The Strange Case of Sodium (S)-N-α-(Methylbenzyl)allylamide: Anion

Communication pubs.acs.org/Organometallics

The Strange Case of Sodium (S)‑N‑α-(Methylbenzyl)allylamide: Anion Rearrangement, Decomposition, and a Peculiar Propyl Addition Emily C. Border, Magdaline Koutsaplis, and Philip C. Andrews* School of Chemistry, Monash University, Clayton, Victoria 3800, Australia S Supporting Information *

ABSTRACT: An unexpected aza-enolate propyl addition complex, [(PhCCH2)(CHC(CH2CH2CH3)CH3)NNa·THF]∞ (1), was isolated when (S)-N-α-(methylbenzyl)allylamine reacted in hexane with nBuNa in the presence of THF. Analytical studies revealed a decomposition of the sodium 1-azaallylamide to a sodium enamide and propene, identified by solution studies and a GC-headspace study, respectively. Propene then adds to the carbanion tautomer of the sodium 1-azaallylamide followed by anionic rearrangements to later form the aza-enolate propyl addition complex.

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of this new species is illustrated in Scheme 1, and the crystal structure is shown in Figure 2. This new sodiated complex

he importance of chiral metal amides in the formation of biologically important molecules means that their solidand solution-state chemistry has been well studied. Unanticipated outcomes continue to arise in well-studied reactions, primarily as a result of metal-mediated decompositions and anionic rearrangements.1 In recent years we have reported on various anionic transformations of (S)-N-α-(methylbenzyl)allylamide, which are both metal (Li vs Na vs K) and Lewis donor mediated, the latter being dependent on whether the coligand is mono-, di-, or tridentate. The three possible forms which result are allylamide, 1-azaallylamide, and the achiral azaenolate species, all shown in Figure 1.2

Scheme 1. Synthesis of the Aza-Enolate Propyl Addition Complex [(PhCCH2)(CHC(CH2CH2CH3)CH3)NNa· THF]∞ (1)

presents both aza-enolate and 1-azaallyl moieties in the anion and, in addition, has incorporated a 3C propyl chain. The asymmetric unit, [(PhCCH2)(CHC(CH2CH2CH3)CH3)NNa·THF], is shown in Figure 2; however, the complex is polymeric in the solid state, as shown in Figure 3. The addition product is isolated in 41% yield. The propyl chain adds at C(10), presumably into the newly forming 1-azaallyl form of the anion. However, the simplicity of this is questioned when we see that the structure also contains an aza-enolate moiety, leading to loss of chirality at C(7). This normally requires the electronic rearrangement of the 1-azaallyl species to generate the new vinylic bond and the concomitant saturated propyl group on the N atom. The aza-enolate moiety is defined by bond lengths for C(7)−C(8) and C(7)−N(1) of 1.357(4) and 1.379(4) Å, respectively. The polymeric structure has each N atom bridging between two Na cations, with each sodium coordinating a molecule of THF, making this formally three-coordinate with a distortedtrigonal-planar geometry (mean bond angle 120°). The

Figure 1. Three different metal amide species from the metalations of (S)-N-α-(methylbenzyl)allylamine in the presence of Lewis donors.

The allylamide anion is retained intact when Li is used in conjunction with monodentate donors, commonly THF and Et2O, supporting its predictable use in the formation of βamino acids and β-lactams.3 The 1-azaallylamide species has been observed when the chiral allylamine reacts with nBuNa in the presence of TMEDA or a large excess of THF, and the achiral aza-enolate form normally arises when the tridentate donor PMDETA is used and/or when nBuK is the metalating agent. When the potential for stoichiometric amounts of THF to induce the formation of the sodium 1-azaallylamide complex was investigated, crystals repeatedly formed which were of an entirely unexpected composition and structure. The formation © XXXX American Chemical Society

Received: December 1, 2015

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DOI: 10.1021/acs.organomet.5b00979 Organometallics XXXX, XXX, XXX−XXX

Communication

Organometallics

allylic proton closest to the N atom, which no longer appears as a doublet at 6.65 ppm, due to the addition of the propyl group. The ortho protons from the benzene ring appear at 7.58 ppm. Solution studies were then designed to determine whether or not THF is important in promoting formation of the new complex. (S)-N-α-(Methylbenzyl)allylamine was added dropwise to nBuNa in hexane at −60 °C and stirred and warmed to room temperature over 30 min. The solvent was removed, and a glassy solid was isolated. Two NMR samples were prepared: one in C6D6 and the other in d8-THF. Within 5 min both the C6D6 and d8-THF samples showed evidence for the formation of the addition product (full details are given in the Supporting Information), though the conversion appears to be much faster in THF. This suggests that the formation of [(PhC CH2)(CHC(CH2CH2CH3)CH3)NNa] is not dependent specifically on the presence of THF. Arenes can act as “nonclassical” Lewis donors with alkali metals mimicking the effect of more typical solvents.5 The d8-THF sample was monitored over time, and by 3 days there is no longer any of the initially formed 1-azaallyl species left. Instead, a full conversion to the addition species [(PhCCH2)(CH C(CH2CH2CH3)CH3)NNa] is observed. These NMR studies also revealed an additional product of the reaction, which is the simple sodium enamide [(PhCCH2)N(H)Na], identified by a doublet at 7.63 ppm corresponding to the ortho protons and two singlets at 2.88 and 2.53 ppm relating to the vinylic protons. Intriguingly, this is analogous to the complex [(PhC CH2)N(H)Na·PMDETA], which was isolated from the decomposition of sodium bis-α-(methylbenzyl)benzylamide.6 The question therefore is whether the source of the propyl moiety in [(PhCCH2)(CHC(CH2CH2CH3)CH3)NNa] is propene resulting from the decomposition of the 1-azaallyl species [(PhC(Me)H)(CHCHCH3)NNa], as illustrated in Scheme 2.

Figure 2. Molecular structure of [(PhCCH 2 )(CHC(CH2CH2CH3)CH3)NNa·THF]∞ (1) with thermal ellipsoids at 50% probability and with vinylic and azaallyl hydrogens shown. All other hydrogen atoms are omitted for clarity. Selected bond lengths (Å) and angles (deg): Na(1)−N(1), 2.489(3); Na(1)−O(1), 2.321(3); Na(1)−C(7), 2.787(3); Na(1)−C(8), 3.117(3); Na(1)− C(9), 2.795(3); N(1)−C(7), 1.379(4); C(7)−C(8), 1.357(4); N(1)− C(9), 1.394(4); C(9)−C(10), 1.349(4); C(10)−C(11), 1.509(4); N(1)−Na(1)−O(1), 95.98(9); Na(1)−N(1)−C(9), 107.05(17); Na(1)−N(1)−C(7), 119.03(18).

Scheme 2. Proposed Decomposition of the Sodium Amide

Figure 3. Polymeric unit of [(PhCCH2)(CHC(CH2CH2CH3)CH3)NNa·THF]∞ (1) with thermal ellipsoids at 50% probability. Hydrogen atoms are omitted for clarity. Selected bond lengths (Å) and angles (deg): Na(1)−N(1), 2.365(3); Na(1)−O(1), 2.321(3); Na(1)−N(1)′, 2.489(3); N(1)−Na(1)−N(1)′, 152.03(7); N(1)− Na(1)−O(1), 95.98(9); O(1)−Na(1)−N(1)′, 111.89(9).

To determine if propene is being produced in the reaction as an intermediate en route to the propyl addition product, a headspace experiment was conducted. This experiment was performed in a closed system, and the reaction mixture was stirred for 1 h before a headspace sample was taken. This sample was injected into a GC, along with a propene standard and a C1−C6 straight chain standard. Due to the flooding of butane in the headspace, resulting from the deprotonation of the amine with nBuNa, only a section of the chromatograph is shown in Figure 4 for simplicity (full chromatographs are provided in the Supporting Information). The propene standard (Figure 4b) can be clearly distinguished from the propane peak (C3) in the C1−C6 standard (Figure 4a) and we can see the small peak that correlates with the propene standard from the sample headspace (Figure 4c). This is evidence for the generation of propene in the reaction, even though it is present in a relatively small amount in the headspace. However, this is not unexpected, given that most of the propene generated in situ is consumed in the formation of [(PhCCH2)(CH C(CH2CH2CH3)CH3)NNa]. There also appears to be a peak

Na(1)−N(1) bond length of 2.489(3) Å is typical of sodium amides.4 However, the low coordination environment means the Na cation forms additional electrostatic interactions with neighboring C atoms (Na(1)−C(7), 2.787(3) Å; Na(1)−C(8), 3.117(3) Å; Na(1)−C(9), 2.795(3) Å) located within electron-rich unsaturated moieties, a common occurrence in these types of group 1 complexes.1,4a Solution studies in C6D6 reveal that the integrity of the amido species is retained in solution. There is a clear change from the expected 1-azaallyl species to the new complex 1 evidenced by two new singlets at 3.75 and 3.57 ppm replacing the quartet at 3.57 ppm and doublet at 1.14 ppm. These vinylic protons are shifted further downfield in comparison with other vinylic protons of aza-enolate species due to the additional azaallyl system in this complex deshielding these protons. There is also a notable singlet at 6.72 ppm, assigned to the B

DOI: 10.1021/acs.organomet.5b00979 Organometallics XXXX, XXX, XXX−XXX

Organometallics

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Communication

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.organomet.5b00979. Table of crystallographic data for compound 1 (CCDC 1439491), NMR spectra, and GC-headspace and other experimental details (PDF) Crystallographic data for compound 1 (CIF)

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Figure 4. Sections of chromatographs of (a) standard C1−C6 straight chain alkane mix, (b) propene standard, and (c) reaction sample from the Schlenk.

AUTHOR INFORMATION

Corresponding Author

*E-mail for P.C.A.: [email protected]. Notes

that correlates with the C1 standard and therefore can be assumed to be methane. The only reasonable source of methane would be from a metal-induced C−C bond cleavage to eliminate methane, a process we have previously reported with a related chiral amine.1a Considering the small amount of methane detected, it can be assumed it is resulting from a minor side reaction in the overall complex reaction mixture. We are uncertain as to why this decomposition occurs; however, we have confirmed the formation of propene. It is well-known that sodium amides can be used for the initiation of the polymerization of vinyl monomers.7 Thus, one possibility is that the carbanion tautomer of sodium 1-azaallylamide (Scheme 3) undergoes an addition in the same manner as

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank the Australian Research Council (DP110104006) and Monash University for financial support. We thank Dr Adam Kessler (Monash) for help with the GC-headspace experiments.

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REFERENCES

(1) (a) Andrews, P. C.; Blair, V. L.; Border, E. C.; Peatt, A. C.; MacLellan, J. G.; Thompson, C. D. Organometallics 2013, 32, 7509. (b) Andrews, P. C.; Blair, V. L.; Koutsaplis, M.; Thompson, C. D. Organometallics 2012, 31, 8135. (2) (a) Andrews, P. C.; Armstrong, D. R.; Clegg, W.; MacGregor, M.; Mulvey, R. E. J. Chem. Soc., Chem. Commun. 1991, 497. (b) Andrews, P. C.; Koutsaplis, M.; Robertson, E. G. Organometallics 2009, 28, 1697. (c) Andrews, P. C.; Calleja, S. M.; Maguire, M. J. Chem. Soc., Dalton Trans. 2002, 3640. (3) (a) Candela-Lena, J. I.; Davies, S. G.; Roberts, P. M.; Roux, B.; Russell, A. J.; Sánchez-Fernández, E. M.; Smith, A. D. Tetrahedron: Asymmetry 2006, 17, 1135. (b) Davies, S. G.; Fenwick, D. R.; Ichihara, O. Tetrahedron: Asymmetry 1997, 8, 3387. (c) Davies, S. G.; Smith, A. D.; Price, P. D. Tetrahedron: Asymmetry 2005, 16, 2833. (d) Davies, S. G.; Garrido, N. M.; McGee, P. A.; Shilvock, J. P. J. Chem. Soc., Perkin Trans. 1 1999, 3105. (e) Davies, S. G.; Fenwick, D. R. Chem. Commun. 1997, 565. (f) Davies, S. G.; Fenwick, D. R. J. Chem. Soc., Chem. Commun. 1995, 1109. (4) (a) 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. (b) Andrews, P. C.; Barnett, N. D. R.; Mulvey, R. E.; Clegg, W.; O’Neil, P. A.; Barr, D.; Cowton, L.; Dawson, A. J.; Wakefield, B. J. J. Organomet. Chem. 1996, 518, 85. (c) Andrews, P. C.; Duggan, P. J.; Fallon, G. D.; McCarthy, T. D.; Peatt, A. C. J. Chem. Soc., Dalton Trans. 2000, 2505. (d) Andrews, P. C.; Calleja, S. M.; Maguire, M.; Nichols, P. J. Eur. J. Inorg. Chem. 2002, 2002, 1583. (5) (a) Gokel, G. W. Chem. Commun. 2003, 2847. (b) Andrews, P. C.; Calleja, S. M.; Maguire, M. J. Organomet. Chem. 2005, 690, 4343. (6) Andrews, P. C.; Duggan, P. J.; Maguire, M.; Nichols, P. J. Chem. Commun. 2001, 53. (7) (a) Goode, W. E.; Snyder, W. H.; Fettes, R. C. J. Polym. Sci. 1960, 42, 367. (b) Sanderson, J. J.; Hauser, C. R. J. Am. Chem. Soc. 1949, 71, 1595. (8) Brown, D. W.; Lindquist, M.; Mahon, M. F.; Malm, B.; Nilsson, G. N.; Ninan, A.; Sainsbury, M.; Westerlund, C. J. Chem. Soc., Perkin Trans. 1 1997, 2337.

Scheme 3. Resonance Structure of the Sodium 1Azaallylamide and Subsequent Addition to Propene

the aforementioned polymerization process. This allows for the addition of the sodium amide to the terminus of propene to give the n-propyl species as seen in the solid-state structure, as opposed to a typical 1,2-addition of propene resulting in the addition of an isopropyl group. However, a second possibility is that it is a radical process, well-known for generating the more highly stabilized radical on the more substituted central carbon atom and supporting the observed regiochemistry.8 When this is followed by a hydride shift, β-hydride elimination of sodium hydride and subsequent deprotonation affording H2(g), this gives both the aza-enolate and aza-allyl moieties required for the species [(PhCCH2)(CHC(CH2CH2CH3)CH3)NNa· THF]∞ (1). The rate-determining step must be the decomposition of the sodium 1-azaallylamide to produce the enamide and propene, as the propene must react quite quickly or a larger amount would have been detected in the headspace as well as observation of its formation in the NMR spectra. It would appear that the addition product forms relatively quickly; however, it takes a period of 3 days to reach a maximum yield. C

DOI: 10.1021/acs.organomet.5b00979 Organometallics XXXX, XXX, XXX−XXX