Highly Enantioselective Isomerization of 4,7-dihydro-1,3-dioxepins Catalyzed by Me-DuPHOS-Modified Dihalogenonickel Complexes and Determination of the Absolute Configuration of the Isomerization products

Full text of DOI:10.1002/1521-3773(20010105)40:1<177::AID-ANIE177>3.0.CO;2-X

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Highly Enantioselective Isomerization of
4,7-Dihydro-1,3-dioxepins Catalyzed by
Me-DuPHOS-Modified Dihalogenonickel
Complexes and Determination of the Absolute
Configuration of the Isomerization Products**
Herbert Frauenrath,* Dirk Brethauer, Stefan Reim,
Martin Maurer, and Gerhard Raabe
Dihalogenonickel complexes bearing chiral ligands have
proved to be efficient catalyst precursors for the asymmetric
isomerization of cyclic allyl acetals. In the isomerization of
5-methylen-1,3-dioxanes to 5-methyl-4H-1,3-dioxins, for ex-
ample, DIOP-modified (DIOP ˆ 2,3-O-isopropylidene-2,3-
dihydroxy-1,4-bis(diphenylphosphanyl)butane) dihalogeno-
nickel complexes activated with lithium triethylborohydride
gave selectivities of up to 92% ee.[1] The enantioselectivities
significantly decreased, when 4,7-dihydro-1,3-dioxepins (1)
were used as substrates. However, we have shown previ-
ously that the selectivities depend on the relationship be-
tween the chelate-ring size of the catalyst and the ring size
of the substrate.[1, 2] Thus, isomerization of 1a by using a
five-membered CHIRAPHOS-modified (CHIRAPHOS ˆ
2,3-bis(diphenylphosphanyl)butane) dichloronickel complex
(2a) at room temperature in THF afforded 2-tert-butyl-
4,5-dihydro-1,3-dioxepin (3a) with 67% ee. In contrast, the
seven-membered DIOP-modified dichloronickel complex
gave 3a under the same reaction conditions with only
38% ee.[3]
Searching for other diphosphanes that form five-mem-
bered-ring nickel chelates we found that 1,2-bis(phosphola-
nyl)benzenes (Me-DuPHOS, Et-DuPHOS) are suitable li-
gands for the asymmetric nickel-catalyzed isomerization of
1.[4, 5] In fact, by employing Me-DuPHOS as a ligand a
breakthrough was achieved in terms of enantioselectivity
(Table 1). Treatment of 1a with [NiCl2((ꢀ)-Me-DuPHOS)]
(2c) at room temperature and activation with LiBHEt3 in
toluene provided (ꢀ)-3a already with 85% ee (Table 1,
entry 5), but incomplete conversion at this temperature
indicated a decreased catalytic activity of the dichloronickel
complex (2c). However, we found that replacing the chloro by
bromo or iodo ligands drastically enhanced the activity of the
nickel catalysts. Thus, isomerizations of 1 with CHIRAPHOS
and DuPHOS bearing NiBr2± or NiI2 ± phosphane complexes
could be performed even at low temperatures yielding vinyl
Scheme 3. Cycloaddition reactions of 1,4-diazidobuta-1,3-dienes 3d,e.
a) Chloroform, 208C, 30 ± 60 min, 86% 16d, 99% 16e; b) acetone,
tetracyanoethylene (TCNE) 208C, 2 ± 20 h, 95% 17d, 91% 17e; c) chloro-
form, 208C, 3 h, 96% 18d.
Â
[8] a) G. Lꢁabbe, A. Hassner, Angew. Chem. 1971, 83, 103 ± 109; Angew.
Chem. Int. Ed. Engl. 1971, 10, 98 ± 104; b) G. Smolinsky, C. A. Pryde in
The Chemistry of the Azido Group (Ed.: S. Patai), Wiley, London,
1971, pp. 555 ± 585; c) A. Hassner in Azides and Nitrenes: Reactivity
and Utility (Ed.: E. F. V. Scriven), Academic Press, Orlando, 1984,
pp. 35 ± 94; d) K. Banert, Methoden Org. Chem. (Houben-Weyl) 1952-,
Vol. E15, 1993 pp. 818 ± 875, 1344 ± 1347, 2348 ± 2349, 3105 ± 3107.
[9] H. Hoberg, C. Fröhlich, Synthesis 1981, 830 ± 831.
[10] D. Landini, A. Maia, F. Montanari, J. Am. Chem. Soc. 1978, 100,
2796 ± 2801; D. Landini, A. Maia, F. Montanari, Nouv. J. Chim. 1979, 3,
575 ± 577; D. Landini, A. Maia, F. Montanari, F. Rolla, J. Org. Chem.
1983, 48, 3774 ± 3777; K. Banert, W. Kirmse, J. Am. Chem. Soc. 1982,
104, 3766 ± 3767; K. Banert, Chem. Ber. 1985, 118, 1564 ± 1574.
[11] Caution should be exercised during isolation of azides, particularly
(E,E)-3d which is explosive.
[12] Isolated yield; the yield of unstable products, which could not be
isolated, e.g. 4 and 9, was determined by 1H NMR spectroscopy
(internal standard).
[13] W. Kirmse, N. G. Rondan, K. N. Houk, J. Am. Chem. Soc. 1984, 106,
7989 ± 7991.
[14] H. A. Brune, W. Schwab, Tetrahedron 1969, 25, 4375 ± 4378.
[15] R. Criegee, A. Moschel, Chem. Ber. 1959, 92, 2181 ± 2184.
[16] G. Maier, M. Schneider, G. Kreiling, W. Mayer, Chem. Ber. 1981, 114,
3922 ± 3934.
[*] Prof. Dr. H. Frauenrath, D. Brethauer, Dr. S. Reim, Dr. M. Maurer
Universität Gh Kassel
[17] R. S. Hansen, W. S. Trahanovsky, J. Org. Chem. 1974, 39, 570 ± 571.
Â
[18] W. Zielinski, Heterocycles 1985, 23, 1639 ± 1644.
Fachbereich 19 - Biologie/Chemie
[19] Also under these conditions, 7 f and 10 f were photochemically stable
as shown in control experiments.
Heinrich-Plett-Strasse 40, 34109 Kassel (Germany)
Fax : (‡ 49)561-8044649
[20] H. Hoberg, C. Fröhlich, J. Organomet. Chem. 1980, 197, 105 ± 109.
[21] There are several reports on the thermal transformation of other
1-azido-1,2-diphenylethenes into azirines which occurred already at
low temperatures: a) F. W. Fowler, A. Hassner, L. A. Levy, J. Am.
Chem. Soc. 1967, 89, 2077 ± 2082; b) K. Banert, M. Hagedorn, C.
Liedtke, A. Melzer, C. Schöffler, Eur. J. Org. Chem. 2000, 257 ± 267.
[22] R. A. Carboni, R. V. Lindsey, J. Am. Chem. Soc. 1959, 81, 4342 ± 4346.
E-mail: frauenra@hrz.uni-kassel.de
Piv.-Doz. Dr. G. Raabe[‡]
Rheinisch-Westfälische Technische Hochschule Aachen
Institut für Organische Chemie
Prof.-Pirlet-Strasse 1, 52074 Aachen (Germany)
‡
[ ] X-ray crystallographic analysis
[**] This work was supported by the Fonds der Chemische Industrie. We
would like to thank Prof. Dr. H. Brunner, Universität Regensburg, for
help in questions concerning analytical data. Me-DuPHOS ˆ 1,2-
bis(2,5-dimethylphospholanyl)benzene.
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acetals (3a ± c) in good to high
enantioselectivities. Best re-
sults were achieved with
[NiI2((ꢀ)-Me-DuPHOS)]
(R)-(–)-3a (98% ee)
(R)-(–)-3b (90% ee)
(R)-(–)-3c (90% ee)
LiAlH4
Et2O, RT
HCl/H2O
30 °C
OH
OH
HO
O
R
O
63-66%
72-74%
HO
H
H
OH
(R)-(+)-7
67-88% ee
6a-c
m-CPBA
CH2Cl2, RT
(2e) as a precatalyst and with
activation by LiBHEt3 in
toluene at ꢀ558C. Under
these conditions, the enantio-
mers(ꢀ)-3b and 3c were ob-
tained at acceptable rates with
90% ee, and (ꢀ)-3a with an
excellent selectivity of 98% ee
(Table 1, entries 11, 13, 15).
The absolute configuration
of the isomerization products
was established by the con-
version of 3 into either 1,2,4-
butanetriol (7) or 2-hydroxy-
g-butyrolactone (9). Both
[H+]/ ∆
O
O
5
O
R'
4
O
R
2
O
O
O
H
R
H
5a: 75%, d.r. 83:17
5b: 73%, d.r. 91:9
5c: 74%, d.r. 75:25
4a: 75%, d.r. 95:5
4b: 74%, d.r. 95:5
4c: 72%, d.r. 87:13
1. HCl/H2O,
OH
O
R' = m-Cl-C6H4
CO2H
30 °C
AgNO3/NaOH
80-82%
2. – H2O
O
R
O
66%
O
H
(R)-(+)-9
80-88% ee
8a,b
Scheme 1. Oxidation and rearrangement of R-(ꢀ)-3 and the conversion of the carboxaldehydes 5 into (R)-(‡)-
1,2,4-butanetriol (7) and (R)-(‡)-2-hydroxy-g-butyrolactone (9), respectively.
transformations proceed by a new oxidation ring-contraction
sequence of 3 to give the carbaldehydes 5 (Scheme 1)
according to our procedure for the synthesis of 4-methyl-1,3-
dioxolan-4-carbaldehydes.[7] Thus, treatment of (ꢀ)-3a ± c
with m-chloroperbenzoic acid and heating the resulting crude
mixture in vacuo in the presence of an acid led directly to
distillation of a diastereomeric mixture of carbaldehydes 5a ±
c. Subsequent reduction with lithium aluminum hydride and
acetal cleavage or oxidation, acetal cleavage, and lactoniza-
tion by azeotropic removal of water furnished (R)-(‡)-7 and
(R)-(‡)-9, respectively. Comparison of the specific rotation
of the product with that of authentic (R)-(‡)-7 and (R)-(‡)-9
determined the 2R,4R configuration for the major diaster-
eomers of 5a ± c and the 2S,4R configuration for the minor
diastereomers. The absolute configuration of (ꢀ)-3a ± c
followed from the relative configuration of acylals 4a ± c
obtained as the primary products of the m-chloroperbenzoic
acid oxidation and isolated, by careful neutralization of the
crude oxidation product, as a mixture of two diastereomers in
a 95:5 to 83:17 ratio. As evidenced by NMR spectroscopic
data, both diastereomers differ in the configuration at C4. In
the case of rac-4b, the major diastereomer could be isolated
in a diastereomerically pure crystalline form from pentane
solution.
Table 1. Asymmetric isomerization of 4,7-dihydro-1,3-dioxepins (1a ± c) using
(R,R)-(‡)-CHIRAPHOS- and (R,R)-(ꢀ)-Me-DuPHOS-modified nickel com-
plexes.
Crystal structure analysis of rac-4b unambiguously con-
firmed the 2RS,4RS,5RS configuration for both conformers in
the asymmetric unit (Figure 1) indicating a preferred trans
Entry Product Pre-
catalyst
Solvent
T
Conversion [%][a]
/
ee
[%][c] (neat)
[a]2D0
[8C] Time(h)[b]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3b
3b
3c
3c
2a
THF
THF
THF
THF
20 100(71)/48
67
ꢀ 23.6
ꢀ 28.4
2a
2b
2b
2c
2c
2d
2d
2e
2e
2e
2e
2e
2e
2e
ꢀ 40
0/48
20 100/48
ꢀ 40 100(83)/72
20 80/96
73
82
85
toluene
toluene ꢀ 55
toluene 20 100/18
toluene ꢀ 55 16/72
toluene 20 100/2.5
0/48
80
92
80
92
98
70
90
78
90
toluene ꢀ 20 100/48
toluene ꢀ 55 100(74)/72
ꢀ 34.9
ꢀ 27.2
ꢀ 22.1
toluene
20 100/2.5
toluene ꢀ 55 100(75)/72
toluene 20 100/2.5
toluene ꢀ 55 100(75)/72
[a] Determined by gas chromatography (GC). Values in parentheses: yields of
isolated product. [b] No further conversion on prolonged reaction times.
[c] Determined by GC. Capillary column: Rt-bDEXcst (30 m, internal diameter
0.32 mm);[6] carrier gas H2.
Figure 1. The symmetrically independent molecules of the asymmetric
unit of rac-4b.
178
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Angew. Chem. Int. Ed. 2001, 40, No. 1

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attack of m-chloroperbenzoic acid in the reaction with 3.[8]
The results reveal, that (ꢀ)-3b and, on the basis of similar
coupling constants in the 1H NMR spectra and similar nuclear
Overhauser enhancement (NOE) effects , most probably (ꢀ)-
3a, c have the R configuration.
[1] H. Frauenrath, S. Reim, A. Wiesner, Tetrahedron: Asymmetry 1998, 9,
1103 ± 1106.
[2] A. Wille, S. Tomm, H. Frauenrath, Synthesis 1998, 305 ± 308.
[3] For the isomerization of 1 with new Ru complexes, see: H. Brunner,
M. Prommesberger, Tetrahedron: Asymmetry 1998, 9, 3231 ±
3239.
[4] (ꢀ)-Me-DuPHOS ˆ (ꢀ)-1,2-Bis[(2R,5R)-2,5-dimethylphospholanyl]-
benzene; M. J. Burk, J. Am. Chem. Soc. 1991, 113, 8518 ± 8519.
[5] J. Albrecht, U. Nagel, Angew. Chem. 1996, 108, 444 ± 446; Angew.
Chem. Int. Ed. Engl. 1996, 35, 407 ± 409, and references therein.
[6] Supplier: RESTEK GmbH, Sulzbacherstrasse 15, 65812 Bad Soden,
Germany.
In conclusion, 4,5-dihydro-1,3-dioxepins (3) are readily
available with high enantiomeric excess by asymmetric
isomerization of 1 employing [NiI2(Me-DuPHOS)] as a
precatalyst. The conversions of 3 into 2-hydroxy-g-butyrolac-
tone (9) and 1,2,4-butanetriol (7) demonstrate new applica-
tions for compounds 3 as chiral synthons in asymmetric
synthesis. Derivates of carbaldehydes 5 and alcohols 6,
prepared by different methods, have already been used for
the synthesis of optical active a-amino acetals, a-amino acids,
and 1,2- and 1,3-diols.[9]
[7] C. Wattenbach, M. Maurer, H. Frauenrath, Synlett 1999, 303 ± 306.
[8] Crystal structure analysis of rac-4b: C15H19O5Cl, Mr ˆ 314.77; crystals
Å
were obtained from pentane (293 K); triclinic space group P1 (no.2),
a ˆ 11.716(3), b ˆ 11.721(4), c ˆ 12.388(3) Š, a ˆ 73.21(2), b ˆ
73.90(3), g ˆ 85.15(3)8, Vˆ 1564.7 Š3, Z ˆ 2  2, 1calcd ˆ 1.336 gcmꢀ3
,
150 K. A total of 8974 reflections were collected on an Enraf-Nonius
CAD4 four-circle diffractometer CAD4, graphite-monochromated
CuKa radiation (l ˆ 1.54179 Š), m ˆ 11.7 cmꢀ1, no absorption correc-
tion. The structure was solved by direct methods (GENSIN[12]
,
GENTAN[13] as implemented in the XTAL3.4 program package[14]).
Hydrogen atoms were fixed in idealized positions without refinement.
Final full-matrix least-squares refinement of 379 parameters (involved
Experimental Section
(R)-(ꢀ)-3a: Catalyst precursor 2e (0.20 g, 0.32 mmol) was dissolved in
toluene at room temperature and activated by LiBHEt3 (0.5 mL, 0.5 mmol,
1m in THF). After cooling to ꢀ558C, a solution of 1a (1.0 g, 6.40 mmol) in
toluene (5 mL) was added, and the mixture was left at this temperature for
48 h. The conversion is monitored by GC. After complete conversion the
mixture was allowed to warm to room temperature and quenched with a
saturated NH4Cl solution (10 mL). The organic layer was separated, and
after removal of the solvent the residue was distilled in vacuo; b.p. 55 ±
608C/18 Torr; yield 0.74 g (4.7 mmol, 74%).
5a: A solution of purified m-chloroperbenzoic acid (3.40 g, 20 mmol)[10] in
dichloromethane (50 mL) was added dropwise at room temperature to a
stirred solution of 3a (2.34 g, 15 mmol) in dichloromethane (10 mL). After
stirring for 30 min and removal of the solvent in vacuo the diastereomeric
aldehydes 5a were distilled off by heating the colorless residue to 1308C ;
b.p. 75 ± 808C/18 Torr; yield 1.50 g (8.70 mmol, 58%). 1H NMR (500 MHz,
CDCl3, 228C, TMS); major diastereomer: d ˆ 0.95 (s, 9H, tBu), 1.65
(ddddd, 1H (eq), J ˆ 13.3, 3.0, 2.7, 1.5, 0.8 Hz, OCH2CH2), 1.77 (dddd, 1H
(ax), J ˆ 13.3, 12.2, 11.8, 5.1 Hz, OCH2CH2), 3.75 (ddd, 1H (ax), J ˆ 12.2,
11.4, 2.7 Hz, OCH2CH2), 4.08 (ddd, 1H (ax), J ˆ 11.6, 3.0, 0.8 Hz,
OCHCH2), 4.19 (ddd, 1H (eq), J ˆ 11.5, 4.9, 1.5 Hz, OCH2CH2), 4.20 (s,
1H, OCHO), 9.66 (dd, 1H, J ˆ 0.8, 0.8 Hz, CHO); 13C NMR (125 MHz,
CDCl3, 228C, TMS); major diastereomer: d ˆ 24.6 (C(CH3)3), 26.0
(C(CH3)3), 35.0 (OCH2CH2), 66.0 (OCH2CH2), 80.0 (OCHCH2), 107.2
(OCHO), 201.5 (CHO). MS (PCI): m/z (%) ˆ 173 (100), 157 (13), 127 (20).
8a: A solution of AgNO3 (2.55 g, 15 mmol) in water (70 mL) was added to
a stirred solution of NaOH (1.20 g, 30 mmol) in water (70 mL). A solution
of aldehyde 5a (0.86 g, 5 mmol) in diethyl ether (15 mL) was added
dropwise to the resulting suspension. After stirring for 12 h at room
temperature, the mixture was filtered and the solid washed with hot water.
The aqueous phase was acidified with 2m HCl, and the precipitated acid
extracted with diethyl ether. After drying the combined ethereal extracts
(MgSO4) the solvent was removed, and the residue recrystallized from
petroleum ether; yield 0.80 g (4.30 mmol, 85%); m.p. 958C. 1H NMR
(500 MHz, CDCl3, 228C, TMS); major diastereomer: d ˆ 0.95 (s, 9H, tBu),
1.91 (m, 2H, OCH2CH2), 3.77 (ddd, 1H (ax), J ˆ 11.6, 11.5, 3.6 Hz,
OCH2CH2), 4.21 (ddd, 1H (eq), J ˆ 11.5, 4.5, 1.7 Hz, OCH2CH2), 4.22 (s,
1H, OCHO), 4.30 (dd, 1H (ax), J ˆ 10.6, 4.3 Hz, OCHCH2), 8.21 (s, 1H,
COOH); 13C NMR (125 MHz, CDCl3, 228C, TMS); major diastereomer:
d ˆ 25.3 (C(CH3)3), 28.7 (C(CH3)3), 35.7 (OCH2CH2), 67.1 (OCH2CH2),
85.0 (OCHCH2), 108.0 (OCHO), 173.4 (COOH).
4855 observed reflections I > 4s(I)), R(Rw) ˆ 0.091 (0.094), w ˆ
ꢀ3
(s2(F) ‡ 0.0004F 2)ꢀ1, residual electron density ꢀ0.90/‡0.86 e Š
.
The asymmetric unit contains two symmetrically independent mole-
cules of rac-4b with different conformations (Figure 1). Crystallo-
graphic data (excluding structure factors) for the structures reported
in this paper have been deposited with the Cambridge Crystallo-
graphic Data Centre as supplementary publication no. CCDC-134153.
Copies of the data can be obtained free of charge on application to
CCDC, 12 Union Road, Cambridge CB21EZ, UK (fax: (‡44)1223-
336-033; e-mail: deposit@ccdc.cam.ac.uk).
[9] a) M. Thiam, F. Chastrette, Tetrahedron Lett. 1990, 31, 1429 ± 1432;
b) M. Thiam, A. Slassi, F. Chastrette, R. Amouroux, Synth. Commun.
1992, 22, 83 ± 95.
[10] For purification of technical m-chloroperbenzoic acid, see: a) N. N.
Schwartz, J. H. Blumbergs, J. Org. Chem. 1964, 29, 1976 ± 1979; L. F.
Fieser, M. Fieser, Reagents for Organic Synthesis, Vol. 1, Wiley, New
York, 1967, pp. 135 ± 136.
[11] J. W. E. Glattfeld, F. V. Sanders, J. Am. Chem. Soc. 1921, 43, 2675 ±
2682.
[12] V. Subramanian, S. Hall, GENSIN, Xtal3.4 Userꢀs Manual (Eds.:
S. R. Hall, G. S. D. King, J. M. Stewart), Lamb, Perth, 1995, pp. 141 ±
148.
[13] S. Hall, GENTAN, Xtal3.4 Userꢀs Manual (Eds.: S. R. Hall, G. S. D.
King, J. M. Stewart), Lamb, Perth, 1995, pp. 148 ± 159.
[14] Xtal3.4 Userꢀs Manual (Eds.: S. R. Hall, G. S. D. King, J. M. Stewart),
Lamb, Perth, 1995.
(R)-(‡)-9: A diastereomeric mixture of 8a (1.88 g, 10 mmol) was stirred
with 18% HCl (30 mL) at 308C for 12 h. After addition of CHCl3 (100 mL)
and the azeotropic removal of water the organic layer was dried (MgSO4).
The solvent was removed, and the residue distilled in high vacuum; b.p.
103 ± 1058C/0.1 Torr; yield 0.67 g (6.60 mmol, 66%); [a]2D0 ˆ ‡17.8 (c ˆ 1 in
H2O) (ref.[11]: [a]2D0 ˆ ‡20.29 (c ˆ 4 in H2O)).
Received: July 11, 2000 [Z15436]
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