Heteroatom Chelation

The Sharpless asymmetric epoxidation (sec. 3.4.D.i) exploits this chelation effect because its selectivity arises from coordination of the allylic alcohol to a titanium complex in the presence of a chiral agent. The most effective additive was a tartaric acid ester (tartrate), and its presence led to high enantioselectivity in the epoxidation.23 An example is the conversion of allylic alcohol 40 to epoxy-alcohol 41, in Miyashita s synthesis of the Cg-Ci5 segment of (-t-)-discodermolide.24 in this reaction, the tartrate, the alkenyl alcohol, and the peroxide bind to titanium and provide facial selectivity for the transfer of oxygen from the peroxide to the alkene. Binding of the allylic alcohol to the metal is important for delivery of the electrophilic oxygen and 

The Cram chelation model (sec. 4.7.B) is an example where the chelation effects of the heteroatom influence the rotamer population and, thereby, the selectivity of the reduction. Zinc borohydride [Zn(BH4)2], effectively chelates the carbonyl oxygen and alcohol oxygen atoms in the reduction of 42 and leads to intermediate 43. Transfer of hydride to the carbonyl gave primarily the anti diastereomer, 45 (4 96, 44/45). When the chelating hydroxyl group was blocked as a tert-butyldiphenylsilyl ether (in 46 - sec. 7.3.A.i), reduction with Red-Al (sec. 4.3) led to a reversal in selectivity (96 4, 47/48).The ability to chelate a heteroatom varies with the reagent used. Lithium aluminum hydride shows less selectivity, due in part to poorer coordination with the heteroatom and reduction of 42 gave a 27 73 mixture of 44 and 45, 

Other heteroatoms can coordinate with reducing agents to afford high selectivity. Reduction of 49 with zinc borohydride, for example, gave a 76 24 mixture of 50 and 51 (61% yield), which was eventually converted by Davis to (-)-SS20846A,263 which is (45 )-hydroxy-(25)-(l-pentadienyl)piperidine and a proposed intermediate in the biosynthesis of the potent antimicrobial agent streptazolin.26b c 

The examples in Sections 6.2.D and 6.2.E show that chelation effects can be controlled by the nature of the heteroatom (alcohol vs. ether, amine vs. amide vs. sulfonamide vs. azide) and the choice of reagent (changing the metal in metal hydrides for example). Such chelating effects have also been used extensively in cyclic systems, and those applications will be discussed in Sections 6.4 and 6.5. 

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Scheme 8-16 Regioselective formation of internal zirconocene upon heteroatom chelating effect...

This hypothesis has been verified starting from (Z)-y-iodoallyl ethers [109], amines [107], and thioethers [107] (Scheme 7-95) that are easily accessible from a propargyl ether [110] or ethyl propiolate [111]. In each case, the heteroatom chelates the vinylmetal to form a rigid five-membered ring and the allyl moiety approaches the vinyl one with a diastereofacial selectivity anti to the alkyl group [112]. 

In certain cases. Type I allylmetal reagents have been shown to give products consistent with a- or yff-heteroatom chelation [72-78]. In 1989, Sakurai reported that the allylation reactions of -hydroxy ketones with allyl- and crotyltrifluorosilanes... 

Chelation itself is sometimes useful in directing the course of synthesis. This is called the template effect (37). The presence of a suitable metal ion facihtates the preparation of the crown ethers, porphyrins, and similar heteroatom macrocycHc compounds. Coordination of the heteroatoms about the metal orients the end groups of the reactants for ring closure. The product is the chelate from which the metal may be removed by a suitable method. In other catalytic effects, reactive centers may be brought into close proximity, charge or bond strain effects may be created, or electron transfers may be made possible. 

Incorporation of a third heteroatom into S-N compounds is now well established, e.g. for C, Si P, As O Sn and Pb, together with the S2N2 chelates of Fe, Co, Ni, Pd and Pt mentioned on p. 725. The field is very extensive but introduces no new concepts into the general scheme of covalent heterocyclic molecular chemistry. Illustrative examples are in Fig. 15.44 and fuller... 

In his original paper,2 Cram disclosed an alternative model that rationalizes the preferred stereochemical course of nucleophilic additions to chiral carbonyl compounds containing an a heteroatom that is capable of forming a complex with the organometallic reagent. This model, known as the Cram cyclic or Cram chelate model, has been extensively studied by Cram9 and by others,410... 

The remainder of the work on Ni(II) complexes involves the use of chelating ligands in which the carbene is functionalised with pendant heteroatom donor(s). The picolyl-functionalised NHC dicationic complex 29 (Fig. 4.11) was tested for ethylene polymerisation after treatment with MAO [34]. This complex was found to be highly active in a preliminary test (330 kg moF bar h" ), giving predominantly linear polyethylene. Unfortunately this work does not seem to have been followed up. The same system was active for norbomene polymerisation (TOF = 24 400 h" over 1 h). Maximum activity was achieved at 80°C whereafter thermal deactivation became significant, although the nature of this deactivation was not studied. The phenoxide-functionalised carbene complex 30 (Fig. 4.11) was also... 

Formation of the least-hindered alkylzirconium complex during the course of the hydrozirconation-isomerization process of alkenes can be altered by the presence of aromatic rings, additional conjugative double bonds, chelating heteroatoms [81, 94] or groups that can be lost by elimination [95, 96]. 

The presence of functional groups containing oxygen-, nitrogen-, and phosphorus-chelating heteroatoms does frequently have regiochemical consequences in the... 

Intramolecular nucleophilic assistance is another distinct possibility for providing activation, and can be realized by coordination of the metal center by a heteroatom (O, N, etc.) within the ligand which transiently forms a chelate-like attachment to the metal. Such a mode of activation was supposed to account for the ease of reaction of vinyl triflates with (zp-isomers of alkenyl-stannanes bearing OH groups in the proximity of the reaction center (71).2 5... 

The alkylation of the sp3 C-H bonds adjacent to a heteroatom becomes more practical when the chelation assistance exists in the reaction system. The ruthenium-catalyzed alkylation of the sp3, C-H bond occurs in the reaction of benzyl(3-methylpyridin-2-yl)amine with 1-hexene (Equation (30)).35 The coordination of the pyridine nitrogen to the ruthenium complex assists the C-H bond cleavage. The ruthenium-catalyzed alkylation is much improved by use of 2-propanol as a solvent 36 The reaction of 2-(2-pyrrolidyl)pyridine with ethene affords the double alkylation product (Equation (31)). 

Some experimental evidences are in agreement with this proposed mechanism. For example, coordinating solvents like diethyl ether show a deactivating effect certainly due to competition with a Lewis base (149). For the same reason, poor reactivity has been observed for the substrates carrying heteroatoms when an aluminum-based Lewis acid is used. Less efficient hydrovinylation of electron-deficient vinylarenes can be explained by their weaker coordination to the nickel hydride 144, hence metal hydride addition to form key intermediate 146. Isomerization of the final product can be catalyzed by metal hydride through sequential addition/elimination, affording the more stable compound. Finally, chelating phosphines inhibit the hydrovinylation reaction. 

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