Intramolecular reactions research

Unfortunately the bicyclic triazolium salt that had successfully been used in our research group for the enantioselective intermolecular benzoin condensation (Enders and Kallfass 2002) did not show any catalytic activity in the intramolecular reaction. We thus searched for alternative, easily accessible enantiopure polycyclic y-lactams as precursors for the synthesis of novel triazolium salts (Enders et al. 2006c for a related study see Takikawa et al. 2006). The rigid polycyclic structure of the catalysts should allow high asymmetric inductions. A first tar-... 

In 1996, our research group observed an activity of triazolium salts, for example (S,. S )-97 as precatalysts in this intramolecular reaction. The stereoselective synthesis of various 4-chromanones (f )-138 via the first asymmetric intramolecular Stetter reaction was performed with enantiomeric excesses of 41%-74% and yields of 22%-73% (Scheme 38) (Enders etal. 1996c). 

Both intermolecular and intramolecular [4+3] cycloaddition reactions are known [6], The first example of this process was published by Fort in 1962 in the course of his studies on the mechanism of the Favorskii rearrangement [7]. He was able to capture the oxyallylic cation generated upon treatment of 1 with base in the presence of furan (Scheme 19.2). While the yield for the process was low, this contribution was seminal. It should be noted that this year (2012) marks the golden anniversary of this reaction. Research in both fundamental and applied aspects of the process continues unabated and the reaction can truly now be called synthetically useful. 

While enantioenriched diols have been broadly used for generating epoxides and a-hydro qr carbonyl compounds, these chiral synthons have been used to generate a number of other useful functional groups. Researchers at Lilly used SAD to generate diol 173 which, upon acidification, condensed on a pendent pro-chiral ketone to generate the enantioenriehed ketal 174 (Scheme 14.65). This intramolecular reaction provided rapid access to the 6,8-dioxabicyclo[3.2.l]octane skeleton of (-)-frontalin and brevieomin. Whilst enantioselectivities were modest in this case (60-70%), the sealemie mixtures still proved useful for the purposes of their research. 

The efficiency of the intramolecular reaction (Equation 2.23) over its intermolecular counterpart (Equation 2.24) is measured by the ratio k,/k2, which has units of molarity (M). Despite the accumulation of large amounts of kinetic data on intramolecular reactions during the last (nearly) four decades, which show the values of kj/kj ranging from 0.5 to -10 A/ , the attempts to explain these values of ki/k2 created nearly 24 seemingly different suggestions as sununa-rized in Table 2.2, and resulted in an uncomfortable debate among some of the most productive researchers in this area. Apparently, some of the suggestions describe essentially same molecular interactions but with different, attractive, and fanciful nomenclature. 

Haward et al.t have reported some research in which a copolymer of styrene and hydroxyethylmethacrylate was cross-linked by hexamethylene diisocyanate. Draw the structural formula for a portion of this cross-linked polymer and indicate what part of the molecule is the result of a condensation reaction and what part results from addition polymerization. These authors indicate that the crosslinking reaction is carried out in sufficiently dilute solutions of copolymer that the crosslinking is primarily intramolecular rather than intermolecular. Explain the distinction between these two terms and why concentration affects the relative amounts of each. 

This chapter has taken the reader through a number of microwave-assisted methodologies to prepare and further functionalize 2-pyridone containing heterocycles. A survey of inter-, intramolecular-, and pericyclic reactions together with electrophilic, nucleophilic and transition metal mediated methodologies has been exemplified. Still, a number of methods remain to be advanced into microwave-assisted organic synthesis and we hope that the smorgasbord of reactions presented in this chapter will inspire to more successful research in this area. 

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