Lewis basic

Other Lewis basic groups can direct the hydrogenation. (Ir seems to be superior to Rh for these cases)... 

In a Lewis-acid catalysed Diels-Alder reaction, the first step is coordination of the catalyst to a Lewis-basic site of the reactant. In a typical catalysed Diels-Alder reaction, the carbonyl oxygen of the dienophile coordinates to the Lewis acid. The most common solvents for these processes are inert apolar liquids such as dichloromethane or benzene. Protic solvents, and water in particular, are avoided because of their strong interactions wifti the catalyst and the reacting system. Interestingly, for other catalysed reactions such as hydroformylations the same solvents do not give problems. This paradox is a result of the difference in hardness of the reactants and the catalyst involved... 

A combination of the promoting effects of Lewis acids and water is a logical next step. However, to say the least, water has not been a very popular medium for Lewis-acid catalysed Diels-Alder reactions, which is not surprising since water molecules interact strongly with Lewis-acidic and the Lewis-basic atoms of the reacting system. In 1994, when the research described in this thesis was initiated, only one example of Lewis-acid catalysis of a Diels-Alder reaction in water was published Lubineau and co-workers employed lanthanide triflates as a catalyst for the Diels-Alder reaction of glyoxylate to a relatively unreactive diene . No comparison was made between the process in water and in organic solvents. 

In a second attempt to extend the scope of Lewis-acid catalysis of Diels-Alder reactions in water, we have used the Mannich reaction to convert a ketone-activated monodentate dienophile into a potentially chelating p-amino ketone. The Mannich reaction seemed ideally suited for the purpose of introducing a second coordination site on a temporary basis. This reaction adds a strongly Lewis-basic amino functionality on a position p to the ketone. Moreover, the Mannich reaction is usually a reversible process, which should allow removal of the auxiliary after the reaction. Furthermore, the reaction is compatible with the use of an aqueous medium. Some Mannich reactions have even been reported to benefit from the use of water ". Finally, Lewis-acid catalysis of Mannich-type reactions in mixtures of organic solvents and water has been reported ". Hence, if both addition of the auxiliary and the subsequent Diels-Alder reaction benefit from Lewis-acid catalysis, the possibility arises of merging these steps into a one-pot procedure. 

The importance of solvent participation in the borderline mechanisms should be noted. Nucleophilic participation is minimized by high electronegativity, which reduces the Lewis basicity and polarizability of the solvent molecules. Trifluoroacetic acid and perfiuoro alcohols are among the least nucleophilic of the solvents used in solvolysis studies. These solvents are used to define the characteristics of reactions proceeding without nucleophilic solvent participation. Solvent nucleophilicity increases with the electron-donating capacity of the molecule. The order trifluoroacetic acid < trifluoroetha-nol <acetic acid < water < ethanol gives a qualitative indication of the trend in solvent nucleophilicity. More will be said about solvent nucleophilicity in Section 5.5. 

The chemistry of Lewis acid-base adducts (electron-pair donor-acceptor complexes) has stimulated the development of measures of the Lewis basicity of solvents. Jensen and Persson have reviewed these. Gutmann defined the donor number (DN) as the negative of the enthalpy change (in kcal moL ) for the interaction of an electron-pair donor with SbCls in a dilute solution in dichloroethane. DN has been widely used to correlate complexing data, but side reactions can lead to inaccurate DN values for some solvents. Maria and Gal measured the enthalpy change of this reaction... 

The initial investigation focused on the use of threitol-derived auxiliaries with various substituent groups on the dioxolane ring (Table 3.3). However, it became evident that the oxygen atoms in the substituents had a detrimental effect on selectivity. Comparison of the diastereoselectivities for the ketals 69-71, which contain Lewis basic sites in the substituents at the 1 and 2 positions, with those from simpler diol derived ketals 72-74 demonstrates the conflicting effects of numerous coordination sites. The simpler, diol-derived ketals provide superior results compared to the threitol derived ketals. The highest diastereoselectivity is observed in the case of the 1,2-diphenyl ethane-1,2-diol derived ketal 74. 

Where FCl is the solute gas-liquid partition coefficient, r is the tendency of the solvent to interact through k- and n-electron pairs (Lewis basicity), s the contribution from dipole-dipole and dipole-induced dipole interactions (in molecular solvents), a is the hydrogen bond basicity of the solvent, b is its hydrogen bond acidity and I is how well the solvent will separate members of a homologous series, with contributions from solvent cavity formation and dispersion interactions. 

Ionophores constitute a large collection of structurally diverse substances that share the ability to complex cations and to assist in the translocation of cations through a lipophilic interface.1 Using numerous Lewis-basic heteroatoms, an ionophore organizes itself around a cationic species such as an inorganic metal ion. This arrangement maximizes favorable ion-dipole interactions, while simultaneously exposing a relatively hydrophobic (lipophilic) exterior. 

Although neither of the two carbonyl groups in 18 is immune to the action of Lawesson s reagent,11 it is possible to bring about the selective conversion of the more Lewis-basic lactam carbonyl to the corresponding thiocarbonyl. Thus, treatment of 18 with Lawesson s reagent results in the formation of thiolactam 19 in 85% overall yield from 13. 

Treatment of commercially available and symmetrical 3,4,5-tri-methoxytoluene (37) with iodine, periodic acid, and acetic acid under the conditions of Suzuki19 results in the formation of symmetrical diiodide 38 in 93 % yield. Although only one of these newly introduced iodine atoms is present in intermediate 13, both play an important role in this synthesis. Selective monodemethylation of 38 with boron trichloride furnishes phenol 39 in 53% yield together with 13 % of a regioisomer. Evidently, one of the Lewis-basic iodine substituents coordinates with the Lewis-acidic boron trichloride and directs the cleavage of the adjacent methyl ether... 

The reaction processes shown in Scheme 8 not only accomplish the construction of an oxepane system but also furnish a valuable keto function. The realization that this function could, in an appropriate setting, be used to achieve the annulation of the second oxepane ring led to the development of a new strategy for the synthesis of cyclic ethers the reductive cyclization of hydroxy ketones (see Schemes 9 and 10).23 The development of this strategy was inspired by the elegant work of Olah 24 the scenario depicted in Scheme 9 captures its key features. It was anticipated that activation of the Lewis-basic keto function in 43 with a Lewis acid, perhaps trimethylsilyl triflate, would induce nucleophilic attack by the proximal hydroxyl group to give an intermediate of the type 44. 

It should be noted that the sense of asymmetric induction in the lithiation/ rearrangement of aziridines 274, 276, and 279 by treatment with s-butyllithium/ (-)-sparteine is opposite to that observed for the corresponding epoxides (i.e. removal of the proton occurs at the (S)-stereocenter) [102], If one accepts the proposed model to explain the selective abstraction of the proton at the (R) -stereo-center of an epoxide (Figure 5.1), then, from the large difference in steric bulk (and Lewis basicity) between an oxygen atom and a tosyl-protected nitrogen atom, it is obvious that this model cannot be applied to the analogous aziridines. 

Jacobsen subsequently reported a practical and efficient method for promoting the highly enantioselective addition of TMSN3 to meso-epoxides (Scheme 7.3) [4]. The chiral (salen)Cl-Cl catalyst 2 is available commercially and is bench-stable. Other practical advantages of the system include the mild reaction conditions, tolerance of some Lewis basic functional groups, catalyst recyclability (up to 10 times at 1 mol% with no loss in activity or enantioselectivity), and amenability to use under solvent-free conditions. Song later demonstrated that the reaction could be performed in room temperature ionic liquids, such as l-butyl-3-methylimidazo-lium salts. Extraction of the product mixture with hexane allowed catalyst recycling and product isolation without recourse to distillation (Scheme 7.4) [5]. 

Transition metals have been used to complex Lewis-basic centers in metathesis substrates and to arrange the reacting olefins in such a way that cycliza-tion is facilitated. Olefin metathesis of 122, for example, proceeds with good yield to the bispyridine macrocycle 123 (Eq. 17) [115]. 

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