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DOI: 10.1055/s-0029-1218353
One-Pot, Three-Component Synthesis of Chiral 4-Alkylidene-2-oxazolidinones
Publication History
Publication Date:
11 November 2009 (online)
Abstract
A one-pot convenient access to chiral 2-oxazolidinones is described. Diethylzinc-mediated asymmetric alkynylation of aldehydes with propiolates in the presence of β-sulfonamide alcohol as the chiral ligand, followed by treatment with isocyanates, yielded chiral 4-alkylidene-2-oxazolidinones.
Key words
oxazolidinone - heterocycle - multicomponent reaction - asymmetric synthesis - alkyne
- 1 For a recent review of multicomponent
reactions, see:
Ganem B. Acc Chem. Res. 2009, 42: 463 - 2 For a recent review of the biological
activities of 2-oxa-zolidinones, see:
Zappia G.Menendez P.Monache GD.Misiti D.Nevola L.Botta B. Mini Rev. Med. Chem. 2007, 7: 389 - 3 For a recent review of 2-oxazolidinones
in synthetic organic chemistry, see:
Zappia G.Cancelliere G.Gacs-Baitz E.Monache GD.Misiti D.Nevola L.Botta B. Curr. Org. Synth. 2007, 4: 238 - 4 For a recent review of the synthesis
of 2-oxazolidinones, see:
Zappia G.Gacs-Baitz E.Monache GD.Misiti D.Nevola L.Botta B. Curr. Org. Synth. 2007, 4: 81 - 5
Ramesh R.Chandrasekaran Y.Megha R.Chandrasekaran S. Tetrahedron 2007, 63: 9153 ; and references therein -
6a
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6b
Ritter S.Horino Y.Lex J.Schmalz H.-G. Synlett 2006, 3309 -
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Tamaru Y.Kimura M.Tanaka S.Kure S.Yoshida Z. Bull. Chem. Soc. Jpn. 1994, 67: 2383 -
6d
Ohe K.Matsuda H.Ishihara T.Chatani N.Kawasaki Y.Murai S. J. Org. Chem. 1991, 56: 2267 -
6e
Kimura M.Kure S.Yoshida Z.Tanaka S.Fugami K.Tamaru Y. Tetrahedron Lett. 1990, 31: 4887 -
6f For a related Pd-catalyzed
transformation, see:
Lei A.Lu X. Org. Lett. 2000, 2: 2699 ; and references therein -
7a
Kato H.Shibata I.Kanazawa N.Yasuda M.Baba A. Eur. J. Org. Chem. 2006, 1117 -
7b
Shibata I.Kato H.Kanazawa N.Yasuda M.Baba A. J. Am. Chem. Soc. 2004, 126: 466 - 8 For a recent review of asymmetric
alkynylations of carbonyl compounds, see:
Trost BM.Weiss AH. Adv. Synth. Catal. 2009, 351: 963 - 9
Lin L.Jiang X.Liu W.Qiu L.Xu Z.Xu J.Chan ASC.Wang R. Org. Lett. 2007, 9: 2329 - 14 A similar mechanism of the isomerization
was reported. See:
Naito H.Hata T.Urabe H. Tetrahedron Lett. 2008, 49: 2298 - 16
Frisch MJ.Trucks GW.Schlegel HB.Scuseria GE.Robb MA.Cheeseman JR.Montgomery JA.Vreven T.Kudin KN.Burant JC.Millam JM.Iyengar SS.Tomasi J.Barone V.Mennucci B.Cossi M.Scalmani G.Rega N.Petersson GA.Nakatsuji H.Hada M.Ehara M.Toyota K.Fukuda R.Hasegawa J.Ishida M.Nakajima T.Honda Y.Kitao O.Nakai H.Klene M.Li X.Knox JE.Hratchian HP.Cross JB.Bakken V.Adamo C.Jaramillo J.Gomperts R.Stratmann RE.Yazyev O.Austin AJ.Cammi R.Pomelli C.Ochterski JW.Ayala PY.Morokuma K.Voth GA.Salvador P.Dannenberg JJ.Zakrzewski VG.Dapprich S.Daniels AD.Strain MC.Farkas O.Malick DK.Rabuck AD.Raghavachari K.Foresman JB.Ortiz JV.Cui Q.Baboul AG.Clifford S.Cioslowski J.Stefanov BB.Liu G.Liashenko A.Piskorz P.Komaromi I.Martin RL.Fox DJ.Keith T.Al-Laham MA.Peng CY.Nanayakkara A.Challacombe M.Gill PMW.Johnson B.Chen W.Wong MW.Gonzalez C.Pople JA. Gaussian 03, Revision E.01 Gaussian, Inc.; Wallingford / CT: 2004.
References and Notes
The absolute configuration of 2-oxazolidinone 1a was assumed based on propargyl alcohol 2 whose absolute configuration was determined by the modified Mosher method.
11The stereochemistry of the alkene moiety was assigned by nuclear Overhauser effect (NOE) experiment. Irradiation of the alkenyl proton caused an increment of the area intensity of the aromatic proton at the meta position of the tosyl group.
12
General Procedure
for One-Pot, Three-Component Synthesis of Chiral 2-Oxazolidinones
(Table 1, Entry 1)
Ethyl propiolate (0.304 mL, 3.00
mmol) was added to a stirred mixture of (S)-2-(methanesulfonylamino)-1,1-diethyl-3-phenyl-1-propanol (108 mg, 0.300 mmol), DME (0.105 mL, 1.00
mmol), and Et2Zn (1.0 M in n-hexane,
3.00
mL, 3.00 mmol) in toluene (6 mL) at r.t. under Ar atmosphere. After
12 h at the same temperature, Ti(Oi-Pr)4 (0.089
mL, 0.300 mmol) was added and the reaction mixture stirred for 0.5
h. To the resulting solution was added cyclohexanecarbaldehyde (0.121
mL, 1.00 mmol) in one portion. After 2 h, tosyl isocyanate (0.490
mL, 3.20 mmol) was added to the mixture. After 12 h, the reaction
was quenched with sat. NH4Cl, and the mixture was extracted with
EtOAc. The combined organic layers were washed with sat. NH4Cl,
H2O, and brine, dried, and the solvent was evaporated.
Purification by column chromatography over silica gel with n-hexane-Et2O (19:1)
as eluent yielded
(R,E)-ethyl 2-(5-cyclohexyl-2-oxo-3-tosyloxazolidin-4-ylidene)acetate
(1a, 316 mg, 77%, 80% ee)
as a colorless amorphous solid.
Characterization
Data of Selected Compounds
(
R
,
E
)-Ethyl 2-(5-Cyclohexyl-2-oxo-3-tosyloxazolidin-4-ylidene)acetate
(1a)
Colorless amorphous solid; [α]D
²6 +148.9
(c 1.00, CHCl3). ¹H
NMR (500 MHz, CDCl3): δ = 0.83-0.91
(m, 1 H), 1.01-1.16 (m, 2 H), 1.22-1.39 (m, 4
H), 1.32 (t, J = 7.3
Hz, 3 H), 1.53-1.61 (m, 1 H), 1.73-1.75 (m, 2
H), 2.01-2.11 (m, 1 H), 2.47 (s, 3 H), 4.19 (q, J = 7.3 Hz,
2H), 5.54 (s, 1 H), 6.45 (s, 1 H), 7.39 (d, J = 7.9
Hz, 2 H), 7.98 (d, J = 7.9
Hz, 2 H). ¹³C NMR (75 MHz, CDCl3): δ = 14.2,
21.8, 23.8, 25.5, 25.6, 26.0, 29.2, 41.7, 60.6, 83.2, 98.3, 128.4
(2 C), 129.9 (2 C), 133.7, 146.8, 149.9, 150.6, 165.7. IR (KBr):
1805, 1709, 1647 cm-¹. MS (EI): m/z (%) = 407
(1.1) [M]+, 362 (10.6) [M - OEt]+,
325 (100) [M + H - C6H11]+,
252 (17.2) [M - Ts]+.
HRMS (EI): m/z [M]+ calcd
for C20H25O6NS: 407.1403; found:
407.1405. HPLC column: DAICEL CHIRALPAK® IC
(250 ¥ 4.6 mm), n-hexane-i-PrOH (91:9), 5 mL/min, t
R = 35.2
min for 1a and t
R = 33.1
min for enantio-1a.
(
R
,
E
)-Ethyl 2-[5-Cyclohexyl-3-(4-fluorophenyl)-2-oxooxazolidin-4-ylidene]acetate
(1d)
Colorless needles; [α]D
²5 +139.8
(c 1.00, CHCl3); mp 160-161 ˚C
(n-hexane-EtOAc). ¹H
NMR (500 MHz, CDCl3): δ = 1.14-1.39
(m, 4 H), 1.25 (t, J = 7.3
Hz, 3 H), 1.52-1.60 (m, 2 H), 1.67-1.70 (m, 1
H), 1.82-1.93 (m, 3 H), 2.26-2.34 (m, 1 H), 4.11
(dq, J = 11.0,
7.3 Hz, 1 H), 4.16 (dq, J = 11.0, 7.3
Hz, 1 H), 4.99 (d, J = 1.8
Hz, 1 H), 5.70 (t, J = 1.8
Hz, 1 H), 7.17-7.29 (m, 4 H). ¹³C
NMR (75 MHz, CDCl3): δ = 14.1,
24.0, 25.65, 25.71, 26.1, 29.6, 41.1, 60.1, 84.0, 91.0, 117.1 [d, ²
J(C,F) = 23.0
Hz, 2 C], 128.6 [d, 4
J(C,F) = 3.1
Hz], 129.2 [d, ³
J(C,F) = 8.7
Hz, 2 C], 155.0, 157.0, 162.6 [d, ¹
J(C,F) = 249.7
Hz], 166.1. IR (KBr): 1792, 1701, 1645 cm-¹.
MS (EI): m/z (%) = 347
(17.6) [M]+, 302 (4.3) [M - OEt]+,
265 (100.0) [M + H - C6H11]+.
HRMS (EI): m/z [M]+ calcd
for C19H22NO4F: 347.1533; found:
347.1556. HPLC column: DAICEL CHIRALPAK® IC
(250 ¥ 4.6 mm), n-hexane-i-PrOH (91:9), 5 mL/min, t
R = 22.0
min for 1d and t
R = 24.1
min for enantio-1d.
(
R
,
E
)-Ethyl 2-[5-(2-Bromophenyl)-2-oxo-3-tosyloxazolidin-4-ylidene]acetate
(1h)
Colorless plates; mp 175-176 ˚C
(n-hexane-EtOAc); [α]D
²³ +204.8
(c 1.00, CHCl3). ¹H
NMR (500 MHz, CDCl3): δ = 1.12
(t, J = 7.3
Hz, 3 H), 2.50 (s, 3 H), 3.98 (dq, J = 11.0, 7.3
Hz, 1 H), 4.02 (dq, J = 11.0,
7.3 Hz, 1 H), 6.67 (d, J = 2.4 Hz,
1 H), 6.93 (d, J = 2.4
Hz, 1 H), 7.08-7.11 (m, 1 H), 7.22-7.25 (m, 2
H), 7.43 (d, J = 8.5
Hz, 2 H), 7.60-7.63 (m, 1 H), 8.05 (d, J = 8.5
Hz, 2 H). ¹³C NMR (75 MHz, CDCl3): δ = 13.9,
21.8, 60.7, 80.1, 100.2, 124.8, 127.6, 127.9, 128.5 (2 C), 130.1
(2 C), 131.1, 133.4 (2 C), 134.6, 147.08, 147.13, 149.7, 164.7.
IR (KBr): 1809, 1714, 1655 cm-¹. MS
(EI):
m/z (%) = 479
(3.6) [M]+, 400 (19.8) [M - Br]+,
371 (6.2)
[M - Br - Et]+,
324 (18.4) [M + H - Br - C6H5]+,
278 (26.7) [M - Br - C6H5 - OEt]+,
91 (100). HRMS (FAB): m/z [M + H]+ calcd
for C20H19BrNO6S: 480.0116; found:
480.0103. HPLC column: DAICEL CHIRALPAK® IC
(250 ¥ 4.6 mm), n-hexane-CH2Cl2 (30:70),
1 mL/min, t
R = 41.7
min for 1h and t
R = 44.8
min for enantio-1h.
In the case of the use of phenyl isocyanate
(Table
[¹]
, entry
5), the slight decrease in optical purity was observed throughout the
one-pot reaction, indicating isomerization of
(E)-alkenylzinc 3b into
alkenylzinc 3a via enol 5.