Unprecedented Meta-Substitution of Calixarenes: Direct Way to Inherently Chiral Derivatives

Abstract

Electrophilic aromatic substitution in the calix[n]arene series is a well-established procedure leading exclusively to para-substituted derivatives. An unprecedented regioselectivity of the mercuration reaction leading to the meta-substituted calix[4]arenes is described. These compounds represent a new type of substitution pattern in classical calixarene chemistry and open the door for the straightforward synthesis of inherently chiral receptors based on calixarenes.

Inherently Chiral Calixarenes: Synthesis and Applications

“…Both involve unusual chemistry to directly install meta ‐functionality without resorting to directing groups, although to date neither has demonstrated an asymmetric version of their method. Lhoták's organomercurial route is arguably better in terms of yield and scope, and allows for the direct incorporation of mercury chloride into the meta ‐position of a calixarene . Whilst the toxicity issues of mercury cannot be ignored, the versatility of this reaction is extremely rich, giving meta ‐functionalised calix[4]arenes that are almost impossible to access by any other method (Scheme ).…”

“…The mono‐ meta ‐mercurial derivative was available in the best yields (60 %), and could be readily transformed into a number of extremely versatile groups as shown in Scheme . The authors have suggested that the unusual selectivity for the meta ‐position is due to favourable cation–π interactions between the mercury(II) atom and a neighbouring aryl ring noted in the crystal structure they obtained . Using two equivalents of mercury trifluoroacetate gives a low yielding mixture of meta,meta ‐ and meta,para ‐organomercurial ICCs (Scheme ), which is less useful than the mono‐mercurial route.…”

“…Lhotµk's organomercurialr oute is arguably better in terms of yield and scope, and allows for the direct incorporation of mercury chloride into the meta-position of ac alixarene. [59][60][61][62][63] Whilstt he toxicity issues of mercury cannotb ei gnored, the versatility of this reactioni se xtremely rich, giving meta-functionalised calix [4]arenes that are almost impossible to access by any otherm ethod( Scheme15). The mono-meta-mercurial derivativew as availablei nt he best yields (60 %), and could be readily transformed into an umber of extremelyv ersatile groups as shown in Scheme 15.…”

“…[60,62,63] The authors have suggested that the unusual selectivityf or the meta-position is due to favourable cation-p interactions between the mercury(II) atom and an eighbouring aryl ring noted in the crystal structure they obtained. [59] Using two equivalents of mercury trifluoroacetate gives al ow yielding mixtureo fmeta,meta-a nd meta,para-organomercurial ICCs (Scheme 16), [61,62] which is less useful than the mono-mercurial route. Whati si nterestingt hough,i st hat the meta,para-organomercurial can be selectively functionalised as the para-organomercurial is more reactive, allowing for two different groups to be introduced sequentially.…”

Rational Strategies for the Selective Functionalization of Calixarenes

“…[29] Depending on the stoichiometry, reactiono fc alix [4]arenes 5.13 or 5.14 with mercury(II)t rifluoroacetate (Hg(TFA) 2 )y ielded either mono-or dimercuratedd erivatives at the meta position (5.15-5.17,Scheme 16). To rationalize this unusual regioselectivity,the authors carriedo ut quantum chemical calculations on the mercuration reaction.…”