Asymmetric O- and C-alkylation of phenols

Full text of DOI:10.1021/ja972453i

J. Am. Chem. Soc. 1998, 120, 815-816
815
Table 1. Enantioselective Phenol Alkylationsa
Asymmetric O- and C-Alkylation of Phenols
allyl
O-alk. ether
rearr. C-alk.
temp (isol
Barry M. Trost* and F. Dean Toste
allyl temp
(isol
%
product
entry phenol carb. (°C) yield, %) eeb (°C) yield, %) ee (%)
Department of Chemistry, Stanford UniVersity
Stanford, California 94305-5080
1
2
1
1
2a
2a
25
-40
5a (96) 60
5a (85) 85
ReceiVed July 21, 1997
94c 50 11a (86)
93
97
3
4
5
6
7
8
9
10
11
12
1
1
1
1
1b
6a
6b
6b
6c
9
2a
2b
2c
2c
2b
2b
2b
2b
2b
8
-78
25
25
0
25
25
25
0
5a (82) 78
5b (88) 97 50 11b (79)
5c (89) 92
5c (85) 93 50 11c (77)
5d (88)
7a (89) 94 50 13a (81)
7b (90) 77
While the aliphatic Claisen rearrangement has proven to be a
major synthetic tool for controlling stereochemistry in C-C bond
formation, the aromatic Claisen rearrangement has not been
exploited as an asymmetric aryl alkylation protocol.1,2 The high
temperatures required for the thermal process make a catalytic
version desirable. However, the reported Lewis acid-catalyzed
versions have led to significant racemization as well as fragmen-
tation accompanying rearrangement.3,4 The utility of a catalytic
Claisen reaction that occurs with excellent chirality transfer also
requires a facile asymmetric O-alkylation of phenols.5,6 We report
the accomplishment of both goals.
For the asymmetric O-alkylation, we examined the use of
asymmetric Pd-catalyzed allylic alkylation. Whereas, standard
allylic carboxylates fail as substrates due to the propensity for
acyl shift to form phenyl esters, carbonates proved efficacious as
shown in the alkylation of p-methoxyphenol (1a) with tert-butyl-
3-cyclopentenyl carbonate (2a, eq 1). Using the ligand 37,8 with
96
80 11d (83)
94h
93
7b (83) 85 80 13b (84)
80
25
7c (90) 95 50d 13ce (91)
93
25 10 (89) 85 50 14 (97)f
91g
a For reaction conditions, see text. b Determined by chiral HPLC
using a Chiracel OD or Chirapak AD column eluting with heptane-
2-propanol mixtures. c After recrystallization from cold pentanes.
d Rearrangement performed with 1 mol % Eu(fod)3. e The ee was
determined by NMR analysis of the corresponding O-methylmandelate
ester. f The yield corresponds to the 6:1 E:Z isomers. g For the major
E isomer 14. h The ee was determined by HPLC of the corresponding
O-methylmandelate ester.
Switching from the five-membered ring allyl carbonate to either
the six- or seven-membered analogue led to reactions that proved
to be more straightforward. Even at room temperature, under
the standard conditions, excellent ee’s of products 5b6,9 and 5c10
were obtained (entries 4-6). Changing the phenol to 6a, 6b, or
6c led to equally gratifying results (eq 2 and Table 1, entries
the palladium complex 4 gave 5a9 in good yield but with a modest
enantioselectivity (see Table 1, entry 1). Lowering the temper-
ature improved the enantioselectivity, but there clearly is an
optimal temperature below which no further improvement pertains
(entries 2 and 3). It should be noted that one recrystallization
from cold pentanes raises the ee from 85% to 94%.
(1) For reviews, see: (a) Wipf, P. In ComprehensiVe Organic Synthesis;
Trost, B. M., Fleming, I., Paquette, L. A., Eds.; Pergamon Press: Oxford,
U.K., 1991; Vol. 5, pp 827-874. (b) Moody, C. J. AdV. Heterocycl. Chem.
1987, 42, 203. (c) Lutz, R. P. Chem. ReV. 1984, 84, 205. (d) Bennett, G. B.
Synthesis 1977, 589. (e) Rhoads, S. J.; Raulins, N. R. Org. React. 1975, 22,
1.
(2) Enders, D.; Knopp, M.; Schiffers, R. Tetrahedron: Asymmetry 1996,
7, 1847. Frauenrath, H. In Houben-Weyl Methods of Organic Chemistry;
Helmchen, G., Hoffmann, R. W., Mulzer, J., Schaumann, E., Eds.; Thieme:
Stuttgart; Vol. E21d, pp 3301-3546. Ziegler, F. E. Chem. ReV. 1988, 88,
1423.
8-11) with formation of ethers 7a,13 7b,14 and 7c.10 In the
synthesis of adduct 7c, the catalyst loading was reduced to 0.25
mol % of palladium precursor 4 and 0.75 mol % of ligand
(10) All new compounds have been satisfactorily characterized spectro-
scopically.
(3) For some recent references, see: (a) Bernard, A. M.; Cocco, M. T.;
Onnis, V.; Piras, P. P. Synthesis 1997, 41. (b) Kim, K. M.; Kim, H. R.; Chung,
K. H.; Song, J. H.; Ryu, E. K. Synth. Commun. 1994, 24, 1859. (c) Maruoka,
K.; Sato, J.; Banno, H.; Yamamoto, H. Tetrahedron Lett. 1990, 31, 377.
(4) (a) Aleksandrova, E. K.; Bunina-Krivorukova, L. I.; Moshimskaya, A.
V.; Bal’yan, Kh. V. Zh. Org. Khim. 1974, 10, 1039; Chem. Abstr. 1974, 81,
49151m. (b) Borgula, T.; Madeja, R.; Gahrni, P.; Hansen, H. J.; Schmid, H.;
Barner, R. HelV. Chim. Acta 1973, 56, 14.
(11) After stirring a solution of the allylic carbonate 2b (261 mg, 1.67
mmol), Pd2dba3‚CHCl3 (4 mg, 0.004 mmol), and the ligand 3 (8 mg, 0.012
mmol) in degassed CH2Cl2 (3.0 mL) at room temperature, under argon, for
15 min, a solution of sesamol 6c (235 mg, 1.70 mmol) in CH2Cl2 was added.
The resulting purple solution became orange and finally yellow after stirring
at room temperature for 4 h. Flash chromatography eluting with 5:1 petroleum
ether:ether afforded the aryl ether 7c (335 mg, 90% yield) as a colorless liquid.
A solution of the aryl ether 7c (175 mg, 0.803 mmol) and Eu(fod)3 (8 mg,
0.008 mmol) in minimal dry chloroform (0.1 mL), under nitrogen, was placed
into a preheated 50 °C oil bath for 8 h. After cooling, direct flash
chromatography, eluting with 5:1 petroleum ether:ether, afforded 13c (160
mg, 91% yield) as a colorless liquid. For larger scale reactions, better results
were obtained by diluting the reaction mixture with ether and washing with
water to remove the europium catalyst prior to chromatography.
(12) Benhamou, M.-C.; Etemad-Hoghadam, G.; Spe´ziale, V.; Lattes, A. J.
Heterocycl. Chem. 1978, 15, 1313.
(5) For problems of racemization associated with O-alkylation of phenols
with enantiopure allyl chlorides, see: Goering, H. L.; Kimoto, W. I. J. Am.
Chem. Soc. 1965, 87, 1748.
(6) An alternative preparation of chiral aryl allyl ethers utilizing a zirconium-
catalyzed kinetic resolution has been reported: Visser, M. S.; Harrity, J. P.
A.; Hoveyda, A. H. J. Am. Chem. Soc. 1996, 118, 3779.
(7) Trost, B. M.; Van Vranken, D. L.; Bingel, C. J. Am. Chem. Soc. 1992,
114, 9327. For a review, see: Trost, B. M. Acc. Chem. Res 1996, 29, 355.
(8) Trost, B. M.; Bunt, R. C. J. Am. Chem. Soc. 1994, 116, 4089.
(9) Hosokawa, T.; Miyagi, S.; Murahashi, S.-I.; Sonoda, A. J. Org. Chem.
1978, 43, 2752. Hosokawa, T.; Miyagi, S.; Murahashi, S.-I.; Sonoda, A.;
Matsuura, Y.; Tanimoto, S.; Kakudo, M. J. Org. Chem. 1978, 43, 719.
(13) Lambrecht, S.; Scha¨fer, H. J.; Fro¨hlich, R.; Grehl, M. Synlett 1996,
283.
(14) Trost, B. M.; Krueger, A. C.; Bunt, R. C.; Zambrano, J. J. Am. Chem.
Soc. 1996, 118, 6520.
S0002-7863(97)02453-0 CCC: $15.00 © 1998 American Chemical Society
Published on Web 01/13/1998

816 J. Am. Chem. Soc., Vol. 120, No. 4, 1998
Communications to the Editor
3.12 With the less electron rich phenol 6b, a lower temperature
was required to improve the ee whereas the p-fluorophenol 1b
was allylated with 94% ee even at room temperature (entry 7 vs
10). The reaction of an acyclic allylic carbonate15 8 with phenol
94b was also examined wherein the results paralleled those seen
in the cyclic case (eq 3 and Table 1, entry 12).
esters 17a,b, which allowed for the determination of the stereo-
chemistry in agreement with the established mnemonic (eq 5).19
With the availability of the allyl aryl ethers of high enantio-
purity, attention focused on the Claisen rearrangement to convert
C-O to C-C stereochemistry. Initial studies examined classical
Lewis acids. Treatment of 5a with boron trichloride (PhH, -40
°C) or diethylaluminum chloride (hexanes, 25 °C) led to the
rearranged product 11a with significant racemization. A lan-
thanide triflate15,16 proved too reactivesagain leading to racem-
ization. On the other hand, the common europium complex 1215a
in chloroform at 50 °C proved effective wherein the chirality of
5a (94% ee) was faithfully transferred to 11a9 (eq 2) in 86% yield
(93% ee). As summarized in Table 1, similar results were
obtained in the other cases. In the case of 6c, performing the
rearrangement with minimal solvent to maintain homogeneity
allowed the use of only 1 mol % of Eu(fod)3.11 The less electron
rich analogues 5d6 and 7b (85% ee) required slightly more
elevated temperatures (80 °C, DCE) but proceeded satisfactorily
to give 11d (83% yield, 94% ee) and 13b13 (84% yield, 80% ee),
respectively. The increased steric hindrance (in the latter case)
and/or the decreased electron richness of the aromatic ring may
account for the slower reaction.
Asymmetric O-alkylation followed by diastereoselective Clais-
en rearrangement constitutes a useful protocol for asymmetric
C-alkylation of phenols. The importance of the lanthanide-
catalyzed Claisen rearrangement is highlighted by (1) the failure
of the thermal reactions in some cases, (2) racemization occurring
in some instances, and (3) subsequent reactions of the initial
products. For example, the thermal reaction of 7b leads solely
to 18a (eq 6) which, for these authors, was undesired since 13b
The acyclic system proved to be more complicated. Rear-
rangement proceeded quite well under the standard conditions
(97% yield) but produced a 6:1 mixture of the E and Z alkene
isomers, 14 and 15, respectively.4b On the basis of chairlike and
boatlike transition states, respectively (eq 4),5,17 the stereochem-
was needed for morphane synthesis.13 In our hands, reaction with
the aldehyde proved more efficient after methylation of the
tricyclic phenol 13b. The product alcohol 18b was converted
into its mandelate ester 18c, used for determining its stereochem-
istry.19 The presence of the double bond in both the O- and
C-alkylation products becomes a focus for further modifica-
tions.13,20 Since rearrangements to the para position of phenols
are also documented,1,3c this process may also consititute asym-
metric para as well as ortho alkylation.5 Such a protocol may be
envisioned for other aryl heteroatom systems (e.g., anilines) and
thus become a more general approach for asymmetric alkylations
of aromatic (including heteroaromatic) rings.1c The prospect of
asymmetric catalysis in the lanthanide-catalyzed rearrangement
with achiral allyl aryl ethers is also suggested.21
Acknowledgment. We thank the National Science Foundation and
the National Institutes of Health, General Medical Sciences Institute, for
their generous support of our programs. Mass spectra were provided by
the Mass Spectrometry Regional Center of the University of CaliforniasSan
Francisco supported by the NIH Division of Research Resources.
istry of the two products should be as depicted in 14 and 15. The
ee of 14 was 91%, which indicated excellent chirality transfer in
the acyclic case as well.
The stereochemistries of 10 and 14 have been previously
established,4b and the stereochemistry of the former also follows
from our previously established mnemonic.6 Further evidence
for this stereochemistry was obtained by hydrogenating 10 and
comparing the saturated product to an authentic sample prepared
by the Mitsonobu reaction of 9 with (S)-2-pentanol.
Supporting Information Available: Characterization data and copies
1
of H NMR and 13C NMR spectra for 5a-d, 7a,b, 9, 12, 14, 16a-d,
17a-c, 18, 20, and 24b (49 pages). See any current masthead page for
ordering and Internet access instructions.
JA972453I
The absolute stereochemistry of the cyclic aryl ethers was
established by regio- and diastereoselective rhodium-catalyzed
hydroboration of 5b,c.18 Hydroboration proceeded smoothly in
the case of the six-membered ring, producing almost exclusively
the 3-alcohol 16a. In the seven-membered-ring compound 5c,
however, a separable 1:1.7 mixture of the 2- and 3-alcohols was
formed. The alcohols 16a,b were converted into their mandelate
(19) Trost, B. M.; Belletire, J. L.; Godleski, S.; McDougal, P. M.; Balkovec,
J. M.; Baldwin, J. J.; Christry, M. E.; Ponticello, G. S.; Varga, S. L.; Springer,
J. P. J. Org. Chem. 1986, 51, 2370. Latypou, S. K. Seco, J. M.; Quinoa, E.;
Riguera, R. J. Org. Chem. 1996, 61, 8569.
(20) For a few illustrations, see: ref 8. Hosokawa, T.; Murahashi, S. I. J.
Synth. Org. Chem. Jpn. 1995, 53, 1009; Heterocycles 1992, 33, 1079; Acc.
Chem. Res. 1990, 23, 49. Youssefyeh, R. D.; Campbell, H. F.; Airey, J. E.;
Klein, S.; Schnapper, M.; Powers, M.; Woodward, R.; Rodriguez, W.; Golec,
B.; Studt, W.; Dodson, S. A.; Fitzpatrick, L. R.; Pendley, C. E.; Martin, G. E.
J. Med. Chem. 1992, 35, 903. Bernard, A. M.; Cocco, M. T.; Onnis, V.; Piras,
P. P. Synthesis 1997, 41. Also, see: Parker, K. A.; Fokas, D. J. Org. Chem.
1994, 59, 3927. Larock, R. C.; Lee, N. H. J. Org. Chem. 1991, 56, 6253.
Nagase, H.; Matsumoto; Yoshiwara, H.; Tajima, A.; Ohno, K. Tetrahedron
Lett. 1990, 31, 4493.
(15) (a) For pioneering work in use of Eu(fod)3 in hetero-Diels-Alder
cycloadditions, see: Bednarski, M.; Danishefsky, S. J. Am. Chem. Soc. 1983,
105, 3716. And in epoxide rearrangements, see: Trost, B. M.; Bogdanowicz,
M. J. J. Am. Chem. Soc. 1973, 95, 5321. (b) Kobayashi, S. Synlett 1994, 689.
(16) Imamoto, T. In Lanthanides in Organic Synthesis; Academic Press:
London, U.K., 1994; Chapter 5, pp 67-118.
(17) Marvel, E. N.; Stephenson, J. L.; Irig, J. J. Am. Chem. Soc. 1965, 87,
1267.
(18) Evans, D. A.; Fu, G. C.; Hoveyda, A. H. J. Am. Chem. Soc. 1992,
114, 6671.
(21) During the preparation of this manuscript, use of a stoichiometric chiral
Lewis acid to mediate rearrangement of achiral substrates derived from catechol
was reported, see: Ito, H.; Sato, A.; Taguchi, T. Tetrahedron Lett. 1997, 38,
14815.