Configurationally labile enantioenriched lithiated 3-arylprop-2-enyl carbamates: Joint experimental and quantum chemical investigations on the equilibrium of epimers

Article abstract of DOI:10.1021/jo101218z

Experimental investigations as well as high-level quantum chemical calculations are performed on the two epimeric pairs of complexes 4.2 and 6.2 obtained by lithiation of cinnamyl carbamate (1) and 1-naphthyl derivative 5 in the presence of BOX ligands (S,S)- and (R,R)-2. Indeed, in the case of configurationally labile complexes and a dynamic thermodynamic resolution, which is found to take place, one of both epimers is energetically favored. The quantum chemical computations allow the prediction of the enantiomeric excess that can be expected.

Full text of DOI:10.1021/jo101218z

pubs.acs.org/joc
Configurationally Labile Enantioenriched Lithiated 3-Arylprop-2-enyl
Carbamates: Joint Experimental and Quantum Chemical Investigations
on the Equilibrium of Epimers
†
Therese Hemery, Robert Huenerbein, Roland Frohlich, Stefan Grimme,* and
Dieter Hoppe*
ꢀ ꢁ
ꢀ
€
€ €
€
Organisch-Chemisches Institut, Westfalische Wilhelms-Universitat Munster, Corrensstrasse 40,
48149 Mu€nster, Germany. †X-ray crystal structure analysis
grimmes@uni-muenster.de; dhoppe@uni-muenster.de
Received June 22, 2010
Experimental investigations as well as high-level quantum chemical calculations are performed on
the two epimeric pairs of complexes 4 2 and 6 2 obtained by lithiation of cinnamyl carbamate (1) and
3
3
1-naphthyl derivative 5 in the presence of BOX ligands (S,S)- and (R,R)-2. Indeed, in the case of
configurationally labile complexes and a dynamic thermodynamic resolution, which is found to take
place, one of both epimers is energetically favored. The quantum chemical computations allow the
prediction of the enantiomeric excess that can be expected.
Introduction
chemical computations allowed the prediction of the enan-
tiomeric ratio quantitatively.2,3
The enantioselective lithiation of prochiral allyl carba-
mates followed by substitution represents a valuable tool for
introduction of a stereogenic center into a molecule.1 In that
context, an important challenge in the investigation of
lithiated allyl carbamates is to determine the selectivity
(enantioselectivity) at the stage of the deprotonation but
also to solve the question of the configurational stability/
lability of the lithiated species. For similar systems, quantum
We previously reported that the deprotonation of cinnamyl
carbamate (1) with the chiral base pair n-butyllithium/(-)-
sparteine led to the formation of mainly one configurationally
unstable diastereoisomer.4 Further substitution reactions with
electrophiles occurred at different rates with both diastereo-
mers, which led to a decreased enantioselectivity compared to
the diastereomeric ratio of the complexes. This led to enan-
tioenriched substitution products with er values up to 93:7.
Herein, we report the joint successful experimental and quan-
tum chemical investigations performed on lithiated “cinna-
myl-type” carbamates obtained after deprotonation in the
presence of chiral bisoxazoline ligands (BOX).5
(1) Reviews: (a) Hoppe, D. Angew. Chem. 1997, 109, 2376. Angew.
€
Chem., Int. Ed. Engl. 1997, 36, 2282. (b) Hoppe, D.; Marr, F.; Bruggemann,
M. In Organolithium in Enantioselective Synthesis; Hodgson, D. M., Ed.;
Topics in Organometallic Chemistry; Springer-Verlag: Berlin, Germany,
2003; Vol. 5, p 61. (c) Beak, P.; Johnson, T. A.; Kim, D. D.; Lim, S. H. In
Organolithium in Enantioselective Synthesis; Hodgson, D. M., Ed.; Topics in
Organometallic Chemistry; Springer-Verlag: Berlin, Germany, 2003; Vol. 5,
p 134. (d) Christoph, G.; Hoppe, D. In The Chemistry of Organolithium
Compounds; Rappoport, Z., Marek, I., Eds.; Whiley: Chichester, UK, 2004;
p 1055. (e) Hoppe, D. Synthesis 2009, 43.
(3) For calculations on related problems see: (a) Bailey, W. F.; Beak, P.;
Kerrick, S. T.; Ma, S.; Wiberg, K. B. J. Am. Chem. Soc. 2002, 124, 1889. (b)
Wiberg, K. B.; Bailey, W. F. J. Org. Chem. 2002, 67, 5365. (c) O‘Brien, P.;
Wiberg, K. B.; Bailey, W. F.; Hermet, J.-P. R.; McGrath, M. J. J. Am. Chem.
Soc. 2004, 126, 15480 and references cited therein.
€
(2) (a) Wurthwein, E.-U.; Hoppe, D. J. Org. Chem. 2005, 70, 4443. (b)
Lange, H.; Huenerbein, R.; Wibbeling, B.; Frohlich, R.; Grimme, S.; Hoppe,
€
€
D. Synthesis 2008, 2905. (c) Lange, H.; Huenerbein, R.; Frohlich, R.;
Grimme, S.; Hoppe, D. Chem. Asian J. 2008, 3, 78. (d) Lange, H.; Bergander,
€
(4) Behrens, K.; Frohlich, R.; Meyer, O.; Hoppe, D. Eur. J. Org. Chem.
1998, 2397.
€
K.; Frohlich, R.; Kehr, S.; Nakamura, S.; Shibata, N.; Toru, T.; Hoppe, D.
Chem. Asian J. 2008, 3, 88. (e) Wurthwein, E.-U.; Hoppe, D. J. Org. Chem.
2008, 73, 9055.
(5) (a) Corey, E. J.;Imai, N.; Zhang,H.-Y. J.Am. Chem. Soc. 1991, 113, 728.
(b) Evans, D. A.; Hinman, K. A.; Faul, M. M. J. Am. Chem. Soc. 1991, 113, 728.
(c) Desimoni, G.; Faita, G.; Jørgensen, K. A. Chem. Rev. 2006, 106, 3561.
€
5716 J. Org. Chem. 2010, 75, 5716–5720
Published on Web 07/28/2010
DOI: 10.1021/jo101218z
r
2010 American Chemical Society

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Hemery et al.
JOCArticle
SCHEME 1. Deprotonation of Cinnamyl Carbamate 1
SCHEME 2. Nonselective Deprotonation of 1
TABLE 1. Substitution of 1 with Different Electrophiles
BOX
product
ElX
yield, %
era
[R]D
2
2
(S)-3a
(S)-3b
(R)-3c
(R)-3d
(R)-3e
Me3SiCl
Ph3SnCl
Me3SiOTf
Ph3SiCl
Et3SiCl
80
50
69
88
75
96:4
94:6
94:6
n.d.
97:3
-11.4b
þ45.8b
þ8.8b
þ0.8b
-2.1c
ent-2
ent-2
ent-2
Fortunately, suitable crystals of 7for X-ray measurement with
anomalous dispersion were obtained and the newly formed ste-
reogenic center was determined to be (S)-configured (Figure 1).
The observed high enantioselectivity shows that the carba-
aDetermined by HPLC analysis on chiral phase. bc 0.89-1.09,
CH2Cl2. cc 1.20, CHCl3.
Results and Discussion
nionic pair 6 2 is configurationally unstable and after addition
3
of the chiral ligand to the racemic mixture, the energetically
more favorable (R)-configured complex is the major species in
the solution.
First, we investigated the deprotonation of cinnamyl car-
bamate (1) using n-butyllithium/BOX 2 (respectively ent-2) as
chiral base pairs, followed by trapping lithium intermediate
with reactive electrophiles (Scheme 1 and Table 1).
The substitution occurred exclusively in the R-position,
and the enantioenriched products (3a-e) (er = 94:6-97:3)
were obtained in moderate to good yield (50-88%). The
configuration of the newly formed stereogenic centers was
determined by comparison of the optical rotation with these
of known examples, and considering an invertive substitu-
tion with tin and silyl electrophiles.1d,4
Carbamate 1 is smoothly deprotonated with 1.2 equiv of
s-butyllithium/diethyl ether in toluene at -78 °C, and the addi-
tion of BOX ligand 2 induces after ligand exchange, through a
dynamic thermodynamic resolution,6 an epimerization of the
stereogenic center to the almost exclusive formation of the
All theses investigations suggest that the complexes 4 2 and
3
6 2 are configurationally labile and that a dynamic thermo-
3
dynamic resolution is taking place,6 which means that one of
both epimers should be energetically favored. Thus, the dia-
stereoisomeric ratios can be investigated by computing the
equilibrium with quantum chemical methods (Scheme 4).
Previously we presented a computational scheme that al-
lowed the prediction of the equilibria of O-benzyl carbamates
with high accuracy.2a,b A slightly modified version of that
procedure was applied here. Note that the maximum accep-
table error of the calculated relative energies should not exceed
0.5 kcal mol-1
.
For a dynamic thermodynamic resolution, the observed
selectivity (er=96:4 for 3a, measured by reaction with TMSCl,
for example) reflects the ratio 96:4 of the epimeric pairs in
solution ((R)-4 2 and (S)-4 2) (Figure 2, eq 1). Furthermore, a
most energetically favored complex (R)-4 2 (Scheme 2).
3
In addition, the silylation of 1 with trimethylsilyl trifluor-
omethanesulfonate, which reacts much faster than TMSCl,
led after 30 min to the formation of (R)-3c in 69% yield and
er of 94:6. Those considerations minimize the possibility of a
diastereotopic differentiation at the stage of the substitution
(dynamic kinetic resolution7), and are evidence for the
3
3
determination of ΔΔG can be done experimentally using eq 2
in Figure 2, excluding any perturbation of the equilibrium.9
Temperature and entropy effects are supposed to be negli-
gible so that the calculated ΔΔE can be compared with the
experimentally found ΔΔG (Figure 2, eq 3). Moreover, sol-
vent effects and zero point vibrational energies (ZPVE) have
been shown to have a minor contribution (both in the range
0.1-0.2 kcal mol-1) by previous calculations on benzyl carba-
mates;2b therefore these effects are not taken into account in
the following.
configurational lability of the lithium complex 4 2.
3
Furthermore, 1-naphthyl derivative 5 was investigated in
order to broaden the method developed for 1. The deproto-
nation/equilibration sequence worked similarly well and 5
could be successfully silylated yielding 7 in good yield and
good enantioselectivity (Scheme 3).
The alkenyl carbamates considered here have the possibi-
lity of a η3-complexation at the lithium center in contrast to
the previously investigated benzyl carbamates.10 For this
(6) (a) Beak, P.; Anderson, D. R.; Curtius, M. D.; Laumer, J. M.; Pippel,
D. J.; Weisenburger, G. A. Acc. Chem. Res. 2000, 33, 715. (b) Clayden, J.;
Lai, L. W.; Helliwell, M. Tetrahedron 2004, 60, 4399. (c) Park, Y. S.; Basu, A.;
Beak, P. Org. Lett. 2006, 8, 2667.
(7) (a) Noyori, R.; Tokumaga, M.; Kitamura, M. Bull. Chem. Soc. Jpn.
1995, 68, 36. (b) Ward, S. Tetrahedron: Asymmetry 1995, 6, 1475. (c)
Caddick, S.; Jenkins, K. Chem. Soc. Rev. 1996, 25, 447. (d) Pellessier, H.
Tetrahedron 2003, 59, 8291.
(9) No precipitation was observed in the flask.
(10) (a) Hoppe, D.; Hoppe, I.; Marsch, K.; Harms, K.; Boche, G. Angew.
Chem. 1995, 107, 2328. Angew. Chem., Int. Ed. Engl. 1995, 34, 2158. (b)
Pippel, D. J.; Weisenburger, G. A.; Wilson, S. R.; Beak, P. Angew. Chem.
1998, 110, 2600. Angew. Chem., Int. Ed. 1998, 37, 2522.
(8) Crystal structure data available in the Supporting Information.
J. Org. Chem. Vol. 75, No. 16, 2010 5717

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SCHEME 3. Nonselective Deprotonation of 7 Followed by Epimerization and Substitution with TMSCl
FIGURE 1. X-ray structure of 7.8
FIGURE 3. Calculated structures of complexes (S)-4 2 (a), (R)-4 2
(b), (S)-6 2 (c), and (R)-6 2 (d) (color key: white = H, orange = C,
red = O, blue = N, gray = Li).
3
3
3
3
FIGURE 2. Mathematical relationships for the determination of
the energy difference of epimeric complexes based on the experi-
mental ratio within the dynamic thermodynamic resolution (eqs 1
and 2). Relationship between quantum chemically determined ΔΔE
values and experimentally determined ΔΔG values.
TABLE 2. Experimental ΔΔG and Calculated ΔΔE for Epimeric
Complexes 4 2 and 6 2
3
3
experimental
calculated
SCHEME 4. Epimeric Complexes of 1 and 5 Investigated by
High-Level Quantum Chemical Calculations
complex
era
ΔΔGb (kcal mol-1
)
erb
ΔΔE (kcal mol-1
)
4 2
3
96:4
94:6
1.2
1.0
78:22
93:7
0.5
1.0
6 2
3
aAfter deprotonation and substitution with TMSCl. bSee Figure 2.
empirical dispersion correction (DFT-D),13 using the def2-
TZVP basis.14
In contrast to our earlier work, the GGA-type func-
tional, previously used to compute the structures, was
substituted by a hydrid functional with a large amount of
Fock exchange to rule out any artificial η3-complexation
caused by so-called self-interaction (overdelocalization)
errors in DFT.15 On the optimized structures, single-point
energies were computed with SCS-MP216 by using the
reason, the computational scheme has been modified. The
geometries of the diastereomeric pairs (R)-4 2 and (S)-4 2 as
3
3
well as of (R)-6 2 and (S)-6 2 were first optimized at the
3
3
DFT level11 employing the BH-LYP-D functional12 and an
(13) (a) Grimme, S. J. Comput. Chem. 2004, 25, 1463. (b) Grimme, S.
J. Comput. Chem. 2006, 27, 1787.
€
(14) Weigend, F.; Haser, M.; Patzelt, H.; Ahlrichs, R. Chem. Phys. Lett.
1998, 294, 143.
(11) For the calculations, the program Turbomole V5.10: Ahlrichs, R.
et al.; University of Karlsruhe: Germany, 2008; see: http://www.turbomole.
com.
(12) BH-LYP: (a) Becke, A. D. Phys. Rev. A 1988, 38, 3098. (b) Lee, C.;
Yang, W.; Parr, R. G. Phys. Rev. B. 1988, 37, 785. (c) Becke, A. D. J. Chem.
Phys. 1993, 98, 1372.
(15) (a) Zhang, Y.; Yang, W. J. Chem. Phys. 1998, 109, 2604. (b)
Schwabe, T.; Grimme, S. Eur. J. Org. Chem. 2008, 5928.
(16) Grimme, S. J. Chem. Phys. 2003, 118, 9095.
5718 J. Org. Chem. Vol. 75, No. 16, 2010

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def2-TZVPP basis14 and employing the resolution of identity
(RI) approximation.17
0.37 mmol, 1.2 equiv), dissolved in toluene (0.5 mL), was added
dropwise at -78 °C within 5 min. The solution was stirred for 2 h
and ClSnPh3 (346 mg, 0.90 mmol, 2.8 equiv) dissolved in toluene
(1.0 mL) was added dropwise and reacted for 3 h. The reaction
was quenched by addition of 2 N HCl (5 mL) and warmed to rt
before addition of Et2O or TBME (5 mL). The organic phase was
separated and the aqueous layer was extracted with Et2O or
TBME (3 ꢀ10 mL). The combined organic phases were neutra-
lized with a sat. aq. NaHCO3 solution (15 mL), then dried with
MgSO4. After evaporation of the solvent under vacuum, the
residue was purified by column chromatography (Et2O/PE =
1:25) yielding 3b (96 mg, 0.16 mmol, 50%) as a yellow oil: Rf 0.64
(Et2O/PE = 1:1), [R]20D þ45.8 (c 0.89, CH2Cl2, er = 94:6); 1H
NMR (400 MHz, CDCl3) δ/ppm 1.03, 1.14 (2 s, 12 H), 3.77, 3.95
(2 br s, 2 H), 5.54 (ddd, J = 20.6, 6.4, 1.6 Hz, 1 H), 6.40 (dd, J =
15.8, 1.6 Hz, 1 H), 6.51 (dd, J = 15.8, 6.4 Hz, 1 H), 7.16-7.19 (m,
5 H), 7.24-7.31 (m, 9 H), 7.55-7.65 (m, 6 H); 13C NMR (100
MHz, CDCl3) δ/ppm 20.3, 21.3, 45.3, 46.5, 73.2, 124.5, 126.1,
126.7, 128.2, 128.4, 128.6, 130.5, 137.4, 137.5, 140.5, 156.1; IR
(ATR) ν/cm-1 3063, 2971, 2933, 1660, 1495, 1479, 1428, 1369,
1351, 1305, 1287, 1212, 1156, 1136, 1072, 1045, 1022, 997, 958,
934, 727, 696. Anal. Calcd for C34H37O2NSn (610.37): C 66.90, H
6.11, N 2.29. Found: C 66.63, H 5.77, N 1.99. Chiral HPLC:
ChiraGrom-1 250 ꢀ 2 mm; i-PrOH/n-hexane = 1:20000; 0.3 mL
min-1; tR1 = 8 min, tR2 = 14 min (main enantiomer).
(1R)-(E)-3-Phenyl-1-triphenylsilylprop-2-enyl N,N-Diisopro-
pylcarbamate (3d). A solution of carbamate 1 (85 mg, 0.32
mmol, 1.0 equiv) and Et2O (0.1 mL) in toluene (2 mL) was
cooled to -78 °C; s-BuLi (1.22 M) (0.27 mL, 0.33 mmol, 1.0 equiv)
was added slowly. After 1 h of deprotonation, a solution of ent-2
(123 mg, 0.37 mmol, 1.1 equiv), dissolved in toluene (0.5 mL), was
added dropwise at -78 °C within 5 min. The solution was stirred
for 2 h and ClSiPh3 (263 mg, 0.89 mmol, 2.8 equiv) dissolved in
toluene (1 mL) was added slowly. After 3 h the reaction was
quenched by addition of 2 N HCl (5 mL) and warmed to rt before
addition of Et2O or TBME (5 mL). The organic phase was sepa-
rated and the aqueous layer was extracted with Et2O or TBME
(3 ꢀ 10 mL). The combined organic phases were neutralized with a
sat. aq. NaHCO3 solution (15 mL), then dried with MgSO4. After
evaporation of the solvent under vacuum, the residue was purified
by column chromatography (toluene) yielding 3d as a colorless
The computed results are, despite the geometric and
electronic complexity of the systems, in perfect agreement
with the experimental values deduced by the deprotonation/
equilibration/substitution sequence (Table 2). For both
lithiated carbamates the preferred diastereomer (R config-
ured intermediate, Figure 3) is predicted correctly; moreover,
the enantiomeric ratio is described quantitatively (error ,1
kcal mol-1).
The obtained complexes show a tendency to an η3-coor-
dination (Figure 3), which is in agreement with the lithiated
conjugated aromatic allyl systems, which have been experi-
mentally elucidated.10
Conclusions
In conclusion, lithiation of 3-arylprop-2-enyl carbamates 1
and 5 in the presence ofBOXligand 2 leadstothe formation of
configurationally labile complexes (4 2 and 6 2), which un-
3
3
dergo an efficient dynamic thermodynamic resolution and
react selectively with reactive electrophiles to form enantio-
merically enriched substitution products in good yields. The
BOX ligands perform a larger discrimination than (-)-spar-
teine in the diastereomeric complexes; it leads to synthetically
useful stereoselctivities. By choice of the BOX ligand, both
enantiomers of the substitution products can be approached.
Furthermore, the quantum chemical calculations performed
on diastereoisomeric pairs (R)-4 2 and (S)-4 2 as well as
3
3
(R)-6 2 and (S)-6 2 confirm the experimentally determined
3
3
enantiomeric ratios.
Experimental Section
(1S)-(E)-3-Phenyl-1-trimethylsilylprop-2-enyl N,N-Diisopro-
pylcarbamate (3a). To a solution of 14 (75 mg, 0.29 mmol, 1.0
equiv) and Et2O (0.1 mL) in toluene (2 mL) was added s-BuLi
(1.28 M) (0.30 mL, 0.38 mmol, 1.3 equiv) slowly at -78 °C. After
1 h of deprotonation, 2 (130 mg, 0.38 mmol, 1.3 equiv), dissolved
in toluene (0.5 mL), was added at -78 °C and the mixture was
stirred for an additional 2 h at -78 °C. After addition of TMSCl
(96 mg, 0.88 mmol, 3.0 equiv) and 2 h of reaction the mixture
was quenched by the addition of 2 N HCl (5 mL) and warmed to
rt before addition of Et2O (5 mL). The organic phase was
separated and the aqueous layer was extracted with Et2O (3 ꢀ
10 mL). The combined organic phases were neutralized with a
sat. aq. NaHCO3 solution (15 mL), then dried with MgSO4.
After evaporation of the solvent under vacuum, purification of
the residue yielded 3a (77 mg, 0.23 mmol, 80%) as a white solid:
mp 65-67 °C (Et2O); Rf 0.38 (Et2O/PE = 1:4); [R]20D -11.4 (c
1.08, CH2Cl2, er = 96:4); 1H NMR (400 MHz, CDCl3) δ/ppm
0.06 (s, 9 H), 1.20 (s, 12 H), 3.81, 4.02 (2 br s, 2 H), 5.24 (dd, J =
6.1, 1.1 Hz, 1 H), 6.21 (dd, J = 15.9, 6.1 Hz, 1 H), 6.33 (dd, J =
solid (155 mg, 0.249 mmol, 88%); mp: 72-74 °C (Et2O); Rf 0.35
D
(toluene); [R]20 þ0.8 (c 1.04, CH2Cl2); H NMR (400 MHz,
1
CDCl3) δ/ppm 0.94, 1.18 (2 br s, 12 H), 3.82 (br s, 2 H), 6.24-6.25
(m, 1 H), 6.27-6.30 (m, 2 H), 7.13-7.63 (m, 20 H); 13C NMR (100
MHz, CDCl3) δ/ppm 20.9, 45.7, 46.2, 67.9, 126.2, 127.6, 127.9,
128.3, 128.8, 130.0, 132.4, 135.0, 135.2, 136.1, 154.9; IR (ATR)
ν/cm-1 3069, 2969, 2934, 1680, 1485, 1427, 1369, 1328, 1285,
1215, 1156, 1112, 1045, 962, 856, 739, 696; HR-MS (ESI) (m/z)
calcd [C34H37NO2Si þ Na]þ = 542.2486, found [C34H37NO2Si þ
Na]þ = 542.2479. The enantiomeric excess could not be deter-
mined, neither by HPLC on chiral stationary phase, nor by GC on
chiral stationary phase or by 1H NMR shift experiments.
(1R)-(E)-3-Phenyl-1-triethylsilylprop-2-enyl N,N-Diisopro-
pylcarbamate (3e). A solution of carbamate 1 (85 mg 0.32 mmol,
1.0 equiv) and Et2O (0.1 mL) in toluene (2 mL) was cooled to
-78 °C; s-BuLi (1.22 M) (0.27 mL, 0.33 mmol, 1.1 equiv) was
added slowly. After 1 h of deprotonation, a solution of ent-2
(129 mg, 0.38 mmol, 1.2 equiv), dissolved in toluene (0.5 mL),
was added dropwise at -78 °C within 5 min. The solution was
stirred for 2 h, then TESCl (139 mg, 0.92 mmol, 2.8 equiv) was
added slowly. After 3 h the reaction was quenched by addition of
2 N HCl (5 mL) and warmed to rt before addition of Et2O or
TBME (5 mL). The organic phase was separated and the
aqueous layer was extracted with Et2O or TBME (3 ꢀ 10 mL).
The combined organic phases were neutralized with a sat. aq.
NaHCO3 solution (15 mL), then dried with MgSO4. After
evaporation of the solvent under vacuum, the residue was
15.9, 1.1 Hz, 1 H), 7.13-7.15 (m, 1 H), 7.20-7.25 (m, 4 H); 13
C
NMR (75 MHz, CDCl3) δ/ppm -3.49, 20.6, 21.4, 45.1, 46.4,
70.5, 126.1, 126.8, 128.2, 128.4, 137.5, 155.6. Chiral HPLC:
ChiraGrom-2 250 ꢀ 2 mm; i-PrOH/n-hexane =1:600; 0.3 mL
min-1; tR = 9 min (main enantiomer), tR = 12 min; the
spectroscopic data are in agreement with the literature.4
(1S)-(E)-3-Phenyl-1-triphenylstannylprop-2-enyl N,N-Diiso-
propylcarbamate (3b). A solution of carbamate 1 (84 mg, 0.32
mmol, 1.0 equiv) and Et2O (0.1 mL) in toluene (2 mL) was cooled
to -78 °C; s-BuLi (1.22 M) (0.27 mL, 0.33 mmol, 1.2 equiv) was
added slowly. After 1 h of deprotonation, a solution of 2 (125 mg,
€
(17) Weigend, F.; Haser, M. Theor. Chem. Acc. 1997, 97, 331.
J. Org. Chem. Vol. 75, No. 16, 2010 5719

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purified by column chromatography (Et2O/PE = 1:10), yielding
3e (90 mg, 0.24 mmol, 75%) as a colorless oil: Rf 0.51 (Et2O/
1 H), 7.11 (dd, J = 15.7, 1.9 Hz, 1 H), 7.42-7.48 (m, 4 H), 7.73 (d, 1
H), 7.83 (m, 1 H), 8.05-8.07 (m, 1 H); 13C NMR (100 MHz,
CDCl3) δ/ppm 3.4, 20.9, 46.2, 70.8, 123.5, 123.9, 124.0, 125.6, 125.8,
1
PE = 1:4), [R]20 -2.1 (c 1.20, CHCl3, er = 97:3); H NMR
D
(400 MHz, CDCl3) δ/ppm 0.68 (q, J = 8.1 Hz, 6 H), 1.01 (t, J =
8.1 Hz, 9 H), 1.27 (d, J = 6.6 Hz, 12 H), 3.98 (br s, 2 H), 5.48 (dd,
J = 6.1, 1.2 Hz, 1 H), 6.29 (dd, J = 15.9, 6.1 Hz, 1 H), 6.38 (dd,
J = 15.9, 1.2 Hz, 1 H), 7.14-7.22 (m, 1 H), 7.23-7.61 (m, 4 H);
13C NMR (100 MHz, CDCl3) δ/ppm 2.1, 7.4, 20.8, 21.3, 45.9,
68.5, 126.1, 126.3, 126.8, 128.4, 128.8, 137.6, 155.2; IR (ATR)
ν/cm-1 3058, 2961, 29376, 1693, 1454, 1426, 1377, 1367, 1333,
1290, 1219, 1158, 1135, 1063, 1045, 1010, 972, 732, 793. Anal.
Calcd for C22H37NO2Si (375.62): C 70.35, H 9.93, N 3.73.
Found: C 70.16, H 9.97, N 3.70. Chiral HPLC: ChiraGrom-2
250 ꢀ 2 mm; i-PrOH/n-hexane = 1:600; 0.3 mL min-1; tR1 = 9
min, tR2 = 15 min (main enantiomer).
(1S)-(E)-3-(1-Naphthyl)-1-trimethylsilylprop-2-enyl N,N-Di-
isopropylcarbamate (7). A solution of carbamate 5 (93 mg,
0.30 mmol, 1.0 equiv) and Et2O (0.1 mL) in toluene (2 mL)
was cooled to -78 °C; s-BuLi (1.22 M) (0.27 mL, 0.33 mmol, 1.2
equiv) was added slowly. After 1 h of deprotonation, a solution
of 2 (128 mg, 0.38 mmol, 1.3 equiv) in toluene (0.5 mL) was
added dropwise at -78 °C within 5 min. The solution was stirred
for 2 h and TMSCl (103 mg, 0.93 mmol, 3.1 equiv) was added
dropwise and reacted for 1 h. After quenching with MeOH
(0.3 mL) at -78 °C and warming to rt, 2 N HCl (0.03 mL) and
Et2O (10 mL) were added and the organic phase was dried with
MgSO4. The solvent was evaporate under reduced pressure and
the crude product was purified by column chromatography
(Et2O/PE = 1:10), yielding 7 (92 mg, 0.27 mmol, 80%) as a
127.3, 128.4, 131.3, 131.6, 133.6, 135.6, 155.6; IR (ATR) ν/cm-1
=
3058, 2963, 2930, 1688, 1472, 1435, 1368, 1314, 1281, 1247, 1213,
1157, 1125, 1065, 1045, 960, 934, 839, 792, 775. Anal. Calcd for
C23H33NO2Si (383.60): C 72.01, H 8.67, N 3.65. Found: C 72.38, H
8.75, N 3.41. Chiral HPLC: Chiracel OD-H; i-PrOH/n-hexane =
1:75; 1.0 mL min-1; tR1 = 5 min (main enantiomer), tR2 = 12 min.
Computational Details. All DFT and SCS-MP216 compu-
tations have been performed with a modified version of
Turbomole11 5.10. The structures were optimized with DFT
employing the BH-LYP12 functional and an empirical disper-
sion correction (DFT-D, s6BH-LYP=0.9).13 An Ahlrichs’ triple ξ
basis set (def2-TZVP) was used for all geometry optimizations.
The final energies were calculated with SCS-MP2 and an
Ahlrichs’ triple ξ basis with additional polarization functions
(def2-TZVPP).14 The resolution of the identity (RI) approxi-
mation17 with auxiliary basis sets from the Turmobole library
was used for both the DFT and MP2 steps. For the numerical
integration a large multiple grid (grid ‘m4’18 option in Turbo-
mole) was used. Both the structure optimizations as well as the
energy calculations were performed with a convergence criterion
of 10-7 hartree.
Acknowledgment. This work was supported by the
Deutsche Forschungsgemeinschaft (SFB 424) and the Inter-
€
national NRW Graduate School of Chemistry, Munster,
Germany (stipends R.H.).
colorless solid: mp 51-56 °C (Et2O); Rf 0.64 (Et2O/PE = 1:1);
D
1
[R]20 þ18.4 (c 1.01, CHCl3, er = 93:7); H NMR (400 MHz,
Supporting Information Available: Experimental proce-
dures, spectroscopic data of all new compounds, X-ray crystal
CDCl3) δ/ppm 0.18 (s, 9 H), 1.29 (br s, 12 H), 3.95, 4.09 (2 br s,
2 H), 5.42 (dd, J = 6.3, 1.9 Hz, 1 H), 6.31 (dd, J = 15.7, 6.3 Hz,
analyze of compound 7, H and 13C NMR spectra, and SCS-
1
MP2 total energies. This material is available free of charge via
the Internet at http://pubs.acs.org.
(18) Numerical quadrature multiple grid (‘grid m4’option in Turbomole):
Treutler, O.; Ahlrichs, R. J. Chem. Phys. 1995, 102, 346.
5720 J. Org. Chem. Vol. 75, No. 16, 2010