Checked by Robert K. Boeckman, Jr., Jacqueline C. Bussolari, and Michael R. Reeder.
1. Procedure
B.
(+)-Dirhodium(II) tetrakis[methyl 2-pyrrolidone-5(R)-carboxylate] acetonitrile-isopropanol solvate, (+)-Rh
2 [(5R)-MEPY]
4 (CH
3CN)
2 (
i-PrOH). A
50-mL, single-necked, round-bottomed flask, equipped with a Teflon-coated stirring bar and nitrogen inlet, is flushed with
nitrogen and charged with
200 mg (0.452 mmol) of rhodium(II) acetate (Note
5),
1.02 g (7.13 mmol) of methyl 2-pyrrolidone-5(R)-carboxylate, and
20 mL of chlorobenzene (Note
6). The flask is fitted with a
Soxhlet extraction apparatus (Note
7) into which is placed a thimble containing 5 g of an oven-dried mixture of 2 parts
sodium carbonate and 1 part of sand (Note
8). The initially green
rhodium acetate, upon mixing with the pyrrolidonecarboxylate forms a blue solution, which is heated at reflux under
nitrogen for 6 hr (Note
9); removal of the solvent under reduced pressure using a rotary evaporator yields a blue, glass-like solid. The solid is dissolved in a minimal volume of
methanol and purified by chromatography on a column containing J.T. Baker BAKERBOND Cyano 40 μm prep LC pacKing (10 g) in
methanol. The dirhodium(II) product forms a broad blue band across the top of the column, which moves imperceptively with
methanol. However, the excess ligand moves rapidly as a yellow/brown band in
methanol and may be collected with the first 100 mL of eluent (Note
10). Subsequent elution with
1.0 vol % acetonitrile in methanol causes an instantaneous color change from blue to red and rapid elution. The entire red band is collected as one fraction, and the solvent is removed under reduced pressure (Note
11), (Note
12). The resulting blue, glass-like solid (
380 mg) is recrystallized by dissolving the solid in
1.0 mL of acetonitrile per
100 mg of solid and then adding an equivalent amount of
isopropyl alcohol. Bright red crystals of Rh
2 (5R-MEPY)
4 (CH
3CN)
2 (i-PrOH) form overnight, and are collected by suction, washed with
isopropyl alcohol and air-dried to yield
240 mg (
0.262 mmol,
58% yield) (Note
13).
2. Notes
2.
HPLC grade methanol (Aldrich Chemical Company, Inc.) was used without further purification.
3. This titration generally requires the addition of
8 mL of aqueous, saturated sodium carbonate solution.
4. The literature value for this ester is reported to be
[α]D −8.7° (EtOH,
c 1.13).
2 The NMR spectra are as follows:
1H NMR (300 MHz, CDCl
3) δ: 2.18–2.56 (m, 4 H), 3.78 (s, 3 H), 4.26 (dd, 1 H, J = 8.5, 5.1), 6.25 (s(br), 1 H);
13C NMR (75 MHz, CDCl
3) δ: 25.3, 29.9, 53.1, 56.1, 173.3, 179.1.
5.
Rhodium(II) acetate is obtained commercially (Degussa Corporation, Aldrich Chemical Company, Inc., AESAR/Johnson Matthey, or Johnson Matthey/Alfa Products) or prepared from
rhodium(III) chloride hydrate (Johnson Matthey) by the standard literature procedure.
3
7. A
micro Soxhlet extraction apparatus (Ace Glass, Inc.) consisting of the extractor, a 50-mL round-bottomed flask, and an Allihn condenser fitted with a 10 × 50 mm thimble is used.
8.
Sodium carbonate is used to trap
acetic acid liberated in the ligand exchange reaction. Sand is included to maintain the porosity of the solid. A layer of sand at the top of the carbonate mixture prevents
sodium carbonate from entering the reaction flask.
9. When the reaction is followed by HPLC using a
μ-Bondapak-CN column with
2% acetonitrile in methanol as the eluent, two bands are observed initially: a broad band eluting with the solvent front [
chlorobenzene and excess
methyl 2-pyrrolidone-5(R)-carboxylate] and a second band at 1.6 min when the flow rate is 1.5 mL/min [
rhodium(II) acetate]. As the reaction progresses, the rhodium(II) acetate band diminishes and is replaced by several bands with longer retention volumes until one major band, in addition to that for
chlorobenzene and ligand, is observed at about 4 min. Only minor impurities elute at intermediate times. A brown-black material, insoluble in all common solvents, is observed in some preparations. The origin of this material is unknown, but its presence decreases product yield by 25%.
11. This material is >95% pure by HPLC analysis.
12. Direct recrystallization is an alternative to chromatography, but decreased yields result because of the large amount of unreacted ligand present. In this procedure
1 mL of acetonitrile is added to the crude, blue glass-like solid. The resulting solution is filtered through glass wool and
5 mL of isopropyl alcohol is added. Overnight refrigeration gives a 38% yield of red crystals that are identical with those described in the procedure.
13. This procedure produced analytically pure crystals with the following physical properties: Anal. Calcd for C
31H
46N
6O
13Rh
2: C, 40.63; H, 5.06; N, 9.17. Found: C, 40.37, H, 5.11; N, 9.12;
1H NMR (300 MHz, CDCl
3) δ: 1.21 (d, 6 H, J = 6.1), 1.35 (d, 1 H, J = 4.4), 1.8–2.4 (m, 12 H), 2.26 (s, 6 H), 2.55–2.70 (m, 4 H), 3.68 (s, 6 H), 3.70 (s, 6 H), 3.95 (dd, 2 H, J = 8.6, 2.1), 3.96–4.08 (m, 1 H), 4.32 (dd, 2 H, J = 8.8, 3.0);
13C NMR (75 MHz, CDCl
3) δ: 2.9, 25.0, 25.2, 26.0, 31.2, 31.4, 51.6, 51.9, 64.0, 66.4, 66.6, 114.9, 175.5, 175.7, 188.3, 188.5.
[α]24D +270.6° (CH
3CN,
c 0.112).
15. This reaction has an induction period. If too much
diketene is added before condensation begins, an exotherm may result. Reaction onset is evident by a color change and a significant increase in temperature.
16. The NMR spectra are as follows:
1H NMR (300 MHz, CDCl
3) δ: 1.72 (s, 3 H), 1.79 (s, 3 H), 2.27 (s, 3 H), 3.45 (s, 2 H), 4.64 (d, 2 H, J = 7.3), 5.32–5.40 (m, 1 H); enol form at 1.96 (s) and 4.99 (s).
13C NMR (75 MHz, CDCl
3) δ: 18.5, 26.2, 30.5, 50.5, 62.6, 118.6, 140.2, 167.7, 201.2 (minor amounts of the enol tautomer may also be present).
17. Commercially available
p-acetamidobenzenesulfonyl azide (Aldrich Chemical Company, Inc.) was preferred over
p-dodecylbenzenesulfonyl azide (Danheiser, R. L.; Miller, R. F.; Brisbois, R. G.
Org. Synth., Coll. Vol. IX 1998, 197, Note 9;
Ref. 4a), or
methanesulfonyl azide4 for reasons of safety, yield, and ease of manipulation. See also Davies, H. M. L.; Cantrell, Jr., W. R.; Romines, K. R.; Baum, J. S.
Org. Synth., Coll. Vol. IX 1998, 422.
18. After this time, no starting β-keto ester is observed upon analysis by TLC.
19. The principal reaction competing with deacylation is ester hydrolysis.
20. The spectral properties are as follows:
1H NMR (300 MHz, CDCl
3) δ: 1.72 (s, 3 H), 1.77 (s, 3 H), 4.66 (d, 2 H, J = 7.3), 4.74 (s, 1 H), 5.32–5.39 (m, 1 H);
13C NMR (75 MHz, CDCl
3) δ: 18.4, 26.2, 46.6, 62.2, 119.2, 139.7, 167.4; IR (thin film) cm
−1: 2109 (C=N
2), and 1694 (C=O).
22. The NMR spectra are as follows:
1H NMR (300 MHz, CDCl
3) δ: 1.17 (s, 3 H), 1.18 (s, 3 H), 1.93 (d, 1 H, J = 6.2), 2.04 (dd, 1 H, J = 6.2, 5.5), 4.13 (d, 1 H, J = 9.8), 4.35 (dd, 1 H, J = 9.8, 5.5);
13C NMR (75 MHz, CDCl
3) δ: 14.2, 25.0, 29.9, 30.3, 66.4, 174.9. Enantiomerically pure
(1R,5S)-(−)-6,6-dimethyl-3-oxabicyclo[3.1.0]hexan-2-one is reported to have
[α]25D −89.9° (CHCl
3,
c 1.4) (calculated).
5
23. A
30 m × 0.32 mm ID Chiraldex B-PH (β-cyclodextrin) column was used under isothermal conditions at 120°C. Retention time of the (1R,5S)-enantiomer was 16.9 min, while the (1S,5R)-enantiomer eluted at 17.9 min. The submitters report that separation also occurred on a 30-m Chiraldex γ-cyclodextrin trifluoroacetate column operated at 140°C; retention times were 14.2 min (1R,5S-enantiomer) and 18.9 min (1S,5R-enantiomer).
24. The submitters report that the recovered catalyst can be reused in the same reaction;
(1R,5S)-(−)-6,6-dimethyl-3-oxabicyclo[3.1.0]hexan-2-one was formed in
83% yield and 88% ee.
All toxic materials were disposed of in accordance with "Prudent Practices in the Laboratory"; National Academy Press; Washington, DC, 1995.
3. Discussion
Dirhodium(II) tetrakis[methyl 2-pyrrolidone-5(R)-carboxylate], Rh
2 (5R-MEPY)
4, and its enantiomer, Rh
2 (5S-MEPY)
4, which is prepared by the same procedure, are highly enantioselective catalysts for intramolecular cyclopropanation of allylic diazoacetates (65-≥94% ee) and homoallylic diazoacetates (71–90% ee),
7,8 intermolecular carbon-hydrogen insertion reactions of 2-alkoxyethyl diazoacetates (57–91% ee)
9 and N-alkyl-N-(tert-butyl)diazoacetamides (58–73% ee),
10 intermolecular cyclopropenation of alkynes with
ethyl diazoacetate (54–69% ee) or
menthyl diazoacetates (77–98% diastereomeric excess, de),
11 and intermolecular cyclopropanation of alkenes with
menthyl diazoacetate (60–91% de for the cis isomer, 47–65% de for the trans isomer).
12 Their use in ≤1.0 mol % in
dichloromethane solvent effects complete reaction of the diazo ester and provides the carbenoid product in 43–88% yield. The same general method used for the preparation of Rh
2 (5R-MEPY)
4 was employed for the synthesis of their isopropyl
7 and neopentyl
9 ester analogs.
Appendix
Compounds Referenced (Chemical Abstracts Registry Number)
silica-alumina
(1R,5S)-(−)-6,6-DIMETHYL-3-OXABICYCLO[3.1.0]HEXAN-2-ONE
DIRHODIUM(II) TETRAKIS[METHYL 2-PYRROLIDONE-5(R)-CARBOXYLATE
(−)-Methyl 2-pyrrolidone-5(R)-carboxylate
(+)-Dirhodium(II) tetrakis[methyl 2-pyrrolidone-5(R)-carboxylate]
(1R,5S)-(−)-6,6-dimethyl-2-oxabicyclo- [3.1.0]hexan-2-one
dirhodium(II) tetraacetamide
ethanol (64-17-5)
acetic acid (64-19-7)
ethyl acetate (141-78-6)
methanol (67-56-1)
ether (60-29-7)
sodium acetate (127-09-3)
acetonitrile (75-05-8)
thionyl chloride (7719-09-7)
sodium chloride (7647-14-5)
sodium carbonate (497-19-8)
nitrogen (7727-37-9)
diketene (674-82-8)
chlorobenzene (108-90-7)
isopropyl alcohol (67-63-0)
dichloromethane (75-09-2)
magnesium sulfate (7487-88-9)
ethyl diazoacetate (623-73-4)
Tetrahydrofuran (109-99-9)
lithium aluminum hydride (16853-85-3)
hexane (110-54-3)
triethylamine (121-44-8)
calcium hydride (7789-78-8)
lithium hydroxide (1310-65-2)
phosphorus pentoxide (1314-56-3)
rhodium(II) acetate
methanesulfonyl azide
p-Acetamidobenzenesulfonyl azide (2158-14-7)
p-acetamidobenzenesulfonamide (121-61-9)
p-dodecylbenzenesulfonyl azide (79791-38-1)
Menthyl
3-Oxabicyclo[3.1.0]hexan-2-one, 6,6-dimethyl-, (1R-cis)- (71565-25-8)
Methyl (R)-2-pyrrolidone-5-carboxylate,
Methyl 2-pyrrolidone-5(R)-carboxylate (64700-65-8)
(R)-(+)-2-pyrrolidone-5-carboxylic acid,
D-pyroglutamic acid (4042-36-8)
rhodium acetate
3-Methyl-2-buten-1-yl acetoacetate (21597-32-0)
3-methyl-2-buten-1-ol (556-82-1)
3-Methyl-2-buten-1-yl diazoacetate,
3-Methyl-2-butenyl diazoacetate (72800-60-3)
rhodium(III) chloride hydrate
dirhodium(II) tetraacetate (15956-28-2)
(1R,3S)-(+)-cis-chrysanthemic acid
menthyl diazoacetate
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