. 6. Communication [1]. Formation and Fragmentation of Alkylcobalamins: the Nucleophilic Addition - Reductive Fragmentation EquilibriumIsolated olefines can be saturated using catalytic amounts of cob(I)alamin in aqueous acetic acid; as electron source an excess of zinc dust is added to the solution containing the homogeneous catalyst. During this overall hydrogenation of isolated double bonds intermediate alkylcobalamins are formed (compare e.g. Schemes 2, 4, 5, 7 and 12). Clear evidence is presented that the nucleophilic attack on the isolated double bond is carried out by cob(I)alamin and not by cob(II)alamin also present in the system (see Scheme 3b and 3c). As this catalytic saturation of olefins depends on the pH of the solution, characterized by a slow reaction at pH = 7.0 compared to the same reduction in aqueous acetic acid (see Scheme 2, 2 → 4, and Scheme 3a), it is reasonable to accept the participation of an electrophilic attack by a proton during the generation of alkylcobalamins. - We use the term nucleophilic addition to describe the formation of alkylcobalamins from a proton, an olefin and cob(I)alamin (compare Schemes 4-7 and 12).A special sequence of experiments showed the nucleophilic addition to be regioselective. Preferentially the higher substituted alkylcobalamin revealed to be produced. Therefore, the nucleophilic addition of cob(I)alamin follows the Markownikoff rule (compare chap. 4: formation and fragmentation of β-hydroxyalkylcobalamins).Under the reaction conditions applied the intermediate alkylcobalamins can be present in base-on and base-off forms. They are known to exist as octahedral complexes and might also be stable to some extent as tetragonal-pyramidal species. In addition the base-off forms can partially be protonated at the dimethylbenzimidazole moiety in aqueous acetic acid (compare Scheme 12). From this equilibrium of intermediate alkylcobalamins three modes of decay disclosed to be possible: (i) The reductive fragmentation leading to an olefin, a proton, and cob(I)alamin is the formal retro-reaction of the nucleophilic addition (see Schemes 2, 4 and 6-12). This equilibrium of an associated alkylcobalamin and the corresponding dissociation products revealed to be a fast process compared to the reductive cleavage of the Co, C-bond cited below (s. (iii)). (ii) As the second reaction pattern an oxidative fragmentation producing an olefin, a hydroxy anion (or water, respectively) and cob (III)alamin has been observed (see Schemes 7, 8, 10 and 12). (iii) The slow reductive cleavage of the Co, C-bond, initiated by addition of electrons (see [1a] [24]), was the third reaction path observed (see Schemes 2, 4-8 and 10-12). - The stereochemistry of the three transformations originating from the intermediate alkylcobalamins is unknown up to now. The antiperiplanar pattern of the fragmentation reactions presented in the Schemes has been chosen arbitrarily (see e.g. Scheme 12).

Notes: Cob(I)alamin as Catalyst. 7. Communication [1]. Retention of Configuration during the Reductive Cleavage of the Co, C-Bond of an AlkylcobalaminUsing catalytic amounts of cob(I)alamin (see Scheme 1) in aqueous acetic acid (-)-α-pinen (1) and (-)-β-pinen (2; s. Scheme 3) have been reduced. A large excess of metallic zinc served as electron source. The saturated products 5-8 (see Scheme 3) and the mechanistic aspects of their generation are discussed. The relative amounts of cis- (5) and trans-pinane (6) lead to the conclusion that the reductive cleavage of the Co, C-bond accompanied by H+ transfer in an alkylcobalamin occurs with retention of configuration. This result is in agreement with the corresponding cleavage of the Co,C-bond of an alkyl[hydroxy-diazaoctahydroporphinato]cobalt complex [9].