Helix Persistence and Breakdown in Oligoureas of Metaphenylenediamine: Apparent Diastereotopicity as a Spectroscopic Marker of Helix Length in Solution Jonathan Clayden,* ,† Loı ¨c Lemie ` gre, †,‡ Gareth A. Morris, † Mark Pickworth, † Timothy J. Snape, †,§ and Lyn H. Jones | School of Chemistry, UniVersity of Manchester, Oxford Road, Manchester M13 9PL, United Kingdom, and Pfizer Central Research, Sandwich CT12 3NT, United Kingdom Received July 23, 2008; E-mail: clayden@man.ac.uk Abstract: Oligomeric ureas derived from m-phenylenediamine with chain lengths of up to seven urea linkages were made by iterative synthetic pathways. Three families were synthesized: 4 and 20, bearing a terminal chiral sulfinyl group; 24, bearing a terminal rotationally restricted amide group, and 30 bearing a terminal achiral bromophenyl group. The distal end of the oligomers was capped with an N-benzyl group to act as a diastereotopic probe. With a terminal sulfinyl group, the 1 H NMR signals arising from the CH 2 group of the diastereotopic probe remained anisochronous even when separated from the stereogenic center by up to 24 bonds (in 20c). With a rotationally restricted amide, anisochronicity was no longer apparent beyond 17 bond lengths (in 24c). No anisochronicity was observable with a terminal bromophenyl group. We interpret these results as indicating that the oligoureas of short lengths adopt a defined helical secondary structure in solution, but that in longer oligomers the helicity breaks down and transmission of chirality in these systems is limited to about 24 bond lengths. We propose that “apparent diastereotopicity” (anisochronicity) provides a general empirical method for identifying secondary structure in solution. Introduction The absolute control of the configuration of new stereogenic centers has been for several decades a central goal of synthetic chemistry. 1 Comparable stereochemical control over conforma- tion, particularly of acyclic molecules, is a more nebulous aim toward which slow progress has been made in recent years. 2 Substitution patterns have been manipulated to induce defined conformational features in alkyl 3 and silyl 4 chains; methods have been developed for the control of slowly interconverting conformers (or atropisomers), 5-9 and the propagation of a chiral influence through global conformational control 10 has been exploited as a means of communicating stereochemical informa- tion over long (nanometer-scale) distances, 11,12 a chemical analogue of biological allostery. 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