New Reactivities and Selectivities

The specific size, shape and hydrophobic environment of the cavity as well as partly desolvation and isolation of the substrates from the bulk solvent can induce new activities and selectivities. The new nticroenvironment within the nanoreactor can for example enforce the substrates to adopt conformations which are not or less populated in the bulk or it can stabilize certain reactive intermediates. In bimolecular reactions the cavity can direct the relative spatial orientation of the two substrates, facilitating selective reactions 

Substrate size- and shape-selective reactions can also be explained in terms of effective concentration and transition state stabilization. 1) In a mixture of substrates a higher concentration can be achieved for those having a complementary size and shape to the nanoreactor portals and cavity (and thus can enter the nanoreactor) compared to those substrates that can not easily enter or do not fit within the cavity. In some cases, when the substrate encapsulation is a slow process (slow diffusion), substrate encapsulation can become the rate-determining step. 2) One can also imagine that substrates of identical size and shape can both enter the cavity, but the transition state of one of the reaction pathways is stabilized to a greater extent than the other. Importantly, for all encapsulated reactions one should keep in mind that the substrate residence time within the nanoreactor and the kinetic rates of the encapsulated reaction should at least have a comparable magnitude.  

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Lubineau, A. Auge, J. Bienayme, H. Queneau, Y. Scherrmann, M.-C. (1993) Aqueous sugar solutions as solvent in organic synthesis new reactivity and selectivity, in Carbohydrates as Organic Raw Materials II, Descotes, G., Ed. VCH, Weinheim, pp. 99-112. 

There are few addition reactions to a,/J-disubstituted enoyl systems 151 that proceed in good yield and are able to control the absolute and relative stereochemistry of both new stereocenters. This is a consequence of problematic A1,3 interactions in either rotamer when traditional templates such as oxazolidinone are used to relieve A1,3 strain the C - C bond of the enoyl group twists, breaking conjugation which results in diminished reactivity and selectivity [111-124], Sibi et al. recently demonstrated that intermolecular radical addition to a,/J-disubstituted substrates followed by hydrogen atom transfer proceeds with high diastereo- and enantioselectivity (151 -> 152 or 153, Scheme 40). 

As will happen, for example, with perfluorotriethylamine, a substance that is a good alternative reaction medium may be found for reactions and it can be easily recycled by simple extractive workup (Nakano and Kitazume, 1999). One of the most important issues in twenty-first century scientific society is the environmental problem. Thus far, there have been increasing demands for substitutes for toxic and/or harmful solvents like CH2CI2. Recently, inert and less toxic fluorous (perfluorinated) fluids have been recognized and are attracting attention as new alternative solvents (Fish, 1999). This fact shows the need to survey the scope and limitations of the utility of these liquids as alternative reaction media for reactions, which are of great current interest due to their unique reactivities and selectivities. 

In 1999, in consideration of the readily structural modifications and fine-tuning of catalysts to attain sufficient reactivity and selectivity, Maruoka and coworkers designed and prepared the structurally rigid, chiral spiro ammonium salts of type 1 derived from commercially available (S)- or (R)-1,1 -bi-2-naphthol as a new C2-symmetric chiral phase-transfer catalyst, and successfully applied this to the highly efficient, catalytic enantioselective alkylation of N-(diphenylmethylene)glycine tert-butyl ester under mild phase-transfer conditions (Scheme 5.1) [7]. 

Researchers at Sepracor later disclosed the use of a new class of chiral oxazaborolidines derived from r/. v-aminoindanol in the enantioselective borane reduction of a-haloketones.6,7 The 5-hydrogen oxazaborolidine ligand 10 was prepared in situ from d,v-aminoindanol 1 and BH3 THF.8 Stock solutions of 5-methyl oxazaborolidine 11-16 were obtained by reaction of the corresponding N-alkyl aminoindanol with trimethyl boroxine.6,7 5-Methyl catalyst 11 was found to be more selective (94% ee at 0°C) than the 5-hydrogen catalyst 10 (89% ee at 0°C), and enantioselectivities with 11 increased at lower temperatures (96% ee at -20°C). The catalyst structure was modified by introduction of A-a I kyI substituents. As a general trend, reactivities and selectivities decreased as the steric bulk or the chelating ability of the A -alkyl substituent increased (Scheme 17.4). 

Me3SiX with X = Cl, Br, I are relatively new reagents that are very reactive and selective for the formation of carbon-halogen bond. 

In a very different area of organic chemistry Ken produced a series of landmark theoretical papers on carbene reactions. He developed a general theory, showing how orbital interactions influence reactivity and selectivity in carbene additions to alkenes. Ken also showed how entropy control of reactivity and negative activation barriers in carbene addition reactions could both be explained by a new, unified model. 

Chiral Lewis bases, 81,82, and 83 modified from HMPA and biquinoline dioxide were developed by several groups for a new type of enantioselective allylation (Sch. 59) [102], Aromatic and conjugate aldehydes react with allyltrichlorosilane with moderate to good ee values under mild eonditions but for aliphatic aldehydes reactivity and selectivity are poor. 

The authors devised the new bidentate titanium catalyst (anthraquinone-l,8-di-oxy)bis(triisopropoxytitanium) (55) and utilized it for the simultaneous coordination of carbonyl substrates [59]. Comparison of the reactivity and selectivity with the corresponding monodentate titanium catalyst 56 in several synthetic examples genuinely demonstrates the high double-activation ability of 55 toward carbonyls under catalytic conditions as illustrated in Scheme 1-20. 

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