Hydrogen Bonding Activation

Finally, the change in selectivity for the methane/pentane couple for the two different substrates (18% for hexane, 56% for cyclohexane) can be explained as follows in the case of cyclohexane, the Ci to C5 products are formed through the second carbon-carbon bond cleavage via the hexyl surface intermediate D whereas in the case of hexane, the initial carbon-hydrogen bond activation step can lead to any of three alkyl surface intermediates (D, E, and F) before arriving at the key metallacychc intermediates... 

G and H. This suggests that the isomerization of the surface alkyl fragments inter-converting D, E, and F, is slow with respect to the second carbon-hydrogen bond activation step and subsequent carbon-carbon bond cleavage. 

Biotin-dUTP derivatives are formed by modification of the C-5 position of uridine. This location is not involved in hydrogen bonding activity with complementary DNA strands, thus hybridization efficiency is not immediately compromised. By contrast, biotin-dCTP or biotin-dATP derivatives involve modification of the bases at the N-4 position of cytosine and the N-6 position of adenine, locations directly involved in hydrogen bond formation with complementary bases. Thus, DNA biotinylation through the use of modified deoxynucleoside triphosphates to be incorporated into existing DNA strands may result in better activity of the probe if dUTP is used over dATP or dCTP. 

Another important reaction principle in modem organic synthesis is carbon-hydrogen bond activation [159]. Bergman, Ellman, and coworkers have introduced a protocol that allows otherwise extremely sluggish inter- and intramolecular rhodium-catalyzed C-H bond activation to occur efficiently under microwave heating conditions. In their investigations, these authors found that heating of alkene-tethered benzimidazoles in a mixture of 1,2-dichlorobenzene and acetone in the presence of di-//-... 

Miscellaneous Reactions Berkessel " has identified peptide-like urea-based bifiinctional organocatalysts for the highly efficient dynamic kinetic resolution of azalactones (Scheme 11.14a). Another selective hydrogen-bonding activation mechanism that enables the addition of pyrroles to ketenes using catalytic quantities of azaferrocene 36 has been introduced by Fu and coworkers (Scheme 11.14b). ° ... 

A new cinchona alkaloid-derived catalyst has been developed for the enantioselective Strecker reaction of aryl aldimines via hydrogen-bonding activation. For reference, see Huang, J. Corey, E. J. Org. Lett. 2004, 6, 5027-5029. 

For the reduction of ketimines with trichlorosylane via a possible hydrogen-bonding activation, see Maikov, A. V. Mariani, A. MacDougall, K. N. Kocovsky, P. Org. Lett. 2004, 6, 2253-2256. 

This review will concentrate on metal-free Lewis acids, which incorporate a Lewis acidic cation or a hypervalent center. Lewis acids are considered to be species with a vacant orbital [6,7]. Nevertheless, there are two successful classes of organocatalysts, which may be referred to as Lewis acids and are presented in other chapter. The first type is the proton of a Brpnsted acid catalyst, which is the simplest Lewis acid. The enantioselectivities obtained are due to the formation of a chiral ion pair. The other type are hydrogen bond activating organocatalysts, which can be considered to be Lewis acids or pseudo-Lewis acids. 

Because a comprehensive discussion of the transition state of hydrogen-bond catalysis will be presented by Berkessel in Chapter 3, the hydrogen bond catalyzed hetero Diels-Alder reaction of butadiene with carbonyl compounds will be discussed briefly here. Huang and Rawal reported that the hetero Diels-Alder reaction of aminodiene with aldehyde exhibited significant solvent effects (Scheme 2.7) [15]. The reaction in CHCfi was accelerated 30 times in comparison with that in THF, while that in i-PrOH was accelerated 630 times. They proposed that the Diels-Alder reaction was promoted by the hydrogen-bond activation of aldehyde. This finding resulted in the development of TADDOL catalyst [3]. 

In addition to the activation of carbonyl compounds and imines, Schreiner studied on thiourea-catalyzed acetalization reaction, in which ortho esters were activated by hydrogen bond [19]. Jacobsen has utilized the hydrogen-bond catalysis in reactions with acyliminium ions, wherein hydrogen bond activates the acylim-inium salt through complexation with chloride [20]. 

In previous work, Corey used the free base form of 34 as an effective chiral ligand in the Os04-promoted dihydroxylation of olefins [90]. He later found that ammonium salt 34 catalyzed the addition of HCN to aromatic N-allyl imines (Scheme 5.50) [91]. The U-shaped pocket of the catalyst is essential in fixing the orientation of the hydrogen-bonded activated aldimine via n-n interactions. 

It should be noted that while formation of a strongly acidic BBA species of type 11 is conceivable, crystallographic evidence from several BBA/substrate complexes implicates hydrogen bonding activation in agreement with a type III mode of activation. 

Figure 6.4 Proposed double hydrogen-bonding activation of nitrones through thiourea derivative 9.

---