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Volumn 15, Issue 32, 2009, Pages 7958-7979

On the dichotomic reactivity of lithiated styrene oxide: A computational and multinuclear magnetic resonance investigation

Author keywords

Carbenoids; Density functional calculations; Lithiation; NMR spectroscopy; Oxygen heterocycles

Indexed keywords

CARBENOIDS; DENSITY FUNCTIONAL CALCULATIONS; LITHIATION; NMR SPECTROSCOPY; OXYGEN HETEROCYCLES;

EID: 68349098693     PISSN: 09476539     EISSN: 15213765     Source Type: Journal    
DOI: 10.1002/chem.200900834     Document Type: Article
Times cited : (37)

References (139)
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    • A relative organolithium stability scale derived from tin-lithium exchange equilibria has been reported for both a-oxy- and a-aminoorganolithium compounds: P. Grana, M. R. Paleo, F. J. Sardina, J. Am. Chem. Soc. 2002, 124, 12511-12514
    • A relative organolithium stability scale derived from tin-lithium exchange equilibria has been reported for both a-oxy- and a-aminoorganolithium compounds: P. Grana, M. R. Paleo, F. J. Sardina, J. Am. Chem. Soc. 2002, 124, 12511-12514,
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    • and references therein; see also: K. Sung, Can. J. Chem. 2000, 78, 562-567.
    • and references therein; see also: K. Sung, Can. J. Chem. 2000, 78, 562-567.
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    • R. Luisi, V. Capriati, L. Degennaro S. Florio, Org. Lett. 2003, 5, 27232726;
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    • Lithiated styrene oxide 2 showed a lifetime in a macro batch system, below -9O°C in THF and in the presence of three equivalents of TMEDA, of only 30 min before decomposition takes place, whereas lithiated 3-methyl-2-phenyloxiranes 3, under the same conditions, proved to be chemically stable for at least 2 h.
    • Lithiated styrene oxide 2 showed a lifetime in a macro batch system, below -9O°C in THF and in the presence of three equivalents of TMEDA, of only 30 min before decomposition takes place, whereas lithiated 3-methyl-2-phenyloxiranes 3, under the same conditions, proved to be chemically stable for at least 2 h.
  • 50
    • 33645404473 scopus 로고    scopus 로고
    • In the present paper the adjective carbenoid is used to describe any carbene-like reactivity of an oxiranyllithium as it was introduced for the first time by: L. Friedman, H. Shechter, J. Am. Chem. Soc. 1959, 81, 5512-5513;
    • In the present paper the adjective "carbenoid" is used to describe any carbene-like reactivity of an oxiranyllithium as it was introduced for the first time by: L. Friedman, H. Shechter, J. Am. Chem. Soc. 1959, 81, 5512-5513;
  • 51
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    • according to G. L. Closs, R. A. Moss, J. Am. Chem. Soc. 1964, 86, 4042-4053, we use the noun carbenoid, instead, with reference to an oxiranyllithium exhibiting an ambiphilic behaviour, that is a nucleophilic as well as an electrophilic reactivity according to the employed experimental conditions.
    • according to G. L. Closs, R. A. Moss, J. Am. Chem. Soc. 1964, 86, 4042-4053, we use the noun "carbenoid", instead, with reference to an oxiranyllithium exhibiting an ambiphilic behaviour, that is a nucleophilic as well as an electrophilic reactivity according to the employed experimental conditions.
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    • As a validation of the choice of basis set, 2 was also optimised at the B3LYP/6-311, G(d,p) level of theory. The average of the differences in bond distances at the two different levels was found to be very small 0.003 Å, see also Table S3 in the Supporting Information, Thus, a geometry optimisation using the smaller basis set seems to be sufficient
    • As a validation of the choice of basis set, 2 was also optimised at the B3LYP/6-311 + G(d,p) level of theory. The average of the differences in bond distances at the two different levels was found to be very small (0.003 Å, see also Table S3 in the Supporting Information). Thus, a geometry optimisation using the smaller basis set seems to be sufficient.
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    • A number of NMR studies on several a-benzyl carbanions have shown that the signal for the ipso-carbon atom is low-field shifted with respect to the corresponding position in the neutral precursor, showing a decrease of π- electron density and, therefore, a net positive charge in the anionic system: a A. Abbotto, S. Bradamante, A. Facchetti, G. A. Pagani, J. Org. Chem. 1999, 64, 6756-6763;
    • A number of NMR studies on several a-benzyl carbanions have shown that the signal for the ipso-carbon atom is low-field shifted with respect to the corresponding position in the neutral precursor, showing a decrease of π- electron density and, therefore, a net positive charge in the anionic system: a) A. Abbotto, S. Bradamante, A. Facchetti, G. A. Pagani, J. Org. Chem. 1999, 64, 6756-6763;
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    • This value is obtained by dividing the total negative charge of the phenyl ring by that of the total organic residue (Ph+Cα +C β, Ooxirane,+corresponding hydrogen atoms, the latter value (e.g, 0.91 in the tri-solvated species) can also be obtained by subtracting from the charge of the system without molecules of solvent, 0.06) the charge on lithium, 0.85
    • oxirane,+corresponding hydrogen atoms); the latter value (e.g., -0.91 in the tri-solvated species) can also be obtained by subtracting from the charge of the system without molecules of solvent (-0.06) the charge on lithium (+0.85).
  • 64
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    • A.-M. Sapse, D. C. Jain, K. Raghavachari in Lithium Chemistry: A Theoretical and Experimental Overview (Eds.: A.-M. Sapse, P. von R. Schleyer), Wiley, New York, 1995, pp. 45-65.
    • A.-M. Sapse, D. C. Jain, K. Raghavachari in Lithium Chemistry: A Theoretical and Experimental Overview (Eds.: A.-M. Sapse, P. von R. Schleyer), Wiley, New York, 1995, pp. 45-65.
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    • In the free lithium salt of the dimer 4 c, the positive charge on lithium is reduced, 0.87) compared to that found in the monomer 2 a, 0.91, Simultaneously, the negative charge in 4 c is more localised, 0.33) on Cα compared to that observed in the monomer 2a, 0.30, while the negative charge on the oxirane oxygen and C β atom is reduced see the Supporting Information
    • β atom is reduced (see the Supporting Information).
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    • As an estimate of the energy difference between structures with broken and closed C-Li bonds, the C-Li-O core of the solvated dimers were frozen and the solvent removed. Optimisation of the remaining atoms was performed and the energy compared to the fully relaxed dimers 4a-d. It was found that the fully relaxed structures were 3-4 kcal mol-1 more stable. An additional energy analysis was performed, in which the C-Li-O core of the unsolvated dimers 4a-d were frozen and the solvent and the remaining atoms were optimised. These structures were now found to be 4-8 kcal mol -1 higher in energy than the fully optimised, 4a(thf) 2, 4d(thf)2, The energy cost of 3-4 kcal mol-1to elongate the C-Li bonds is thus compensated by the better THF solvation for such structures
    • -1to elongate the C-Li bonds is thus compensated by the better THF solvation for such structures.
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    • 8]THF as the solvent system of choice.
    • 8]THF as the solvent system of choice.
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    • It has been reported R. A. Gossage, J. T. B. H. Jastrzebski, C. van Koten, Angew. Chem. 2005, 117, 1472-1478;
    • It has been reported (R. A. Gossage, J. T. B. H. Jastrzebski, C. van Koten, Angew. Chem. 2005, 117, 1472-1478;
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    • Angew. Chem. Int. Ed. 2005, 44, 1448-1454 that when a stable heteroaggregate, kinetically inert to further reaction with the starting material, forms during a metalation reaction it generally tends to lower the yield of the final adduct after quenching of the reaction mixture with an electrophilic source ; this drawback cannot be overcome even in the presence of an excess of the same organolithium. NMR and experimental data (ref. [14]) showed that just 1.2 equivalents of sBuLi proved to be sufficient to promote a complete consumption of the starting oxirane providing at the same time an almost quantitative α-deuteration of lithiated styrene oxide.
    • Angew. Chem. Int. Ed. 2005, 44, 1448-1454) that when a "stable" heteroaggregate, kinetically inert to further reaction with the starting material, forms during a metalation reaction it generally tends to lower the yield of the final adduct after "quenching" of the reaction mixture with an electrophilic source ; this drawback cannot be overcome even in the presence of an excess of the same organolithium. NMR and experimental data (ref. [14]) showed that just 1.2 equivalents of sBuLi proved to be sufficient to promote a complete consumption of the starting oxirane providing at the same time an almost quantitative α-deuteration of lithiated styrene oxide.
  • 81
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    • For leading references to structural studies of RLi/R'OLi mixed aggregates, see: a reference [28]
    • For leading references to structural studies of RLi/R'OLi mixed aggregates, see: a) reference [28]
  • 86
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    • Surprinsingly, a literature search failed to reveal any systematic NMR spectroscopic study of mixed aggregates derived from sBuOLi and sBuLi in polar solvents. Indeed, very recently, only computational studies of mixed nBuLi/Li-iV-methyl-2-pyrrolidine methoxide aggregates in both hexane and THF (H. K. Khartabil, P. C. Gros, Y. Fort, M. F. Ruiz-Lopez, J. Org. Chem. 2008, 73, 9393-9402)
    • Surprinsingly, a literature search failed to reveal any systematic NMR spectroscopic study of mixed aggregates derived from sBuOLi and sBuLi in polar solvents. Indeed, very recently, only computational studies of mixed nBuLi/Li-iV-methyl-2-pyrrolidine methoxide aggregates in both hexane and THF (H. K. Khartabil, P. C. Gros, Y. Fort, M. F. Ruiz-Lopez, J. Org. Chem. 2008, 73, 9393-9402)
  • 87
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    • and of sBuLi with chiral lithium alkoxides in THF (L. M. Pratt, O. Kwon, T. C. Ho, N.V. Nguyen, Tetrahedron 2008, 64, 5314-5321) have been reported.
    • and of sBuLi with chiral lithium alkoxides in THF (L. M. Pratt, O. Kwon, T. C. Ho, N.V. Nguyen, Tetrahedron 2008, 64, 5314-5321) have been reported.
  • 88
    • 68349091932 scopus 로고    scopus 로고
    • Further investigations on sBuLi/sBuOLi mixtures are underway and will be reported in due course
    • Further investigations on sBuLi/sBuOLi mixtures are underway and will be reported in due course.
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    • Angew. Chem. Int. Ed. 2004, 43, 2206-2225;
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  • 96
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    • remarkably, the first crystalline Lewis base adduct of sBuLi (as a monomer) with a chiral diamine such as (R,R)-N,N,N',N'-tetramethyL-l,2-diamino cyclohexane has recently been published: C. Strohmann, V. H. Gessner, J. Am. Chem. Soc. 2007, 129, 8952-8953;
    • d) remarkably, the first crystalline Lewis base adduct of sBuLi (as a monomer) with a chiral diamine such as (R,R)-N,N,N',N'-tetramethyL-l,2-diamino cyclohexane has recently been published: C. Strohmann, V. H. Gessner, J. Am. Chem. Soc. 2007, 129, 8952-8953;
  • 97
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    • in this complex, the lithium centre appears barely shielded by the ligand and so available to offer a free coordination site for the formation of intermediates in accordance to the CIPE mechanism, e F. Affortunato, S. Florio, R. Luisi, B. Musio, J. Org. Chem. 2008, 73, 9214-9220.
    • in this complex, the lithium centre appears barely shielded by the ligand and so available to offer a free coordination site for the formation of intermediates in accordance to the CIPE mechanism, e) F. Affortunato, S. Florio, R. Luisi, B. Musio, J. Org. Chem. 2008, 73, 9214-9220.
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    • 13C-enriched styrene oxide was reacted with sBuLi.
    • 13C-enriched styrene oxide was reacted with sBuLi.
  • 103
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    • 13C-COSY); 74.7 with 59.2; 73.0 with 60.3 ppm.
    • 13C-COSY); 74.7 with 59.2; 73.0 with 60.3 ppm.
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    • S. Schade, G. Boche, J. Organomet. Chem. 1998, 550, 381-395;
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    • For an outstanding review on the role of TMEDA in organolithium chemistry, see
    • For an outstanding review on the role of TMEDA in organolithium chemistry, see: D. B. Collum, Acc. Chem. Res. 1992, 25, 448-454.
    • (1992) Acc. Chem. Res , vol.25 , pp. 448-454
    • Collum, D.B.1
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    • In principle, with our special triple resonance probehead (with the inner coil selectively tuned to 13C frequency and the outer coil tunable between the frequencies of 7Li (see the Experimental Section) such a two-dimensional NMR shift correlation, based on scalar spin-spin coupling, may be performed. However, one of the main drawbacks to take into account in setting up this type of experiment is related to the fast relaxation of 7Li which poses problems for the line-width of the 7Li resonances; in fact, 7Li is a nucleus with a moderate quadrupolar moment exhibiting short longitudinal (T1) and transversal (T2) relaxation times. As a consequence, the transverse magnetisation arising from broad signals may be completely lost during the preparation delays of the HMQC pulse sequence due to relaxation through T2, so that no correlations will be finally observed. This effect will be a
    • 2.
  • 114
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    • e = 1.17 h. However, the new 2D spectrum did not show additional cross-peaks.
    • e = 1.17 h. However, the new 2D spectrum did not show additional cross-peaks.
  • 115
    • 68349106196 scopus 로고    scopus 로고
    • Even if reductive alkylation reactions compete to some extent soon after the lithiation process, most probably with concomitant elimination of Li 2O as byproduct, it seems improbable that a lithium peak may be associated to such a salt because of its complete insolubility in THF. Commercial Li2O, indeed, proved to be completely insoluble in THF. Moreover, addition of water to a suspension of Li2O in THF leads to the dissolution of this salt and a peak at <3, 0.57 ppm (referenced externally to 0.3 M LiCl in [D4]MeOH) emerges in 7LiNMR spectrum. This peak most probably refers to LiOH because when a solution was prepared from commercial LiOH in THF/H20, a similar chemical shift value was observed. Therefore, the peak at <3, 0.57 ppm might in principle be assigned to LiOH or to alkoxides, as discussed in the main body of the paper
    • 20, a similar chemical shift value was observed. Therefore, the peak at <3 = 0.57 ppm might in principle be assigned to LiOH or to alkoxides, as discussed in the main body of the paper.
  • 116
    • 68349108919 scopus 로고    scopus 로고
    • Concentration-dependent studies were frustrated by the very high reactivity of 2. The only successful and feasible dilutions (in order to obtain homogeneous samples to be compared) could only be performed directly in the NMR tube by adding solvent. Any attempt to pull a portion of the sample containing the oxiranyllithium up into a syringe in order to dilute it more, led to a considerable quenching and decomposition of the anion. That is why the precious sample of optically active and doubly enriched styrene oxide was only diluted (in the NMR tube) up to a factor of 2. Isolated samples of racemic lithiated styrene oxide, prepared at higher dilution up to 0.03 M, showed that the various aggregates continued to compete with the monomeric species; however, they were always in slow equilibration on the NMR timescale
    • Concentration-dependent studies were frustrated by the very high reactivity of 2. The only successful and feasible dilutions (in order to obtain "homogeneous" samples to be compared) could only be performed directly in the NMR tube by adding solvent. Any attempt to pull a portion of the sample containing the oxiranyllithium up into a syringe in order to dilute it more, led to a considerable quenching and decomposition of the anion. That is why the "precious" sample of optically active and doubly enriched styrene oxide was only diluted (in the NMR tube) up to a factor of 2. Isolated samples of racemic lithiated styrene oxide, prepared at higher dilution (up to 0.03 M), showed that the various aggregates continued to compete with the monomeric species; however, they were always in slow equilibration on the NMR timescale.
  • 118
    • 68349086145 scopus 로고    scopus 로고
    • Similarly, a dimeric triple ion has recently been found to interconvert slowly on the NMR timescale with both monomeric contact and solvent-separated ion pairs; see reference [50b].
    • Similarly, a dimeric triple ion has recently been found to interconvert slowly on the NMR timescale with both monomeric contact and solvent-separated ion pairs; see reference [50b].
  • 119
    • 0000339985 scopus 로고    scopus 로고
    • An interesting case of diastereomeric ether solvates under slow exchange in dimethyl ether solution, in which lithium behaves as a centre of chirality, has been reported: H.J. Reich, K.J. Kulicke, J. Am. Chem. Soc. 1996, 118, 273-274
    • An interesting case of diastereomeric ether solvates under slow exchange in dimethyl ether solution, in which lithium behaves as a centre of chirality, has been reported: H.J. Reich, K.J. Kulicke, J. Am. Chem. Soc. 1996, 118, 273-274.
  • 120
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    • A case of a dimeric TMEDA-complexed 2-lithiobenzofuran, in which a single C-O bond is Li-bridged and a single lithium adopts a pentacoordinate structure (the other one being tetracoordinate), has been reported: S. Harder, J. Boersma, L. Brandsma, J. A. Kanters, W. Bauer, R. Pi, P. von R. Schleyer, H. Schöllhorn, U. Thewalt, Organometallics 1989, 8, 1688-1696.
    • A case of a dimeric TMEDA-complexed 2-lithiobenzofuran, in which a single C-O bond is Li-bridged and a single lithium adopts a pentacoordinate structure (the other one being tetracoordinate), has been reported: S. Harder, J. Boersma, L. Brandsma, J. A. Kanters, W. Bauer, R. Pi, P. von R. Schleyer, H. Schöllhorn, U. Thewalt, Organometallics 1989, 8, 1688-1696.
  • 121
    • 68349103606 scopus 로고    scopus 로고
    • 4 tetramer, while the remaining two generate a second tetrameric aggregate: K. Sorger, W. Bauer,
    • 4 tetramer, while the remaining two generate a second tetrameric aggregate: K. Sorger, W. Bauer,
  • 124
    • 68349095582 scopus 로고    scopus 로고
    • A recent computational investigation performed on lithiated ethylene oxide by Pratt suggested that this type of oxiranyllithium might indeed exist as a mixture of two six-centre diastereomeric dimers and three diastereomeric tetramers, the latter characterised by an higher distortion of their geometry compared to that of alkyllithium tetramers just owing to lithium chelation by the oxirane oxygen atoms: L. M. Pratt, B. Ramachandran, J. Org. Chem. 2005, 70, 72387242
    • A recent computational investigation performed on lithiated ethylene oxide by Pratt suggested that this type of oxiranyllithium might indeed exist as a mixture of two six-centre diastereomeric dimers and three diastereomeric tetramers, the latter characterised by an higher distortion of their geometry compared to that of alkyllithium tetramers just owing to lithium chelation by the oxirane oxygen atoms: L. M. Pratt, B. Ramachandran, J. Org. Chem. 2005, 70, 72387242.
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    • W. H. Glaze, J. Lin, E. G. Felton, J. Org. Chem. 1965, 30, 12581259.
    • W. H. Glaze, J. Lin, E. G. Felton, J. Org. Chem. 1965, 30, 12581259.
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    • In Table 1 is shown the calculated chemical shieldings for the free and solvated monomer applying two different basis sets. It is observed that the more flexible basis set, including two d-functions on heavy atoms, gives a slightly better agreement with the experimentally observed chemical shifts. However, the small difference between the methods encouraged us to use the smaller basis set in the studies of the larger aggregates involving the dimer 4. The chemical shift dependence on the level of geometry optimisation was also examined for compound 2. Only small differences could be observed, which indicates that the smaller basis set (6-31, Gd) adequately represents compound 2. See also B. J. Lynch, Y. Zhao, D. G. Truhlar, J. Phys. Chem. A 2003, 107, 1384-1388
    • In Table 1 is shown the calculated chemical shieldings for the free and solvated monomer applying two different basis sets. It is observed that the more flexible basis set, including two d-functions on heavy atoms, gives a slightly better agreement with the experimentally observed chemical shifts. However, the small difference between the methods encouraged us to use the smaller basis set in the studies of the larger aggregates involving the dimer 4. The chemical shift dependence on the level of geometry optimisation was also examined for compound 2. Only small differences could be observed, which indicates that the smaller basis set (6-31 + Gd) adequately represents compound 2. See also B. J. Lynch, Y. Zhao, D. G. Truhlar, J. Phys. Chem. A 2003, 107, 1384-1388.
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    • 2O; see: H. Günther, J. Braz. Chem. Soc. 1999, 10, 241-262.
    • (1999) J. Braz. Chem. Soc , vol.10 , pp. 241-262
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