Using Dipoles to Control the Directionality of Functional Groups: Syn‐ and Anti‐Oriented Benzene‐1,3‐dicarboxamides

Abstract

Poles apart: The relative orientation of a pair of functional groups—amides in this case—can be controlled by the choice of the substituent that lies between them. Groups which are effectively cylindrically symmetrical (Me, Cl) allow direct interaction between the dipoles of the amides and induce an anti orientation, whereas polar groups (OCOR, OSO2R, SO2R) interact with the dipole of both amides to yield a syn orientation (see picture).

Transmission of stereochemical information over nanometre distances in chemical reactions

“…The anti alignment preferred in aromatic dicarboxamides turns out to be quite general, even with more remote relationships between the amide substituents. 37 The NMR spectrum of xanthene-1,8-dicarboxamide 40, for example, contains a single 6 H singlet corresponding to the gem-dimethyl group, and double lithiation and electrophilic quench yields a compound 41 which in principle contains two stereogenic axes and may therefore exist as a pair of diastereoisomers. However, only a single diastereoisomer is obtained, which NMR showed to be C 2 symmetric, HPLC on a chiral stationary phase showed to be chiral and racemic, and X-ray crystallography showed to have the stereochemistry shown in Scheme 15.…”

Conformational switching between diastereoisomeric atropisomers of arenedicarboxamides induced by complexation with Lewis acids

“…In toluene, up to 10 : 1 selectivity for anti-2c was obtained, reducing to 2 : 1 in polar solvents. Presumably the preference for anti stereochemistry is driven by dipole repulsion, 12 which is greatest in non-polar solvents. Monitoring epimerisation from syn to anti-2c in toluene at 77 uC allowed evaluation of a half-life for this process of 32.2 h, corresponding to a barrier to interconversion syn-2c A anti-2c of 109.5 kJ mol 21 and from anti-2c A syn-2c of 103.1 kJ mol 21 .…”

Chiral Auxiliaries - Principles and Recent Applications

“…213 Clayden and co-workers showed that a chiral oxazolidine can influence the conformation of a long carbon chain and finally control the addition to an aldehyde group at the opposite end of the molecule (Scheme 75). [214][215][216] Most impressively, the auxiliary and the electrophilic aldehyde can be separated by more than 20 C-C bonds, and nevertheless, the Grignard addition to 200 still is highly diastereoselective (>90% de) (Scheme 75). 214 Once again, minimization of the overall dipole moment is key to the success of this transformation.…”