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Notes: The olefins 2, 7, 11, and 19, have been reduced using catalytic amounts of cob(I)alamin(I(I)). During a slow saturation, the catalyst is able to differentiate the two diastereotopic faces of the endocyclic double bonds in 11 (t1/2 4 h,. cf. Scheme 3) are reduced much faster. A rationalization of the data can be obtained formulating tertiary alkylcobalamins as intermediates. Of the oxime 6 (cf. Scheme 2) and the p- bromobenzoate 23 (cf. Scheme 5) the structures have been determined by X-ray analysis.

Notes: Hydrogen bonds as presented in Figure 2 cannot account for the enantioselective attack of cob(I)alamin (4(I)) or heptamethyl cob(I)yrinate (5(I)) on one of the two enantiotopic faces of the substrates. The attack of the strongly nucleophilic 3dz2 orbital is preferentially directed to the re-side of the starting materials with (Z)-configuration and leads, after the highly stereoselective reductive cleavage of the Co, C bond, to saturated products with (S)-configuration in varying enantiomeric excesses (see Schemes 1, 3 and Table 1).

Notes: The olefinic system in 3β-methoxy-4-cholesten-6 a-ol (2) is reduced using cob (I)alamin (1(I); see Scheme 1) as catalyst, aqueous acetic acid as solvent and metallic zinc as electron source (cf. Schemes 2 and 3). Experimental evidence for an attack of 1(I) on both faces of the double bond is presented. By the same catalyst (1 R)-10, 10-dimethyl-2-pinene- 10-carbonitrile (9) is first transformed to the menthene derivative 11 (see Schemes 4 and 5). The ring opening is then followed by a fast saturation of the disubstituted olefinic system in 11, and ultimately the remaining double bond is reduced in a slow reaction. The cis-configurated saturated menthane derivative 16 is the main final product (16/17 ≈ 10:1).

Notes: Cob(I) alamin (1(I))-catalyzed reduction of the aldehyde 2 led to the two crystalline cyclopropanols 3 and 4 (see Scheme 2). The protolytic ring-opening starting from 3 produced the saturated aldehydes 6 and 7;8 was formed in traces only (see Scheme 3). The protolysis starting from 3 led, therefore, mainly to retention of configuration at the spiro C-atom (7); ring-opening with inversion was observed in traces only (8). Starting from 4, the protolysis produced 9 and 7; the absence of 8 showed this protolysis to proceed 9 and 7; the absence of 8 showed this protolysis to proceed exclusively with inversion of configuration at the spiro center. Of the p-bromobenzoate 5 (cf. Scheme 2) the structure has been determined by X-ray analysis.

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: 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].

Notes: The cob(I) alamin(1(I))-catalyzed2 transformation of the aldehyde 2 has been studied (cf. Table 1). Kinetic examinations showed a rapid isomerization of 2 to 3 (cf. Fig. 1 and 2). From the transformations in glacial AcOH, the two cyclopropanols 5 and 7 were isolated as main products (cf. Tables 1-3 and Fig. 1 and 2). Using large amounts of 1(I), the aldehyde 4 was very slowly transformed. Accepting the intermediate formation of 6 interconnected Co-complexes, i. e. A, B, C, D, E and F (cf. Scheme), the generation of all the products observed can be explained.

Notes: The cob (I)alamin- (1(I)) and the heptamethyl cob(I)ynnate- (2(I)) catalyzed transformation of an epoxide to the corresponding saturated hydrocarbon 3→4→5 is examined (see Schemes 1 and 3-5). Under the reaction conditions, the epoxyalkyl acetate 3 is opened by the catalysts with formation of appropriate (b̃-hydroxyalkyl)-corrinoid derivatives (13, 14, 17, 18, see Schemes 12 and 14). Triggered by a transfer of electrons to the Co-corrin-π system, the Co, C-bond of the intermediates is broken, generating the alkenyl acetate 4 (cf. Schemes 12 and 14) following an electrofugal fragmentation (cf. Schemes 2 and 12). The double bond of 4 is also attacked by the catalysts, leading to the corresponding alkylcorrinoids (15, 19, see Schemes 12 and 14) which in turn are reduced by electrons from metallic zinc, the electron source in the system, inducing a reductive cleavage of the Co, C-bond with production of the saturated monoacetate 5 (see Schemes 2, 5 and 12). In the cascade of steps involved, the transfer of electrons to the intermediate alkylcorrinoids (13-15, 17-19, see Schemes 12 and 14) is shown to be rate-limiting. Comparing the two catalytic species 1(I) and 2(I), it is shown that the ribonucleotide loop protects intermediate alkylcobalamins to some extent from an attack by electrons. The protective function of the ribonucleotide side-chain is shown to be present in alkylcobalamins existing in the base-on form (cf. Chap. 4 and see Scheme 14).

Notes: Synthesis of Stereisomeric Pinanthromboxane Derivatives and Evaluation of the Compounds as Platelet Aggregation InhibitorsStarting from the two enantiomeric myrtenols ((-)-1 and (+)-1; cf. Scheme 1), the synthesis of twelve stereoisomeric pinanthromboxane derivatives ((+)- and (-)-10, -11, -14, -15, -21 and -22) is described (cf. Schemes 1-4). Biological data from the evaluation as platelet aggregation inhibitors (cf. Table 6 and 7), thromboxane synthetase inhibitors (cf. Table 8) and from the assessment as antagonists of leukotriene E4 induced bronchoconstriction (cf. Table 9) are presented.