Catalytic asymmetric intramolecular aminopalladation: Improved palladium(II) catalysts

Article abstract of DOI:10.1021/jo047763f

(Chemical Equation Presented) Cobalt oxazoline palladacyclic (COP) complex 4 containing acetate as a bridging ligand is an excellent catalyst for asymmetric intramolecular aminopalladation to synthesize 4-vinyloxazolidin-2- ones in 91-98% ee. In contrast

Full text of DOI:10.1021/jo047763f

TABLE 1. Enantioselective Conversion of 5 to (S)-6a
Catalytic Asymmetric Intramolecular
Aminopalladation: Improved Palladium(II)
Catalysts
catalyst
(mol %)
solvent
(% HOAc)
time
(h)
yieldb
(%)
eec
entry
(%)
1d
2d
3
2 (5.0)
3 (5.0)
4 (1.0)
4 (1.0)
4 (5.0)
4 (1.0)
4 (1.0)
4 (0.1)
4 (1.0)
CH2Cl2 (0)
CH2Cl2 (0)
CH2Cl2 (0)
CH2Cl2 (5)
CH2Cl2 (15)
CH2Cl2 (20)
HOAc (100)
CH2Cl2 (20)
CH2Cl2 (20)
48
48
6
51
87
>99
87
77
94
71
87
90
92
90
Stefan F. Kirsch and Larry E. Overman*
4
7
Department of Chemistry, 516 Rowland Hall,
University of California, Irvine, California 92697-2025
5
4.5
10
16
4.5
29
>99
94
6
7
75
leoverma@uci.edu
8
4e
9f
87
95
Received December 21, 2004
a Conditions: 23 °C, [substrate] ) 0.6 M. b Yield after column
chromatography. c Determined by HPLC analysis using a Chiracel
OD-H column ((2%). d 23 °C, [substrate] ) 1.5 M. e Conversion
(%, by NMR analysis). f Reaction conducted at 0 °C.
derivatives of (Z)-butene-1,4-diol using the ferrocene
oxazoline palladacyclic (FOP) catalyst 1b.4,5 For example,
cyclization of (Z)-allylic N-tosylcarbamate 5 with 0.5-5
mol % of FOP trifluoroacetate catalyst 1b in 1:1 CH2-
Cl2-MeNO2 at room temperature produced the vinyl-
oxazolidinone 6 in good yield (91-98%) and enantio-
selectivity (90-93% ee) (eq 1). Unfortunately, the iodine-
bridged precatalyst 1a was inactive, thus requiring 1a
to be preactivated by reaction with 4 equiv of silver(I)
trifluoroacetate. We disclose herein a better palladium-
(II) catalyst for this reaction, di-µ-acetatobis[(η5-(S)-(pR)-
2-(2′-(4′-methylethyl)oxazolinyl)cyclopentadienyl,1-C,3′-
N)(η4-tetraphenylcyclobutadiene)cobalt]dipalladium (COP-
OAc, 4),6 which does not require preactivation with a
silver salt.
Recently, we reported that the cobalt oxazoline palla-
dacyclic catalysts 2 (COP-Cl) and 3 (COP-hfacac) promote
the asymmetric rearrangement of prochiral allylic imi-
dates to form enantioenriched chiral allylic amides
without activation by silver salts7 and that COP complex
4 (COP-OAc) catalyzes the asymmetric reaction of these
precursors with carboxylic acids to form chiral allylic
esters.8 Thus, we examined initially the asymmetric
cyclization of allylic N-tosylcarbamate 5 to 2-oxazolidi-
none 6 using these three COP catalysts. As summarized
in Table 1, COP-Cl (2) displayed low reactivity, producing
vinyloxazolidinone 6 in modest enantiopurity (entry 1).
Monomeric COP catalyst 3 was more effective, giving
oxazolidinone (S)-6 in 87% yield and 94% ee after 48 h
at room temperature (entry 2).9 Catalyst 4 containing
acetate as a bridging ligand showed enhanced reactivity.
Cobalt oxazoline palladacyclic (COP) complex 4 containing
acetate as a bridging ligand is an excellent catalyst for
asymmetric intramolecular aminopalladation to synthesize
4-vinyloxazolidin-2-ones in 91-98% ee. In contrast to previ-
ously reported Pd(II) catalysts, COP-OAc (4) promotes the
asymmetric cyclization of (Z)-allylic N-tosylcarbamates with-
out prior activation by silver salts.
Significant development of the catalytic asymmetric
chemistry of palladium(II) has occurred only in the past
decade.1-3 In 2002, we reported the asymmetric construc-
tion of enantioenriched 4-vinyloxazolidin-2-ones from
(1) For the first examples, see: (a) Hosokawa, T.; Miyagi, S.;
Murahashi, D.-I.; Sonoda, A. J. Chem. Soc., Chem. Commun. 1978,
687-688. (b) Hosokawa, T.; Uno, T.; Inui, S.; Murahashi, S.-I. J. Am.
Chem. Soc. 1981, 103, 2318-2323. (c) Hosokawa, T.; Murahashi, S.-I.
Acc. Chem. Res. 1990, 23, 49-54.
(2) Tsuji, J. Palladium Reagents and Catalysts: New Perspectives
for the 21st Century; Wiley: Chichester, England, 2004.
(3) Allylic imidate rearrangements: (a) Calter, M.; Hollis, T. K.;
Overman, L. E.; Ziller, J.; Zipp, G. G. J. Org. Chem. 1997, 62, 1449-
1456. (b) Hollis, T. K.; Overman, L. E. Tetrahedron Lett. 1997, 38,
8837-8840. (c) Uozumi, Y.; Kato, K.; Hayashi, T. Tetrahedron:
Asymmetry 1998, 9, 1065-1072. (d) Cohen, F.; Overman, L. E.
Tetrahedron: Asymmetry 1998, 9, 3213-3222. (e) Jiang, Y.; Longmire,
J. M.; Zhang, X. Tetrahedron Lett. 1999, 40, 1449-1450. (f) Leung,
P.-H.; Ng, K.-H.; Li, Y.; White, A. J. P.; Williams, D. J. J. Chem. Soc.,
Chem. Commun. 1999, 2435-2436. (g) Donde, Y.; Overman, L. E. J.
Am. Chem. Soc. 1999, 121, 2933-2934. (h) Kang, J.; Hyung, K. Y.;
Choi, D. H. Tetrahedron Lett. 2002, 43, 9509-9512. (i) Kang, J.; Kim,
T. H.; Yew, K. H.; Lee, W. K. Tetrahedron: Asymmetry 2003, 14, 415-
418. Synthesis of heterocycles: (j) Uozumi, Y.; Kato, K.; Hayashi, T.
J. Am. Chem. Soc. 1997, 119, 5063-5064. (k) Uozumi, Y.; Kyota, H.;
Kato, K.; Ogasawara, M.; Hayashi, T. J. Org. Chem. 1999, 64, 1620-
1625. (l) Zhang, Q.; Lu, X. J. Am. Chem. Soc. 2000, 122, 7604-7605.
(m) Arai, M. A.; Kuraishi, M.; Arai, T.; Sasai, H. J. Am. Chem. Soc.
2001, 123, 2907-2908. (n) Tietze, L. F.; Sommer, K. M.; Zinngrebe,
J.; Stecker, F. Angew. Chem., Int. Ed. 2005, 44, 257-259. Other
reactions: (o) Sodeoka, M.; Ohrai, K.; Shibasaki, M. J. Org. Chem.
1995, 60, 2648-2649. (p) Sugiura, M.; Nakai, T. Angew. Chem., Int.
Ed. Engl. 1997, 36, 2366-2368. (q) Hagiwara, E.; Fujii, A.; Sodeoka,
M. J. Am. Chem. Soc. 1998, 120, 2474-2475. (r) El-Qisairi, A.; Hamed,
O.; Henry, P. M. J. Org. Chem. 1998, 63, 2790-2791. (s) Mikami, K.;
Hatano, M.; Terada, M. Chem. Lett. 1999, 55-56. (t) Perch, N. S.;
Widenhoefer, R. A. J. Am. Chem. Soc. 1999, 121, 6960-6961. (u) Stark,
M. A.; Jones, G.; Richards, C. J. Organometallics 2000, 19, 1282-1291.
(4) Overman, L. E.; Remarchuk, T. P. J. Am. Chem. Soc. 2002, 124,
12-13.
(5) For a non-asymmetric variant of this reaction, see: Lei, A.; Liu,
G.; Lu, X. J. Org. Chem. 2002, 67, 974-980.
(6) (a) Anderson, C. E.; Kirsch, S. F.; Overman, L. E.; Richards, C.
J.; Watson, M. P. Org. Synth., submitted for publication; available from
the senior author upon request. (b) Stevens, A. M.; Richards, C. J.
Organometallics 1999, 18, 1346-1348. (c) COP-OAc can be generated
from COP-Cl6a,b by reaction in CH2Cl2 at room temperature with 2.5
equiv of AgOAc, followed by filtration through silica gel. (S)-COP-Cl
is available currently from Aldrich Chemical Co. (64663-6); both (S)-
and (R)-COP-OAc will be available commercially shortly.
(7) (a) Kirsch, S. F.; Overman, L. E.; Watson, M. P. J. Org. Chem.
2004, 69, 8101-8104. (b) Anderson, C. E.; Overman, L. E. J. Am. Chem.
Soc. 2003, 125, 12412-12413. (c) Overman, L. E.; Owen, C. E.; Pavan,
M. M.; Richards, C. J. Org. Lett. 2003, 5, 1809-1812.
(8) Kirsch, S. F.; Overman, L. E. J. Am. Chem. Soc., in press.
10.1021/jo047763f CCC: $30.25 © 2005 American Chemical Society
Published on Web 03/11/2005
J. Org. Chem. 2005, 70, 2859-2861
2859

Thus, oxazolidinone (S)-6 was obtained in excellent yield
after 6 h in CH2Cl2 at room temperature in the presence
of 1 mol % of COP-OAc (4), although enantiopurity was
modest (entry 3). To our surprise, adding acetic acid as
a cosolvent significantly improved enantioselection in
forming oxazolidinone (S)-6, although the catalysis rate
was slowed somewhat (entries 4-7).10 The best compro-
mise between reaction rate and enantioselectivity was
realized using a 4:1 mixture of CH2Cl2-HOAc, in which
case oxazolidinone (S)-6 was produced in in 94% yield
and 92% ee after 10 h using 1 mol % of catalyst 4 (entry
6). Performing the cyclization of carbamate 5 at 38 °C
slightly increased the reaction rate with little erosion in
enantioselectivity. Reducing the catalyst concentration
to 0.1 mol % led to only 4% conversion after 4.5 h at room
temperature (entry 8). Enantiomeric purity of (S)-6 was
improved to 95% ee at 0 °C, however a reaction time of
29 h was required to obtain a satisfactory yield (entry
9). As the use of an excess of a silver salt is not required
for the COP-OAc catalyzed cyclization of 5 to (S)-6, this
method is more practical than the one we reported
previously.4
It is also possible to conduct the COP-OAc-catalyzed
cyclization with crude allylic N-tosylcarbamates prepared
in situ from the reaction an allylic alcohol with an
N-sulfonylisocyanate, a modification that is particularly
advantageous with tertiary allylic alcohols whose sulfo-
nylcarbamate derivatives are quite labile. Three ex-
amples of this sequence are shown in eqs 2-4. In each
case, the 5,5-disubstituted 2-vinyloxazolidin-2-one prod-
uct was produced in high enantiomeric purity (91-98%
ee) and in good overall yield (81-89%) when the cycliza-
tion was carried out at 38 °C in 4:1 CH2Cl2-HOAc using
1 mol % of COP-OAc (4). As observed with FOP catalyst
1b, the intramolecular aminopalladation method re-
ported herein is limited to (Z)-allylic acetates; E stereo-
isomers were not transformed at room temperature or
at 38 °C.
In conclusion, we have described an improved method
for the palladium(II)-catalyzed asymmetric cyclization of
prochiral (Z)-4-acetoxy-3-alkenyl N-tosylcarbamates to
give chiral 2-vinyloxazolidin-2-ones. As preactivation of
the catalyst by reaction with silver salts is not required,
the COP-OAc (4) catalyzed reaction has distinct advan-
tage over the FOP-catalyzed procedure described earlier
from our laboratories.4
6]4,5 as a colorless solid (75 mg, 0.28 mmol; 94%): mp 75-77 °C
(lit.4 mp 69-72 °C); [R]25589 ) -30.5 (c ) 2.1, CHCl3) [lit.4 [R]25
Experimental Section.
589
) -29.0 (c ) 1.1, CHCl3)]; HPLC analysis indicated an enan-
tiomeric excess of 92% [Chiralcel OD-H column; flow: 1.0 mL/
min; hexanes/i-PrOH, 90:10; 230 nm; minor enantiomer (+)-6,
tR ) 25.95 min; major enantiomer (-)-6, tR ) 27.93 min]; other
characterization data were identical to those reported.4
Prochiral (Z)-4-acetoxybut-2-enyl tosylcarbamate (5) and (Z)-
acetoxybutenols 7, 9, and 11 were prepared by literature
procedures.4,5
Representative Procedure for COP-OAc-Catalyzed Cy-
clization of Tosylcarbamates. COP-OAc (4; 1 mol %, 3.0 ×
10-3 mmol, 4.5 mg) was added to a solution of tosylcarbamate 5
(98 mg, 0.30 mmol) in CH2Cl2-HOAc (4:1, v/v; 0.5 mL), and the
reaction vial was sealed, protected from light, and maintained
at room temperature. After 10 h, the orange solution was
concentrated under reduced pressure. Purification of the residue
by flash chromatography on silica gel with 8:2 hexanes-EtOAc
as eluent gave 3-p-toluenesulfonyl-4-vinyloxazolidin-2-one [(S)-
Representative Procedure for COP-OAc-Catalyzed Cy-
clization of Crude Tosylcarbamates Prepared in Situ.
p-Toluenesulfonyl isocyanate (0.64 mmol, 130 mg, 0.097 mL) was
added dropwise to an ice-cold solution of alcohol 9 (0.50 mmol,
99 mg) in CH2Cl2 (0.5 mL). The ice bath was removed, and the
solution was allowed to warm to room temperature. After 3 h,
the mixture was concentrated under reduced pressure. To this
residue were added CH2Cl2-HOAc (4:1, v/v; 0.5 mL) and COP-
OAc (4; 1 mol %, 5.0 × 10-3 mmol, 7.6 mg), and the reaction
vial was sealed, protected from light and maintained at room
temperature for 5 h, and then warmed to 38 °C for 15 h. The
orange solution was concentrated under reduced pressure.
Purification of the residue by flash chromatography on silica gel
(9) COP-hfacac (3) was also used in solvents other than CH2Cl2. In
CH3CN, acetone and THF under identical conditions, catalyst 3 showed
lower reactivity with enantioselectivities e60% ee.
(10) The origin of this effect remains unclear.
2860 J. Org. Chem., Vol. 70, No. 7, 2005

with 85:15 hexanes-EtOAc as eluent gave vinyl-substituted
2-oxazolidinone (S)-104 as a colorless solid (137 mg, 0.41 mmol;
Humboldt Foundation for a Feodor Lynen Fellowship
(S.F.K.).
82%): mp 106-108 °C; [R]25 ) -37.1 (c ) 2.8, CHCl3) [lit.4
589
[R]25 ) -35.9 (c ) 1.0, CHCl3)]; HPLC analysis indicated an
589
enantiomeric excess of 97% [Chiralcel OD-H column; flow: 1.0
mL/min; hexanes/i-PrOH, 90:10; 230 nm; minor enantiomer (+)-
10, tR ) 10.11 min; major enantiomer (-)-10, tR ) 12.36 min];
other characterization data were identical to those reported.4
Supporting Information Available: Copies of HPLC
traces used to determine enantiopurity of cyclization products;
copies of 1H and 13C NMR spectra for 2-oxazolidinone products.
This material is available free of charge via the Internet at
http://pubs.acs.org.
Acknowledgment. We thank the NSF (CHE-
9726471) for financial support and the Alexander von
JO047763F
J. Org. Chem, Vol. 70, No. 7, 2005 2861