Cycloaddition hydrogen bonding effect

Zhang, C. and Guo, X. C., Intramolecular hydrogen-bond effect in meta-cycloaddition of arene to olefin, Synth. Commun., 24, 3157,1994. 

Hydrogen bonding also accounts for the stereoselectivity found in the cycloaddition to 4-substituted 4-hydroxy-2-cyclopentenones (175). The importance of this effect is evident by comparing the results from 26 with those of unprotected 25 as illustrated in Scheme 6.30. The acetylation of the hydroxy group causes a drop in the ratio of diastereoisomers from 85 15 to 57 43 (175). 

Reductions of these ring systems are common. Most often, active hydrogen techniques are employed to cleave weak heteroatom-heteroatom bonds. Reductions of the glycoluril derivatives are less common due to the lack of such a weak bond. Some recent examples include reactions by Chan et al. <2003TL395> who employed Raney nickel and hydrogen to effect cleavage of an N-O bond in their synthesis of new heterocyclic compounds via 1,3-dipolar cycloaddition chemistry (Equation 15). 

The (5)-tryptophan-derived oxazaborolidenes utilized in this aldol study have been previously examined by Corey as effective catalysts for enantioselective Diels-Alder cycloaddition reactions [6]. Corey has documented unique physical properties of the complex and has proposed that the electron-rich indole participates in stabilizing a donor-acceptor interaction with the metal-bound polarized aldehyde. More recently, Corey has formulated a model exemplified by 7 in which binding by the aldehyde to the metal is rigidified through the formation of a hydrogen-bond between the polarized formyl C-H and an oxyanionic ligand [7], The model illustrates the sophisticated design elements that can be incorporated into the preparation of transition-metal complexes that lead to exquisite control in aldehyde enantiofacial differentiation. 

To enable linear templates to be used as general devices for building molecules, we have identified an ability of rigid bifunctional molecules to serve as linear templates in the organized environment of the solid state [6-12], The templates operate by assembling two complementary molecules by way of hydrogen bonds for a UV-induced [2 + 2] cycloaddition reaction [18]. By using the solid state as a medium for reaction, we have been able to circumvent the structure effects of... 

The HDA reaction allows for rapid access to chiral six-membered heterocyclic structures that serve as valuable intermediates in organic synthesis. The first highly enantioselective HDA reaction promoted by a chiral hydrogen bond donor was reported from the Rawal laboratory. While investigating the cycloaddition reactions of amino-siloxy diene 115, it was observed that this diene was exceptionally reactive to heterodienophiles, and underwent HDA reactions with various aldehydes at room temperature, even in the absence of any added catalyst (Scheme 6.14). Subsequent treatment of the intermediate cycloadducts (116) with acetyl chloride afforded the corresponding dihydro-4-pyrones (117) in good overall yields [101]. Further studies of this reaction revealed a pronounced solvent effect,... 

A clear correlation between the stabilisation of the endo-transition structure and the size of substituent at the 2-position of an 1-oxa-1,3-butadiene is again seen in the cycloaddition of the N-acetyl-enaminoketone 8-20 to 8-12. As expected, the reaction of 8-20 a to give 8-21 a and 8-22 a shows only a very small AAV, whereas with growing bulkiness of R as in 8-20 b and 8-20 c an increase of AAV is observed with the formation of the trans-cycloadduct 8-22 as the major product under high pressure. Because of the pressure effect it can clearly be deduced that 8-22 is formed via an endo-Z-anti-transition structure, presumably due to a strong hydrogen bond in the (Z)-diastereomer and a steric discrimination of the ( )-diastereomer of 8-20. However, an exo-E-anti-transition structure would give the same product (Fig. 8-7) [548]. 

Diels-Alder reactions have been performed in most alternative reaction media. For certain substrates this reaction is significantly accelerated in fluorous solvents (Figure 1.9) This has been ascribed to a fluorophobic effect, analogous to the better-known hydrophobic effect where there is an inverse relationship between reaction rate and the solubility of reagents. However, it should be noted that in general cycloaddition reactions (including Diels-Alder reactions) are faster in water and this can be attributed to additional hydrogen bond stabilization of the transition state. 

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