Chiral catalyst enhancement of diastereocontrol for O-H insertion reactions of styryl- and phenyldiazoacetate esters of pantolactone

Article abstract of DOI:10.1016/S0040-4039(02)01282-0

The chiral dirhodium(II) catalyst Rh₂(MEAZ)₄ increases diastereocontrol for intermolecular O-H insertion reactions of diazo esters having a chiral auxiliary over that achieved with Rh₂(OAc)₄.

Full text of DOI:10.1016/S0040-4039(02)01282-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 5929–5931
Chiral catalyst enhancement of diastereocontrol for OꢀH
insertion reactions of styryl- and phenyldiazoacetate esters of
pantolactone
Michael P. Doyle* and Ming Yan
Department of Chemistry, University of Arizona, Tucson, AZ 85721-0041, USA
Received 6 May 2002; revised 12 June 2002; accepted 28 June 2002
Abstract—The chiral dirhodium(II) catalyst Rh2(MEAZ)4 increases diastereocontrol for intermolecular OꢀH insertion reactions of
diazo esters having a chiral auxiliary over that achieved with Rh2(OAc)4. © 2002 Elsevier Science Ltd. All rights reserved.
Efficient, highly stereoselective oxygen–hydrogen inser-
tion has long been sought in catalytic reactions of diazo
compounds.1–3 Two pathways for these reactions were
thought possible. The first, a direct insertion reaction
analogous to the concerted CꢀH insertion,4 was deemed
to be improbable because of the absence of similar
reactivity/selectivity outcomes between the two pro-
cesses. The second, and most likely, pathway was ylide
formation followed by rapid 1,2-hydrogen shift
(Scheme 1).3,5 Here two conditions arise: (1) that the
metal-associated ylide (1) undergoes concerted hydro-
gen shift/metal dissociation and (2) that free ylide (2)
formation precedes hydrogen shift. Although ylide reac-
tions were long believed to proceed through the free
ylide, there is now considerable evidence that the for-
mer pathway may account for product formation in
favorable instances.6 However, there have been no
reports of enantioselective OꢀH insertion reactions
from the use of chiral catalysts.1–3,7
Moody investigated diastereoselectivity in the OꢀH
insertion reactions of water and alcohols with phenyldi-
azoacetates of several chiral alcohols with dirhodium-
(II) acetate as the catalyst.8 Chiral auxiliaries from
(−)-borneol, (+)- and (−)-menthol, (+)-8-phenylmenthol,
(+)- and (−)-2-phenylcyclohexanol, and (−)-10-
(dichlorohexylsulfamoyl)-10-isoborneol were used, and
reactions with water, methanol, 2-propanol, and tert-
butyl alcohol were studied. However, selectivities were
highly variable, and the highest diastereomer ratios
achieved (with 8-phenylmenthol and MeOH) were less
than 77:23. Landais has provided an example with the
styryldiazoacetate pantolactone ester and water where
75:25 dr was realized using Rh2(OAc)4 as the catalyst.9
We have investigated the OꢀH insertion reactions of
(R)-(−)-pantolactone esters of phenyldiazoacetate and
trans-styryldiazoacetate with and without the use of
chiral dirhodium(II) catalysts. We report here that there
is significant enhancement of diastereoselectivity with
Scheme 1.
* Corresponding author.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01282-0

5930
M. P. Doyle, M. Yan / Tetrahedron Letters 43 (2002) 5929–5931
latter favoring the R-enantiomer by more than 2:1.
Variation of the alcohol in reactions of R-5 catalyzed
by Rh2(4R-MEAZ)4 gave similar results: H2O (dr=
18:82), PhOH (dr=24:76), PhCH2OH (dr=21:79),
H2CꢁCHCH2OH (dr=27:73). Neither isopropyl alco-
hol nor tert-butyl alcohol gave even moderate yields of
OꢀH insertion products. Reactions of menthyl and
8-phenylmenthyl esters of trans-styryldiazoacetate with
4 as the catalyst and both H2O and MeOH as nucle-
ophiles were also investigated. However, enhancements
(D) were much lower (1–16) than those reported in
Table 1.
chiral dirhodium(II) carboxamidate catalysts, and there
is a special role for pantolactone in these reactions.
Methyl trans-styryldiazoacetate undergoes facile OꢀH
insertion in reactions with methanol catalyzed by
Rh2(OAc)4 to form only 3 (Eq. (1)).10 With the chiral
catalyst Rh2(4S-MEAZ)4 (4), previously shown to be
highly effective for diazo decomposition of vinyldia-
zoacetates,11 3 was formed in high yield but with only
5% ee. The pantolactone esters of trans-styryldiazoac-
etate (5) prepared in high yield by standard methods,
were similarly treated. With Rh2(OAc)4
a 54:46
diastereomer ratio was realized, but with Rh2(4S-
MEAZ)4 and its enantiomer, Rh2(4R-MEAZ)4,
diastereomer ratios were 42:58 and 24:76, respectively,
indicating not only a significant catalyst influence on
stereoselectivity but also significant characteristics of
match/mismatch in diastereoisomer selection. The dom-
inant stereoisomer was dependent on the configuration
of the pantolactone auxiliary rather than on the
configuration of the catalyst ligands. The absolute
configuration of the major diastereoisomer was based
on that previously reported for methyl 2-hydroxy-4-
phenylbutanoate.12
With the pantolactone ester of phenyldiazoacetate (13)
the influence of catalyst was even more pronounced
than that reported in Table 1 (Eq. (2)). Rh2(4R-
MEAZ)4 inverts the diastereomer preference of
Rh2(OAc)4 in reactions with MeOH and substantially
enhances the diastereomer preference in reactions with
H2O (Table 2). Consideration was given to intramolec-
ular entrapment of the intermediate carbene as a car-
bonyl ylide (15), but attempts to trap this species by
dipolar cycloaddition (DMAD) were not successful.
Table 1. Diastereocontrol in OꢀH insertion reactions of 5
with methanola
(1)
OꢀH insertion product
Diazo
compound
Catalyst
Yield (%)b
drc
Dd
R-5
R-5
Rh2(OAc)4
Rh2(4S-MEAZ)4 52
55
54:46
42:58
0
12
(4)
R-5
Rh2(4R-MEAZ)4 74
(4)
24:76
30
R-5
S-5
S-5
R-5
S-5
R-5
S-5
9
9
80
83
83
57
80
44
83
39:61
71:29
75:25
44:56
76:24
45:55
77:23
15
17
21
10
22
9
The OꢀH insertion product from reactions of R-5 with
MeOH catalyzed by CuPF6/6, Rh2(5S-MEPY)4 (7) and
Rh2(4S-MPPIM)4 (8) was not observed. However,
diazo decomposition of 5 occurred readily in the pres-
ence of catalysts 9–12, and these results are reported in
Table 1. The most suitable catalyst for OꢀH insertion
into methanol is Rh2(MEAZ)4, and there is no obvious
advantage from this catalyst’s ligand ester group. The
use of Rh2(4R-MEAZ)4 with R-5 and Rh2(S-DOSP)4
(9) with S-5 give complementary results, the former
favoring the S-enantiomer by more than 3:1 and the
10
11
11
12
12
23
a Reactions were performed at room temperature in CH2Cl2 using 0.5
mol% of catalyst and 2.0 equiv. of methanol.
b Weight yield of product after chromatography.
c Diastereoisomer ratio=2R:2S.
d Change in dr from result with Rh2(OAc)4.

M. P. Doyle, M. Yan / Tetrahedron Letters 43 (2002) 5929–5931
5931
Table 2. Diastereocontrol in OꢀH insertion reactions of
2. Padwa, A.; Hornbuckle, S. F. Chem. Rev. 1991, 91, 263.
3. Miller, D. J.; Moody, C. J. Tetrahedron 1995, 51, 10811.
4. (a) Doyle, M. P.; Westrum, L. J.; Wolthuis, W. N. E.;
See, M. M.; Boone, W. P.; Bagheri, V.; Pearson, M. M.
J. Am. Chem. Soc. 1993, 115, 958; (b) Taber, D. F. In
Houben-Wehl, Methods of Organic Chemistry; Helmchen,
G., Ed.; Georg Thieme: Stuttgart, 1995; Vol. E21; (c)
Doyle, M. P. In Catalytic Asymmetric Synthesis, 2nd ed.;
Ojima, I., Ed.; Wiley-VCH: New York, 2000; Chapter 5.
5. (a) Cox, G. G.; Moody, C. J.; Austin, D. J.; Padwa, A.
Tetrahedron 1993, 49, 5109; (b) Moody, C. J.; Miller, D.
J. Tetrahedron 1998, 54, 2257.
6. (a) Kitagaki, S.; Anada, M.; Kataoka, O.; Matsuno, K.;
Umeda, C.; Watanabe, N.; Hashimoto, S. J. Am. Chem.
Soc. 1999, 121, 1417; (b) Doyle, M. P.; Forbes, D. C.;
Protopova, M. N.; Stanley, S. A.; Vasbinder, M. M.;
Xavier, K. R. J. Org. Chem. 1997, 62, 7210; (c) Hodgson,
D. M.; Stupple, P. A.; Johnstone, C. Tetrahedron Lett.
1997, 38, 6471; (d) Doyle, M. P.; Forbes, D. C.; Vas-
binder, M. M.; Peterson, C. S. J. Am. Chem. Soc. 1998,
120, 7653.
13a
(2)
OꢀH insertion product
Catalyst
ROH, R=
Yield (%)b
drc
Dd
Rh2(OAc)4
Me
Me
Me
H
H
H
82
70:30
51:49
30:70
57:43
74:26
85:15
0
19
40
0
17
18
Rh2(4S-MEAZ)4
Rh2(4R-MEAZ)4
Rh2(OAc)4
Rh2(4S-MEAZ)4
Rh2(4R-MEAZ)4
76e
86e
85
69
82
a Reaction conditions were the same as those reported in Table 1.
b Weight yield of product after chromatography.
c Diastereomer ratio: R:S.8
d Change in dr from result with Rh2(OAc)4.
e Reaction performed in refluxing CH2Cl2.
7. Hodgson, D. M.; Pierard, F. Y. T. M.; Stupple, P. A.
Chem. Soc. Rev. 2001, 30, 50.
8. (a) Aller, E.; Brown, D. S.; Cox, G. G.; Miller, D. J.;
Moody, C. J. J. Org. Chem. 1995, 60, 4449; (b) Aller, E.;
Cox, G. G.; Miller, D. J.; Moody, C. J. Tetrahedron Lett.
1994, 35, 5949.
9. (a) Landais, Y.; Pianchenault, D.; Weber, V. Tetrahedron
Lett. 1994, 35, 9549. The first uses of pantolactone as a
chiral auxiliary in catalytic reactions are attributable to
Davies. See: (b) Davies, H. M. L.; Huby, N. J. S.;
Cantrell, W. R., Jr.; Olive, J. L. J. Am Chem. Soc. 1993,
115, 9468.
Still the overall results demonstrate that diastereoselec-
tivity enhancement can be achieved with the use of a
chiral catalyst, and future investigations of ylide-based
transformations should take this into account.
10. No other isomeric product was observed as they were in
molybdenum-catalyzed reactions with methyl styryldia-
zoacetate. See: Davies, H. M. L.; Yokota, Y. Tetrahedron
Lett. 2000, 41, 4851.
11. Doyle, M. P.; Davies, S. B.; Hu, W. Org. Lett. 2000, 2,
1145.
Acknowledgements
12. Corey, E. J.; Link, J. O. Tetrahedron Lett. 1992, 33, 3431.
13. Evans, D. A.; Peterson, G. S.; Johnson, J. S.; Barnes, D.
M.; Campos, K. R.; Woerpel, K. A. J. Org. Chem. 1998,
63, 4541.
14. Doyle, M. P.; Winchester, W. R.; Hoorn, J. A. A.;
Lynch, V.; Simonsen, S. H.; Ghosh, R. J. Am. Chem.
Soc. 1993, 115, 9968.
The support of the National Science Foundation and
the National Institutes of Health (GM 46503) is grate-
fully acknowledged. We thank Huw M. L. Davies for
providing us with a generous sample of Rh2(S-DOSP)4
(9).
15. Doyle, M. P.; Zhou, Q.-L.; Raab, C. E.; Roos, G. H. P.;
Simonsen, S. H.; Lynch, V. Inorg. Chem. 1996, 35, 6064.
16. Davies, H. M. L.; Bruzinski, P.; Hutcheson, D. K.; Fall,
M. J. J. Am. Chem. Soc. 1996, 118, 6897.
References
17. Doyle, M. P.; Zhou, Q.-L.; Simonsen, S. H.; Lynch, V.
1. Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic
Methods for Organic Synthesis with Diazo Compounds:
From Cyclopropanes to Ylides; John Wiley & Sons: New
York, 1998; Chapter 8.
Synlett 1996, 697.
18. Hu, W.; Timmons, D. J.; Doyle, M. P. Org. Lett. 2002, 4,
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