Professor Roger W. Alder

A major theme of my research has been the preparation and study of interesting molecules - nature has no monopoly on these, and making new molecules with unusual properties is intellectually challenging and potentially useful.

Stable Diaminocarbenes

Since their isolation in 1991, the study of stable diaminocarbenes has blossomed spectacularly, due to their intrinsic interest, and also because they have been shown to be extremely useful ligands for transition metals in catalytically-active complexes. We have contributed to this field in several important ways.1

We showed that stable imidazol-2-ylidenes are powerful bases, with pKa 24 in DMSO.2 We prepared3 the first stable acyclic diaminocarbene, (i-Pr2N)2C, thus permitting the measurement of rotational barriers which give information on p-bonding in these species. We then found that carbenes as simple as (Me2N)2C can be easily observed at ambient temperatures and only dimerise slowly,4although at the time we did not appreciate that these were complexed to Li. We also prepared the first stable aminooxy- and aminothio-carbenes (see 1 and 2 below) thus demonstrating that elements other than nitrogen can provide adequate stabilisation.5 We then found that diaminocarbenes form complexes with Li, Na, and even K species, and determined the crystal structure of one potassium complex;6 this has important implications for the properties of these carbenes. W have used high-level density functional (DFT) calculations to study both diaminocarbene itself and (Me2N)2C with respect to the kinetics and thermodynamics of dimerisation, and the barriers to Ccarbene-N rotation.7 There are still some puzzling features of the rotation barriers for acyclic carbenes 12-14 and further experimental studies are planned.

We have studied dimerization of the set of simple carbenes 314 on which we can also carry out good quality DFT calculations.

We have discovered that for six-membered ring carbenes like 6, dimerisation is thermodynamically 100 kJ mol-1 less favourable than for acyclic carbenes like 12. DFT calculations amd homodesmic comparisons suggest that this is not due to unexpected stability trends for the dimers, as we first thought, but to destabilisation of acyclic carbenes by opening up the N-C-N bond angle and by twisting around the N-C bonds.

Even when dimerisation is thermodynamically favourable it can be extremely slow; thus metal-free 13 does not dimerise in one week at ambient temperature in THF. We believe that dimers are usually formed by reaction of carbenes with amidinium ions rather than direct reaction between two carbenes, and in the case of 4, we have observed the intermediate protonated dimer ion 15 by NMR.8 A review of carbene dimerization will appear shortly.9

The great majority of studies of diaminocarbenes as ligands for transition metals have utilised five-membered ring carbenes; in a collaboration with Professor Guy Lloyd-Jones, we are investigating the ligand properties of acyclic, six-, and seven-membered ring carbenes.

Computational organic chemistry

The availability of user-friendly computational software and the increasing speed of computers, have led me towards an increasing interest in calculational organic chemistry. Thus in recent years we have:

1.         Predicted that Th-symmetrical P8(C=C)6, 16, will be a remarkably stable small heterofullerene with carbon atoms less pyramidal than in C60, but that the corresponding nitrogen species Th-N8(C=C)6, in sharp contrast, is strongly destabilized relative to Th-(HC)8(C=C)6, and we have exposed the causes of this extraordinarily large difference (nearly 1000 kJ mol-1).10

2.         We have recently shown that Prins cyclisations, Grob fragmentations, and some Cope rearrangements may also be stepwise, via cationic intermediatessuch as 17 and 18 with a novel type of aromaticity in s-bonds.11 Experimental work to test these ideas is now underway in collaboration with Professor Chris Willis.

3.         We studied the thermal rearrangement of azulene to naphthalene (see below) during the 1970s. Radicals powerfully catalysed the reaction, and we proposed that two concurrent mechanisms were occurring in this novel type of reaction. We recently revisited this rearrangement and showed, using DFT methods,12 that alternative mechanisms proposed since 1980 can be excluded and that our original proposals can account semi-quantitatively for all known products from substituted and labelled azulenes.

We have gone on to show that related radical-promoted mechanisms are probably important for the so-called Stone-Wales rearrangements in C60 chemistry.13

Conformational Control by Quaternary Centres

In 1990, we demonstrated that quaternary centres have profound effects on the conformations of the surrounding chains,14 and we have pursued the preparation of novel polymers based on these ideas.15 We recognised the potential of (Ar2CCH2CH2)n polymers (Ar2 = 2,2´-biphenylyl) to provide even greater level of control of secondary structure, such that an essentially straight (all-anti) chain is formed, and we developed routes to oligomers such as 18 and related polymers involving novel anionic ring-opening polymerisation of spiro[cyclopropane-1,9'-fluorene].15 Most recently, we have prepared related oliogmers, e.g. 19, in which the aryl groups have the potential for redox chemistry, either directly or via stacking interactions.

Other interests

I maintain an interest in several other areas where we have made contributions in the past:

Strong Amine Bases

In 1968, we discovered16 that 1,8-bis(dimethylamino)naphthalene (pKa 12.1) was at least a million-fold more basic than typical aromatic amines. This diamine (Proton Sponge (Aldrich)) is very weakly nucleophilic, and undergoes proton transfer reactions surprisingly very slowly. This work was developed17 to give naphthalene bases with pKa >16; we also showed that simple medium-ring bases (e.g. 1,6-dimethyl-1,6-diazacyclodecane) can function as proton sponges.18 Proton Sponge has been extensively used as a reagent, and new developments of this theme continue to appear. I am currently studying the factors responsible for the high basicity of Proton Sponge, prompted by a suggestion19 that flattening at the nitrogen atoms was important – I am sceptical of this! These studies have led me to new designs for C2-chiral proton sponges with predicted pKas around 25.

Intrabridgehead Chemistry

During the 1970s we began a study of bicyclic medium-ring compounds, especially bridgehead diamines, and developed ring cleavage strategies for making these compounds.20, 21 Important information on reactive intermediates (e.g. carbocations) was obtained in the past by placing the reactive centre at the bridgehead of a bicyclic system. The distinctive feature of our work was to study compounds where two bridgehead atoms interact across a medium-ring system.

In an intrabridgehead22, 23 situation, the orientation and distance between orbitals at the two bridgehead atoms can be closely controlled, enabling careful scrutiny of both attractive and repulsive bonding. Thus repulsive interactions between lone pairs were studied by photoelectron spectroscopy and electrochemistry, and the stability of the radical cation from 1,6-diazabicyclo[4.4.4]tetradecane allowed the first X-ray determination of the length of a three-electron -bond.67

Studies of bicyclic medium-ring compounds have significance in several other directions. These strained compounds gain relief by intrabridgehead bond formation, exactly reversing the usual situation in small ring compounds.23 The ring systems studied are precisely in the range where in,out isomerism24 becomes possible; many examples of this were demonstrated, and the borderlines defined. Thus in out-6H-1-azabicyclo[4.4.4]tetradecane, the lone pair is inside but must invert to protonate which increases strain, so this compound is an astonishingly weak base (pKa 0.6).22 On the other hand, many diamines could be protonated both outside and inside. Some inside protonations were shown to occur by an unprecedented redox-promoted reaction23 and, as one result, I was led to propose a new classification of redox-promoted substitution reactions.25 Inside-protonated ions have strong intrabridgehead hydrogen bonds, and detailed studies of these were made by spectroscopic and structural methods.23 This work gained new significance in the light of the debate about the importance of low-barrier hydrogen bonds in enzymic catalysis. Inside-protonated ions represent the smallest host-guest compounds (there are strong parallels between our studies and Lehn’s cryptand work) and our work has prompted significant experimental and theoretical studies by other groups. We extended our own studies to intrabridgehead P...P bonding, with results which are a complete contrast to those with diamines, e.g. the observation of stable P(IV)+-P(V)-H and P(IV)+-P(V)-O- species.26, 27 We found that, in strained bridgehead situations, phosphines invert readily and, in one case, we encountered an extraordinary kinetic effect, with a diphosphine species going from in,in to in,out via a less-stable out,out-structure.28

Powerful Alkylating Agents

The usefulness of methyl fluorosulfate as a convenient and powerful methylating agent was reported in 1968.29, 30 As Magic Methyl (Aldrich Chemical Company) it was used extensively as a reagent until there was a fatality in the Netherlands from its use. The reagent preferred today (methyl triflate) is almost certainly just as toxic!

References

 

 

1              R. W. Alder, in 'Diaminocarbenes: exploring structure and reactivity', ed. G. Bertrand, New York, 2002.

2              R. W. Alder, P. R. Allen, and S. J. Williams, J. Chem. Soc., Chem. Commun., 1995, 1267.

3              R. W. Alder, P. R. Allen, M. Murray, and A. G. Orpen, Angew. Chem., Int. Ed. Engl., 1996, 35, 1121.

4              R. W. Alder and M. E. Blake, Chem. Commun. (Cambridge), 1997, 1513.

5              R. W. Alder, C. P. Butts, and A. G. Orpen, J. Am. Chem. Soc., 1998, 120, 11526.

6              R. W. Alder, M. E. Blake, C. Bortolotti, S. Bufali, C. P. Butts, E. Linehan, J. M. Oliva, A. G. Orpen, and M. J. Quayle, Chem. Commun. (Cambridge), 1999, 241.

7              R. W. Alder, M. E. Blake, and J. M. Oliva, J. Phys. Chem. A, 1999, 103, 11200.

8              R. W. Alder, L. Chaker, and F. P. V. Paolini, Chem. Commun. (Cambridge), 2004, 0000.

9              R. W. Alder, M. E. Blake, L. Chaker, J. N. Harvey, F. P. V. Paolini, and J. Schütz, Angew. Chem. Int. Ed. Engl., 2004, 43, 0000.

10             R. W. Alder, J. N. Harvey, P. V. Schleyer, and D. Moran, Org. Lett., 2001, 3, 3233.

11             R. W. Alder, J. N. Harvey, and M. T. Oakley, J. Am. Chem. Soc, 2002, 124, 4960.

12             R. W. Alder, S. P. East, J. N. Harvey, and M. T. Oakley, J. Am. Chem. Soc., 2003, 125, 5375.

13             R. W. Alder and J. N. Harvey, J. Am. Chem. Soc., 2004, 126, 2490.

14             R. W. Alder, C. M. Maunder, and A. G. Orpen, Tetrahedron Lett., 1990, 31, 6717.

15             R. W. Alder, P. R. Allen, K. R. Anderson, C. P. Butts, E. Khosravi, A. Martin, C. M. Maunder, A. G. Orpen, and C. B. St. Pourcain, J. Chem. Soc., Perkin Trans. 2, 1998, 2083.

16             R. W. Alder, P. S. Bowman, W. R. S. Steele, and D. R. Winterman, Chem. Commun., 1968, 723.

17             R. W. Alder, Chem. Rev., 1989, 89, 1215.

18             R. W. Alder, P. Eastment, N. M. Hext, R. E. Moss, A. G. Orpen, and J. M. White, J. Chem. Soc., Chem. Commun., 1988, 1528.

19             A. F. Pozharskii, O. V. Ryabtsova, V. A. Ozeryanskii, A. V. Degtyarev, O. N. Kazheva, G. G. Alexandrov, and O. A. Dyachenko, J. Org. Chem., 2003, 68, 10109.

20             R. W. Alder, R. B. Sessions, A. J. Bennet, and R. E. Moss, J. Chem. Soc., Perkin Trans. 1, 1982, 603.

21             R. W. Alder, P. Eastment, R. E. Moss, R. B. Sessions, and M. A. Stringfellow, Tetrahedron Lett., 1982, 23, 4181.

22             R. W. Alder, Acc. Chem. Res., 1983, 16, 321.

23             R. W. Alder, Tetrahedron, 1990, 46, 683.

24             R. W. Alder and S. P. East, Chem. Rev. (Washington, D. C.), 1996, 96, 2097.

25             R. W. Alder, J. Chem. Soc., Chem. Commun., 1980, 1184.

26             R. W. Alder, C. P. Butts, A. G. Orpen, D. Read, and J. M. Oliva, J. Chem. Soc.-Perkin Trans. 2, 2001, 282.

27             R. W. Alder, C. P. Butts, A. G. Orpen, and D. Read, J. Chem. Soc.-Perkin Trans. 2, 2001, 288.

28             R. W. Alder and D. Read, Angew. Chem., Int. Ed., 2000, 39, 2879.

29             M. G. Ahmed, R. W. Alder, G. H. James, M. L. Sinnott, and M. C. Whiting, Chem. Commun., 1968, 1533.

30             R. W. Alder, Chem. Ind. (London), 1973, 983.