Checked by David Coffen, Louis A. Portland, Bryant Rossiter, and Gabriel Saucy.
1. Procedure
Caution! All manipulations for the preparation of the transition-metal complexes and the catalytic isomerization should be carried out under dry nitrogen or argon. All solvents used are distilled under dry nitrogen over metallic sodium, or after drying over calcium sulfate (in the case of acetone) immediately before use.
A.
[(+)-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl]-(η4-1,5-cyclooctadiene) rhodium(I) perchlorate. [Rh{(+)-BINAP} (1,5-C8H12)] ClO4. A
dry, 250-mL Schlenk flask, filled with dry
nitrogen or
argon and equipped with a
magnetic stirring bar, is charged with
0.53 g (1.08 mmol) of chloro-(1,5-cyclooctadiene)rhodium(I) dimer (Note
1). Then
40 mL of dry acetone is added using an airtight syringe. The flask is protected from light by wrapping it with aluminum foil and
0.45 g (2.17 mmol) of silver perchlorate is added to the stirred suspension. The mixture is stirred for 1 hr at ambient temperature. The colorless precipitate of
silver chloride is removed by suction filtration under
argon through a stainless-steel cannula fitted with a filter tip (Note
2). The precipitates are washed with
5 mL of acetone. To the pale-orange filtrate and the washings is added
1.34 g (2.16 mmol) of (+)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl [(+)-BINAP] (Note
3) and the resulting dark-red solution is stirred under
argon for 18 hr at ambient temperature. The reaction mixture is concentrated under reduced pressure (60 mm) to ca. 3 mL. Then
30 mL of ether is slowly added with a syringe. The resulting mixture is stirred at ambient temperature for 18 hr. The orange solid is filtered off under
argon and washed with
5 mL of ether. The crude product is dissolved in
50 mL of dry acetone and the solution is concentrated to ca. 3 mL under 60 mm pressure. Dry
ether (30 mL) is slowly added and the mixture is stirred for 18 hr. The deep-orange crystals are collected by filtration, washed with
5 mL of dry ether, and dried under vacuum to afford
2.07 g of recrystallized product, 230–235°C (dec) (Note
4).
[(−)-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl] (η4-1,5-cyclooctadiene) rhodium(I) perchlorate: [Rh{(−)-BINAP}(1,5-C8H12)] ClO4 is similarly prepared from
0.53 g (1.08 mmol) of chloro-(1,5-cyclooctadiene)rhodium(I) dimer,
0.45 g (2.17 mmol) of silver perchlorate, and
1.34 g (2.16 mol) of (−)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl [(−)-BINAP] (Note
5) in
acetone. The crude product is recrystallized from
acetone–ether as above to give
2.02 g of orange powder, mp
230°C (dec) (Note
6).
B.
(R)-(−)-N,N-Diethyl-(E)-citronellalenamine [(R)-(−)-N,N-Diethyl-3,7-dimethyl-1(E),6-octadienylamine].
From N,N-diethylgeranylamine. A
500-mL, three-necked, round-bottomed flask equipped with a
magnetic stirrer, a
reflux condenser and an
argon inlet is charged with
373 mg (0.40 mmol) of [(−)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl](η4-1,5-cyclooctadiene)rhodium(I) perchlorate. The flask is evacuated and refilled with
argon 4 times. Another 500-mL, three-necked, round-bottomed flask is charged with
83.8 g (0.40 mol) of N,N-diethylgeranylamine (Note
7) and
250 mL of distilled tetrahydrofuran (Note
8) under an argon blanket. This solution is transferred under
argon by cannula to the flask containing the catalyst, which is then evacuated and refilled with
argon twice. The reaction mixture is stirred and heated at reflux for 21 hr (Note
9). The solution is cooled to room temperature and the solvent is removed under vacuum (60 mm) at 45°C. The residue is vacuum-distilled through a
10-cm Vigreux column to give
78.7 g (
93.9%) of
(R)-(−)-N,N-diethyl-(E)-citronellalenamine as a colorless liquid, bp
84–85°C (1.1 mm),
[α]D25 −66.5° (
hexane,
c 10.2). The product is 97.2% chemically pure by GLC analysis (Note
10),(Note
11),(Note
12).
From N,N-diethylnerylamine. Similarly,
83.8 g (0.40 mol) of N,N-diethylnerylamine (Note
13) is isomerized with
373 mg (0.40 mmol) of [(+)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl](η4-1,5-cyclooctadiene)rhodium(I) perchlorate catalyst in
250 mL of THF (Note
8) at reflux for 70 hr (Note
9) to give
77.2 g (
92.1%) of
(R)-(−)-N,N-diethyl-(E)-citronellalenamine,
[α]D25 −66.9° (
hexane,
c 10.7). The chemical purity of the product is 91.7% by GLC (Note
10), (Note
12), and (Note
14).
C.
(R)-(+)-Citronellal. [
(R)-(+)-3,7-Dimethyl-6-octanal]. A
500-mL, round-bottomed flask equipped with a magnetic stirrer and an
ice bath is charged with
33.4 g (0.16 mol) of (R)-(−)-N,N-diethyl-(E)-citronellalenamine in
80 mL of ether at 0°C. To this stirred solution is added
80 mL of a 1 : 4 glacial acetic acid–deionized water solution in one portion (Note
15). The reaction mixture is stirred for 5 min at 0°C and then at room temperature for 25 min. The
ether layer is separated and washed successively with 50 mL of water, two
50-mL portions of saturated aqueous sodium bicarbonate solution, 50 mL of water, and
50 mL of saturated brine. The ether layer is dried over anhydrous
sodium sulfate and filtered (Note
16). The
ether solution is concentrated at 40°C under reduced pressure (60 mm) to a pale-yellow liquid. The liquid is distilled through a 10-cm Vigreux column to give
22.5 g (
91.4%) of
(+)-citronellal as a colorless liquid, bp
79–80°C (7 mm),
[α]D25 +15.7° (neat, d 0.851). The product is 99.4% chemically pure by GLC and has an optical purity of 95.2% (Note
17).
2. Notes
1. Chloro(η
4-1,5-cyclooctadiene)rhodium(I) dimer [RhCl(1,5-C
8H
12)] can be prepared according to the method described in
Inorganic Syntheses.
3 The checkers used material purchased from the Aldrich Chemical Company, Inc.
2. This can also be done as previously described in
Inorganic Syntheses.
4
4. The submitters obtained
1.5–1.7 g of analytically pure material with mp
164°C (dec). The
1H NMR (CD
2Cl
2) of this product showed signals at δ: 2.00–2.62 (m, 8 H, -CH
2-), 4.58 (br signal, 2 H, -CH=), 4.84 (br signal, 2 H, -CH=), 6.42–8.22ppm (m, 32 H, aromatic). Anal. calcd. for (C
52H
44ClO
4Rh): C, 66.93; H, 4.75; Cl, 3.80. Found: C, 66.66; H, 4.89; Cl, 3.92.
6. The submitters used
THF–ether for recrystallization, in which case the product was obtained as a THF-solvated complex,
[Rh{(−)-BINAP} (1,5-C8H12)]ClO4 THF, in the form of deep-orange crystals, mp
153°C (dec). Its
1H NMR (CD
2Cl
2) spectrum clearly showed the presence of the solvating tetrahydrofuran; δ: 1.60–2.00 (m. 4 H, -CH
2- of THF), 2.00–2.62 (m, 8 H, -CH
2-), 3.40–3.80 (m, 4 H, -CH
2O- of THF), 4.58 (br signal, 2 H, -CH=), 4.82 (br, signal, 2 H, -CH=), 6.40–7.97 (m, 32 H, aromatic). Anal. calcd. for (C
52H
44ClO
4RhC
4H
8O): C, 66.90; H, 5.21; Cl, 3.53. Found: C, 66.55; H, 5.62; Cl, 3.68.
7.
N,N-Diethylgeranylamine was prepared according to the method described in
Org. Synth., Coll. Vol. VIII, 1993, 188. The submitters used material of 99.7% purity (determined by GLC; Hitachi 063 with
OV-101 in fused silica, 0.2-mm × 25-m column) that was obtained by careful distillation through a column with one hundred theoretical plates, bp
70°C (2 mm), and redistilled over
calcium hydride before use. The checkers used a
32-cm Goodloe column and collected the amine at 105°C (2.4 mm), which had a purity of 100% (GLC).
8.
Acetone or
methanol also may be used. However,
tetrahydrofuran gives the best results. The solvents should be strictly dry because water deactivates the catalyst.
9. The submitters ran the reaction at 60°C for 24 hr.
10. Purity of the product and progress of the isomerization can be determined by GLC (
Triton X 305 packed in a 0.2 mm × 30 m glass column from Gasukuro Kogyo Co. Ltd., or a
column-crosslinked 5% phenylmethyl silicone,
25-m high-performance capillary column supplied by Hewlett Packard. Starting temperature, 125°C; rate 3°/min; final temperature, 180°C). The product enamine is 100% (
E)-isomer. The spectral properties of the product are as follows: IR (neat) cm
−1: 3045, 2960, 2915, 2860, 2720, 1660, 1655, 1450, 1377, 1298, 1245, 1196, 1100, 985, 937, 886, 830, 784, 740;
1H NMR (acetone d
6) δ: 0.96 (d, 3 H,
J = 7.2), 1.01 (t, 6 H,
J = 7.1), 1.1–1.4 (m, 2 H), 1.58 (br s, 3 H), 1.66 (br s, 3 H), 1.8–2.1 (m, 3 H), 2.92 (q, 4 H,
J = 7.1), 3.93 (d of d, 1 H,
J = 14.6, 8.4), 5.11 (br t, 1 H,
J = 7.3), 5.79 (d of d, 1 H,
J = 14.6, 0.8).
11. The submitters report
92–96% yields of 98% chemically pure product, bp
80–82°C (1 mm),
[α]D25 −74.3° (
hexane,
c 10.0). The specific rotation was corrected for this purity (Note
12). A specific rotation of
[α]D25 −77.6° (
hexane) is estimated for the pure enamine.
12. The product is very moisture sensitive and should be handled under dry
nitrogen or
argon. Despite this precaution, the product is always contaminated by small amounts of
(+)-citronellal, which has an optical rotation opposite to that of the enamine. To determine the optical purity of the product enamine, the specific rotation measured therefore must be corrected for the
(+)-citronellal impurity. It is more reliable to base optical purity on the specific rotation of the
citronellal obtained by hydrolysis of the enamine (Part C). The absolute method using HPLC of the diastereomeric amide derivative
5 also may be useful as a check of the optical purity.
13.
N,N-Diethylnerylamine was prepared according to the method described in
Org. Synth., Coll. Vol. VIII, 1993, 190, and distilled over
calcium hydride and stored under
nitrogen below −20°C. GLC–MS analysis (Hitachi 063 and Hitachi RMU-6MG with OV-101 in fused silica, 0.2-mm × 25-m column) of
N,N-diethyl-nerylamine used by the submitters showed a purity of 94.9%, and contained
N,N-diethyl-2-ethylede-6-methyl-5-heptenylamine (0.2%),
N,N-diethyl-2,7-dimethyl-2,6-octadienylamine (1.5%),
N,N-diethyl-3-methylene-7-methyl-6-octenylamine (2.1%), and unidentifiable products (1.3%) as impurities, but not the (
E)-isomer,
N,N-diethylgeranylamine. The checkers distilled the nerylamine through a 32-cm Goodloe column, bp
102°C (3 mm), and achieved a purity of 98.6%.
14. The submitters obtained
90–95% yields of 94% chemically pure product,
[α]D24 −73.1° (
hexane,
c 10.0; corrected for the
citronellal impurity).
15. The submitters conducted the hydrolysis step in a mixture of
2 N sulfuric acid and toluene. The acid is added dropwise at 0°C at a rate that keeps the pH of the mixture at 4–5. Control of pH is critical.
16. Rapid workup after the acid hydrolysis is desirable.
17. A specific rotation of
[α]D25 +16.5° (neat) is reported for optically pure
citronellal.
6
3. Discussion
With the same catalyst systems, other prochiral
N-alkyl- or
N,N-dialkylallylamines can also be isomerized efficiently to the corresponding optically active imines or (
E)-enamines, respectively. For example, with
[Rh{(+)-BINAP} (1,5-C8H12)] ClO4, ([substrate]/[Rh] = 100, in THF, 40°C, 23 hr) a secondary
allylamine,
N-cyclohexylgeranylamine, and an allylamine with styrene-type conjugation,
N,N-dimethyl-3-phenyl-2(E)-butenylamine, are isomerized to give
(S)-(−)-N-cyclohexylcitronellalimine (chemical yield,
100%; optical yield, 96%) and
(R)-(−)-N,N-dimethyl-3-phenyl-1(E)-butenylamine (chemical yield,
84%; optical yield, 90%), respectively.
Appendix
Compounds Referenced (Chemical Abstracts Registry Number)
brine
(R)-(−)-N,N-DIETHYL-(E)-CITRONELLALENAMINE
1-(E), 6-Octadienamine, (R)-(−)-N,N-diethyl-3,7-dimethyl- and 6-octenal, 3,7-dimethyl-, (R)-(+)-
[Rh{(+)-BINAP} (1,5-C8H12)] ClO4
chloro-(1,5-cyclooctadiene)rhodium(I) dimer
(+)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl [(+)-BINAP]
[Rh{(−)-BINAP}(1,5-C8H12)] ClO4
(−)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl [(−)-BINAP]
(R)-(−)-N,N-Diethyl-(E)-citronellalenamine [(R)-(−)-N,N-Diethyl-3,7-dimethyl-1(E),6-octadienylamine]
[Rh{(−)-BINAP} (1,5-C8H12)]ClO4 THF
N,N-diethyl-2-ethylede-6-methyl-5-heptenylamine
muscone
(+)-7-hydroxydihydrocitronellal
[Rh{(−)-BINAP} (1,5-C8H12)] ClO4
(S)-(−)-citronellal
(−)-N,N-diethyl-(E)-citronellalenamine
N-phenyl- or N,N-diphenylgeranylamine
sulfuric acid (7664-93-9)
acetic acid (64-19-7)
methanol (67-56-1)
ether (60-29-7)
sodium bicarbonate (144-55-8)
silver chloride (7783-90-6)
sodium sulfate (7757-82-6)
nitrogen (7727-37-9)
calcium sulfate (7778-18-9)
acetone (67-64-1)
toluene (108-88-3)
sodium (13966-32-0)
Allylamine (107-11-9)
Tetrahydrofuran,
THF (109-99-9)
hexane (110-54-3)
calcium hydride (7789-78-8)
argon (7440-37-1)
1,5-cyclooctadiene
citronellal,
(+)-citronellal (106-23-0)
silver perchlorate (7783-93-9)
N,N-Diethylnerylamine,
N,N-diethyl-nerylamine (40137-00-6)
N,N-Diethylgeranylamine (40267-53-6)
rhodium(I) perchlorate
citronellol (106-22-9)
1-menthol
α-tocopherol (59-02-9)
cyclohexylcitronellalimine
(R)-(+)-2,2'-Bis(diphenylphosphino)-1,1'-binapthyl,
(S)-(−)-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (76189-56-5)
(R)-(+)-Citronellal (2385-77-5)
N,N-diethyl-2,7-dimethyl-2,6-octadienylamine
N,N-diethyl-3-methylene-7-methyl-6-octenylamine
(+)-N,N-diethyl-(E)-citronellalenamine
N-cyclohexylgeranylamine
N,N-dimethyl-3-phenyl-2(E)-butenylamine
dimethyl-3-phenyl-1(E)-butenylamine
N,N-dimethyl-2-propenylamine (2155-94-4)
N,N-dimethyl-2(E)-butenylamine
N,N-dimethyl-2-methyl-2-propenylamine
N,N-dimethyl-3-methyl-2-butenylamine
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