Ultra-remote stereocontrol by conformational communication of information along a carbon chain

© 2004 Nature Publishing Group

dioxide dielectrics of similar thickness. For example, for 3.5-nm-thick SiO2, Sekine et al. reported a current density of 1026 A cm22

(at 2.5 V) and a breakdown field of 14.5 MV cm21 (ref. 21). Lo et al.have modelled electron tunnelling through SiO2 dielectrics andreported a current density of 1026 A cm22 (at 2.5 V) for 3.5-nm-thick SiO2 and a current density of 1022 A cm22 (at 2.5 V) for2.5-nm-thick SiO2 (ref. 22). These results suggest that for very thindielectrics, molecular monolayers may provide better performancethan inorganic oxides. (We note that capacitors fabricated withoutSAM, that is, with gold contacts evaporated directly on the plasma-activated silicon, show leakage current densities greater than100 A cm22, confirming that the contribution of the native oxidefilm to the insulation characteristics is minimal and that theformation of a high-quality molecular SAM is essential.)

We have also carried out bias stress measurements on Si/SAM/Aucapacitors. For a stress period of 106 s, the data show only a slightdegradation in the insulating properties of the monolayer, indicat-ing a charge-to-breakdown of greater than 0.01 C cm22, similar toSiO2 (see Fig. 2).

To integrate TFTs into circuits and displays it is often necessary todefine the source and drain contacts by photolithography. Theschematic cross-section of a pentacene TFT with a PhO-OTS gatedielectric and photolithographically defined contacts is shown inFig. 3. After depositing the SAM on the activated silicon substrate,gold was thermally evaporated and patterned by photolithographyand wet chemical etching. Following the gold etch, the photo resistwas stripped in acetone. No special precautions were taken toprotect the SAM. The contact angle changed from initially 988after SAM deposition, to 918 after the Au etch, to 938 after strippingthe photo resist, showing that the SAM was not damaged by the wetchemical processing. Transistors were completed by thermallyevaporating the pentacene active layer. Figure 3 shows the electricalcharacteristics of a TFTwith a channel length of 5mm and a channelwidth of 100 mm. The transistor has a threshold voltage of 20.7 V, asubthreshold swing of 140 mV per decade, a carrier mobility of0.05 cm22 V21 s21, and a transconductance of 0.01mSmm21, to ourknowledge the largest transconductance reported for an organictransistor.

Our results show that large operating voltages are not an intrinsicfeature of organic transistors, and that the operating voltage andpower dissipation of organic devices can be dramatically reduced byexploiting the self-assembly of silane-based molecular dielectrics.With a thickness of 2.5 nm, these dielectrics provide a gate capaci-tance near 1 mF cm22, so that the TFTs can be operated with voltagesof 2 V or less, and yet sustain gate fields of 14 MV cm21 andshow gate current densities as low as 1029 A cm22. In addition,the SAM dielectrics are sufficiently robust to allow the use ofstandard semiconductor manufacturing methods (includingphotolithography and metal etching), which may even permittheir use as a gate dielectric in advanced silicon CMOStechnology. A

Received 5 March; accepted 31 August 2004; doi:10.1038/nature02987.

1. Rogers, J. A. et al. Paper-like electronic displays: Large-area rubber-stamped plastic sheets of

electronics and microencapsulated electrophoretic inks. Proc. Natl Acad. Sci. USA 98, 4835–4840

(2001).

2. Sheraw, C. D. et al. Organic thin-film transistor-driven polymer-dispersed liquid crystal displays on

flexible polymeric substrates. Appl. Phys. Lett. 80, 1088–1090 (2002).

3. Huitema, H. E. A. et al. Plastic transistors in active-matrix displays. Nature 414, 599 (2001).

4. Crone, B. K. et al. Organic oscillator and adaptive amplifier circuits for chemical vapor sensing. J. Appl.

Phys. 91, 10140–10146 (2001).

5. Bartic, C., Campitelli, A. & Borghs, G. Field-effect detection of chemical species with hybrid organic/

inorganic transistors. Appl. Phys. Lett. 82, 475–477 (2003).

6. Crone, B. et al. Large-scale complementary integrated circuits based on organic transistors. Nature

403, 521–523 (2000).

7. de Leeuw, D. M. et al. Polymeric integrated circuits: fabrication and first characterisation. 2002 Int.

Electron Device Meeting (IEDM) Tech. Dig., 293–296 (2002).

8. Baude, P. et al. Pentacene-based radio-frequency identification circuitry. Appl. Phys. Lett. 82,

3964–3966 (2003).

9. Klauk, H. et al. Pentacene organic transistors and ring oscillators on glass and on flexible polymeric

substrates. Appl. Phys. Lett. 82, 4175–4177 (2003).

10. Collet, J., Tharaud, O., Chapoton, A. & Vuillaume, D. Low-voltage, 30 nm channel length, organic

transistors with a self-assembled monolayer as gate insulating films. Appl. Phys. Lett. 76, 1941–1943

(2000).

11. Boulas, C., Davidovits, J. V., Rondelez, F. & Vuillaume, D. Suppression of charge carrier tunneling

through organic self-assembled monolayers. Phys. Rev. Lett. 76, 4797–4800 (1996).

12. Collet, J. & Vuillaume, D. Nano-field effect transistor with an organic self-assembled monolayer as

gate insulator. Appl. Phys. Lett. 73, 2681–2683 (1998).

13. Schutz, M. Self-Assembled Monolayers on Oxidized Surfaces—Anti-Corrosion and Insulation Behavior

PhD thesis, 192–193, Univ. Stuttgart (2002).

14. Lenfant, S., Krzeminski, C., Delerue, C., Allan, G. & Vuillaume, D. Molecular rectifying diodes from

self-assembly on silicon. Nano Lett. 3, 741–746 (2003).

15. Kelley, T. W. et al. High-performance OTFTs using surface-modified alumina dielectrics. J. Phys.

Chem. B 107, 5877–5881 (2003).

16. Klauk, H. et al. High-mobility polymer gate dielectric pentacene thin film transistors. J. Appl. Phys. 92,

5259–5263 (2002).

17. Halik, M. et al. Relationship between molecular structure and electrical performance of

oligothiophene organic thin film transistors. Adv. Mater. 15, 917–922 (2003).

18. Kelly, T. W. et al. High performance organic thin film transistors. MRS Symp. Proc. 771, 169–179

(2003).

19. Fontaine, P. et al. Octadecyltrichlorosilane monolayers as ultrathin gate insulating films in metal-

insulator-semiconductor devices. Appl. Phys. Lett. 62, 2256–2258 (1993).

20. Thompson, S. et al. A 90 nm logic technology featuring 50 nm strained silicon channel transistors, 7

layers of Cu interconnects, low k ILD, and 1 mm2 SRAM cell. 2002 Int. Electron Device Meeting (IEDM)

Tech. Dig., 61–64 (2002).

21. Sekine, K., Saito, Y., Hirayama, M. & Ohmi, T. Highly reliable ultrathin silicon oxide film formation at

low temperature by oxygen radical generated in high-density krypton plasma. IEEE Trans. Electr. Dev.

48, 1550–1555 (2000).

22. Lo, S. H., Buchanan, D. A., Taur, Y. & Wang, W. Quantum-mechanical modeling of electron tunneling

current from the inversion layer of ultra-thin-oxide nMOSFETs. IEEE Electr. Dev. Lett. 18, 209–211

(1997).

Supplementary Information accompanies the paper on www.nature.com/nature.

Acknowledgements M.S. and S.M. were supported by the PhD Fellowship of the Deutsche

Forschungsgemeinschaft.

Competing interests statement The authors declare that they have no competing financial

interests.

Correspondence and requests for materials should be addressed to M.H.

([email protected]).

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Ultra-remote stereocontrol byconformational communication ofinformation along a carbon chainJonathan Clayden, Andrew Lund, Lluıs Vallverdu & Madeleine Helliwell

Department of Chemistry, University of Manchester, Oxford Road, ManchesterM13 9PL, UK.............................................................................................................................................................................

Many receptors1 and allosteric proteins2 function through bind-ing of a molecule to induce a conformational change, which theninfluences a remote active site. In synthetic systems, comparableintramolecular information transfer can be effected by using theshape of one part of a molecule to control the stereoselectivity ofreactions occurring some distance away3. However, the need fordirect communication with the reaction site usually limits suchremote stereocontrol to distances of not more than about fivebond lengths. Cyclic structures overcome this problem by allow-ing the controlling centre and the reaction site4,5 to approach eachother, but the information transfer spans only short absolutedistances. Truly remote stereocontrol can, however, be achievedwith rigid compounds containing amide groups: the conformationof the amides can be controlled by stereogenic centres6–9 andresponds to that of neighbouring amide groups10–12 and in turninfluences stereoselective reactions13. This strategy has allowedremote stereocontrol spanning 8 (ref. 11) or 9 (ref. 12) bonds.

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Here we demonstrate stereocontrol over a reaction taking placemore than 20 bond lengths from the controlling centre, corre-sponding to a linear distance of over 2.5 nm. This transmission ofinformation, achieved by conformational changes relayedthrough the molecule, provides a chemical model of allosteryand might serve as a molecular mechanism for communicatingand processing information14–16.

The scheme in Fig. 1 illustrates how information about the shapeof the unit at A can be transmitted to the environment at B throughthe conformation of a series of freely rotating units u, v, w, … z. Thistransmission of information depends on the reliability of three typesof interaction: (1) the interaction between A and the nearby flexibleunit u; (2) the interaction between adjacent units u and v, v and wand so on, such that each unit can respond to the spatial orientationof its neighbours; and (3) the influence of z on the environment atB. In chemical terms, A could be a stereogenic centre whose shape isa consequence of its absolute stereochemistry, units u to z could befreely rotating but unsymmetrical functional groups, and B could bea prochiral reactive site, the stereoselectivity of whose reactions isgoverned by its local environment.

Compounds containing amide groups display all three types ofinteraction: stereogenic centres can govern the conformation ofamides6–9, information about conformation can be passed betweenpairs of amides10–12, and amide conformation can control stereo-selective reactions13. In aromatic tertiary amides, the plane ofthe aromatic ring and the rigid amide are perpendicular to eachother17–19. Observations on ring systems bearing more than oneamide group suggest that the amides interact so as to minimize theoverall dipole of the molecule10–12. These features, and the fact thatamides are relatively rigid and unreactive, makes aromatic tertiaryamides ideal building blocks to realize the information transmissionsystem sketched in Fig. 1.

On the basis of the known conformational preference of 1 (ref. 11)and 2 (ref. 12) we designed and synthesized bisxanthenes 3 and 4(Fig. 2). All four compounds 1–4 prefer conformations with an antiarrangement of the amide carbonyl groups (shown in blue), andvariable temperature nuclear magnetic resonance (VT NMR)experiments indicate that the 80:20 preference of 3 for the anticonformation shown is increased to a .95:5 preference for the anti,anti, anti conformation in 4.

Xanthene 6 and bisxanthene 8, chiral but racemic derivatives of 1

and 4, were synthesized by the sequence of ortholithiation andpalladium-catalysed coupling reactions20,21 shown in Fig. 3.(1R,2S)-(2)-Ephedrine condensed with the formyl groups of 6and 8 to form the chiral oxazolidine rings22 of 9 and 10, illustrated inred in Fig. 4. In line with earlier observations7,8, the asymmetryof the oxazolidine ring should impose a right-hand (P) twistpreference on the adjacent amide group for steric and electronicreasons. The X-ray crystal structure of 9 (see page 25 of theSupplementary Information) confirmed the preferred arrangementof the amides (blue in Fig. 4) relative to each other and relative to theoxazolidine (red in Fig. 4).

The sharp NMR spectra of 9 and 10 at 23 8C indicated that theyeach adopt a single conformation in solution, with the confor-mational preference imposed by the chiral oxazolidine ring propa-gated through the amide groups and thus placing the conformationof the final amide in the chain under the ultimate control ofthe absolute stereochemistry of the stereogenic centres in the(1R,2S)-(2)-ephedrine. The ability of this terminal amide toimpose relayed stereocontrol over the remote construction of anew stereogenic centre was determined by formylating 9 and 10 andadding nucleophiles to the resultant aldehydes 11 and 12, asillustrated in Fig. 4.

NMR (see Supplementary Figs S1 and S2) showed that, ana-logous to earlier work23, addition of nucleophiles PhMgBr andEtMgBr to 11 and 12 gave the alcohols syn-13 (R ¼ Et ¼ ethyl orR ¼ Ph ¼ phenyl) and syn-14 (R ¼ Et or R ¼ Ph) as .95% of asingle diastereoisomer, each of which was isolated in high yield. Forcomparison, authentic mixtures of syn- and anti-13 and 14 wereformed by relatively unselective addition of phenyllithium to 11 and12 or by diluting the reaction of EtMgBr with 11 and 12 with Et2O,which resulted in the formation of significant amounts of the antidiastereoisomer23. Hydrolysis of such mixtures derived from (2)-11and (2)-12 confirmed the identity of (R)-anti-15 and (S)-anti-16.Thermal equilibration of (S)-syn-15 and (R)-syn-16 confirmed theidentity of (S)-anti-15 and (R)-anti-16.

Figure 1 A strategy for conformational communication of information. Figure 2 Conformational preference in arenedicarboxamides 1–4.

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Figure 3 Synthesis of bisxanthene 8. Reagents: (i) n-BuLi, N,N,N0,N

0-

tetramethylethylenediamine (TMEDA), THF at 278 8C; (ii) B(OMe)3 then H2O; (iii)

Me2NCHO; (iv) (1RS,2SR)-(^)-ephedrine, toluene, D; (v) I2; (vi) CF3CO2H, H2O, THF;

(vii) Pd2dba3 (2 mol%), 9-diphenylphosphinylphenanthrene (9-DPPP) (8 mol%),

Ba(OH)2·8H2O, xylene, 115 8C, 50 min. (Yields in parentheses are based on recovered

starting material.) Me, methyl; D, heat; dba, dibenzylideneacetone.

Figure 4 Remote stereocontrol in a xanthene and a bisxanthene. The influence of the

oxazolidine ring shown in red (located at ‘A’ in the cartoon) over the orientation of the

amides shown in blue (w, x, y, z ) governs the formation of the new stereogenic centre

shown in green (located at ‘B’). Reagents: (i) (1R,2S )-(2)-ephedrine, toluene, D;

(ii) n-BuLi (9) or s-BuLi (10), TMEDA, THF, 278 8C; (iii) Me2NCHO; (iv) EtMgBr, THF,

278 8C; (v) PhMgBr, THF, 278 8C; (vi) CF3CO2H, H2O, THF.

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While NMR confirmed that diastereoselective addition to theterminal formyl groups of 11 and 12 was locally diastereoselective,the efficiency of the remote transmission of information had to beconfirmed by measurement of the absolute stereochemical purity ofthe new hydroxyl-bearing centre shown in green in Fig. 4. To thisend, racemic ephedrine was used to make (^)-9 and (^)-10, whichwere then converted to racemic (^)-syn-13 and (^)-syn-14. Stir-ring enantiomerically pure and racemic 13 and 14 with aqueousacid cleaved the oxazolidine ring, and gentle heating partiallyscrambled the conformation of the amide substituents, givingenantiomerically enriched and racemic 15 and 16 as mixtures ofdiastereoisomers. Comparison by analytical HPLC on a chiralstationary phase (Chiralcel-ODH, 250 £ 4.6 mm) of the alcoholsresulting from each sequence showed that, for the alcohols 15 and16 derived from enantiomerically pure oxazolidines, the two majordiastereoisomeric peaks were accompanied by almost undetectablequantities of their enantiomers (see Supplementary Figs S4 and S5).Alcohols 15 and 16 therefore have .90% enantiomeric excess (ee):the conformation of the hydroxyl-bearing centre has been con-trolled by almost complete (.95:5) transmission of stereochemicalinformation from the ephedrine-derived oxazolidine at one end of11 and 12, through conformationally responsive amide groups,to the other end of the molecule. Stereochemical controldue to intermolecular transfer of stereochemical information(for example, complexation of one molecule of 11 or 12 to thenucleophile as it adds to another) is ruled out by the fact thatnucleophilic additions to (^)-11 and (^)-12 are as diastereo-selective as nucleophilic addition to the enantiomerically purecompounds.

The information-relaying capacity of the amides was confirmedby re-forming an oxazolidine ring from the formyl group ofthe diastereoisomeric mixture of aldehydes 15 and 16 using(1S,2R)-(þ)-ephedrine in place of (1R,2S)-(2)-ephedrine, as illus-trated for 16 (R ¼ Et) in Fig. 5. The new, enantiomeric oxazolidineof 17 at A (shown in red) now imposes an M sense of twist on thefirst amide of the chain (‘w’ in the cartoon), which propagatesthrough the amides to rotate the final amide (‘z’) into an antirelationship with the stereogenic centre at B (shown in green). Theswitch from syn to anti stereochemistry is clearly evident in theNMR spectra of the products (see Supplementary Figs S1 and S2).The syn ! anti switches are not complete, probably because of thehigher kinetic barrier to amide rotation in 13 and 14 whencompared with 9 and 10.

We find that the length over which stereochemical informationcan be communicated is limited by the efficiency of the synthesis ofthe substrates, rather than by the reliability of each stage in theinformation relay. The bisxanthene 10 was extended to a tris-xanthene 20 by iodination and coupling with the boronic acid 19(Fig. 6), but we were unable to synthesize a tetraxanthene by any

Figure 5 Inverting relative stereochemistry from a distance. Inverting the shape of A causes

a mis-match with the orientation of w. The conformational change caused by the resulting

realignment of w propagates through 17 to z, whose reorientation influences the position of

signals in the NMR spectrum at B. Reagents: (i) (1S,2R )-(þ)-ephedrine; (ii) toluene, D.

Figure 6 Ultra-remote stereocontrol in a trisxanthene. The influence of the oxazolidine ring

shown in red (located at ‘A’ in the cartoon) over the orientation amides shown in blue (u, v,w,

x, y, z ) governs the formation of the new stereogenic centre shown in green (located at ‘B’).

Reagents; (i) n-BuLi, TMEDA, THF, 278 8C; (ii) I2; (iii) B(OMe)3; (iv) CF3CO2H; (v) Pd2dba3

(4 mol%), 9-DPPP (16 mol%), Ba(OH)2·8H2O, xylene, 115 8C, 20 min; (vi) EtMgBr, THF,

278 8C; (vii) PhMgBr, THF, 278 8C; (viii) CF3CO2H, H2O, THF; (ix) EtOAc, 50 8C, 4 days.

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reasonable coupling. The X-ray crystal structure of 20 (see page 33of the Supplementary Information) was consistent with theexpected preferred ‘all anti’ arrangement of the six amides (shownin blue in Fig. 6). Nucleophilic addition of EtMgBr and PhMgBr to20 proceeded with .95% diastereoselectivity by NMR, giving (S)-syn-21 (R ¼ Et or R ¼ Ph). Hydrolysis of the oxazolidine gave 22,initially as .95% a single stereoisomer (by NMR and HPLC; seeSupplementary Figs S3 and S6) and, after heating at 50 8C for 4 days,as a 1:1 mixture of syn and anti diastereoisomers. Determination ofstereochemical purity at the new stereogenic centre of 22 (R ¼ Ph)by HPLC and comparison with (^)-22 (Supplementary Fig. S6)indicated (1,23)-asymmetric induction: stereochemical infor-mation is transmitted over 22 bond lengths, spanning a totaldistance in excess of 25 A, with .95% reliability.

To date, the most remote stereocontrol using relayed confor-mational interactions has been (1,10)-asymmetric induction12, sothe (1,23)-asymmetric induction in 20 constitutes a significantadvance, particularly given the modular construction of the oligo-xanthenes. Examples of (1,8-9)-, (1,10-12)-, (1,13-14)- and (1,15)-asymmetric induction (refs 24, 25, 5 and 26, and 27, respectively)are known, but these generally involve intramolecular coordinationof the reaction site to the source of stereochemical information.Such coordination is impossible in 11, 12 and 20, where thexanthene monomers can only rotate relative to one another. Thereaction site is therefore spatially remote from the source of

stereochemical information, and is not merely separated by manyintervening bonds.

It is evident from the HPLC traces (Supplementary Figs S4–S6)that alcohols 15, 16 and 22 are enantiomerically pure. Assignmentof the absolute configuration at their hydroxyl-bearing centres wasmade by indirect methods on the basis that there is (1) a preferencefor an anti conformational relationship between the amides inrelated simpler compounds11,12 that is also evident in the X-raycrystal structures of 11 and 20, and (2) reliable chelation-controlledsyn selectivity in the addition of Grignard reagents to simple2-formylnaphthamides23. Further confirmation of the preferredstereochemistry of the aldehydes 11, 12 and 20 is obtained bycondensing them with a second equivalent of (1R,2S)-(2)-ephe-drine. The oligoxanthene portion of 11 and 20 should exhibitoverall C 2 symmetry, which would be ‘matched’ by incorporationof two homochiral ephedrine units and thus allow 23 and 25to adopt, enantioselectively, single C 2 symmetric conforma-tions. Indeed, both 11 and 20 condense cleanly with (1R,2S)-(2)-ephedrine to yield symmetrical products (Fig. 7). In contrast, thebisxanthene portion of 12 with its odd number of biaryl linkages isexpected to prefer overall S 2 symmetry, like 2, 3 and 4 (which allhave a centre of symmetry), and therefore to be achiral. The twohomochiral ephedrine moieties of 24 are mismatched with thissymmetry, and a symmetrical diastereoisomer or 24 would beexpected to form only with difficulty. When this condensation

Figure 7 Symmetry matching in bis-oxazolidines. Information about the shape of one end of the molecule is relayed to the other, leading to a symmetry match in the axially chiral 23 and

25 but a symmetry mis-match in the pseudo-centrosymmetric bis-xanthene 24.

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was carried out, the bisoxazolidine 24 formed was unsymmetrical,with one of the oxazolidine rings epimeric with the other. Thepseudo-S 2 symmetry of 24 forces the two oxazolidine centres(marked with asterisks in Fig. 7) to seek pseudo-enantiomericconformations, which can only happen if one oxazolidine adoptsunusual endo relative stereochemistry28, allowing it to retain thefavourable oxazolidine–amide interaction.

Extending information transmission in these systems beyond the2.5 nm reported here will depend on the efficacy of additionalcoupling reactions: the conformational relay itself seems remark-ably robust, with no significant degradation of information qualityeven after six relay steps. The synthetic versatility of amides, and inparticular their ability to act as branch points, may make relatedcompounds valuable components of future molecular devices forthe transmission and processing of information15,16. A

Received 26 May; accepted 10 August 2004; doi:10.1038/nature02933.

1. Krauss, G. Biochemistry of Signal Transduction and Regulation (Wiley-VCH, Weinheim, 1999).

2. Perutz, M. Mechanisms of Cooperativity and Allosteric Regulation in Proteins (Cambridge Univ. Press,

Cambridge, 1990).

3. Eliel, E. L. & Wilen, S. H. Stereochemistry of Organic Compounds Ch. 12 (Wiley, New York, 1994).

4. Mikami, K., Shimizu, M., Zhang, H.-C. & Maryanoff, B. E. Acyclic stereocontrol between remote

atom centers via intramolecular and intermolecular stereo-communication. Tetrahedron 57,

2917–2951 (2001).

5. Linnane, P., Magnus, N. & Magnus, P. Induction of molecular asymmetry by a remote chiral group.

Nature 385, 799–801 (1997).

6. Clayden, J., Mitjans, D. & Youssef, L. H. Lithium-sulfoxide-lithium exchange for the asymmetric

synthesis of atropisomers under thermodynamic control. J. Am. Chem. Soc. 124, 5266–5267

(2002).

7. Clayden, J. & Lai, L. W. (2)-Ephedrine as an auxiliary for the asymmetric synthesis of atropisomeric

amides by dynamic resolution under thermodynamic control. Tetrahedron Lett. 42, 3163–3166

(2001).

8. Clayden, J., Lai, L. W. & Helliwell, M. Using amide conformation to “project” the stereochemistry of a

(2)-ephedrine-derived oxazolidine: a pair of pseudoenantiomeric chiral amido-phosphine ligands.

Tetrahedron 12, 695–698 (2001).

9. Clayden, J. & Lai, L. W. Enantioselective synthesis of atropisomeric amides by dynamic resolution:

thermodynamic control with a proline-derived diamine resolving agent. Angew. Chem. Intl Edn 38,

2556–2558 (1999).

10. Clayden, J., Pink, J. H. & Yasin, S. A. Conformationally interlocked amides: remote asymmetric

induction by mechanical transfer of stereochemical information. Tetrahedron Lett. 39, 105–108

(1998).

11. Clayden, J., Kenworthy, M. N. & Youssef, L. H. Axial chirality in xanthene-4,5-dicarboxamides: 1,9-

stereocontrol mediated by remote interactions between conformationally constrained amide groups.

Tetrahedron Lett. 41, 5171–5174 (2000).

12. Clayden, J., Lund, A. & Youssef, L. H. Conformational preference and remote (1,10) stereocontrol in

biphenyl-2,2 0 -dicarboxamides. Org. Lett. 3, 4133–4136 (2001).

13. Clayden, J. Stereocontrol with rotationally restricted amides. Synlett, 810–816 (1998).

14. Krauss, R. & Koert, U. Molecular signal transduction by conformational transmission. Synlett,

598–608 (2003).

15. Balzani, V., Credi, A. & Venturi, M. The bottom-up approach to molecular-level devices and

machines. Chem. Eur. J. 8, 5524–5542 (2002).

16. Sauvage, J.-P. Transition-metal containing rotaxanes and catenanes in motion: toward molecular

machines and motors. Acc. Chem. Res. 31, 611–619 (1998).

17. Cuyegkeng, M. A. & Mannschreck, A. Chromatographic separation of enantiomers and barriers to

enantiomerization of axially chiral aromatic carboxamides. Chem. Ber. 120, 803–809 (1987).

18. Bowles, P. et al. Atroposelectivity in the reactions of ortholithiated tertiary amides with aldehydes.

J. Chem. Soc. Perkin Trans. 1, 2607–2616 (1997).

19. Ahmed, A. et al. Barriers to rotation about the chiral axis of tertiary aromatic amides. Tetrahedron 54,

13277–13294 (1998).

20. Snieckus, V. Directed ortho metalation. Tertiary amide and O-carbamate directors in synthetic

strategies for polysubstituted aromatics. Chem. Rev. 90, 879–933 (1990).

21. Yin, J., Rainka, M. P., Zhang, X.-X. & Buchwald, S. L. A highly active Suzuki catalyst for the

synthesis of sterically hindered biaryls: novel ligand coordination. J. Am. Chem. Soc. 124, 1162–1163

(2002).

22. Clayden, J., Lai, L. W. & Helliwell, M. Dynamic resolution of atropisomeric amides using

proline-derived imidazolidines and ephedrine-derived oxazolidines. Tetrahedron 60, 4399–4412

(2004).

23. Clayden, J., McCarthy, C., Westlund, N. & Frampton, C. S. Atroposelective attack of nucleophiles on

2-formyl-1-naphthamides and their derivatives: chelation and non-chelation control. J. Chem. Soc.

Perkin Trans. 1, 1363–1378 (2000).

24. Date, M. et al. Efficient 1,8- and 1,9-asymmetric inductions in the Grignard reaction of d- and 1-keto

esters of 1,1 0 -binaphthalen-2-ols with an oligoether tether as the 2 0 -substituent: application to the

synthesis of (-)-malyngolide. J. Chem. Soc. Perkin Trans. 1, 645–653 (2001).

25. Tamai, Y. et al. Efficient 1,8- to 1,12-asymmetric induction in Grignard reactions of q-keto esters by

using BINOL or its 2 0 -oligoether derivatives as the chiral auxiliary. J. Chem. Soc. Perkin Trans. 1,

1141–1142 (1999).

26. Magnus, N. & Magnus, P. 1,13- and 1,14-asymmetric induction; remote control. Tetrahedron Lett. 38,

3491–3494 (1997).

27. Heinemann, C. & Demuth, M. Short biomimetic synthesis of a steroid by photoinduced electron

transfer and remote asymmetric induction. J. Am. Chem. Soc. 121, 4894–4895 (1999).

28. Agami, C. & Rizk, T. Kinetic control of asymmetric induction during oxazolidine formation from

(2)-ephedrine and aromatic aldehydes. Tetrahedron 41, 537–540 (1985).

Supplementary Information accompanies the paper on www.nature.com/nature.

Acknowledgements We are grateful to the EPSRC for support of this work.

Competing interests statement The authors declare that they have no competing financial

interests.

Correspondence and requests for material should be addressed to J. C. ([email protected]). The

Cambridge Crystallographic Database deposition numbers for X-ray crystal structures are, for 9,

244658 and for 20, 244659.

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Extreme climate of the globaltroposphere and stratospherein 1940–42 related to El NinoS. Bronnimann1,2, J. Luterbacher3, J. Staehelin1, T. M. Svendby4,G. Hansen5 & T. Svenøe6

1Institute for Atmospheric and Climate Science, ETH Zurich, Honggerberg HPP,CH-8093 Zurich, Switzerland2Lunar and Planetary Laboratory, University of Arizona, Tucson, Arizona 85721,USA3NCCR Climate and Institute of Geography, University of Bern, Hallerstrasse 12,CH-3012 Bern, Switzerland4Department of Physics, University of Oslo, PO Box 1048, Blindern, N-0316 Oslo,Norway5Norwegian Institute for Air Research, Polar Environmental Centre, HjalmarJohansens Gate 14, N-9296 Tromsø, Norway6Norwegian Polar Institute, Ny-Alesund, PO Box 505, N-9171 Longyearbyen,Norway.............................................................................................................................................................................

Although the El Nino/Southern Oscillation phenomenon is themost prominent mode of climate variability1 and affects weatherand climate in large parts of the world, its effects on Europe andthe high-latitude stratosphere are controversial2–5. Using histori-cal observations and reconstruction techniques, we analyse theanomalous state of the troposphere and stratosphere in theNorthern Hemisphere from 1940 to 1942 that occurred duringa strong and long-lasting El Nino event. Exceptionally low surfacetemperatures in Europe and the north Pacific Ocean coincidedwith high temperatures in Alaska. In the lower stratosphere, ourreconstructions show high temperatures over northern Eurasiaand the north Pacific Ocean, and a weak polar vortex. In addition,there is observational evidence for frequent stratospheric warm-ings and high column ozone at Arctic and mid-latitude sites.We compare our historical data for the period 1940–42 withmore recent data and a 650-year climate model simulation. Weconclude that the observed anomalies constitute a recurringextreme state of the global troposphere–stratosphere system innorthern winter that is related to strong El Nino events.

Scientists in the early 1940s observed unusually high values oftotal ozone over several sites in Europe, but did not present anexplanation. At the same time, exceptional climatic conditions wereregistered at the Earth’s surface, but were never analysed in a large-scale context. Moreover, a prolonged El Nino occurred in 1939–42,raising the question of a possible relation between El Nino, Euro-pean climate, and the northern stratosphere6. In order to study thisperiod in detail, we have compiled, digitized and re-evaluated allavailable total ozone observations7–9 and several tens of thousandsof geopotential height (GPH) and temperature profiles from radio-

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