The absolute configuration of the products of the enantioselective rhodium(I)/BINAP-catalyzed enyne cyclization

Article abstract of DOI:10.1002/adsc.200303225

The absolute configuration of the product 7 obtained from a rhodium-catalyzed enyne cyclization of 6 with the (R)-BINAP ligand was determined by anomalous diffraction in the X-ray crystal structure analysis.

Full text of DOI:10.1002/adsc.200303225

FULL PAPERS
The Absolute Configuration of the Products of the
Enantioselective Rhodium(I)/BINAP-Catalyzed Enyne
Cyclization
A. Stephen K. Hashmi,a,* Patrick Haufe,a Andreas Rivas Nass,b Jan W. Batsc
a
Institut f¸r Organische Chemie, Universit‰t Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany
Fax: ( ‡ 49)-711-685-4321, e-mail: hashmi@hashmi.de
b
Umicore AG & Co. KG, Precious Metals Chemistry, Rodenbacher Chaussee 4, 63403 Hanau, Germany
c
Institut f¸r Organische Chemie und Chemische Biologie, Johann Wolfgang Goethe-Universit‰t Frankfurt,
Marie-Curie-Str. 11, 60439 Frankfurt, Germany
Received: December 9, 2003; Accepted: February 25, 2004
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de.
Abstract: The absolute configuration of the product 7 Keywords: alkenes; alkynes; asymmetric catalysis;
obtained from a rhodium-catalyzed enyne cyclization cyclization; homogeneous catalysis; rhodium
of 6 with the (R)-BINAP ligand was determined by
anomalous diffraction in the X-ray crystal structure
analysis.
Introduction
direct assignment of the configuration in other products
by correlation with the optical rotation or the CD
The intramolecular and transition metal-catalyzed ver- spectra.
sion of the Alder-ene reaction,[1] the enyne cyclization,
has become an important tool in organic synthesis. Since
Trost et al.×s[2] initial work with palladium catalysts, Results and Discussion
many other groups have contributed and several other
metals have proven to be catalytically active.[3] In these For the determination of the absolute configuration by
reactions from a planar sp2-carbon in the starting anomalous diffraction a heavy atom is feasible. Thus we
material, a tetrahedral stereogenic center is generated chose to use a brosyl-protected amine, the brosyl group
in the product. Among several efforts for a catalytic should also facilitate crystallization.
enantioselective version of that reaction in the past
Starting from propargylamine 1 and iodobenzene 2
years,[4,5] so far the most convincing synthetic results the primary amine 3 was synthesized by a Sonogashira
come from Zhang et al.×s recent work with rhodium(I) coupling.[11]
catalysts.[6,7,8]
Protection with brosyl chloride led to the secondary
Zhang et al. achieved excellent enantioselectivities sulfonamide 4, of which an X-ray crystal structure
and good to excellent yields.[6,7,8] But the absolute analysis could be obtained (Figure 1).[12] The phenyl
configuration of the newly formed stereogenic center group labeled C10 through C15 is planar within the
remained unknown. Just recently Zhang et al. inves- experimental uncertainty. The phenyl group labeled C1
tigated the kinetic resolution of racemic substrates and through C6 shows a small deviation from planarity:
were able to assign the diastereoselectivity and from that, atoms Br and S deviate by 0.18 and 0.13 ä, respectively,
in the case of starting materials with known configu- in the same direction from the plane of this phenyl
ration of the stereogenic center already present, also the group. The angle between the planes of the two phenyl
absolute configuration of the products.[9]
groups is 76.68. The molecule shows two intramolecular
...
À
At the same time, in continuation of our recent contacts: a possible p p contact between the C1 C6
work,[10] we wanted to assign the absolute configuration bond and atom C8 of the triple bond (C8 C1 3.41 ä
...
...
...
À
of the products of an enantioselective reaction by a and C8 C6 3.44 ä) and a C H p interaction be-
crystal structure analysis. The absence of additional tween the C11 H11 bond and the C4 C5 bond
stereogenic centers in the starting material would avoid (H11 C4 2.94 ä and H11 C5 2.73 ä). The mole-
possible matched/mismatched cases and allow a more cules are connected by intermolecular N H O hydro-
À
À
...
...
...
À
Adv. Synth. Catal. 2004, 346, 421 424
DOI: 10.1002/adsc.200303225
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421

A. Stephen K. Hashmi et al.
FULL PAPERS
molecule shows a number of intramolecular contacts:
...
...
...
...
H6 O12.50 ä, H7A O1 2.48 ä, H16B O2 2.41 ä,
...
...
H7B C17 2.71 ä, H16A C8 2.66 ä and H11 C5
2.98 ä. The molecules form centrosymmetric dimers
...
À
connected by intermolecular C H Br contacts with
...
H
Br distances of 2.89 ä. The dimers are connected
...
...
À
by two intermolecular C H O contacts and two
intermolecular C(phenyl) H p(phenyl) interactions
À
to layers parallel to the 0 0 1 plane. Neighboring layers
are connected only by a very weak intermolecular
...
À
C H O interaction.
The Rh(I)/(R)-BINAP-catalyzed isomerization af-
forded (E),(R)-7 with an ee of 98.5%. The optical
rotation of the sample was [a]2D0: À 81.88 (c 0.5 g/100 mL
CHCl3). We again succeeded in obtaining single crystals
of (E),(R)-7 (Figure 3).[12] The five-membered ring has
an envelope conformation: atom C10 deviates 0.62 ä
from the plane through N/C7/C8/C9 in the direction of
the C11/C12/C13 side chain. The C9 C11 bond is in a
pseudo-equatorial position with respect to the five-
membered ring. The phenyl group attached to C14 is
À
À
almost coplanar with the C8 C14 double bond: the
Scheme 1.
angle between the planes of the phenyl ring and the
double bond system is 4.58. This coplanarity results in a
rather short intramolecular distance of 2.50 ä between
...
À
À
gen bonds [N O1 (at x-1, y, z): 2.994 (2) ä] to chains C7 and H20. Consequently the C7 C8 C14 angle is
running in the crystallographic a direction, which also almost 58 larger than the corresponding C9 C8 C14
corresponds to the long dimension of the crystal. The angle. The plane of the C11 C12 double bond lies
chains may also be stabilized by p p interactions almost perpendicular to the C8 C9 C10 plane. There is
À
À
À
...
À
À
...
...
À
between phenyl C atoms [C3 C6 (at x À 1, y, z) 3.39 ä a short intramolecular C H p interaction between
...
À
À
and C14 C11 (at x À 1, y, z) 3.33 ä]. Neighboring the C14 H14 bond and the C11 C12 double bond with a
...
chains are connected by a weak intermolecular H14 C11 contact distance of only 2.62 ä. The mole-
... ... ...
À
À
À
C H N, C H O and C H Br interactions.
cules form stacks in the crystallographic a direction,
Then a Mitsunobu reaction with (Z)-2-penten-1-ol which corresponds to the needle axis of the crystal. The
(Z)-5 furnished (Z)-6. The vicinal coupling of the two molecules in the stacks are connected by two intermo-
...
...
À
vinylic protons of 10.8 Hz nicely reflects the (Z)- lecular C H O interactions with H O distances of
configuration of the double bond. In addition, a crystal 2.60 ä and 2.65 ä and an intermolecular
structure analysis confirmed that structure (Figure 2).[12] C H p(phenyl) interaction with an H Cg distance
Both phenyl groups are planar within the experimental of 2.68 ä (Cg is the centroid of the phenyl ring labeled
uncertainty. The angle between the planes of the two C15 through C20). Neighboring stacks are connected by
...
...
À
...
À
phenyl groups is 49.28. The N atom is non-planar: the an additional intermolecular C H O interaction and
sum of the three valence angles about N is 349.98. The two weak intermolecular C H Br interactions.
...
À
Figure 1. Crystal structure of 4.
Figure 2. Crystal structure of (Z)-6.
422
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Enantioselective Rhodium(I)/BINAP-Catalyzed Enyne Cyclization
FULL PAPERS
d ˆ 1.60 (br s, 2H), 3.67 (s, 2H), 7.29 7.31 (m, 3H), 7.39 7.43
(m, 2H).
4-Bromo-N-(3-phenyl-2-propynyl)-
benzenesulfonamide (4)
To a stirred solution of 3 (351 mg, 2.68 mmol), Et3N (560 mL)
and 4-(N,N-dimethylamino)pyridine (DMAP; 3.10 mg,
26.8 mmol) in dichloromethane (DCM; 10 mL) at 08C 4-
bromobenzenesulfonyl chloride (754 mg, 2.95 mmol) was
added in portions. The reaction mixture was stirred at 08C
for 15 minutes and then at room temperature overnight. Water
(5 mL) was added, the phases were separated and the aqueous
phase was extracted with two portions of DCM (3 mL each).
The combined organic phases were dried over Na2SO4, filtered
and the solvent was evaporated under vacuum. The resulting
solid was recrystallized from petroleum ether/DCM to furnish
pale yellow needles of 4; yield: 374 mg (1.07 mmol, 40%); Rf
(petroleum ether:ethyl acetate; 10:1) ˆ 0.29; mp 125 1278C;
1H NMR (CDCl3, 500 MHz): d ˆ 4.05 (d, J ˆ 6.2 Hz, 2H), 4.68
(t, J ˆ 6.2 Hz, 1H), 7.04 (m, 2H), 7.22 (m, 3H), 7.57 (d, J ˆ
8.9 Hz, 2H), 7.73 (d, J ˆ 8.9 Hz, 2H); 13C NMR (CDCl3,
125 MHz): d ˆ 34.2 (t), 83.2 (s), 85.5 (s), 122.1 (s), 128.4 (s),
128.7 (d, 2C), 129.1 (d), 129.4 (d, 2C), 131.9 (d, 2C), 132.8 (d,
2C), 139.5 (s); IR (neat): n ˆ 3280, 1573, 1430, 1390, 1169, 1089,
1054, 823, 756 cmÀ1; MS [EI (‡), 70 eV]: m/z (%) ˆ 351 (3)
Figure 3. Crystal structure of (E),(R)-7.
Although the large number of very weak reflections in
the data set resulted in rather large R values, the
absolute configuration of the structure was derived from
the value of theFlack x parameter[x ˆ 0.07(3)] to be (R)
as shown in Figure 3. It also nicely confirmed the (E)-
configuration of the new stereogenic double bond which
was deduced from the vicinal H-H coupling constant of
15.1 Hz in analogy to our earlier work.[10]
The CD-spectrum of (E),(R)-7 shows a maximum at
252 nm and a minimum at 230 nm (see supplementary
material).
‡
‡
[MH ], 202 (10), 130 (100) [M
brosyl], 146 (23), 103 (16);
anal. calcd. for C15H12BrNO2S (350.2): C 51.44, H 3.45, N 4.00;
found: C 51.10, H 3.61, N 3.95.
Conclusion
The configuration of the enantioselective reaction
forming a new stereogenic center in the product from
an achiral substrate investigated here is in complete
accord with Zhang×s results of the diastereoselective
kinetic resolution forming a second stereogenic center
in the product from a substrate already possessing a
stereogenic center. The (R)-BINAP-ligand on rhodium
(I) induces the (R)-configuration of that new center. The
CD data measured should help to assign the config-
uration in other related products.
(Z)-4-Bromo-N-(2-pentenyl)-N-(3-phenyl-2-
propynyl)benzenesulfonamide (6)
In analogy to a literature procedure[14] for comparable
substrates, at 08C 4 (202 mg, 577 mmol), PPh3 (212 mg,
808 mmol) and (Z)-2-penten-1-ol (5; 80.0 mL, 65.0 mg,
750 mmol) were dissolved in THF (10.0 mL). Then diisopropyl
azodicarboxylate (DIAD; 160 mL) was added dropwise, the
solution was allowed to warm to room temperature and then
stirred overnight. The solvent was removed under vacuum,
ethyl acetate (10 mL) was added and after washing with
saturated NaCl solution the organic phase was dried over
Na2SO4. Column chromatography (petroleum ether:DCM;
5:1) afforded 6 as a white solid; yield: 211 mg (505 mmol, 88%);
Rf (petroleum ether:ethyl acetate, 12:1) ˆ 0.26; mp 63 658C;
1H NMR (CDCl3, 500 MHz): d ˆ 0.89 (t, J ˆ 7.5 Hz, 3H), 2.04
(qdd, J ˆ 7.5 Hz, 7.5 Hz, 1.6 Hz, 2H), 3.86 (d, J ˆ 7.5 Hz, 2H),
4.23 (s, 2H), 5.27 (dtt, J ˆ 10.8 Hz, 7.5 Hz, 1.6 Hz, 1H), 5.63(dtt,
J ˆ 10.8 Hz, 7.5 Hz, 1.6 Hz, 1H), 6.95 7.00 (m, 2H), 7.17 7.22
(m, 3H), 7.53 (d, J ˆ 8.7 Hz, 2H), 7.69 (d, J ˆ 8.7 Hz, 2H);
13C NMR (CDCl3, 125 MHz): d ˆ 14.2 (q), 20.7 (t), 36.5 (t), 43.2
(t), 81.5 (s), 85.8 (s), 121.9 (d), 122.3 (d), 127.8 (s), 128.4 (d, 2C),
128.6 (d), 129.4 (d, 2C), 131.4 (d, 2C), 132.2 (d, 2C), 138.0 (s),
138.4 (d); IR (neat): n ˆ 2932, 1574, 1490, 1471, 1443, 1389,
1352, 1274, 1165, 1091, 1010, 900, 823 cmÀ1; MS [EI (‡), 70 eV]:
Experimental Section
3-Phenyl-2-propynylamine (3)
In a Schlenk flask containing propargylamine (1; 328 mg,
5.95 mmol) in absolute THF at room temperature were added
Pd(PPh3)2Cl2 (83.7 mg, 119 mmol, 2 mol %), CuI (45.4 mg,
238 mmol, 4 mol %) and Et3N (1.66 mL, 1.21 g, 12.0 mmol)
with stirring. Then iodobenzene (2; 1.00 mL, 1.82 g,
8.92 mmol) was injected. After 16 hours the solvent was
removed and the product was purified by column chromatog-
raphy (petroleum ether:ethyl acetate:MeOH; 1:1:1) to afford
3; yield: 351 mg (2.68 mmol, 45%). The 1H NMR spectrum was
in accordance with the literature data.[13] Rf (petrol ether:ethyl
‡
‡
m/z (%) ˆ 417 (1)[M H], 198 (48) [M brosyl], 143 (18), 115
(100), 91 (15); anal. calcd. for C20H20BrNO2S (418.4): C 57.42,
H 4.82, N 3.35; found: C 57.23, H 4.88, N 3.29.
1
acetate:MeOH; 1:1:1) ˆ 0.26; H NMR (CDCl3, 300 MHz):
Adv. Synth. Catal. 2004, 346, 421 424
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A. Stephen K. Hashmi et al.
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(E),(R)-3-Benzylidene-1-(4-bromobenzenesulfonyl)-4- References
(1-propenyl)pyrrolidine [(E),(R)-7]
[1] K. Alder, F. Pascher, A. Schmitz, Ber. Dtsch. Chem. Ges.
1943, 76, 27 53.
[2] B. M. Trost, Acc. Chem. Res. 1990, 23, 34 42; B. M.
Trost, M. J. Krische, Synlett 1998, 1 16.
[3] C. Aubert, O. Buisine, M. Malacria, Chem. Rev. 2002,
102, 813 834.
[4] M. Hatano, M. Terada, K. Mikami, Angew. Chem. 2001,
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[5] A. Goeke, M. Sawamura, R. Kuwano, Y. Ito, Angew.
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1996, 35, 662 663.
[6] P. Cao, X. Zhang, Angew. Chem. 2000, 112, 4270 4272;
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2002, 114, 4708 4711; Angew. Chem. Int. Ed. Engl. 2002,
41, 4526 4529.
In a Schlenk tube compound 6 (83.7 mg, 200 mmol) in dichloro-
ethane (2.0 mL) was degassed. Then [CODRhCl]2 (4.9 mg,
10 mmol) and (R)-BINAP (12.5 mg, 20 mmol) were added. The
solution was stirred for a minute, then a few milligrams of
AgSbF6 were added. The reaction was monitored by TLC,
finally column chromatography (petroleum ether:DCM; 1:1)
gave (E),(R)-7 as a colorless solid; yield: 69.5 mg (166 mmol,
83%). Crystallization from diethyl ether provided a single
crystal for a crystal structure analysis. The ee was 98.5% as
determined by analytical HPLC on a Chiralpak AS 10m
column, isocratic hexane:15% ethanol as the eluent and
comparison with a racemic sample obtained by the same
procedure using rac-BINAP as the ligand [column 250 Â
4.6 mm; flow 1.0 mL/min, temperature 258C, c 1 mg/mL
hexane:ethanol ˆ 1:1, elution times: 7.11 min for the (‡)-
enantiomer and 8.10 min for the (À)-enantiomer]. Rf (petro-
leum ether:DCM; 1:1) ˆ 0.31; mp 129 1318C; IR (neat): n ˆ
3333, 2961, 2866, 1574, 1466, 1447, 1386, 1343, 1164, 1088, 1052,
[8] A. Lei, M. He, S. Wu, X. Zhang, Angew. Chem. 2002,
114, 3607 3610; Angew. Chem. Int. Ed. Engl. 2002, 41,
3457 3460.
1
1005, 963, 814, 739, 688, 616, 574 cmÀ1; H NMR (500 MHz,
CDCl3): d ˆ 1.65 (dd, J ˆ 6.5 Hz, 1.6 Hz, 3H), 2.72 (dd with
similar coupling constants, thus t, J ˆ 9.1 Hz, 9.1 Hz, 1H),
3.32 3.34 (m, 1H), 3.55 (dd, J ˆ 9.1 Hz, 7.7 Hz, 1H), 3.90 (ddd
with two similar coupling constants, thus dt, J ˆ 14.9 Hz,
2.5 Hz, 2.5 Hz, 1H), 4.25 (ddd, J ˆ 14.9 Hz, 2.5 Hz, 1.5 Hz,
1H), 5.12 (ddq, J ˆ 15.1 Hz, 8.2 Hz, 1.6 Hz, 1H), 5.55 (dqd, J ˆ
15.1 Hz, 6.5 Hz, 0.8 Hz, 1H), 6.13 (dd, J ˆ 4.8 Hz, 2.5 Hz, 1H),
7.05 7.07 (m, 2H), 7.16 7.19 (m, 1H), 7.26 7.29 (m, 2H), 7.59
(d, J ˆ 8.8 Hz, 2H), 7.62 (d, J ˆ 8.8 Hz, 2H); 13C NMR
(125 MHz, CDCl3): d ˆ 18.4 (q), 48.7 (d), 51.0 (t), 52.8 (t),
124.5 (d), 127.6 (d), 128.3 (s), 128.5 (d, 2C), 128.8 (d), 129.0 (d,
2C), 129.6 (d, 2C), 130.3 (d), 132.8 (d, 2C), 135.5 (s), 136.7 (s),
[9] A. Lei, M. He, X. Zhang, J. Am. Chem. Soc. 2003, 125,
11472 11473.
[10] A. S. K. Hashmi, P. Haufe, A. Rivas Nass, Adv. Synth.
Catal. 2003, 345, 1237 1241.
[11] S. Thorand, N. Krause, J. Org. Chem. 1998, 63, 8551
8553.
[12] CCDC-226041 (4) and CCDC-226042 [(E)-(R)-7] con-
tain the supplementary crystallographic data for this
paper. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html (or from the
Cambridge Crystallographic Data Centre, 12 Union
Road, Cambridge CB2 1EZ, UK; fax: ( ‡ 44)-1223-336-
033; or e-mail: deposit@ccdc.cam.ac.uk). Due to inter-
esting polymorphism the crystal structure of 6 will be
published separately: J. W. Bats, P. Haufe, A. S. K.
Hashmi, Acta Cryst. Sect. C 2004, to be published.
[13] H. G. Richey Jr., L. M. Moses, M. S. Domalski, W. F.
Erickson, A. S. Heyn, J. Org. Chem. 1981, 46, 3773
3780.
‡
139.6 (s); MS [EI (‡), 70 eV]: m/z (%) ˆ 419 (28) [M ‡ H], 328
‡
‡
‡
(89), 221 (8) [brosyl ], 198 (59) [M
brosyl], 197 (64) [M
brosyl H], 155 (40), 115 (32), 104 (66), 91 (100); anal. calcd. for
C20H20BrNO2S (418.4): C 57.42, H 4.82, N 3.35; found: C 57.35,
H 4.87, N 3.33; [a]20: À 81.88 (c 0.5 g/100 mL, CHCl3). CD data
in the supplementDary material.
Acknowledgements
[14] K. M. Brummond, H. Chen, P. Still, L. You, J. Am.
Chem. Soc. 2002, 124, 15186 15187.
A. S. K. H. thanks the Fonds der Chemischen Industrie, the
Karl-Ziegler Stiftung and Dr. K. Schˆllkopf at Schering AG for
their generous support.
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Adv. Synth. Catal. 2004, 346, 421 424