Organometallics 2009, 28, 1697–1704
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Thermodynamically Favored Anion Rearrangements in Li and Na Complexes of (S)-N-r-(Methylbenzyl)allylamine Philip C. Andrews,* Magdaline Koutsaplis, and Evan G. Robertson School of Chemistry, Monash UniVersity, P.O. Box 23, Melbourne, Victoria 3800, Australia ReceiVed December 9, 2008
Metalation of the chiral amine (S)-N-R-(methylbenzyl)allylamine with nBuM (M ) Li, Na) leads to the formation of complexes with three distinct isomeric anion forms: allylamide [(PhC(H)CH3NCH2CHd CH2)]-, 1-aza-allyl [(PhC(H)CH3NC(H)CHCH3)]-, and aza-enolate [(PhC(dCH2)N(CH2CH2CH3)]-. The anionic form is dependent on the metal, the Lewis donor, and the thermal history of the complex. From their use in asymmetric syntheses and a previously described hmpa (hexamethylphosphoramide) complex, the allylamide form predominates with Li at room temperature in the presence of monodentate donors. The use of the bidentate donor tmeda (N,N,N′,N′-tetramethylethylenediamine) results in the crystallization and characterization of the 1-aza-allylic complex (S)-{[(PhC(H)CH3NC(H)CHCH3)Li}2 · tmeda]∞, in which the allylamide moiety has undergone a 1,3-sigmatropic rearrangement. In the crystal structure, the tmeda molecules bridge rather than chelate the Li cations. The tridentate donor pmdta (N,N,N′,N′,N′′pentamethyldiethylenetriamine) gives crystals of [(PhC(dCH2)N(CH2CH2CH3)M · pmdta] (M ) Li, Na) in which a further rearrangement occurs to an aza-enolate form, resulting in a loss of chirality. Theoretical calculations on the various anion forms and the role of the metal and Lewis donors supported the solidstate observations, revealing a -75 kJ mol-1 energy gain on rearrangement of the anion from allylamide to either the aza-allylic or the aza-enolate form. Introduction Structural investigations of chiral lithium amides (CLAs) have experienced a period of steady growth over the past decade,1-4 largely in response to their extensive use in asymmetric synthesis as reagents and chiral auxiliaries, and through their application in kinetic resolution.5-7 In particular, Davies and co-workers have long demonstrated the successful application of CLAs in their conjugate addition to R,β-unsaturated esters yielding products with high ee values,8,9 as in the synthesis of β-amino acid and β-lactam derivatives.9,10 Ultimate selectivity is highly influenced and dependent upon the structures of the CLA complexes and of the intermediates formed on their reaction with organic substrates. Extensive solution and solid-state studies of CLAs have demonstrated the complex and often unexpected * To whom correspondence should be addressed. E-mail: phil.andrews@ sci.monash.edu.au. (1) Barr, D.; Berrisford, D. J.; Jones, R. V. H.; Slawin, A. M. Z.; Snaith, R.; Stoddart, F.; Williams, D. J. Angew. Chem., Int. Ed. 1998, 28, 1044. (2) Andrews, P. C.; Duggan, P. J.; Fallon, G. D.; McCarthy, T. D.; Peatt, A. C. J. Chem. Soc., Dalton Trans. 2000, 2505. (3) Pate, F.; Oulyadi, H.; Harrison-Marchand, A.; Maddaluno, J. Organometallics 2008, 27, 3564. (4) Li, D.; Sun, C.; Liu, J.; Hopson, R.; Li, W.; Williard, P. G. J. Org. Chem. 2008, 73, 2373. (5) Asami, M.; Kanemaki, N. Tetrahedron Lett. 1989, 30, 2125. (6) Rodeschini, V.; Simpkins, N. S.; Wilson, C. J. Org. Chem. 2007, 72, 4265. (7) Bigi, A.; Mordini, A.; Thurner, A.; Faigl, F.; Poli, G.; Toke, L. Tetrahedron: Asymmetry 1998, 9, 2293. (8) Cailleau, T.; Cooke, J. W. B.; Davies, S. G.; Ling, K. B.; Naylor, A.; Nicholson, R. L.; Price, P. D.; Roberts, P. M.; Russel, A. J.; Smith, A. D.; Thomson, J. E. Org. Biomol. Chem. 2007, 5, 3922. (9) Davies, S. G.; Smith, A. D.; Price, P. D. Tetrahedron: Asymmetry 2005, 16, 2833. (10) Davies, S. G.; Garrido, N. M.; Kruchinin, D.; Ichihara, O.; Kotchie, L. J.; Price, P. D.; Price Mortimer, A. J.; Russel, A. J.; Smith, A. D. Tetrahedron: Asymmetry 2006, 17, 1793.
structures their aggregated forms adopt.3,4,11,12 Through the investigation of such aggregates, a more complete understanding of the asymmetric induction exhibited by CLAs can be formed, potentially leading to the design and synthesis of better, more selective reagents. Several groups, particularly those of Williard and Hilmersson, have highlighted the diverse nature of CLA aggregates and the subtle but dramatic effects changing the solvent and/or Lewis donor can have on their formation and hence in determining the most reactive species.4,11-16 This is exemplified in synthesis by observed inversions of stereochemistry in products when different solvents and Lewis donors are employed.17 CLAs are most commonly synthesized and used in situ, usually on the understanding that, although the aggregation states may be fluxional, the anion, when formed, is stable and does not undergo any unintended rearrangement.6,9,18 In the absence of solid and solution-state structural information, what influences any observed selectivity is usually left to speculation. One important variable that can provide for unexpected outcomes is base-induced changes in the anion structure or form. Metalpromoted anion rearrangements are common and widely (11) Sott, R.; Granander, J.; Williamson, C.; Hilmersson, G. Chem.Eur. J. 2005, 11, 4785. (12) Sott, R.; Granander, J.; Diner, P.; Hilmersson, G. Tetrahedron: Asymmetry 2004, 15, 267. (13) Williard, P. G.; Sun, C. J. Am. Chem. Soc. 1997, 119, 11693. (14) Sott, R.; Hakansson, M.; Hilmersson, G. Organometallics 2006, 25, 6047. (15) Sott, R.; Granander, J.; Hilmersson, G. J. Am. Chem. Soc. 2004, 126, 6798. (16) Vestergren, M.; Eriksson, J.; Hilmersson, G.; Hakansson, M. J. Organomet. Chem. 2003, 682, 172. (17) Node, M.; Hashimoto, D.; Katoh, T.; Ochi, S.; Ozeki, M.; Watanabe, T.; Kajimoto, T. Org. Lett. 2008, 10, 2653. (18) Clayden, J.; Knowles, F. E.; Baldwin, I. R. J. Am. Chem. Soc. 2005, 127, 2412.
10.1021/om801165e CCC: $40.75 2009 American Chemical Society Publication on Web 02/27/2009
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reported,19-21 an important example being the [1,2] and [2,3] Wittig sigmatropic rearrangement, which has found wide range application in the base-promoted synthesis of homoallylic alcohols from allyl ethers.22-24 In studying such phenomena, Fraenkel and co-workers have established that allylic anions can undergo facile rearrangements.25,26 Deprotonation and subsequent coordination by a Li cation can allow delocalization within the allylic anion, the extent influenced by the degree of solvation. Resonance stabilization and the presence of the metal mean that such anionic rearrangements can be thermodynamically favored. Lithium is often the metal of choice when preparing group 1 organometallic reagents, predicated mostly on the availability of reagents and their ease of handling, but also stems from the belief that the heavier alkali metals are too reactive to provide high selectivity. Most attempts at maximizing regio- or stereoselectivity tend to focus on temperature, ligand choice, and solvent effects before considering the influence a change in metal may have. As counterion to the nucleophile, the role of the metal cation is often ambiguous, if considered at all. However, in addition to supporting anion rearrangements, the metal can also induce anion transformations. This is well illustrated by the combined effect of metal, solvent, and aggregation state on the amidefaza-allyl transformations observed for dibenzylamine27 and its chiral analogues (S)-R-(methylbenzyl)benzylamine and (R,R)-bis-(R-methylbenzyl)amine.28,29 In the formation of the aza-allylic anions, the latter lose their chirality, negating their application and effectiveness as chiral reagents.28 Nonetheless, in synthesis, such resonance-stabilized anions are important intermediates in cycloaddition reactions as well as providing a basis for the presence or lack of selectivity of CLA.30,31 More recently, our attention has focused on the metalation and structural chemistry of (S)-N-R-(methylbenzyl)allylamine (S-N-R-mba) (Scheme 1). Lithiated S-N-R-mba is the CLA of choice in conjugate addition reactions due to the ease of selective deprotection of the allyl group via application of Wilkinson’s catalyst.32 Reports on the successful formation of 1,4-addition products with high enantioselectivity indicate retention of the allylamide form of the lithiated complex prior to deprotection.9 However, our investigations into the sodiation of S-N-R-mba demonstrated that a facile 1,3-sigmatropic rearrangement is
Andrews et al. Scheme
1.
Observed Transformations Following Metallation
of
S-N-r-mba
possible after isolation of the chiral 1-aza-allyl complex33 (S){[(PhC(H)CH3NC(H)CHCH3)Na · tmeda], 1. This complex was initially structurally confirmed as the tmeda adduct, but the anion rearrangement also occurs in THF solution alone.34 Its conjugate addition to tBu cinnamate resulted in the highly stereoselective formation of a novel chiral aminocyclohexane product containing six new vicinal stereogenic centers.34 The metal and solvent dependency of the rearrangement was confirmed when the hmpa (hexamethylphosphoramide) adduct of the lithium amide, (S){[(PhC(H)CH3NCH2CHdCH2)Li · hmpa]2, 2, could be forced to rearrange to the aza-allyl form (ca. 75% conversion by NMR) in toluene at 90 °C.35 These results prompted a more detailed study, and we now report the synthesis and solid-state structures of [(PhC(dCH2)N(CH2CH2CH3)M · pmdta], complexes 3 (M ) Li) and 4 (M ) Na), respectively, both of which have undergone rearrangement to an η1-N-aza-enolate with a consequent loss of chirality. In addition, we report the solid-state structure of (S)-[{(PhC(H)CH3NC(H)CHCH3)Li} · tmeda]∞, complex 5, in which the previously observed 1,3-sigmatropic shift has been promoted by overnight storage at room temperature. The stability of the various anions relative to each other and to the parent amine, as well as the effects of solvation on the metal cation and its consequent interaction with the anion, have been studied by theoretical calculations.
Results and Discussion (19) Caro, C. F.; Lappert, M. F.; Merle, P. G. Coord. Chem. ReV. 2001, 210-221, 605. (20) Theodorou, V.; Skobridis, K.; Karkatsoulis, A. Tetrahedron 2007, 63, 4284. (21) Enders, D.; Bachstadter, D.; Kremer, K. A. M.; Marsch, M.; Harms, K.; Boche, G. Angew. Chem., Int. Ed. Engl. 1988, 27, 1522. (22) Strunk, S.; Schlosser, M. Eur. J. Org. Chem. 2006, 4393. (23) Clayden, J. Organolithiums: SelectiVity for Synthesis; Pergamon: Oxford, 2002. (24) Barbazanges, M.; Meyer, C.; Cossy, J. Tetrahedron Lett. 2008, 49, 2902. (25) Fraenkel, G.; Chow, A.; Fleischer, R.; Liu, H. J. Am. Chem. Soc. 2004, 126, 3983. (26) Fraenkel, G.; Chen, X.; Gallucci, J.; Ren, Y. J. Am. Chem. Soc. 2008, 130, 4140. (27) Andrews, P. C.; Armstrong, D. R.; Baker, D. R.; Mulvey, R. E.; Clegg, W.; Horsburgh, L.; O’Neil, P. A.; Reed, D. Organometallics 1995, 14, 427. (28) Andrews, P. C.; Duggan, P. J.; Fallon, G. D.; McCarthy, T. D.; Peatt, A. C. J. Chem. Soc., Dalton Trans. 2000, 2505. (29) Andrews, P. C.; Duggan, P. J.; Maguire, M.; Nichols, P. J. Chem. Commun. 2001, 53. (30) Neumann, F.; Lambert, C.; Schleyer, P. V. J. Am. Chem. Soc. 1998, 120, 3357. (31) Pearson, W. H.; Stoy, P. Synlett 2003, 903. (32) Davies, S. G.; Fenwick, D. R. J. Chem. Soc., Chem. Commun. 1995, 11, 1109.
Synthesis and Solid-State Analysis of 3 and 4. Repeated attempts to crystallize the more extensively used lithiated S-NR-mba derivatives with various monodentate Lewis bases have proved mostly unsuccessful, except for the previously reported dimeric hmpa adduct, 2.35 Most products are isolated as highly viscous impure oils, and structural information is derived from NMR spectra. These spectra support observations from their use in synthesis that when prepared at low temperature and used in situ the complex persists as a lithiated allylamine. Because such reactions are typically conducted in donor solvents such as THF and Et2O, the data corroborate the evidence obtained through elucidation of the structure of complex 2 that monodentate ligands support retention of the allylamide structure. For N-substituted benzylamines, most anion changes are observed when donors of higher denticity are employed.27,29,33 (33) Andrews, P. C.; Calleja, S. M.; Maguire, M.; Nichols, P. J. Eur. J. Inorg. Chem. 2002, 1583. (34) Koutsaplis, M.; Andrews, P. C.; Bull, S. D.; Duggan, P. J.; Fraser, B. H.; Jensen, P. Chem. Commun. 2007, 34, 3580. (35) Andrews, P. C.; Minopoulos, M.; Robertson, E. G. Eur. J. Inorg. Chem. 2006, 14, 2865.
Anion Rearrangements of R-(Methylbenzyl)allylamide
Organometallics, Vol. 28, No. 6, 2009 1699
Figure 1. ORTEP drawing of 3, showing hydrogens on benzyl and propyl fragments.
Lithiation of S-N-R-mba in the presence of 1 equiv of the tridentate donor pmdta in hexane at -78 °C resulted in the precipitation of a pale yellow solid. As the reaction warmed to room temperature, the solid solubilized and an orange oil separated from solution. After the solvent was minimized by evaporation in vacuo and stored at -24 °C, yellow cubic crystals deposited from the viscous orange oil. Singlecrystal X-ray analysis revealed the complex to be [(PhC(dCH2)N(CH2CH2CH3)Li · pmdta], 3, shown in Figure 1. The complex crystallizes in the monoclinic space group P21/n as two asymmetric monomers. Bond lengths and angles within each monomer are essentially identical. Comparison of the 1H NMR spectra of 3 and the remaining orange oil indicated that their compositions are consistent with each other. An analysis of the NMR spectra for all complexes is given in more detail below. The structure of the anion in complex 3 can be described as an η1-N-aza-enolate. The amide contains a newly formed propyl group and loses its chiral center on formation of the new delocalized double bond in the former benzylmethyl moiety. The Li cation is formally 4 coordinate with a Li-Namido bond distance of 2.003(7) Å, which is typical for such Li-N bonds,35-37 and with the three N-Li bonds from pmdta adopts a tetrahedral geometry. The formation of the aza-enolate is characterized by bond lengths of 1.370(5) Å for C(7)-C(8) and 1.359(5) Å for C(7)-N(1), which are comparable with other characterized lithium aza-enolate complexes.21 In comparison, CdC and C-N bond distances in enamine structures are of the order of 1.345 and 1.400 Å, respectively, with the sum of the bond lengths being almost equal.38 While there is no interaction of the Li cation with the delocalized aza-enolate unit, additional agostic contacts can be considered between Li and H(5), 2.794 Å, and Li and H(10B), 2.674 Å.39 The most important structural feature of 3, however, is the evidence of anion rearrangement. Also, in contrast to the amidefaza-allyl conversion for [(Ph(Me)CH)(PhCH2)NLi · (36) Andrews, P. C.; Duggan, P. J.; Fallon, G. D.; McCarthy, T. D.; Peatt, A. C. J. Chem. Soc., Dalton Trans. 2000, 1937. (37) Armstrong, D. R.; Henderson, K. W.; Kennedy, A. R.; Kerr, W. J.; Mair, F. S.; Moir, J. H.; Moran, P. H.; Snaith, R. J. Chem. Soc., Dalton Trans. 1999, 4063. (38) Brown, K. L.; Damm, L.; Dunitz, J. D.; Eschenmoser, A.; Hobi, R.; Kratky, C. HelV. Chim. Acta 1978, 61, 3108. (39) Barr, D.; Clegg, W.; Mulvey, R. E.; Snaith, R. J. Chem. Soc., Chem. Commun. 1984, 285.
Figure 2. ORTEP drawing of 4, showing hydrogens on benzyl and propyl fragments.
pmdta] and for [(PhC(H)CH3)(CH2CHdCH2)NLi · hmpa]2, which require heating to above 60 °C,29,36 the conversion happens at or below room temperature, similar to the low temperature conversion observed for [(PhCH)2NLi · pmdta].27 Evidence suggests that the presence of pmdta assists in promoting such rearrangements or transformations and that this may stem from the ability to support monomer formation. The thermally promoted conversion of (S)-[(PhC(H)CH3)(CH2CHdCH2)NLi · hmpa]2, 2, to its isomer [(PhC(H)CH3NC(H)CHCH3)Li · hmpa] in toluene at 90 °C suggests that the transition from allylamide to the aza-enolate form observed in 3 is most likely sequential rather than concerted and that the solvation of the cation and the aggregation state are important aspects of this. These are considered in the theoretical calculations described below. In contrast to the formation of [(PhC(H)CH3NC(H)CHCH3)Li · hmpa], crystals of the sodium analogue (S)-{[(PhC(H)CH3NC(H)CHCH3)Na · tmeda], 1, are readily formed and isolated at room temperature.33 In light of the results with Li, the next part of the study was to investigate what impact using pmdta would have on the form adopted by the sodiated allylamide. As previously described, the sodiated allylamide readily precipitates upon addition of S-N-R-mba to a suspension of nBuNa in hexane at 0 °C. The orange precipitate thereby formed is readily solubilized upon addition of pmdta, giving a bright red solution. Storage of this solution at -24 °C overnight results in the deposition of prismatic red crystals. Single-crystal X-ray diffraction analysis revealed the crystals to be of the monomer [(PhC(dCH2)N(CH2CH2CH3)Na · pmdta], 4, the sodium analogue of 3 described above. The complex crystallizes in the monoclinic space group P21/n with four molecules in the unit cell and is shown in Figure 2. Each of the molecules in the unit cell are essentially identical with bond angles and bond lengths falling within the standard deviation. Coincident with deposition of the crystals is the separation of a bright red oil from solution, and, as found with 3, NMR spectroscopy revealed the composition of the oil to be wholly consistent with the crystal form of 4. This made it difficult to measure the mp of both complexes 3 and 4 because it is close to room temperature.
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Andrews et al.
Figure 3. ORTEP drawing of 5, with all hydrogens omitted for clarity.
The main structural difference with the lithium analogue 3 is that, although 4 can still formally be considered a sodium amide with a typical Na(1)-N(1) bond distance of 2.323(4) Å,40 the Na cation is now located centrally over the delocalized C(5)C(6)-C(7)N(1) atoms with distances for Na-C(5-7) of 2.929(4), 3.044(4), and 3.028(4) Å, respectively. The remaining bond distances to pmdta of Na(1)-N(2) 2.434(4), Na(1)-N(3) 2.458(4), and Na(1)-N(4) 2.477(4) Å are marginally shorter than those found in the monomeric 2-aza-allyl complex {[Ph(Me)CNC(H)Ph]Na · pmdta},28 which displays a similar coordination environment. As in 3, delocalization through the aza-enolate unit, C(8)C(7)N(1), is characterized by the bond lengths C(7)-C(8) 1.376(6) and C(7)-N(1) 1.360(5) Å (cf., 1.370(5) and 1.359(5) Å in 3, respectively), and again there are no metal interactions involving C(8). While in 3 there is some evidence of weak Ph · · · Li interactions through the agostic Li · · · H(5) bond, this is much more pronounced in 4 where Na bonds with the C(5) and C(6) atoms. This interaction is facilitated by the rotation of the Ph group to become more coplanar with the aza-enolate moiety. The different bonding arrangements in 3 and 4 are highlighted by further comparing the relationship of the metal with the C(9)-N(1)-C(7)-C(6) atoms. Deviation from the plane for the N atom in 4 is only 1.1°, caused by the inclusion of the N anion in delocalization, while in 3 the greater σ bonding contribution for N-Li results in a 9° deviation. Synthesis and Solid-State Analysis of 5. Anion rearrangements in [(PhC(H)CH3)(CH2CHdCH2)NLi · L]n are thermally promoted when L is the monodentate donor hmpa and occur at or below room temperature when L is the tridentate donor pmdta. However, two different anion forms are observed. Noting that with sodium two different anion isomers, 4 and 1, are also formed with pmdta and tmeda, respectively, the next step was to investigate the combination of the lithiated allylamide and the bidentate donor tmeda. As such, nBuLi was added slowly to a stirring solution of S-N-R-mba and tmeda in hexane at -78 °C. This resulted in the precipitation of a yellow solid, which dissolved upon warming to room temperature. At this point, small droplets of orange oil formed on the side of the Schlenk flask. Overnight, this yellow solution deposited a large crop of colorless prismatic crystals. Single-crystal X-ray analysis on the crystals identified them as (S)-{[(PhC(H)CH3NC(H)CHCH3)Li}2tmeda]∞, 5. The complex crystallizes in the mono(40) Andrews, P. C.; Barnett, N. D.; Mulvey, R. E.; Clegg, W.; O’Neil, P. A.; Barr, D.; Cowton, L.; Dawson, A. J.; Wakefield, B. J. Organomet. Chem. 1996, 518, 85.
Figure 4. Dimeric unit in 5 showing the Li coordination environment. N(3) and N(4) belong to bridging tmeda molecules. All hydrogen atoms omitted for clarity.
clinic space group P21, and a representation of the polymeric structure is shown in Figure 3. The anion form is the same as that seen in the sodium analogue, 1, and as with pmdta the rearrangement occurs at or below room temperature although with a different outcome. This formation of the η1-N-aza-allyl anion is characterized by bond lengths of N(1)-C(9)-C(10) 2.367(6), 2.347(6) Å and N(2)-C(20)-C(21) 2.363(5), 2.379(6) Å, which are comparable to those observed in the sodium analogue 1. The polymer is composed of dimeric units of the lithium azaallyl complex (Figure 4) connected by bridging tmeda molecules. The dimeric units are structurally similar to those in [(PhC(H)CH3NC(H)CHCH3)Na · tmeda]2, although the larger Na cation in 1 is able to incorporate tmeda as a chelating ligand. If only the interactions with N atoms are considered, the geometry at the Li atom is planar 3 coordinate with Li(1)-N(1) and Li(2)-N(2) bond distances of 2.087(7) and 2.067(8) Å, respectively. Both are, as expected, slightly shorter than the dative bonds from tmeda: Li(1)-N(3) 2.134(7) and Li(2)-N(4) 2.184(7) Å. However, both Li centers also interact with the C
Anion Rearrangements of R-(Methylbenzyl)allylamide
atoms in the aza-allylic unit and form close contacts with bond lengths Li(1)-C(9) 2.294(5), Li(1)-C(10) 2.438(7), Li(2)-C(20) 2.277(8), and Li(2)-C(21) 2.265(6) Å. The unusual structural feature of 5 is the binding mode of tmeda and its role in polymerization. There are very few examples of tmeda acting solely in a bridging mode41,42 without some involvement by the chelating form, and these arise for lithium amides, not surprisingly, with sterically hindered ligands: (iPr)2N and 2,6-dimethylpiperidinido.43,44 In their study on the polymeric form of LDA, [(iPr)2NLi · tmeda]∞, Williard and Collum noted that tmeda does not have a tendency to bind dimeric lithium amides in a chelating manner and tends not to affect deaggregation as strongly as THF.43 The structure obtained for 5 would seem to support these conclusions. Solution Studies on Complexes 3, 4, and 5. In solution, the formation of the η1-N-aza-enolate anion present in complexes 3 and 4 has been characterized by NMR spectroscopy. Because the chemical shifts for 3 and 4 are very similar (see Experimental Section), only those pertaining to the spectrum of 4 will be used to illustrate the change in anion. In the 1H NMR spectrum of the free amine ligand, the benzylic proton is observed as a quartet at 3.57 ppm and the R-methyl group as a doublet at 1.1 ppm. In complexes 3 and 4, both of these signals are distinctly absent; however, the spectrum is marked by the emergence of two new signals assigned to diastereotopic protons at 3.80 and 3.49 ppm associated with the new terminal vinylic fragment (PhC(dCH2)N-). The allyl group in the free amine is characterized by a set of four signals: a multiplet at 5.75 ppm (CH2CHCH2), two doublets of quartets at 5.04 and 4.94 ppm (CH2CHCH2), and a multiplet at 2.95 ppm (CH2CHCH2). All of these signals are absent in the spectra of 3 and 4 where the chemical shifts, multiplicities, and coupling constants of the signals support the formation of a propyl fragment. These include a triplet at 3.54 ppm (CH2CH2CH3), a multiplet at 1.8 (CH2CH2CH3), and a triplet at 1.32 ppm (CH2CH2CH3). Analogous information is obtained from the 13C NMR spectra of 3 and 4. The 1H NMR spectrum of complex 5 can be readily compared to (S)-{[(PhC(H)CH3NC(H)CHCH3)Na · tmeda], 1,33 and is distinct from that of 3 and 4. Interestingly, again the effect of the different metals on the chemical shifts observed for the anions is minimal. Only a difference of 0.3 ppm is observed, even though the spectrum of 5 was collected in C6D6 and data on 1 were obtained with strongly coordinating d8-THF as the solvent. The rearranged allyl group of 5 is characterized by the following signals: a doublet at 6.92 ppm (C(H)dC(H)CH3), a multiplet at 3.93 ppm (C(H)dC(H)CH3), and a doublet at 1.96 ppm (C(H)dC(H)CH3). What is different about the spectrum of complex 5 in comparison to 1 is the chemical shifts of the CH2 and CH3 signals of tmeda. In complex 1, tmeda is characterized by two singlets at 2.29 (NCH2) and 2.14 ppm (NCH3), respectively. In contrast, the presence of tmeda in complex 5 is characterized by a single broad singlet at 1.91 ppm, which is within the expected range when tmeda is coordinated to Li.27,45 In probing possible fluxional behavior (41) Cole, M. L.; Junk, P. C.; Louis, L. M. J. Chem. Soc., Dalton Trans. 2002, 20, 3906. (42) Galka, C. H.; Trosch, D. J. M.; Rudenauer, I.; Gade, L. H.; McPartlin, M. Inorg. Chem. 2000, 39, 4615. (43) Bernstein, M. P.; Romesberg, F. E.; Fuller, D. J.; Harrison, A. T.; Collum, D. B.; Liu, Q.; Williard, P. G. J. Am. Chem. Soc. 1992, 114, 5100. (44) Clegg, W.; Horsburgh, L.; Couper, S. A.; Mulvey, R. E. Acta Crystallogr. 1999, 55, 867. (45) Armstrong, D. R.; Barr, D.; Clegg, W.; Hodgson, S. M.; Mulvey, R. E.; Reed, D.; Snaith, R.; Wright, D. S. J. Am. Chem. Soc. 1989, 111, 4719.
Organometallics, Vol. 28, No. 6, 2009 1701 Scheme
2.
Possible Transformations Following Metallation
of
S-N-r-mba
between bridging and chelating tmeda in 5, variable temperature H NMR (300 MHz) spectra were obtained in d8-toluene in the range 30 to -70 °C. However, even at the lowest temperature, there was no evidence of asymmetry in the binding modes; only a slight movement in chemical shift and signal broadening was observed. Theoretical Calculations. To investigate the energetic trends associated with the reactions and the anion forms, theoretical calculations were performed using the Gaussian 03 suite of programs.46 Initially, an extensive set of geometry optimizations were performed using density functional theory at the B3LYP/ 6-31G(d) level. Ligand structures were selected corresponding to the typical allylamide anion seen in complex 2, labeled (i), and the anion forms observed in complexes 3-5, labeled (ii) and (iii). Possible intermediates were constructed and are shown as 2-01-2-04 in Scheme 2. Bare anions were studied as well as structures with the ligands bound to a lithium or sodium ion via the nitrogen atom. Conformational freedom was explored, but for simplicity only the anti/trans conformers (generally the more stable form) are presented in Table 1. It is immediately evident that (ii) and (iii) are far more stable than (i) (Chart 1). Also, intermediate 2-02 stands out as the most feasible intermediate on the pathway from (ii)f(iii), which is in agreement with resonance stabilization notions as depicted 1
(46) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03; Gaussian, Inc.: Wallingford, CT, 2004.
1702 Organometallics, Vol. 28, No. 6, 2009
Andrews et al.
Table 1. Relative Energies ∆G (kJ mol-1) Incorporating the Thermal Correction to Gibbs Energy Computed at B3LYP/6-31G(d) Levela
b
structure
bare anion
Li+ adduct
Na+ adduct
(i) (ii) trans (iii) anti 2-01 2-02 2-03 2-04
130.8 28.0 3.4 153.2 -19.7 -b 170.4
80.3 0.0 6.1 95.8 16.3 175.9c -b
85.4 0.0 5.0 14.3
(B3LYP)a (B3LYP)b (B3LYP+z.p.)b (MP2)c
n)0
n)1
n)2
n)3
6.1 -4.1 -2.6 -2.7
3.6 -5.2 -4.0 -6.2
-2.4 -9.9 -9.0 -9.2
-4.8 -4.3 -2.8 -13.7
a B3LYP/6-31G(d). b B3LYP/6-311+G(d,p). z.p. ) zero point correction. c MP2/6-311+G(d,p).
Chart 1. Gibbs Energy Diagram for Intermediates at the B3LYP/6-311+G(d,p) Level
Table 2. Computed Relative Internal Energies (∆E) and Gibbs Energies (∆G) (kJ mol-1) at Higher Levels of Theory structure (ii) trans
no. NH3 ∆E ∆E ∆E ∆E
a Intermediate (ii) is in trans and (iii) in anti configuration. Dissociates. c Undergoes rearrangement of bonds.
(i)
Table 3. Internal Energy Differences (kJ mol-1) between Li+ Adducts of Structures (ii) and (iii), Expressed as ∆E ) E(ii) - E(iii)
(iii) anti
2-02
∆E (B3LYP)a ∆E (B3LYP)b ∆E (B3LYP+z.p.)b ∆G (B3LYP)b,c ∆E (MP2)d
Li+ Adducts 80.3 0.0 75.5 4.1 73.1 2.6 72.6 0.0 72.0 2.7
6.1 0.0 0.0 1.0 0.0
16.3 15.8 13.2 14.9 25.0
∆E (B3LYP)a ∆E (B3LYP)b ∆E (B3LYP+z.p.)b ∆G (B3LYP)b,c ∆E (MP2)d
Na+ Adducts 85.4 0.0 80.9 8.5 77.8 6.4 74.8 6.6 78.2 6.8
5.0 0.0 0.0 0.0 0.0
14.3 16.1 12.7 13.8 25.0
a B3LYP/6-31G(d). b B3LYP/6-311+G(d,p), z.p. ) zero point correction. c ∆G includes the thermal correction to Gibbs energy computed at B3LYP/6-311+G(d,p) level. d MP2/6-311+G(d,p).
in Scheme 2. A significant energetic preference (25 kJ mol-1) for (iii) over (ii) in the bare anions is canceled with the addition of a Li+ or Na+ cation. Energetics were further investigated using B3LYP and MP2 calculations with a larger 6-311+G(d,p) basis set. Results are summarized in Table 2. Consistently, starting structure (i) is around 70-80 kJ mol-1 higher in energy than (ii) and (iii), which have comparable stabilities. The proposed intermediate 2-02 is energetically very accessible, at around 10-20 kJ mol-1 above (ii).
Finally, the effect of adding ligands to the cation was simulated by adding different numbers of ammonia molecules to the lithium bound species for (ii) and (iii). These calculations are summarized in Table 3, and the structures are shown in Figure 5. Overall, the trend is for increased stability of (iii) relative to (ii) as the number of ammonia molecules is increased, as indicated by the negative ∆E (kJ mol-1). Presumably the ammonia molecules help to neutralize the cation charge, and hence partially revert to the situation in the absence of the cation (with (iii) energetically preferred over (ii)). In summary, this calculated trend correlates with the observations in the solution and solid states. The allylamide anion is found in the presence of monodentate donors (THF, Et2O, hmpa) exemplified by complex 2, where the complex is dimeric with one coordinated hmpa molecule per Li cation. This supports the observed reactivity of the lithium amide in asymmetric synthesis. The bidentate donor tmeda causes rearrangement to the 1-azaallylic form seen in complex 5 and calculated as isomeric form (ii). The tridentate donor pmdta promotes a further favorable rearrangement to the isomeric form (iii) observed in complex 3. Also apparent is the movement of Li+ away from the π ring, with the styrene moiety becoming more planar and the Li-N bond having greater σ character (Figure 5). These observed trends are replicated in the structures involving Na cations, complexes 1 and 4.
Conclusion The alkali metal complexes of the chiral amine R-(methylbenzyl)allylamine are prone to undergo anionic rearrangements depending on the metal, the denticity of the donor solvent, the thermal history of the complex, and its aggregation state. Three different anionic forms have been observed: allylamide [(PhC(H)CH3NCH2CHdCH2)]-, 1-aza-allyl [(PhC(H)CH3NC(H)CHCH3)]-, and aza-enolate [(PhC(dCH2)N(CH2CH2CH3)]-. The allylamide form predominates in the presence of monodentate donors at ambient temperatures and is the common form found for the application of the lithiated complex in synthesis. The bidentate donor tmeda causes rearrangement to the 1-azaallylic form, while the tridentate donor pmdta induces further rearrangement to an aza-enolate isomer. For the latter anion, the chirality of the complex originally derived from the benzylic carbon is lost as the new vinylic moiety is formed. Both of these rearrangements are facile and occur at or below room temperature. Ab initio calculations on the various anion forms and possible intermediates indicate a large increase in stabilization energy (ca. -75 kJ mol-1) on rearranging from the allylamide form to the two delocalized forms. Examining the influence of the degree of donor coordination on the Li cation and its relationship to the anion showed that the 1-aza-allyl isomer is most favored by bidentate coordination while the 1-aza-enolate form is most favored by tridentate coordination, and that the anion progressively adopts a more planar arrange-
Anion Rearrangements of R-(Methylbenzyl)allylamide
Organometallics, Vol. 28, No. 6, 2009 1703
Figure 5. Li structures of (iii) computed at the MP2/6-311+G(d,p) level, showing successive addition of ammonia molecules.
ment. These calculated structures correlate with those observed experimentally.
Experimental Section The synthetic protocols for the reactions reported herein were carried out under dry inert atmosphere conditions. All synthesis and manipulations were undertaken with the use of a vacuum/ nitrogen line and Schlenk techniques and where appropriately handled in an argon glovebox. Water and oxygen were removed from hexane using the MBRAUN SPS-800 solvent purification system and stored over 4 Å molecular sieves. Prior to use, THF was dried by reflux over Na, and pmdta and tmeda were dried by reflux over CaH2 and stored over 4 Å molecular sieves. nBuLi (1.6 M in hexane) was purchased from Aldrich and standardized before use. nBuNa and S-N-R-mba were synthesized according to the literature procedures.47,48 1H and 13C NMR spectra were recorded on Bruker DRX 400 MHz and Bruker DRX 300 MHz spectrometers with chemical shifts referenced internally to C6D6. All elemental analyses were performed by CMAS, Melbourne, Australia. Crystallography Details. Crystallographic data were obtained on an Enraf Nonius Kappa CCD diffractometer with graphite monochromated Mo KR (λ0 ) 0.71073 Å) radiation at 123 K. All single crystals were mounted on a glass fiber under oil.49 Data were collected and processed using the Nonius software. Structures were solved and refined by full-matrix least-squares on F2 and expanded using direct methods with all calculations performed by SHELXS 97 software50 and X-seed interface.51 All hydrogen atoms were placed in calculated positions (C-H ) 0.95 Å) and included in the final least-squares refinement. All other atoms were located and refined anisotropically. Synthesis and Characterization of {[(PhC(CH2)N)-(CH2CH2CH3)Li · pmdta]}, 3. nBuLi (3.13 mL, 1.6 M, 5 mmol) was added dropwise to a stirring solution of S-N-R-mba (0.81 g, 5 mmol) and pmdta (1.04 mL, 5 mmol) in hexane (10 mL) at -78 °C. A yellow precipitate formed, and the reaction was left to warm slowly to room temperature over 30 min. An orange oil separated out of solution. The solvent was reduced in vacuo to a minimum, and the dark orange oil was stored at -24 °C. A large crop of prismatic yellow crystals deposited. Any remaining solvent was removed via cannula, and the crystals were washed with cold hexane, dried in vacuo, and stored in a glovebox. Yield: 1.16 g, (68%). 1H NMR (400 MHz, C6D6, 30 °C): δ 8.04 (2H, d, 3JHH 7.0 Hz, ortho-H), 7.26 (2H, m, Ar-H), 7.17 (1H, m, Ar-H), 3.78 (1H, br s, dCH2a), 3.55 (1H, br s, dCH2b), 3.48 (2H, t, 3JHH 7.6 Hz, N-CH2), 2.02 (2H, m, CH2CH2CH3), 1.93 (12H, s, N(CH3)2), 1.80 (8H, br s, N(CH2)2), 1.62 (br s, 3H, NCH3), 1.30 (3H, t, 3JHH 7.3 Hz, CH2CH2CH3). 13C NMR (100 MHz, C6D6, 30 °C): δ 164.4 (CdCH2), 152.5 (ipso-C), 128.2 (Ar-C), 127.9 (Ar-C), 127.0 (47) Lochmann, L.; Pospisil, J.; Lim, D. Tetrahedron Lett. 1966, 2, 257. (48) Yus, M.; Foubelo, F.; Falvello, L. R. Tetrahedron: Asymmetry 1995, 6, 2081. (49) Stalke, D. Chem. Soc. ReV. 1998, 27, 171. (50) Sheldrick, G. M. SHELXS97: Program for the Solution of Crystals Sturctures; University of Goettingen, Go¨ttingen, 1997. (51) Barbour, L. J. XSEED: A Graphical Interface for Use with the SHELXS Program Suite; University of Missouri, Missouri, 1999.
(CdCH2), 125.8 (Ar-C), 64.7 (NCH2), 57.5 ((CH3)2NCH2), 53.9 (CH2N(CH3)), 45.8 ((CH3)2NCH2), 44.3 (CH2N(CH3), 24.7 (CH2CH3), 13.7 (CH2CH3). Anal. Calcd for C20H37LiN4: C, 70.6; H, 11.0; N, 16.5. Found: C, 70.6; H, 11.0; N, 16.5. Crystallographic Data for 3. C20H37LiN4, M ) 340.48, yellow cubic, 0.25 × 0.25 × 0.25 mm3, monoclinic, space group P21/n (No. 14), a ) 9.0521(18), b ) 29.043(6), c ) 16.517(3) Å, b ) 92.25(3)°, V ) 4338.9(15) Å3, Z ) 8, Dc ) 1.042 g/cm3, F000 ) 1504, Nonius Kappa CCD, Mo KR radiation, l ) 0.71073 Å, T ) 123(2) K, 2θmax ) 50.0°, 20 401 reflections collected, 7492 unique (Rint ) 0.1396). Final GOF ) 0.990, R1 ) 0.0987, wR2 ) 0.2383, R indices based on 3969 reflections with I > 2σ(I) (refinement on F2), 464 parameters, 0 restraints. Lp and absorption corrections applied, m ) 0.062 mm-1. Synthesis and Characterization of {[(PhC(CH2)N)-(CH2CH2CH3)Na · pmdta]}, 4. A beige suspension of nBuNa (0.4 g, 5 mmol) in hexane (10 mL) was sonicated for 20 min. S-N-R-mba was added dropwise to the stirring suspension at 0 °C, resulting in an orange color change as the reaction was stirred at room temperature for 30 min. pmdta (1.04 mL, 5 mmol) was added dropwise to the reaction at room temperature, which solubilized the orange precipitate forming a red solution. The red solution was filtered via cannula. Storage of the solution at -24 °C overnight resulted in the deposition of prismatic red crystals. The solvent was removed via cannula, and crystals were washed with cold hexane, dried in vacuo, and stored in the glovebox. Yield: 1.09 g (61%). 1 H NMR (400 MHz, C6D6, 30 °C): δ 8.03 (2H, d, 3JHH 6.8 Hz, ortho-H), 7.16 (2H, m, Ar-H), 7.08 (1H, m, Ar-H), 3.80 (1H, d, 2 JHH 1.7 Hz, dCH2a), 3.54 (2H, t, 3JHH 7.3 Hz, CH2CH2CH3), 3.49 (1H, d, 2JHH 1.6 Hz, dCH2b), 1.97 (br s, 3H, NCH3), 1.91 (12H, s, N(CH3)2), 1.86 (2H, m, CH2CH2CH3), 1.76 (8H, s, N(CH2)2), 1.32 (3H, t, 3JHH 7.4 Hz, CH2CH2CH3). 13C NMR (100 MHz, C6D6, 30 °C): δ 164.1 (CdCH2), 153.0 (Ar-C), 127.6 (Ar-C), 127.3 (CdCH2), 125.8 (Ar-C), 62.1 (NCH2), 57.8 ((CH3)2NCH2), 55.8 (CH2N(CH3)), 45.8 ((CH3)2NCH2), 43.2 (CH2N(CH3), 28.6 (CH2CH3), 13.9 (CH2CH3). Anal. Calcd for C20H37N4Na: C, 67.2; H, 10.4; N, 15.7. Found: C, 67.4; H, 10.5; N, 15.8. Crystallographic Data for 4. C20H37N4Na, M ) 356.53, red prismatic, 0.25 × 0.2 × 0.1 mm3, monoclinic, space group P21/n (No. 14), a ) 8.7889(18), b ) 16.337(3), c ) 16.098(3) Å, β ) 103.60(3)°, V ) 2246.8(8) Å3, Z ) 4, Dc ) 1.054 g/cm3, F000 ) 784, Nonius Kappa CCD, Mo KR radiation, λ ) 0.71073 Å, T ) 173(2) K, 2θmax ) 50.0°, 16 538 reflections collected, 3948 unique (Rint ) 0.1165). Final GOF ) 1.122, R1 ) 0.1033, wR2 ) 0.2764, R indices based on 2531 reflections with I > 2σ(I) (refinement on F2), 232 parameters, 0 restraints. Lp and absorption corrections applied, µ ) 0.080 mm-1. Synthesis and Characterization of [(S)-r-{(PhC(H)CH3NC(H)CHCH3)Li}2 · tmeda]∞, 5. nBuLi (3.13 mL, 1.6 M, 5 mmol) was added dropwise to a stirring solution of S-N-R-mba (0.81 g, 5 mmol) and tmeda (0.37 mL, 2.5 mmol) in hexane (10 mL) at -78 °C. A yellow precipitate formed, and the reaction was left to warm slowly to room temperature over 30 min. An orange oil formed, which was solubilized by some gentle heating, and the reaction was stored at room temperature. Over 1-2 days a crop of colorless prismatic crystals deposited. The solvent was removed via cannula, and the crystals were washed with cold hexane, dried in vacuo, and stored
1704 Organometallics, Vol. 28, No. 6, 2009 in a glovebox. Yield: 0.48 g (42%). mp: 125-126 °C to an orange melt. 1H NMR (300 MHz, C6D6, 30 °C): δ 7.49 (2H, d, 3JHH 7.3 Hz, ortho-H), 7.25 (2H, t, 3JHH 7.4 Hz, meta-H), 7.09 (1H, t, 3JHH 7.3 Hz, para-H), 6.92 (1H, d, 3JHH 13.1 Hz, NC(H)dC), 4.34 (1H, q, 3JHH 6.5 Hz, PhC(H)CH3), 3.93 (1H, m, NC(H)dC(H)), 1.96 (3H, d, 3JHH 5.9 Hz, C(H)dC(H)CH3), 1.91 (8H, br s, tmeda), 1.61 (3H, d, 3JHH 6.6 Hz, PhC(H)CH3). 13C NMR (75 MHz, C6D6, 30 °C): δ 151.5 (ipso-C), 151.0 (NC(H)dC), 128.4 (ortho-C), 127.5 (meta-C), 125.8 (para-C), 79.5 (C(H)dC(H)CH3), 61.1 (PhC(H)CH3), 57.1 (NCH2), 45.8 (N(CH3)2), 26.2 (PhC(H)CH3), 16.7 (C(H)dC(H)CH3). Anal. Calcd for C14H22LiN2: C, 74.5; H, 9.7; N, 12.5. Found: C, 74.6; H, 9.8; N, 12.4. Crystallographic Data for 5. C14H22LiN2, M ) 225.28, colorless prismatic, 0.2 × 0.1 × 0.1 mm3, monoclinic, space group P21 (No. 4), a ) 8.1036(16), b ) 18.364(4), c ) 9.850(2) Å, b ) 108.81(3)°, V ) 1387.6(5) Å3, Z ) 4, Dc ) 1.078 g/cm3, F000 ) 492, Nonius Kappa CCD, Mo KR radiation, l ) 0.71073 Å, T ) 173(2) K,
Andrews et al. 2θmax ) 55.6°, 14 432 reflections collected, 6375 unique (Rint ) 0.1153). Final GOF ) 1.031, R1 ) 0.0929, wR2 ) 0.2198, R indices based on 3955 reflections with I > 2σ(I) (refinement on F2), 315 parameters, 1 restraint. Lp and absorption corrections applied, m ) 0.062 mm-1. Absolute structure parameter ) 4(4) (Flack, H. D. Acta Crystallogr. 1983, A39, 876-881).
Acknowledgment. We thank the Australian Research Council and Monash University for financial support. Quantum chemistry calculations were carried out using the Australian Partnership for Advanced Computing (APAC) National Facility (project n29). Supporting Information Available: CIF data. This material is available free of charge via the Internet at http://pubs.acs.org. OM801165E
