Diastereoselective cyclopropanation of α,β-unsaturated acetals of a novel camphor-derived chiral auxiliary

Article abstract of DOI:10.1039/a806867d

Reaction of selected α,β-unsaturated aldehydes with phenyl 2,3-dihydroxybornane-10-sulfonate affords acetals which undergo diastereoselective (> 99% de) Simmons-Smith cyclopropanation.

Full text of DOI:10.1039/a806867d

Diastereoselective cyclopropanation of a,b-unsaturated acetals of a novel
camphor-derived chiral auxiliary
Perry T. Kaye* and Warner E. Molema
Department of Chemistry, Rhodes University, Grahamstown, 6140, South Africa. E-mail: chpk@hippo.ru.ac.za
Received (in Cambridge, UK) 3rd September 1998, Accepted 6th October 1998
Reaction of selected a,b-unsaturated aldehydes with phenyl
CH3
2,3-dihydroxybornane-10-sulfonate affords acetals which
H
undergo diastereoselective ( > 99% de) Simmons-Smith
cyclopropanation.
O
Ph
O
H
The cyclopropyl group occurs in various natural products1 and,
due to its inherent ring strain, finds use as a structural
intermediate in synthesis.2 Barrett and Kasdorf,3 for example,
have exploited the Charette methodology4 in tandem asym-
metric cyclopropanation reactions in the synthesis of a nucleo-
side containing five cyclopropane units. The Simmons-Smith
reaction5 is commonly used to construct cyclopropane deriva-
tives, and asymmetric applications involving the use of chiral
acetals6 and ketals7 have been described. We have recently
reported8 moderate diastereoselectivity (40–70% d.e.) in the
Simmons-Smith cyclopropanation of a,b-unsaturated acetals,
using bornane-2,3-diol as a chiral auxiliary. Increasing steric
demand at C-10 of the bornane skeleton was expected to
enhance diastereofacial selectivity, and here we report the
H
H
H
SO3Ph
6c
Fig. 1 NOE interactions observed in the NOESY spectrum of the acetal
6c.
synthesis and use of phenyl 2-exo,3-exo-dihydroxybornane-
10-sulfonate 4 as a highly efficient chiral auxiliary for the
asymmetric cyclopropanation of a,b-unsaturated acetal deriv-
atives.
Treatment of (+)-camphor-10-sulfonyl chloride 1 with phe-
nol in pyridine at 0 °C afforded the phenyl ester 2 in 81% yield
(Scheme 1), the corresponding camphorquinone 3† being
obtained by subsequent selenous acid (H2SeO3) oxidation.
Reduction of the diketone 3 with NaBH4 gave the required diol
4, which was unambiguously characterised by elemental
(HRMS) and spectroscopic analysis.‡
i
ii
O
Following the procedure developed for the synthesis of
bornane-2,3-diol acetals,8 the diol 4 was condensed with the
a,b-unsaturated aldehydes 5a–c to give the corresponding
acetals 6a–c in 64–74% yield. 1H and 13C NMR analyses
indicated the formation of a single diastereomeric acetal in each
case. The presence of heteroatoms and bulky substituents is
known to inhibit pseudorotation in 1,3-dioxolane rings9 and, in
the systems studied here, fusion to the rigid bicyclic bornane
skeleton is likely to lock the 1,3-dioxolane ring into an envelope
conformation. Steric factors are expected to favour formation of
the exo-acetals—an expectation supported by the NOE inter-
actions observed for the cinnamaldehyde acetal 6c (Fig. 1) and
confirmed by single crystal X-ray analysis of this compound
(Fig. 2).§
O
O
O
SO2Cl
SO3Ph
SO3Ph
1
2
3
iii
OH
OH
O
R
O
iv
SO3Ph
4
H
SO3Ph
H
R
6a–c
The Simmons-Smith organozinc reagent exhibits high affin-
ity for ethereal oxygen, and transition state steric demands are
considered to be significant.10 Computer modelling¶ (Fig. 3)
clearly indicates the capacity of the phenyl sulfonate moiety to
hinder access to the ‘front’ face of the unsaturated acetals 6a–c,
and initial coordination of the organozinc reagent to the less
O
v
5a–c
H
O
O
OH
H
R
H
Ph
vi
+
OH
H
O
SO3Ph
SO3Ph
7a–c
4
8c
vii
H
R
OH
S
a R = Me
b R = Pr
c R = Ph
+
OH
S
SO3Ph
4
9a–c
Scheme 1 Reagents and conditions: i, PhOH, pyridine; ii, H2SeO3, dioxane;
iii, NaBH4, MeOH; iv, TsOH, MgSO4, benzene; v, Et2Zn, CH2I2, CH2Cl2,
210 °C; vi, (for
R
=
Ph) TsOH, THF–H2O, reflux, 72 h; vii,
Fig. 2 X-Ray crystal structure of the acetal 6c at 173 K, showing the
crystallographic numbering.
HSCH2CH2SH, TsOH, CH2Cl2.
Chem. Commun., 1998, 2479–2480
2479

76.1 (C-2 and C-3) and 122.0, 127.3, 130.0 and 149.1 (Ar-C); m/z 308
(M2H2O, 0.001%) and 94 (100).
§ Crystal data for 6c: C25H28O5S, M = 440.53; crystal size 0.36 3 0.18 3
0.08 mm, orthorhombic, space group P212121; a
= 6.8183(4), b =
13.0928(8), c = 25.198(2) Å, V = 2249(2) Å3, Z = 4, F(000) = 936, Dc
= 1.301 g cm23, m = 0.178 mm21. Data collection (Siemens SMART CCD
diffractometer; graphite-monochromated Mo-Ka radiation, l = 0.71070 Å,
T = 173 K), w22q scans, 1.62 < q < 28.26°, 13981 reflections collected
(29 @ h @7, 217 @ k @ 17, 226 @ l @17), 5049 unique with I > 2s(I).
Hydrogen atoms were placed in calculated positions and the structure was
solved by direct methods using SHELXTL (ref. 13); full-matrix least-
squares refinement converged at R1 = 0.810, wR2 = 0.1713, GOF = 1.133.
Max., min. peaks in final difference map = 0.221, 20.253 e Å21. CCDC
182/1049.
Fig. 3 Computer-modelled space-filling structure of a rotamer of the acetal
6c, in which the phenyl sulfonate moiety effectively blocks access to one
face of the double bond.
¶ Using the computer modelling software package, HYPERCHEM®.
∑ As evidenced by both 1H and 13C NMR spectroscopy.
** A solution of the acetal 7c and PTSA (2 equiv.) in THF–H2O (5:1) was
hindered acetal oxygen O(7) is predicted to precede methylene
delivery from the ‘back’.
26
boiled under reflux for 72 h to afford the aldehyde 8c (10%), [a]D 2324
(c 0.333, CHCl3), corresponding to (2)-(1R,2R)-2-phenylcyclopropane-
carbaldehyde {[a] 2340 (c 0.363, CHCl3)} (ref. 11).
Cyclopropanation of the acetals 6a–c was effected by their
dropwise addition (as solutions in dry CH2Cl2) to a cold,
vigorously stirred mixture of Et2Zn and CH2I2 in CH2Cl2.8
Work-up and preparative layer chromatography afforded the
cyclopropyl derivatives 7a–c in good material yield (76–95%)
and with complete diastereoselectivity ( > 99% de).∑ Confirma-
tion of the predicted stereochemical bias was achieved by
hydrolysis of acetal 7c to afford the known11 laevorotatory (1R,
2R)-aldehyde 8c;** the remarkable resistance of the acetal 7c to
acidic hydrolysis under various conditions is attributed to steric
crowding. Release of the chiral auxiliary 4 (in 83–87% yield)
from the cyclopropyl derivatives 7a–c was finally achieved by
transthioacetalisation,12 the corresponding dithiolanes 9a–c
being isolated in 87–92% yield.††
†† The cyclopropyl dithiolanes 9a–c (87–92%) and the diol 4 (83–87%)
were obtained from the acetals 7a–c, following a method described by
Caballero et al. (ref. 12) and gave satisfactory elemental (HRMS) and
spectroscopic analyses. Optical rotation data for the dithiolanes are as
26
26
follows: 9a: [a]D 235.2 (c 0.774, CHCl3); 96: [a]D 218.9 (c 2.144,
26
CHCl3); 9c [a]D 288.4 (c 1.300, CHCl3).
1 See, for example, A. Mori, I. Arai, H. Yamamoto, H. Nakai and Y. Arai,
Tetrahedron, 1986, 42, 6447; A. G. M. Barrett, K. Kasdorf, A. J. P.
White and D. J. Williams, J. Chem. Soc., Chem. Commun., 1995,
649.
2 H. N. C. Wong, M.-Y. Hon, C.-W. Tse, Y.-C. Yip, J. Tanko and T.
Hudlicky, Chem. Rev., 1989, 89, 165.
3 A. G. M. Barrett and K. Kasdorf, Chem. Commun., 1996, 325.
4 A. B. Charette and H. Juteau, J. Am. Chem. Soc., 1994, 116, 2651.
5 H. E. Simmons and R. D. Smith, J. Am. Chem. Soc., 1958, 80, 5323.
6 I. Arai, A. Mori and H. Yamamoto, J. Am. Chem. Soc., 1985, 107, 8254;
J. Kang, G. J. Lim, S. K. Yoon and M. Y. Kim, J. Org. Chem., 1995, 60,
564.
We thank the Foundation for Research and Development
(FRD) and Rhodes University for generous financial support,
and Dr Leanne Cook (University of the Witwatersrand) for the
X-ray crystallographic analysis.
7 E. A. Mash, S. K. Math and C. J. Flann, Tetrahedron, 1989, 45,
4945.
Notes and references
† Selected data for 3: yellow crystals, 48%, mp 78–82 °C (Found: M+
322.0846. C16H18O5S requires M, 322.0875).
‡ Selected data for 4: 51%, mp 126–130 °C (from CCl4) (Found: M+
326.1194. C16H22O5S requires M, 326.1188); umax(KBr)/cm21 3300 (OH)
and 1370 and 1150 (SO2O); dH (400 MHz; CDCl3) 0.84 and 1.14 (6H, 2 3
s, 8- and 9-Me), 1.08, 1.49 and 1.76 (4H, 3 3 m, 5-CH2 and 6-CH2), 1.86
(1H, d, 4-H), 3.05 and 3.21 (2H, 2 3 m, 2- and 3-OH), 3.46 (2H, dd,
10-CH2), 3.88 and 4.16 (2H, 2 3 m, 2- and 3-H) and 7.27–7.43 (5H, m, Ar-
H); dC(100 MHz; CDCl3) 20.8 and 21.9 (C-8 and C-9), 23.7 and 29.4 (C-5
and C-6), 49.1 and 49.4 (C-1 and C-7), 49.8 (C-10), 50.4(C-4), 75.7 and
8 P. T. Kaye and W. E. Molema, Synth. Commun., in press.
9 W. E. Willy, G. Binsch and E. L. Eliel, J. Am. Chem. Soc., 1970, 92,
5394.
10 T. L. Cairns, H. E. Simmons and S. A. Vladuchick, Org. React., 1972,
20, 1.
11 H. Abdallah, R. Cree and R. Carrie, Tetrahedron Lett., 1982, 23, 503.
12 M. Caballero, M. Garcia-Valverde, R. Pedrosa and M. Vicente,
Tetrahedron: Asymmetry, 1996, 7, 219.
13 G. M. Sheldrick, SHELXTL Ver. 5.03, 1996, Institut für Anorg.
Chemie, Göttingen.
Communication 8/06867D
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Chem Commun., 1998, 2479–2480