Crystal structures of the chiral diamine (R,R)-TMCDA with the commonly used alkyllithium bases methyllithium, iso-propyllithium, and sec-butyllithium

Article abstract of DOI:10.1021/ja072970t

(R,R)-N,N,N′,N′-Tetramethyl-1,2-diaminocyclohexane [(R,R)-TMCDA] coordinated alkyllithiums crystallize as dimeric [MeLi·(R,R)-TMCDA]₂ and [i-PrLi·(R,R)-TMCDA]₂ and monomeric s-BuLi·(R,R)-TMCDA. s-BuLi·(R,R)-TMCDA is the first structu

Full text of DOI:10.1021/ja072970t

Published on Web 06/27/2007
Crystal Structures of the Chiral Diamine (R,R)-TMCDA with the Commonly
Used Alkyllithium Bases Methyllithium, iso-Propyllithium, and sec-Butyllithium
Carsten Strohmann* and Viktoria H. Gessner
Institut fu¨r Anorganische Chemie, UniVersita¨t Wu¨rzburg, Am Hubland, 97074 Wu¨rzburg, Germany
Received April 27, 2007; E-mail: mail@carsten-strohmann.de
Combinations of organolithium compounds and chiral diamines,
like (-)-sparteine and its derivatives as well as (R,R)-N,N,N′,N′-
tetramethyl-1,2-diaminocyclohexane [(R,R)-TMCDA], are widely
utilized in asymmetric synthesis.1,2 Whereas sec-butyllithium and
(-)-sparteine have proven to be a powerful reagent for asymmetric
deprotonation, (R,R)-TMCDA and its (S,S)-enantiomer turns out
to be more reactive but with modest enantioselectivity.3 For
determination of the structure/reactivity relationships of chiral
alkyllithium bases the characterization of the solid-state structures
is of great importance. Although the first (-)-sparteine coordinated
Figure 1. Structures of lithium alkyls with coordinating (R,R)-TMCDA.
alkyllithium structures have been uncovered, no structures with sec-
butyllithium, the most frequently used lithium base in asymmetric
synthesis, have been determined so far.4 Although NMR studies
conducted by Collum et al. have determined that n-BuLi and (R,R)-
TMCDA form a dimer in solution, solid-state structures of this C2-
symmetric diamine complexed with alkyllithium bases are not
known so far.5 Here, we present the first molecular structures of
(R,R)-TMCDA with the alkyllithium bases MeLi (1), i-PrLi (2) and
s-BuLi (3) (Figure 1). Monomer 3 is the first Lewis base-
coordinated adduct of s-BuLi, which is highly reactive owing to
Figure 2. Molecular structure of [MeLi‚(R,R)-TMCDA]2 (1) in the crystal.
Selected bond lengths (Å) and angles (deg) (some hydrogens omitted): C1-
Li1, 2.252(7); C1-Li2, 2.277(7); C2-Li1, 2.214(7); C2-Li2, 2.219(7);
Li1-N1, 2.168(7); Li1-N2, 2.184(7); Li2-N3, 2.176(6); Li2-N4, 2.179-
(7); Li1-C1-Li2, 64.4(2); Li1-C2-Li2, 65.9(2); C2-Li1-C1, 114.0(3);
C2-Li2-C1, 112.8(3).
its monomeric structure.
The dimeric adduct [MeLi‚(R,R)-TMCDA]2 (1) crystallizes from
pentane/diethylether in the orthorhombic crystal system, space group
P212121 (Figure 2).6 The central structural motif of this aggregate
is a central four-membered Li-C-Li-C ring, as is typical for
dimeric alkyllithium compounds.7 The sum of angles of 357.1° in
this ring shows that there is a slight deformation toward an envelope
conformation. The Li-C distances in the central four-membered
ring range from 2.214(7) to 2.277(7) Å, and the Li-N distances
range from 2.168(7) to 2.184(7) Å, which are comparable with the
two other known dimeric MeLi adducts.4c,d Altogether, the lithium
centers have four contacts each: two to the nitrogen centers of the
(R,R)-TMCDA ligands and two to the methyl units. Besides the
(-)-sparteine and one of its (()-surrogate coordinated MeLi, 1 is
the only known dimeric aggregate of methyllithium.4c,d Other
commonly used amines, diamines, or ethers are not able to break
the tetrameric aggregate of methyllithium.7-9
The structure of [i-PrLi‚(R,R)-TMCDA]2 (2), which crystallizes
from pentane in the monoclinic crystal system, space group P21, is
analogous to that of compound 1 (two dimeric molecules were
detected in the asymmetric unit; one of them is shown in Figure
3). The central four-membered Li-C-Li-C ring also shows a
slight deformation toward an envelope conformation (sum of ring
angles 357.1° and 357.1°) but with a remarkable increase in the
Li-C and Li-N distances. The distances between the lithium
centers and the carbon centers range from 2.206(6) to 2.332(6) Å
and the Li-N distances range from 2.219(5) to 2.256(6) Å.
Compound 2 is the first dimeric adduct of i-PrLi.4b,10
Figure 3. Molecular structure of [i-PrLi‚(R,R)-TMCDA]2 (2) in the crystal.
Selected bond lengths (Å) and angles (deg) (some hydrogens omitted):
C11-Li2, 2.234(11), C11-Li1, 2.332(6); C14-Li1, 2.206(6); C14-Li2,
2.321(6); Li1-N1, 2.240(6); Li1-N2, 2.219(5); Li2-N3, 2.256(6); Li2-
N4, 2.229(6); Li2-C11-Li1, 66.0(2); Li1-C14-Li, 2 66.7(2); C14-Li1-
C11, 109.2(2); C11-Li2-C14, 108.6(2)
indicate a destabilization of the dimeric structure.7 This tendency
is confirmed by computational studies: at the B3LYP/6-31+G(d)
level we find a decrease in the energy required for breaking the
dimer into two monomers. Whereas cleavage of [MeLi‚(R,R)-
TMCDA]2 needs 78.5 kJ‚mol-1 [i-PrLi‚(R,R)-TMCDA]2 requires
,
28.5 kJ‚mol-1, and the fictitious [s-BuLi‚(R,R)-TMCDA]2 requires
merely 17.8 kJ‚mol-1. Because of entropic effects the monomeric
s-BuLi‚(R,R)-TMCDA (3) can be isolated from pentane/cyclohex-
ane. Considered together, the compounds presented in Figure 1
The significantly lengthened Li-C and Li-N distances in 2
compared with similar compounds are due to steric interactions
between the methyl groups of the i-Pr chain and the ligand and
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J. AM. CHEM. SOC. 2007, 129, 8952-8953
10.1021/ja072970t CCC: $37.00 © 2007 American Chemical Society

C O M M U N I C A T I O N S
In summary, the first (R,R)-TMCDA-coordinated organolithium
adducts show a clear influence of the size of the organolithium on
the type of aggregation. In addition to the mechanism of aromatic
deprotonation proposed by Collum et al. via triple ions or open
dimers, the highly reactive monomeric s-BuLi‚(R,R)-TMCDA may
react by interactions involving the open lithium center of a
monomeric species.13 We are currently investigating structure/
reactivity patterns based on the observed molecular structures.
Acknowledgment. We are grateful to the Deutsche For-
schungsgemeinschaft and The Fonds der Chemischen Industrie for
support.
Figure 4. Molecular structure of [s-BuLi‚(R,R)-TMCDA]2 (3) in the crystal
(disordered sec-Butyl). Selected bond lengths (Å) and angles (deg) (some
hydrogens omitted): C11B-Li, 2.118(12); C11A-Li, 2.104(11); Li-N1,
2.054(5); Li-N2, 2.076(6); N1-Li-N2, 86.71(17); N1-Li-C11A, 122.0-
(4); N2-Li-C11A, 146.1(4); N1-Li-C11B, 144.0(5); N2-Li-C11B,
122.5(4).
Supporting Information Available: Crystallographic (CIF), ex-
perimental, and computational data. This material is available free of
charge via the Internet at http://pubs.acs.org.
References
(1) For reviews, see: (a) Hoppe, D.; Hense, T. Angew. Chem., Int. Ed. Engl.
1997, 36, 2282. (b) Beak, P.; Basu, A.; Gallagher, D. J.; Park, Y. S.;
Thayumanavan, S. Acc. Chem. Res. 1996, 29, 2283.
(2) For examples: (a) Hoppe, D.; Hintze, F.; Tebben, P. Angew. Chem., Int.
Ed. Engl. 1990, 29, 1422. (b) Kerrick, S. T.; Beak, P. J. Am. Chem. Soc.
1991, 113, 9708. (c) Whisler, M. C.; Beak, P. J. Org. Chem. 2003, 68,
1207. (d) Coldham, I.; Copley, R. C. B.; Haxell, T. F. N.; Howard, S.
Org. Biomol. Chem. 2003, 1, 1532. (e) Metallinos, C.; Szillat, H.; Taylor,
N. J.; Snieckus, V. AdV. Synth. Catal. 2003, 345, 370.
(3) (a) Dearden, M. J.; Firkin, C. R.; Hermet, R.; O’ Brian, P. J. Am. Chem.
Soc. 2002, 124, 11870. (b) McGrath, M. J.; Bilke, J. L.; O’Brien, P. Chem.
Commun. 2006, 2607. (c) Wu¨rthwein, E.-U.; Behrens, K.; Hoppe, D.
Chem. Eur. J. 1999, 5, 3459. (d) Wiberg, K. B.; Bailey, W. F. Tetrahedron
Lett. 2000, 41, 9365.
(4) (a) Strohmann, C.; Seibel, T.; Strohfeldt, K. Angew. Chem., Int. Ed. 2003,
42, 4531. (b) Strohmann, C.; Strohfeldt, K.; Schildbach, D. J. Am. Chem.
Soc. 2003, 125, 13672. (c) Vestergren, M.; Eriksson, J.; Hilmersson, G.;
Håkansson, M. J. Organomet. Chem. 2003, 682, 172. (d) Strohmann, C.;
Strohfeldt, K.; Schildbach, D.; McGrath, M. J.; O’ Brien, P. Organome-
tallics 2004, 23, 5389. (e) Strohmann, C.; Dilsky, S.; Strohfeldt, K.
Organometallics 2006, 25, 41. (f) Strohmann, C.; Da¨schlein, C.; Auer,
D. J. Am. Chem. Soc. 2006, 128, 704.
(5) (a) Hoffmann, D.; Collum, D. B. J. Am. Chem. Soc. 1998, 120, 5810. (b)
Rutherford, J. L.; Hoffmann, D.; Collum, D. B. J. Am. Chem. Soc. 2002,
124, 264.
(6) X-ray crystallography data for 1, 2, and 3 have been deposited with the
Cambridge Crystallographic Data Center as supplementary publication
Nos. CCDC 644635 (1), CCDC 644636 (2), and CCDC 644637 (3).
Figure 5. Molecular structure (crystal) (a), space-filling model (crystal)
(b) and Connolly surface mapped with electrostatic potential [B3LYP/6-
31+G(d) probe radius, 1.2 Å] of compound (S)-3.
clearly demonstrate the strong effect of the size of the alkyllithium
compound on the type of aggregation.
The monomeric compound 3 crystallizes in the orthorhombic
crystal system, space group P212121. In the crystal disorder of both
possible diastereomers, [(R)-s-BuLi‚(R,R)-TMCDA] and [(S)-s-
BuLi‚(R,R)-TMCDA], in a 55:45 ratio was observed and refined
using a split model (both diastereomers are shown in Figure 4).
Calculations at the B3LYP/6-31+G(d) level showed a marginal
energetic difference of 0.7 kJ‚mol-1 between the two diastereomers,
further confirming the coexistence of both in 3. The Li-C distances
[2.118(12) and 2.104(11) Å] and Li-N distances [2.054(5) to 2.076-
(6) Å] are typically shorter than in comparable dimeric compounds.7
Monomer 3 is the first Lewis base adduct of sec-butyllithium with
a known crystal structure and a rare example of a monomeric
saturated alkyllithium compound.4a,11 As compounds 2 and 3 show,
the oft-suggested structural analogy between i-PrLi and s-BuLi is
not in any case appropriate.
(7) Stey, T.; Stalke, D. In The Chemistry of Organolithium Compounds;
Rappoport, Z., Marek, I., Eds; Wiley: Chichester, U.K., 2004; Chapter
1.
(8) (a) Weiss, E.; Lambertsen, T.; Schubert, B.; Cockcroft, J. K.; Wiedenmann,
A. Chem. Ber. 1990, 79, 123. (b) Lucken, E. A. C.; Weiss, E. J.
Organomet. Chem. 1965, 2, 197. (c) Ko¨stner, H.; Thoennes, D.; Weiss,
E. J. Organomet. Chem. 1978, 160, 1. (d) Ogle, C. A.; Huckabee, B. K.;
Johnson, H. C., IV; Sims, P. F.; Winslow, S. D.; Pinkerton, A. A.
Organometallics 1993, 12, 1960.
(9) Walfort, B.; Lameyer, L.; Weiss, W.; Herbst-Irmer, R.; Bertermann, R.;
Rocha J.; Stalke, D. Chem.sEur. J. 2001, 7, 1417 (here, also a formal
monomer but with three C-Li contacts is discussed).
The monomeric s-BuLi‚(R,R)-TMCDA provides an impressive
demonstration of the structure/reactivity relationship of organo-
lithium compounds. As depicted by the space-filling model and
the Connolly surface of compound 3 (Figure 5) the lithium center
is barely shielded by the ligand and positively polarized. Thus it
offers a free coordination site for the formation of intermediates
via coordination of electrophiles in accordance to the CIPE
mechanism.12 The effects of the open lithium center are also seen
in the strong reactivity of 3, which is able to deprotonate non-
coordinating benzene and toluene in substoichiometric amounts of
(R,R)-TMCDA.
(10) Siemeling, U.; Redecker, T.; Neumann, B.; Stammler, H.-G. J. Am. Chem.
Soc. 1994, 116, 5507.
(11) Similar monomers: (a) Schu¨mann, U.; Kopf, J.; Weiss, E. Angew. Chem.,
Int. Ed. 1985, 24, 215. (b) Zarges, W.; Marsch, M.; Harms, K.; Boche,
G. Chem. Ber. 1989, 122, 2303. (c) Arnold, J.; Knapp, V.; Schmidt, J. A.
R.; Shafir, A. J. Chem. Soc., Dalton Trans. 2002, 3273. (d) Strohmann,
C.; Seibel, T.; Schildbach, D. J. Am. Chem. Soc. 2004, 126, 9876.
(12) Whisler, M. C.; MacNeil, S.; Snieckus, V.; Beak, P. Angew. Chem., Int.
Ed. 2004, 43, 2206.
(13) (a) Chadwick, S. T.; Rennels, R. A.; Rutherford, J. L.; Collum, D. B. J.
Am. Chem. Soc. 2000, 122, 8640. (b) Romesberg, F. E.; Collum, D. B. J.
Am. Chem. Soc. 1994, 116, 9187. (c) Chadwick, S. T.; Ramirez, A.; Gupta,
L.; Collum, D. B. J. Am. Chem. Soc. 2007, 129, 2259.
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