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DOI: 10.1055/s-0031-1289540
Fragment-Based Reaction Discovery of Non-Ene-Type Carbon-Carbon Bond-Forming Reactions: Catalytic Asymmetric Oxetane Synthesis by Screening Olefinic Reactants without Allylic Hydrogen
Publication History
Publication Date:
19 October 2011 (online)
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Abstract
Through fragment-based reaction discovery, catalytic asymmetric [2+2] cycloaddition was found to produce oxetanes from trifluoropyruvate and olefinic reactants without allylic hydrogen. This non-ene-type carbon-carbon bond-forming reaction smoothly proceeded under the influence of chiral Pd or Cu complexes as Lewis acid catalysts. The [2+2] cycloaddition afforded the oxetane derivatives in high yields and enantioselectivities even under 0.1 mol% catalyst loading and solvent-free conditions.
Key words
fragment-based - Lewis acid catalyst - [2+2] cycloaddition - oxetane - trifluoromethyl
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References and Notes
Crystal data for 16:
C21H27F3N2O5;
orthorhombic; space group P212121; a = 6.3390
(11) Å, b = 17.252
(3) Å, c = 20.143
(4) Å; V = 2202.9
(7) ų; Z = 4; D
calc = 1.340 Mgm-³; µ = 0.112
mm-¹. All measurements were made
with
a Bruker APEXII CCD area detector with graphite monochromated Mo-Kα radiation
at 93 K. Of the 9577 reflections that were collected, 3935
were unique (R
int = 0.0329). R
1 = 0.0716, wR = 0.1805,
goodness of fit = 1.052; Flack Parameter = 0.1
(13), shift/error = 0.000. CCDC-838360
contains the supplementary crystallographic data for this paper.
These data can be obtained free of charge from the Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif
Enantioselective [2+2] Cycloaddition
Catalyzed by (
S
,
S
)-
t
-Bu-Box-Cu(2)
(Table 2, entry 1); Typical Procedure: (S,S)-t-Bu-Box-Cu(OTf)2 catalyst
was prepared by the addition of Cu(OTf)2 (3.6 mg, 0.01
mmol) to (S,S)-2,2′-isopropylidenebis(4-tert-butyl-2-oxazoline) (3.2 mg, 0.011 mmol)
under an argon atmosphere. The mixture was dried under vacuum for
1 h, then Et2O (1.0 mL) was added under an argon atmosphere
and the resulting suspension was stirred vigorously for 1 h at r.t.
To the solution at -40 ˚C were added
ethyl trifluoropyruvate 3 (26.5 µL,
0.2 mmol) followed by tri(isopropyl)silyl enol ether (9a; 20.0 mg, 0.1 mmol). After stirring
at -40 ˚C for 2.5 h, the reaction mixture
was directly loaded onto a short silica gel column (hexane-EtOAc,
1:1) to remove the catalyst. The solution was evaporated under reduced
pressure. Purification by silica-gel chromatography (hexane-EtOAc,
20:1) gave the corresponding oxetane 11a (84% yield)
as a clear liquid. The cis/trans ratio was determined by ¹9F
NMR analysis (cis/trans, 99:1; the major configuration
of the oxetane products was determined to be cis from
the results of NOE experiments, which are summarized in Scheme
[4]
).
(2
S
,4
R
)-Ethyl 2-Trifluoromethyl-4-(triisopropylsiloxy)-oxetane-2-carboxylate
(11a): ¹H NMR (300 MHz, CDCl3): δ = 1.06
(m, 21 H), 1.33 (t, J = 7.2
Hz, 3 H), 2.82 (dd, J = 12.6,
4.2 Hz, 1 H), 3.11 (dd, J = 12.6,
5.1 Hz, 1 H), 4.33 (q, J = 7.2
Hz, 2 H), 5.90 (dd, J = 5.1,
4.2 Hz, 1 H); ¹³C NMR (75.5
MHz, CHCl3): δ = 11.8, 13.9, 17.5,
37.6 (q, J
C-F = 0.8
Hz), 62.6, 76.1 (q, J
C-F = 33.2
Hz), 95.7, 122.3 (q, J
C-F = 283.1
Hz), 167.6; ¹9F NMR (282 MHz, CDCl3): δ = -79.0
(s, 3 F); FTIR (neat): 2947, 2896, 2870, 1751, 1466, 1390,
1286, 1187, 1113, 1039, 919, 883, 685 cm-¹;
HRMS (APCI-TOF): m/z [M + H]+ calcd
for C16H29F3O4Si: 371.1865;
found: 371.1889; [α]D
²4 -4.48
(c 1.08, CHCl3) for 98% ee
(cis/trans = 99:1);
GC (column, CP-Chirasil-Dex CB, i.d. 0.25 mm × 25
m, CHROMPACK; carrier gas, nitrogen 75 kPa; column temp. 120 ˚C;
injection and detection temp. 150 ˚C): t
R = 36.2 (major
isomer), 38.3 (minor isomer) min.
(2
S
,3
R
,4
R
)-Ethyl 3-Benzyloxymethyl-2-trifluoromethyl-4-(triisopropylsiloxy)oxetane-2-carboxylate
(11g): ¹H NMR (300 MHz, CDCl3): δ = 1.07
(m, 21 H), 1.31 (t, J = 7.2 Hz,
3 H), 3.62 (ddd, J = 9.6,
5.7, 4.2 Hz, 1 H), 3.75 (dd, J = 9.6,
4.2 Hz, 1 H), 4.13 (dd, J = 9.6,
9.6 Hz, 2 H), 4.32 (m, 2 H, OCH
2CH3),
4.46 (d, J = 18.6
Hz, 1 H), 4.50 (d, J = 18.6 Hz,
1 H), 5.96 (d, J = 5.7
Hz, 1 H), 7.29 (m, 5 H); ¹³C
NMR (75.5 MHz, CDCl3): δ = 11.8, 13.9,
17.5, 47.5, 62.6, 63.1 (q, J
C-F = 2.3
Hz), 73.4, 80.3 (q, J
C-F = 32.5
Hz), 97.3, 122.2 (q, J
C-F = 285.4
Hz), 127.7, 127.8, 128.3, 137.7, 167.5; ¹9F NMR
(282 MHz, CDCl3): δ = -72.8
(s, 3 F); FTIR (neat): 2947, 2869, 1750, 1656, 1466, 1278,
1200, 1091, 1028, 883, 688 cm-¹;
HRMS (ESI-TOF): m/z [M + Na]+ calcd
for C24H37F3NaO5Si:
513.2260; found: 513.2281; [α]D
²5 +30.68 (c 1.39, CHCl3) for 90% ee
(cis/trans = 97:3);
HPLC (column, CHIRALPAK AS-H, Hexane/2-Propanol = 97/3, flow
rate 0.6 mL/min, 20 ˚C, detection, UV
218 nm): t
R = 33.6
( minor isomer), 41.5 (major isomer)
min.
Enantioselective [2+2] Cycloaddition
Catalyzed by (
S
)-BINAP-Pd(1b)
(Table 2, entry 3); Typical Procedure:
To a solution
of PdCl2[(S)-BINAP] (8.0
mg, 0.01 mmol) in toluene (1.0 mL) was added AgSbF6 (7.6
mg, 0.022 mmol) at r.t. under an argon atmosphere. After stirring
for 30 min, ethyl trifluoropyruvate 3 (26.5 µL,
0.2 mmol) and freshly distilled vinyl acetate 9h (9.3 µL,
0.1 mmol) were added to the mixture at -20 ˚C.
After stirring at -20 ˚C for 15 h, Et3N (50 µL)
was added and the mixture was directly loaded onto a short silica
gel column (hexane-EtOAc, 1:1) to remove the catalyst.
The solution was evaporated under reduced pressure. Purification
by silica-gel chromatography (hexane-EtOAc, 4:1) gave the
corresponding oxetane product 11h as a
clear liquid (88% yield). The diastereo-meric ratio was
determined by ¹9F NMR analysis (dr = 77:23).
Enantioselective [2+2] Cycloaddition
Catalyzed by (
S
)-BINAP-Pd(1b)
under Solvent-Free Conditions (Table 2, entry 7): To a solution
of PdCl2[(S)-BINAP] (4.0
mg, 0.005 mmol) in ethyl trifluoropyruvate 3 (1.3
mL, 10 mmol) was added silver hexafluoroantimonate (3.8 mg, 0.011
mmol) at r.t. under an argon atmosphere. After stirring for 30 min, freshly
distilled vinyl acetate 9h (461 µL,
5 mmol) was added to the mixture at -20 ˚C.
After stirring at -20 ˚C for 48 h, Et3N
(50 µL) was added and the mixture was directly loaded onto
a short silica gel column (hexane-EtOAc, 1:1) to remove
the catalyst. The solution was evaporated under reduced pressure.
Purification by silica gel chromatography (hexane-EtOAc,
4:1) gave the corresponding oxetane product 11h as
a clear liquid (86% yield). The diastereo-meric ratio was
determined by ¹9F NMR analysis (dr = 92:8).
(2
R
)-Ethyl 4-Acetoxy-2-(trifluoromethyl)oxetane-2-carboxylate
(11h): ¹H NMR (300 MHz, CDCl3): δ = 1.33
(t, J = 7.2
Hz, 3 H), 2.12 (s, 3 H), 3.04 (ddq, J = 13.2,
4.2 Hz, J
H-F = 0.6
Hz, 1 H), 3.27 (dd, J = 13.2,
5.4 Hz, 1 H), 4.36 (q, J = 7.2
Hz, 2 H), 6.48 (dd, J = 5.4,
4.2 Hz, 1 H); ¹³C NMR (75.5
MHz, CDCl3): δ = 13.6, 20.5, 33.4,
62.8, 78.1 (q,
J
C-F = 34.0
Hz), 93.4, 122.7 (q, J
C-F = 283.1
Hz), 165.4, 168.8; ¹9F NMR (282.4 MHz, CDCl3): δ = -79.4
(s, 3 F, major isomer), -79.3 (s, 3 F,
minor isomer); FTIR (neat): 2990, 1764, 1447, 1371, 1308, 1219,
1096, 1037, 961, 679 cm-¹;
HRMS (APCI-TOF): m/z [M + H]+ calcd
for C9H11F3O5: 257.0637;
found: 257.0680; [α]D
²5 +42.97
(c 1.21, CHCl3) for 98% ee/94% ee
(dr = 85:15); GC (column, CP-Chirasil-Dex
CB, i.d. 0.25 mm × 25 m, CHROMPACK; carrier
gas, nitrogen 75 kPa; column temp 85 ˚C; injection and
detection temp, 115 ˚C): t
R = 20.0
( major isomer), 22.0 (minor isomer) min.