Rhodium-catalyzed enantioselective cyclopropanation of olefins with N-sulfonyl 1,2,3-triazoles

Article abstract of DOI:10.1021/ja908075u

(Figure Presented) N-Sulfonyl 1,2,3-triazoles readily form rhodium(II) azavinyl carbenes, which react with olefins to produce cyclopropanes with excellent diastereo- and enantioselectivity and in high yield.

Full text of DOI:10.1021/ja908075u

Published on Web 11/24/2009
Rhodium-Catalyzed Enantioselective Cyclopropanation of Olefins with
N-Sulfonyl 1,2,3-Triazoles
Stepan Chuprakov, Sen Wai Kwok, Li Zhang, Lukas Lercher, and Valery V. Fokin*
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road,
La Jolla, California 92037
Received September 22, 2009; E-mail: fokin@scripps.edu
Diazocarbonyl compounds 1 are well-known precursors to metal
carbenes 2 (eq 1).1 The versatile reactivity of the latter is recognized
by numerous synthetic applications.2 In contrast, related azavinyl
carbenes 3 have not been employed in synthesis,3 primarily because
of the limited availability of corresponding R-diazoimines.4 These
reactive intermediates can be viewed as synthetic equivalents of
formyl carbenes, in which both amine and aldehyde functions can
be revealed by simple transformations, thus significantly expanding
Figure 1. Rh(II) carboxylates for asymmetric cyclopropanation.
the repertoire of chiral molecules that may be accessed via carbene-
based synthetic methods. Herein we report a first example of highly
Table 1. Optimization of the Enantioselective Cyclopropanation of
Styrene with N-Sulfonyl 1,2,3-Triazolesa
diastereo- and enantioselective Rh(II)-catalyzed cyclopropanation
employing azavinyl carbenes 3 derived from 1-sulfonyl 1,2,3-
triazoles 4. The latter can be obtained using the copper-catalyzed
cycloaddition reaction of alkynes with sulfonyl azides.5
entry
triazole
catalyst
yield (%)c
ee (%)d
1
2
3
4
5
6
7
8
4a (R ) p-Tol)
Rh2(S-DOSP)4
Rh2(S-PTAD)4
Rh2(S-PTTL)4
Rh2(S-NTTL)4
Rh2(S-PTTL)4
Rh2(S-NTTL)4
Rh2(S-NTTL)4
Rh2(S-NTTL)4
Rh2(S-DOSP)4
Rh2(S-NTTL)4
92
91
87
28
74
76
78
88
96
96
97
4a
4a
4a
42e f
,
4b (R ) Me)
4b
4c (R ) n-C8H17)
4d (R ) i-Pr)
4d
4c
91
95
99
83
75
90
Our recent success in the Rh-catalyzed transannulation of
N-sulfonyl 1,2,3-triazoles had proven that these easily available,
reasonably stable, and seemingly unreactive compounds are reliable
precursors of azavinyl carbenes.6 Accordingly, we further explored
Rh(II) catalysis with 1,2,3-triazoles, targeting enantioselective
transformations. To this end, we examined the cyclopropanation
of styrene with 1-sulfonyl-4-phenyl-1,2,3-triazoles 4 in the presence
of various chiral Rh(II) complexes7 (Figure 1) in 1,2-dichloroethane
at 80 °C (Table 1). The resulting sulfonyl imines 5 were smoothly
converted into the corresponding aldehyde 6a by treatment with
K2CO3 in wet methanol.
9
-16
96
10g
a Conditions: triazole
4 (0.2 mmol), styrene (1.0 mmol), Rh(II)
b
1
catalyst (0.002 mmol), 1,2-dichloroethane (0.5 mL). Determined by H
NMR analysis of the crude reaction mixture. c NMR yield of 6a after
hydrolysis. d Determined by chiral HPLC. e Reaction did not proceed at
temperatures below 100 °C. f dr ) 3:1. g Using 1.2 equiv of styrene and
0.5 mol % catalyst at 65 °C.
DOSP)4 complex provided the opposite enantiomer,9a albeit with
very low ee (entry 9).
Further optimization revealed that this cyclopropanation reaction
performed well at lower temperature (65 °C) with reduced catalyst
loading (entry 10). Notably, only a slight excess of olefin (1.2 equiv)
was required, and no slow-addition techniques (e.g., a syringe pump)
were needed.12
With the optimized conditions for the cyclopropanation with
1,2,3-triazoles in hand, we examined the scope with respect to the
olefin (Scheme 1). As illustrated in Scheme 1, a broad range of
substituted styrenes participated in the reaction, affording cyclo-
propanecarbaldehydes13 6b-f in good to excellent yields and high
enantioselectivity. Significantly less reactive 1-hexene afforded the
corresponding n-butyl-substituted cyclopropane 6g in 70% yield
and 96% ee. Interestingly, trans-methylstyrene produced tetrasub-
stututed cyclopropane 6h with excellent enantioselectivity, while
the cyclopropanation of the cis analogue delivered almost racemic
product 6i. It is worth mentioning that in the last three cases, the
First, we found that the use of 1-toluenesulfonyl derivative 4a
with Rh2(S-DOSP)48 catalyst afforded cyclopropanecarboxaldehyde
6a in high yield with excellent trans diastereoselectivity. However,
the enantioselectivity of the reaction was low (Table 1, entry 1).
Next, Rh2(S-PTAD)49 and Rh2(S-PTTL)410 catalysts were examined,
providing 6a with over 70% ee (entries 2 and 3). Increased steric
demand of the ligands on rhodium resulted not only in very sluggish
reaction but also in drastic erosion of the diastereoselectivity (entry
4). We hypothesized that switching to a less sterically encumbered
carbene precursor might improve the overall performance of the
reaction. Indeed, 1-mesyl triazole 4b reacted smoothly in the
presence of Rh2(S-PTTL)4 catalyst, furnishing the cyclopropane
product with 88% ee (entry 5). To our great delight, Rh2(S-
11
NTTL)4 in combination with 4b (entry 6) allowed for excellent
enantioselectivity (96% ee) and yield (95%). Remarkably, n-
octylsulfonyl and isopropylsulfonyl triazoles 4c and 4d, respectively,
provided similar results with Rh2(S-NTTL)4 catalyst (entries 7 and
8). Interestingly, cyclopropanation of 4d in the presence of Rh2(S-
9
18034 J. AM. CHEM. SOC. 2009, 131, 18034–18035
10.1021/ja908075u  2009 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1. Enantioselective Cyclopropanation with 1,2,3-Triazoles:
Scope of Olefinsa
is now available. The azavinyl carbenes readily react with olefins
under experimentally simple conditions, providing cyclopropane-
carboxaldehydes and N-sulfonyl homoaminocyclopropanes in gen-
erally excellent yields with high enantioselectivity. Further studies
of the scope, origin of high selectivity, and mechanism of the
reaction are underway in our laboratories.
Acknowledgment. Financial support of this work by the
National Institute of General Medical Sciences, National Institutes
of Health (GM087620), and the Skaggs Institute for Chemical
Biology is gratefully acknowledged.
a Unless specified otherwise, all reactions were carried out on a 0.5 mmol
scale with 1.2 equiv of olefin under ambient atmosphere. b Determined by
1H NMR analysis of the crude reaction mixture. c Using 2.0 equiv of alkene.
Supporting Information Available: Experimental details, charac-
terization data, NMR spectral charts, and crystallographic data for 7a
(CIF). This material is available free of charge via the Internet at http://
pubs.acs.org.
Scheme 2. Enantioselective Cyclopropanation of Styrene with
N-Methanesulfonyl 1,2,3-Triazolesa
References
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a All reactions were carried out on a 0.5 mmol scale with 1.2 equiv of
olefin under ambient atmosphere. b Determined by 1H NMR analysis of
the crude reaction mixture. c Performed at 80 °C.
(7) Rh(II) carboxamidates were incompetent in this transformation. See the
Supporting Information for the full catalyst screening data.
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Examination of the scope of the process with respect to the
1-sulfonyl 1,2,3-triazoles (Scheme 2) revealed that substrates
possessing both electron-rich and electron-deficient aryl groups at
C4 reacted smoothly to produce cyclopropanes 6j-m with excellent
enantioselectivity. Moreover, heteroaryl- and alkenyl-substituted
triazoles were competent substrates for this reaction (6n, 6o; Scheme
2), further demonstrating the utility of this methodology.
While the instability of sulfonyl imines 5 toward hydrolysis
precluded their isolation in pure form, we recognized that reduction
of 5 immediately after their synthesis could provide an easy access
to chiral homoaminocyclopropanes. Indeed, cyclopropanation of a
series of styrenes followed by the treatment of the crude imine
product with LiAlH4 furnished N-(cyclopropylmethyl) sulfonamides
7a-c in good yields with excellent enantioselectivity (eq 2).
In summary, a novel and very efficient Rh(II)-catalyzed asym-
metric cyclopropanation methodology that utilizes stable and readily
available N-sulfonyl 1,2,3-triazoles as azavinyl carbene precursors
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