Enantioselective Photocatalytic [3 + 2] Cycloadditions of Aryl Cyclopropyl Ketones

Article abstract of DOI:10.1021/jacs.6b01728

Control of stereochemistry in photocycloaddition reactions remains a substantial challenge; almost all successful catalytic examples to date have involved [2 + 2] photocycloadditions of enones. We report a method for the asymmetric [3 + 2] photocycloaddition of aryl cyclopropyl ketones that enables the enantiocontrolled construction of densely substituted cyclopentane structures not synthetically accessible using other catalytic methods. These results show that the dual-catalyst strategy developed in our laboratory broadens synthetic chemists' access to classes of photochemical cycloadditions that have not previously been feasible in enantioselective form.

Full text of DOI:10.1021/jacs.6b01728

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Communication
Enantioselective Photocatalytic [3+2]
Cycloadditions of Aryl Cyclopropyl Ketones
Adrian G. Amador, Evan M. Sherbrook, and Tehshik P. Yoon
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.6b01728 • Publication Date (Web): 25 Mar 2016
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Journal of the American Chemical Society
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Enantioselective Photocatalytic [3+2] Cycloadditions of Aryl Cyclo-
propyl Ketones
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Adrian G. Amador, Evan M. Sherbrook, Tehshik P. Yoon*
Department of Chemistry, University of Wisconsin–Madison, 1101 University Avenue, Madison, Wisconsin, 53706, United States
Supporting Information Placeholder
ABSTRACT: Control of stereochemistry in photocycloaddi-
We therefore became interested in designing an asymmet-
tion reactions remains a substantial challenge, and almost all
ric version of the photocatalytic [3+2] cycloaddition be-
successful catalytic examples to date have involved [2+2]
tween aryl cyclopropyl ketones and alkenes that our labora-
tory reported several years ago (Scheme 1). While enanti-
photocycloadditions of enones. We report a method for the
9
asymmetric [3+2] photocycloaddition of aryl cyclopropyl
oselective cycloadditions of highly activated “donor–
ketones that enables the enantiocontrolled construction of
10
acceptor” cyclopropanes are known, no catalytic asymmet-
densely substituted cyclopentane structures that are not syn-
ric [3+2] cycloadditions of less activated cyclopropyl ketones
thetically accessible using other catalytic methods. These
have yet been reported. Our photocatalytic process involves
results show that the dual-catalyst strategy developed in our
photoreduction of a Lewis acid activated aryl cyclopropyl
laboratory broadens synthetic chemists’ access to classes of
ketone (1) to afford a ring-opened distonic radical anion that
can react in an intramolecular fashion with a wide range of
alkene partners. While this methodology enables the facile
synthesis of structurally diverse cyclopentane-containing
polycyclic compounds (e.g. 2), the reaction gives high yields
photochemical cycloadditions that have not previously been
feasible in enantioselective form.
Stereocontrolled cycloadditions are valued in synthetic
chemistry both as methods to construct the ring systems that
are ubiquitous in chiral bioactive compounds and as model
reactions to evaluate new concepts in enantioselective syn-
only in an intramolecular context, requires stoichiometric
La(OTf)3 as a Lewis acid catalyst, and employs 5 equiv of
TMEDA as both a ligand for La3+ and a reductive quencher
2+
of Ru*(bpy)3 , rendering the use of a chiral diamine ligand
1
thesis. Control over the absolute stereochemistry of photo-
unattractive. In this communication, we report the develop-
ment of an enantioselective photocatalytic [3+2] cycloaddi-
tion that successfully address all of these challenges.
chemical cycloadditions, however, remains a substantial chal-
2
lenge without a general solution. A relatively small number
3
4
of highly enantioselective organocatalytic and Lewis acid
Scheme 1. Precedent and project objectives
catalyzed photocycloadditions have been described in the
past several years, but these successful methods have been
focused upon [2+2] cycloadditions of enones. No strategies
for photocatalytic stereocontrol have emerged that appear to
be broadly applicable to the asymmetric catalysis of other
classes of photocycloaddition reactions.
n Prior work (ref 9)
O
5 mol% Ru(bpy)3Cl2
La(OTf)3 (1 equiv)
TMEDA (5 equiv)
Me CO2Et
H
O
O
Me
Ph
Ph
OEt
MeCN
visible light
1
2
H
+ e–
– e–
[La]O
Ph
[La]O
O
Our laboratory recently reported a dual catalyst system for
enantioselective [2+2] photocycloaddition using a chiral
Lewis acid in tandem with a transition metal photoredox
CO2Et
Me
Me
Ph
OEt
5
catalyst. The success of this strategy relies upon the ability to
tune the structure of the stereocontrolling chiral catalyst for
optimal selectivity without adversely affecting the perfor-
mance of the photocatalyst. We speculated, therefore, that
this combination of catalytic strategies might successfully
control the stereochemical behavior of many of the reactions
n Challenges:
a
a
a
a
Develop effective conditions for intermolecular cycloaddition
Reduce Lewis acid co-catalyst concentration
Replace TMEDA with chiral ligand + achiral amine quencher
High enantioselectivity
6,7,8
now known to be amenable to photoredox catalysis.
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Page 2 of 5
Table 1 outlines optimization studies for a model asym- 6). As an alternative strategy, we wondered if we might stabi-
1
2
3
4
5
6
7
8
metric [3+2] cycloaddition between phenyl ketone 3 and
styrene. We initially examined conditions based upon those
we reported for the racemic intramolecular reaction, employ-
lize the active Gd-pybox complex by increasing the coordi-
nating ability of the chiral ligand. Indeed, while chloride-
12
substituted ligand L4 resulted in no product formation, elec-
tron-rich methoxy-substituted ligand L5 provided 6 in excel-
lent yield (entry 8). Dimethylamino-substituted ligand L6
provided optimal rate and stereoselectivity (entry 9), and
with this ligand, the Lewis acid loading could be decreased to
10 mol% with little effect on ee (entry 10). Lowering the
temperature to 0 °C resulted in an increase in the enantiose-
lectivity to 85% ee (entry 11). The ee was further improved
at –20 °C, but we observed an increased proportion of an
undesired reductive ring-opening product (entry 12). In-
creasing the bulk of the ester substituent provided somewhat
higher ee at 0 °C (entry 13), and the occurrence of the reduc-
tive ring-opening side-product could be minimized by lower-
ing the concentration of i-Pr2NEt (entry 14). Under these
optimized conditions, cycloadduct 7 was obtained in 95%
2+
ing 2.5 mol% Ru(bpy)3 as the photocatalyst, 1 equiv
La(OTf)32+ as a Lewis acid co-catalyst, and i-Pr2NEt as a re-
ductive quencher. Consistent with our prior observations,
the intermolecular reaction was sluggish, and the addition of
chiral ligands strongly inhibited the reaction (entries 1 and
2). A screen of other Lewis acidic metal triflate complexes
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11
revealed that Gd(III) pybox complexes could provide
somewhat better conversions and, gratifyingly, experimental-
ly significant enantioselectivity, with a maximum ee of 59%
using the s-Bu-substituted pybox ligand L3 (entries 3–5).
Table 1. Optimization studies.
2.5% Ru(bpy)3(PF6)2
Lewis acid, ligand
2 equiv i-Pr2NEt
O
Ph
O
Ph
Ph
Ph
+
13
yield, 93% ee, and 3:1 d.r..
visible light
MeCN, 6 h
CO2R
CO2R
(5 equiv)
Table 2. Alkene Substrate Scopea
3 R = Et
4 R = t-Bu
6 R = Et
7 R = t-Bu
5
2.5% Ru(bpy)3(PF6)2
10% Gd(OTf)3, 20% L6
2 equiv i-Pr2NEt
Ph
X
O
O
Ph
90% yield
93% ee
3:1 d.r.
L1 R = i-Pr; X = H
Ph
Ph
L2 R = t-Bu; X = H
L3 R = s-Bu; X = H
L4 R = s-Bu; X = Cl
L5 R = s-Bu; X = OMe
L6 R = s-Bu; X = NMe2
+
O
O
visible light
MeCN, 6–24 h
N
CO2t-Bu
4
7
CO2t-Bu
(5 equiv)
N
N
R
R
O
Entry
Conditionsa
100 % La(OTf)3
Yieldb
25 %
dr; % ee
14:1; ---
8
9
Ar = p-MeOC6H4, 89% yield, 91% ee, 3:1 d.r.
Ar = p-MeC6H4, 90% yield, 89% ee, 3:1 d.r.
Ar
Ph
1
2
10 Ar = p-CF3C6H4, 81% yield, 89% ee, 2:1 d.r.
11 Ar = p-BrC6H4, 86% yield, 90% ee, 2:1 d.r.
12 Ar = o-MeC6H4, 75% yield, 87% ee, 2:1 d.r.
100 % La(OTf)3, 100% L2
100 % Gd(OTf)3, 100 % L1
100 % Gd(OTf)3, 100 % L2
100 % Gd(OTf)3, 100 % L3
100 % Gd(OTf)3, 200 % L3
100 % Gd(OTf)3, 200 % L4
100 % Gd(OTf)3, 200 % L5
100 % Gd(OTf)3, 200 % L6
10 % Gd(OTf)3, 20% L6
5 %
15 %
96 %
25 %
36 %
0 %
--- ; ---
CO2t-Bu
3
3:1; 38 %
3:1; 45 %
2:1; 59 %
3:1; 63 %
---;---
O
O
O
Me
4
Ph
Ph
Ph
Ph
N
5
6
CO2t-Bu
CO2t-Bu
CO2t-Bu
7
13 55% yield
86% ee, 2:1 d.r.
14 80% yield
15 95% yield
90% ee, 3:1 d.r.
97% ee, 3:1 d.r.
8
90 %
89 %
96 %
80%
41 %
86 %
95 %
2:1; 64 %
2:1; 85 %
2:1; 79 %
3:1; 85 %
3:1; 91 %
3:1; 90 %
3:1; 93 %
O
O
O
Me
Me
9
Ph
Ph
Ph
10
11
12
13c
14c,d
10 % Gd(OTf)3, 20% L6, 0 °C
10 % Gd(OTf)3, 20% L6, –20 °C
10 % Gd(OTf)3, 20 % L6, 0 °C
10 % Gd(OTf)3, 20 % L6, 0 °C
CO2t-Bu
CO2t-Bu
CO2t-Bu
16 95% yield
>99% ee, 2:1 d.r.
17 59% yield
18 77% yield
87% ee, 3:1 d.r.
96% ee, 3:1 d.r.
a Reactions irradiated with a 23 W CFL for 6 h. Yields report-
ed are the combined isolated yields of all diastereomers. Major
diastereomer shown.
a Reactions carried out on 0.045 mmol scale, irradiating with a
23 W CFL for 6 h. b Yields determined by 1H-NMR using phenan-
threne as an internal standard. Using 4 instead of 3. Using 1
equiv of i-Pr2NEt.
c
d
We next conducted an exploration of the scope of the en-
antioselective cycloaddition under these conditions. Table 2
outlines the effect of varying the structure of the alkene reac-
14
tion partner. We have proposed a stepwise cycloaddition
Analysis of reaction progress revealed that Gd(OTf)3 and
i-Pr2NEt slowly formed an inactive Lewis acid-base complex
over several hours, which coincided with a concomitant de-
crease in the rate of product formation. We increased the
ligand-to-metal ratio in an attempt to slow formation of a
deactivated complex, albeit with little beneficial effect (entry
initiated by radical addition of a ring-opened distonic radical
anion to an alkene. Consistent with this proposal, simple
aliphatic alkenes are not reactive. However, a variety of elec-
tronically modified styrenes react smoothly and with good ee
(8–10). Potentially reactive aryl halides are well tolerated
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Journal of the American Chemical Society
(11), providing a handle for derivatization of the enantioen- with the chiral Gd(III) Lewis acid; the resulting ketyl radical
1
2
3
4
5
6
7
8
riched cycloadducts. The enantioselectivity is relatively in-
sensitive to the position of substituents on the aryl ring (12).
While heterocycles containing Lewis basic heteroatoms re-
sulted in a loss in stereoselectivity, alkenes bearing less basic
heterocycles such as carbazoles react smoothly with good ee
(13). Internal olefins, unfortunately, were unreactive under
these reaction conditions; however, 1,1-disubstituted sty-
renes react smoothly and provide excellent ee (14–16). Fi-
nally, dienes are also competent reaction partners, affording
vinyl cyclopentane products in good ee (17, 18).
([Gd]-4•–) undergoes reversible ring-opening followed by
slow stepwise cycloaddition with styrene to afford product
ketyl radical [Gd]-7•–. Formation of the neutral product 7
could occur either by chain-propagating electron transfer to
another equivalent of substrate or by chain-terminating re-
duction of the photogenerated amine radical cation.
Scheme 2. Proposed mechanism for enantioselective
[3+2] cycloaddition.
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[Gd]
Ph
O
O
[Gd]-4
CO2t-Bu
7
Table 3. Cyclopropane Substrate Scopea
Ph
Ph
CO2t-Bu
[
d] Gd]-4•–
Ph
O
[G
19 R = OMe, 88% yield, 91% ee, 3:1 d.r.
20 R = Me, 90% yield, 96% ee, 3:1 d.r.
21 R = Cl, 90% yield, 92% ee, 3:1 d.r.
22 R = CF3, 87% yield, 99% ee, 3:1 d.r.
[RuI]
i-Pr2NEt
R
4
CO2t-Bu
[Gd]O
Ph
Ph
O
i-Pr2NEt
O
Ph
Ph
O
[RuII
]
[RuII]*
Me
Ph
Ph
[Gd]O
Ph
CO2t-Bu
[Gd]-7•–
CO2t-Bu
hν
[
d] Gd]-4•–
O
[G
N
CO2t-Bu
CO2t-Bu
Me
[Gd]O
Ph
23 57% yield,
94% ee, 2:1 d.r.
24 87% yield
89% ee, 3:1 d.r.
25 47% yield
88% ee, >20:1 d.r.
Ph
O
Ph
Ph
Ph
O
O
CO2t-Bu
Ph
Ph
Ph
Me
Me
Me
2.5% Ru(bpy)3(PF6)2
10% Gd(OTf)3, 20% L6
2 equiv i-Pr2NEt
O
Ph
D
O
26 57% yieldb
53% ee, >20:1 d.r.
27 85% yieldb
89% ee, 5:1 d.r.
28 88% yieldb
94% ee, 5:1 d.r.
Ph
D
Ph
Ph
(1)
(2)
(3)
+
D
D
visible light
CO2t-Bu
a
CO2t-Bu
d2-7
Yields reported are the combined isolated yields of all dia-
stereomers. Major diastereomer shown. Reaction conducted
4
d2-5
b
kH/kD = 0.78 ± 0.01
using 20 mol% Gd(OTf)3 and 30 mol% L6 at –20 °C for 48 h.
2.5% Ru(bpy)3(PF6)2
10% Gd(OTf)3, 20% L6
2 equiv i-Pr2NEt
O
Ph
O
Ph
CO2t-Bu
Ph
Ph
+
The scope of this reaction with respect to the aryl ketone
component is summarized in Table 3. The aryl moiety toler-
ates significant electronic perturbation: both electron-rich
and electron-deficient substituents provided the correspond-
ing cyclopentanes in good yield and excellent ee (19–22).
Heteroaryl cyclopropyl ketones are also tolerated (23), alt-
hough the ee suffers if the heterocycle is positioned to pro-
vide an alternate site for Lewis acid chelation. Arene substit-
uents at the 3-position have minimal impact on the selectivi-
ty of the reaction (24). However, 2-substituents have a large
deleterious effect, which would be expected if the ketone
were coordinated to the chiral Lewis acid in the enantioselec-
tivity-determining step. The ester moiety can be replaced by
a ketone with minimal impact on the stereoselectivity (25),
but a methyl-substituted cyclopropane provides poor ee
(26). On the other hand, cyclopropyl ketones bearing gemi-
nal β-dialkyl substituents afford excellent ee, although higher
Lewis acid concentrations were required for optimal rate
(27, 28).
visible light
CO2t-Bu
t-BuO2C
CO2t-Bu
29
30 85% yield
97% ee, 7:1 d.r.
2.5% Ru(bpy)3(PF6)2
10% Gd(OTf)3, 20% L6
2 equiv i-Pr2NEt
Ph
O
O
Ph
Me
Me
+
Ph
Ph
visible light
Me
t-BuO2C
CO2t-Bu
31
Me
32 76% yield
95% ee, >20:1 d.r.
The mechanism proposed in Scheme 2 is supported by
several lines of evidence. First, a reaction with deuterium-
labeled styrene d2-5 gives an inverse secondary kinetic iso-
tope effect (kH/kD = 0.78) consistent with a rate-limiting
intermolecular C–C bond-forming step (eq 1). Second,
Tanko has reported that the ring-opening of similar cyclo-
15
16
propyl ketyl radicals is reversible and endergonic. To vali-
date this expectation, we monitored a reaction starting with
the cis isomer of 4 and found that the cyclopropane was
completely isomerized to the trans isomer within 1 h, well
before the reaction was complete. This reversible cleavage is
consistent with the observation that racemic β,β’-
disubstituted cyclopropane 29 undergoes stereoconvergent
cycloaddition to cyclopentyl ketone 30 in good diastereose-
Scheme 2 depicts our working model for the mechanism of
2+
this reaction. Photoexcitation of Ru(bpy)3 and reductive
+
quenching by i-Pr2NEt affords Ru(bpy)3 . Subsequent elec-
tron transfer to phenyl ketone 4 occurs only upon activation
17
lectivity and excellent ee (eq 2). The cycloaddition of un-
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symmetrically substituted cyclopropyl ketone 31 also pro-
Page 4 of 5
ACKNOWLEDGMENT
1
2
3
4
5
6
7
8
vides excellent stereoselectivity as well as exclusive chemose-
lectivity for the formation of enantioenriched cyclopentane
32 and not its constitutional isomer (eq 3).
We thank Ilia Guzei for determination of the absolute configura-
tion of 11 by X-ray crystallographic analysis. The authors are
grateful to the NIH (GM098886) for financial support and to
Sigma–Aldrich for a generous gift of RuCl3. The NMR facilities
at UW–Madison are supported by a generous gift from the Paul
J. Bender fund.
While the scope of this new asymmetric [3+2] cycloaddi-
tion is complementary to the established enantioselective
reactions of donor-acceptor cyclopropanes, the aryl ketone
moiety required for the initial one-electron reduction process
imposes an undesirable limitation on scope. Thus we won-
dered if the aryl ketone could be removed with retention of
stereochemistry through a Baeyer–Villiger cleavage. Indeed,
the p-methoxyphenyl ketone cycloadduct 19 undergoes
completely regioselective oxidation to afford 33 in good
yield, the activated ester of which is poised for further ma-
nipulation into diverse carboxylic acid derivatives. Under
identical conditions, p-trifluoromethylphenyl ketone 34 un-
dergoes regiocomplementary oxidation to afford benzoate
ester 35. Thus, the applicability of this [3+2] photocycload-
dition method to reactions of electronically varied aryl ke-
tones provides a flexible strategy for the conversion of the
enantioenriched products to a diverse array of five-
membered carbocyclic derivatives.
9
REFERENCES
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1
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6.
2
For reviews on asymmetric photochemical synthesis, see: (a) Rau, H.
Chem. Rev. 1983, 83, 535–547. (b) Inoue, Y. Chem. Rev. 1992, 92, 741–
770. (c) Brimioulle, R.; Lenhart, D.; Maturi, M. M.; Bach, T. Angew. Chem.
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3
(a) Müller, C.; Bauer, A.; Bach, T. Angew. Chem. Int. Ed. 2009, 48,
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5608. (f) Maturi, M. M.; Bach, T. Angew. Chem. Int. Ed. 2014, 53, 7661–
7664.
Scheme 3. Cleavage of the aryl ketone moiety.
MeO
Ph
O
Ph
O
m-CPBA
O
4
(a) Guo, H.; Herdtweck, E.; Bach, T. Angew. Chem. Int. Ed. 2010, 49,
TFA, CH2Cl2
MeO
CO2t-Bu
7782–7785. (b) Brimioulle, R.; Guo, H.; Bach, T. Chem. Eur. J. 2012, 18,
7552–7560. (c) Brimioulle, R.; Bach, T. Angew. Chem. Int. Ed. 2014, 53,
12921–12924. (d) Brimioulle, R.; Bach, T. Science 2013, 342, 840–843.
5 Du, J.; Skubi, K. L.; Schultz, D. M.; Yoon, T. P. Science 2014, 344, 392–
396.
CO2t-Bu
19 91% ee
33 84% yield, 89% ee
F3C
Ph
Ph
O
m-CPBA
O
6
TFA, CH2Cl2
O
Me
Me
Prier, C. K. Rankic, D. A.; MacMillan, D. W. C. Chem. Rev. 2013, 113,
F3C
Me
Me
5322–5363.
34 83% ee
35 82% yield, 83% ee
7
For an application of tandem Lewis acid/photoredox catalysis to an
asymmetric conjugate addition reaction, see: Espelt, L. R.; M
son, I. S.; Wiensch, E. M.; Yoon, T. P. J. Am. Chem. Soc. 2015, 137, 2452–
cPher-
These studies have several important implications. From a
practical perspective, this method provides an asymmetric
catalytic method to assemble structurally complex five-
membered carbocycles, which are a class of compounds that
remain challenging to prepare in enantioenriched form. More
broadly, these results demonstrate that the combination of
chiral Lewis acid and photoredox catalysis offers a robust and
potentially general approach to photochemical stereocontrol
that is broadly applicable to the increasing number of power-
ful transformations achievable using photoredox catalysis.
2455.
8
For a recent review of dual catalysis approaches in photoredox cataly-
sis, see: Hopkinson, M. N.; Sahoo, B.; Li, J.-L.; Glorius, F. Chem. Eur. J.
2014, 20, 3874–3886.
9 Lu, Z.; Shen, M.; Yoon, T. P. J. Am. Chem. Soc. 2011, 133, 1162-1164.
10
For examples, see: (a) Parsons, A. T.; Johnson, J. S. J. Am. Chem. Soc.
2009, 131, 3122–3123. (b) Parsons, A. T.; Smith, A. G.; Neel, A. J.; John-
son, J. S. J. Am. Chem. Soc. 2010, 132, 9688–9692. (c) Trost, B. M.; Morris,
P. J. Angew. Chem. Int. Ed. 2011, 50, 6167–6170. (d) Xiong, H.; Xu, H.;
Liao, S.; Xie, Z.; Tang, Y. J. Am. Chem. Soc. 2013, 135, 7851–7853. (e)
Hashimoto, T.; Kawamata, Y.; Maruoka, K. Nat. Chem. 2014, 6, 702–705.
11
For examples of the use of (pybox)Gd(III) complexes in asymmetric
ASSOCIATED CONTENT
catalysis, see: (a) Evans, D. A.; Wu, J. J. Am. Chem. Soc. 2003, 125, 10162–
10163. (b) Evans, D. A.; Song, H.-J.; Fandrick, K. R. Org. Lett. 2006, 8,
3351–3354. (c) Suga, H.; Ishimoto, D.; Higuchi, S.; Ohtsuka, M.; Arikawa,
T.; Tsuchida, T.; Kakehi, A.; Baba, T. Org. Lett. 2007, 9, 4359–4362. (d)
Suga, H.; Higuchi, S.; Ohtsuka, M.; Ishimoto, D.; Arikawa, T.; Hashimoto,
Y.; Misawa, S.; Tsuchida, T.; Kakehi, A.; Baba, T. Tetrahedron 2010, 66,
3070–3089.
Supporting Information. The Supporting Information is avail-
able free of charge via the Internet at http://pubs.acs.org”: De-
tailed experimental procedures and compound characterization
data (PDF); X-ray crystallographic data for 11.
12
(a) Nishiyama, H.; Yamaguchi, S.; Kondo, M.; Itoh, K. J. Org. Chem.
AUTHOR INFORMATION
1992, 57, 4306–4309. (b) Park, S.-B.; Murata, K.; Matsumoto, H.;
Nishiyama, H. Tetrahedron: Asymm. 1995, 6, 2487–2494. (c) Wang, H.;
Wang, H.; Liu, P.; Yang, H.; Xiao, J.; Li, C. J. Mol. Catal. A: Chem. 2008,
Corresponding Author
*tyoon@chem.wisc.edu
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285, 128–131. (d) Bettencourt-Dias, A. d.; Barber, P. S.; Viswanathan, S.;
Lill, D. T. d.; Rollet, A.; Long, G.; Altun, S. Inorg. Chem. 2010, 49, 8848–
Feld, M.; Stefani, A. P.; Szwarc, M. J. Am. Chem. Soc. 1962, 84, 4451–
4453.
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8861.
Tanko, J. M.; Drumright, R. E. J. Am. Chem. Soc. 1992, 114, 1844–
13
The d.r. reflects the ratio of the major diastereomer shown and an ep-
1854.
17
imer at the ester-bearing carbon. Only a trace of a presumed third diastere-
The minor diastereomer of 31 can be isolated and resubjected to the
reaction conditions with no loss of stereochemical integrity. Thus the dia-
stereoselectivity does not reflect an equilibrium ratio.
1
omer was observable by H NMR analysis of the unpurified reaction mix-
ture and could not be isolated for identification.
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The absolute configuration of 11 was determined by X-ray crystallo-
graphic analysis; the configuration of other cycloadducts were assigned by
analogy.
O
[Gd]Ln
Ph
O
Me
Me
chiral
Lewis acid
Ph
Ph
Me
CO2t-Bu
t-BuO2C
Me
[Ru]*
+
photoredox
catalyst
95% ee
23 examples
Ph
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