Anomalous face-selectivity in sharpless asymmetric dihydroxylation of o-allylbenzamides

Full text of DOI:10.1021/jo9607323

4190
J . Org. Chem. 1996, 61, 4190-4191
An om a lou s F a ce-Selectivity in Sh a r p less
Asym m etr ic Dih yd r oxyla tion of
o-Allylben za m id es
Piero Salvadori,*,† Stefano Superchi,†,‡ and
Filippo Minutolo†,§
C.N.R. Centro Studi Macromolecole Stereordinate ed
Otticamente Attive, Dipartimento di Chimica e Chimica
Industriale, Universita` di Pisa, via Risorgimento 35,
I-56126 Pisa, Italy, and Scuola Normale Superiore, piazza
dei Cavalieri 7, I-56127 Pisa, Italy
Received April 23, 1996
The osmium tetraoxide-catalyzed asymmetric dihy-
droxylation (AD) of olefins has proved to be one of the
most useful and reliable procedures, in both the homo-
geneous1 and the heterogeneous2 phase, for the synthesis
of chiral diols. An important feature of this reaction is
the possibility of achieving both enantiomers using, as
chiral ligands, derivatives of the pseudoenantiomeric
alkaloids dihydroquinine (DHQ) and dihydroquinidine
(DHQD). Moreover, an empirical face-selectivity rule
(Figure 1) proposed by Sharpless et al.3a allows3 predic-
tions upon the absolute stereochemistry of diols obtained
in the AD process with the two classes of alkaloid ligands.
This rule, based on a very large amount of examples and
supported by molecular mechanics studies,1 is commonly
used as a guideline for the choice of the right ligand. To
date, only a few exceptions have been found to the
Sharpless rule, mainly concerning the AD of vinylidenic
substrates,4 and of chiral olefins,5 where double diaste-
reoselection was involved. A sole case of reversal of
π-facial selectivity in an achiral monosubstituted olefin
has been recently reported.6 Herein, we report several
exceptions to the Sharpless face-selectivity rule in the
AD of differently substituted o-allylbenzamides.
F igu r e 1.
Sch em e 1a
Looking for new synthetic methods toward optically
active dihydroisocoumarins,7,8 we designed a strategy
involving at first the copper-mediated regioselective
allylation of benzamides9 for the construction of the
* To whom correspondence should be addressed. Tel.: +39-50-
918273. Fax: +39-50-918260.
† C.N.R.-C.S.M.S.O.A., Universita` di Pisa.
‡ Present address: Dipartimento di Chimica, Universita` della
Basilicata, via Nazario Sauro, 85, I-85100 Potenza, Italy.
§ Scuola Normale Superiore.
(1) Kolb, H. C.; Van Nieuwenhze, M. S.; Sharpless, K. B. Chem. Rev.
1994, 94, 2483 and references therein.
(2) Some examples are given in: (a) Pini, D.; Petri, A.; Salvadori,
P. Tetrahedron 1994, 50, 11321. (b) Petri, A.; Pini, D.; Salvadori, P.
Terahedron Lett. 1995, 36, 1549.
(3) (a) Kolb, H. C.; Andersson, P. G.; Sharpless, K. B. J . Am. Chem.
Soc. 1994, 116, 1278. (b) Sharpless, K. B.; Amberg, W.; Beller, M.;
Chen, H.; Hartung, J .; Kawanami, Y.; Lu¨bben, D.; Manoury, E.; Ogino,
Y.; Shibata, T.; Ukita, T. J . Org. Chem. 1991, 56, 4585. (c) Sharpless,
K. B.; Amberg, W.; Bennani, Y. L.; Crispino, G. A.; Hartung, J .; J eong,
K.-S.; Kwong, H.-L.; Morikawa, K.; Wang, Z.-M.; Xu, D.; Zhang, X.-L.
J . Org. Chem. 1992, 57, 2768.
(4) (a) Hale, K. J .; Manaviazar, S.; Peak, S. A. Tetrahedron Lett.
1994, 35, 425. (b) Krysan, D. J . Tetrahedron Lett. 1996, 37, 1375.
(5) (a) Iwashima, M.; Kinsho, T.; Smith, A. B., III. Tetrahedron Lett.
1995, 36, 2199. (b) Carreira, E. M.; Du Bois, J . J . Am. Chem. Soc. 1994,
116, 10825. (c) Krysan, D. J .; Rockway, T. W.; Haight, A. R. Tetrahe-
dron: Asymmetry 1994, 5, 625.
(6) After the preparation of the present manuscript, we became
aware of the following paper: Boger, D. L.; McKie, J . A.; Nishi, T.;
Ogiku, T. J . Am. Chem. Soc. 1996, 118, 2301.
(7) Superchi, S.; Pini, D.; Salvadori, P.; Marinelli, F.; Rainaldi, G.;
Zanelli, U.; Nuti-Ronchi, V. Chem. Res. Toxicol. 1993, 6, 46.
(8) Superchi, S.; Minutolo, F.; Pini, D.; Salvadori, P. J . Org.Chem.
1996, in press.
a
Key: synthetic route to 4a -e.
carbon skeleton. Afterwards, the AD process was used
for the introduction of the chiral centers (Scheme 1).
The regioselective ortho-allylation of the N,N′-dieth-
ylbenzamides was carried out via a sequence of lithiation,
copper transmetalation, and coupling with an allylic
bromide (84-93% yield). The o-allyl benzamides 2a -e
were submitted to AD reaction and the resulting diols
3a -e cyclized under basic conditions to 3-(hydroxymeth-
ylene)dihydroisocoumarins 4a -e (60-71% yield).
The stereochemical outcome of the AD process, in
terms of ee and absolute configuration (Table 1), was
determined for the dihydroisocoumarins 4a -e, as the
cyclization step did not affect the chiral centers. Indeed,
(9) Pini, D.; Superchi, S.; Salvadori, P. J . Organomet. Chem. 1993,
452, C4.
S0022-3263(96)00732-3 CCC: $12.00 © 1996 American Chemical Society

Communications
J . Org. Chem., Vol. 61, No. 13, 1996 4191
Ta ble 1. P r ep a r a tion of Dih yd r oisocou m a r in s 4a -e
fr om o-a llylben za m id es 2a -e
Ta ble 2. CD Da ta of Dih yd r oisocou m a r in s 4a -g a n d
Com p ou n d s 6a a n d 7a
Sharpless
rule
product confign eeb agreement
product
λmax (nm) (∆ꢀ)b,c
absolute
(R)-4a
(S)-4b
(R)-4c
278 sh (+2.4), 251 (+7.3), 230 (-8.4), 206 (+19)
302 (-2.8), 257 (-5.7), 237 (+1.4), 207 (-9.8)
296 (+3.0), 268 (+9.6), 248 (-2.4), 231 (+6.7), 215
(+0.6), 203 (+11)
316 (-1.9), 261 (-5.9), 240 (+0.1), 224 sh (-2.9), 209
(-12)
entry olefin
liganda
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
2a
2a
2a
2b
2b
2c
2c
2c
2c
2c
2d
2d
2e
2e
2e
DHQD-PHN
(DHQD)2PHAL
DHQD-CLB
DHQD-PHN
(DHQD)2PHAL
DHQD-PHN
DHQ-PHN
(DHQD)2PHAL
(DHQ)2PHAL
DHQD-CLB
DHQD-PHN
(DHQD)2PHAL
DHQD-PHN
DHQ-PHN
4a
4a
4a
4b
4b
4c
4c
4c
4c
4c
4d
4d
4e
4e
4e
R
S
R
R
S
R
S
S
R
S
S
S
R,R
S,S
S,S
44
16
15
40
16
40
32
10
7
11
30
64
90
86
81
Y
N
Y
Y
N
Y
Y
N
N
N
N
N
Y
Y
Y
(S)-4d
(S,S)-4e 305 (-2.2), 258 (-4.7), 238 (+3.2), 209 (-7.7)
(R)-4f
(R)-4g
6a
295 (-1.2), 268 (+6.8), 248 (-1.8), 233 (+6.6), 221
(-1.4), 200 (+15)
295 (-2.7), 268 (+7.4), 247 (-2.4), 234 (+8.1), 221
(-2.1), 200 (+15)
290 sh (-1.6), 282 sh (-2.4), 254 (-6.7), 232 (+9.2),
207(-16)
302 (-0.4), 268 (+3.0), 246 (-0.8), 232 (+2.6),
195 (+2.4)
(S)-7a
a
b
See ref 12. ∆ꢀ values were corrected considering the ee’s of
the samples. c All spectra were recorded on methanolic solutions
of products, except for 6 (EtOH) and 7 (CH3CN).
(DHQ)2PHAL
a
AD reactions were carried out according to ref 3b for PHN
and CLB-based ligands and according to ref 3c for PHAL-based
b
ligands. Ee’s were determined by HPLC on a Chiralpack AD
column.
in the AD of a vinylidenic olefin.4b The chlorobenzoate-
based catalyst DHQD-CLB gave in one case the expected
major enantiomer (olefin 2a , entry 3, Table 1) and in
another the opposite enantiomer (olefin 2c, entry 10,
Table 1), but always with poor ee’s.
To be more precise, the major enantiomer in the
phenanthrene catalyzed (DHQD-PHN and DHQ-PHN)
reactions of 2c (entries 6 and 7, Table 1) was the minor
enantiomer in the phthalazine-catalyzed ((DHQD)2-
PHAL and (DHQ)2-PHAL) reactions of the same olefin
(entries 8 and 9, Table 1). The same was found for olefins
2a (entries 1 and 2, Table 1) and 2b (entries 4 and 5,
Table 1). The unexpected enantiomers were always
obtained with phthalazine catalysts. Olefin 2d always
gave the product 4d with the unexpected configuration,
both with DHQD-PHN and (DHQD)2-PHAL, although
a higher ee was reached with the phthalazine catalyst
(entries 11 and 12, Table 1). Finally, the internal trans
olefin 2e provided the expected enantiomer in high ee’s
with all the ligands employed (DHQD-PHN, DHQ-
PHN, and (DHQ)2-PHAL), showing a definitely different
behavior from its analogous terminal olefin 2b.
F igu r e 2.
the hindered rotation of the benzamido group10 in diols
3a -e generates an additional atropoisomeric chiral
center, complicating both the HPLC and NMR analyses
of such compounds. In many cases the final product
4a -e was obtained with an unexpected absolute config-
uration (vide infra).
These results confirm that the Sharpless mnemonic
model fails with several monosubstituted olefins contain-
ing a benzamido group,6 although it preserves its ef-
fectiveness with an extremely large variety of olefins. Any
attempt to rationalize these results are beyond the scope
of this paper. Still, it provides an insight into this special
class of terminal olefins, which constitute important
exceptions to the π-facial selectivity model. We hope that
these findings can help and stimulate further work aimed
at refining such models and establishing a reliable
mechanism for AD reaction.
The absolute configuration of dihydroisocoumarins
4a -e was determined either by chemical correlation to
58,11 (Figure 2) or by comparison of CD spectra (Table 2)
with compounds of known stereochemistry, such as 612
and 712 (Figure 2).
As shown in Table 1, the stereochemical sense of the
AD process was, in many cases, opposite to that expected
from the Sharpless rule, which predicts, for these sub-
strates, the R configuration from DHQD-based ligands
and the S configuration from DHQ-based ligands. More-
over, in most cases, changing the ligand from phenan-
threne (PHN) to phthalazine (PHAL), while keeping the
chiral cinchona alkaloid constant, reversed the sense of
the π-facial selectivity of the AD reaction (Table 1, entries
1-10). A similar behavior has recently been observed
Ack n ow led gm en t. F.M. thanks E.N.I.-Rome for a
fellowship. Support by C.N.R., Progetto Strategico
Tecnologie Chimiche Innovative is acknowledged.
Su p p or tin g In for m a tion Ava ila ble: General procedures,
1H and 13C NMR data, elemental analyses of all new products
(2a -d and 4a -g), CD spectra of dihydroisocoumarins 4a -g
from Table 2, and a detailed discussion on absolute configu-
ration assignments (15 pages).
(10) Oki, M. Application of Dynamic NMR Spectroscopy to Organic
Chemistry; VCH Publishers: Weinheim, Germany, 1985; pp 178-182
and references therein.
(11) Shimojima, Y.; Hayashi, H.; Ooka, T.; Shibukawa, M.; Iitaka,
Y. Tetrahedron Lett. 1982, 23, 5435.
(12) Antus, S.; Snatzke, G.; Steinke, I. Liebigs Ann. Chem. 1983,
2247.
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