Gold(I)-catalyzed cascade cycloadditions between allenamides and carbonyl-tethered alkenes: An enantioselective approach to oxa-bridged medium-sized carbocycles

Article abstract of DOI:10.1002/anie.201302713

Gold standard: Allenamides react with aldehydes or ketones having γ, δ, or ε alkenyl groups, upon activation with suitable gold catalysts, to provide oxa-bridged systems containing seven- to nine-membered carbocycles, in a formal cascade cycloaddition. By using chiral phosphoramidite/gold or bisphosphine/gold catalysts it is possible to obtain the oxa-bridged seven- and eight-membered rings with good to high enantioselectivity. Copyright

Full text of DOI:10.1002/anie.201302713

Angewandte
Chemie
DOI: 10.1002/anie.201302713
Gold Catalysis
Gold(I)-Catalyzed Cascade Cycloadditions between Allenamides and
Carbonyl-Tethered Alkenes: An Enantioselective Approach to Oxa-
Bridged Medium-Sized Carbocycles**
Hꢀlio Faustino, Isaac Alonso, Josꢀ L. MascareÇas,* and Fernando Lꢁpez*
During the last decade, research in homogeneous gold
catalysis has experienced an extraordinary growth, resulting
[1]
in the discovery of a variety of powerful transformations.
Particularly relevant, in terms of versatility and synthetic
potential, are those reactions involving the cycloaddition of
two or more unsaturated components, as a variety of cyclic
and polycyclic systems can be rapidly assembled in an
[2]
efficient and usually stereoselective manner. In this context,
we and others have reported several intramolecular gold-
[
3]
catalyzed cycloadditions involving allenes, as well as inter-
molecular cycloadditions of allenamides to dienes, (4+2), or
[
4,5]
to alkenes, (2+2). The high regioselectivity observed in the
[5a]
(
2+2) annulations, together with the intrinsic requirement
of a carbocation-stabilizing group at the alkene, suggests that
this reaction proceeds through a cationic pathway such as that
[
6]
depicted in the Scheme 1 (upper).
In light of this mechanism, we envisioned that intercep-
tion of the carbocationic intermediate II by an internal
nucleophile might result in the assembly of interesting
bicycles through the cationic cascade shown in the Scheme 1
Scheme 1. Previously reported (2+2) cycloadditions and the proposed
formal cascade cycloaddition.
[7]
(
bottom). Depending on the endo or exo trapping of the
cation II’, the transformation could yield either fused- or
bridged-bicyclic skeletons of type 5 or 6. Herein, we
demonstrate the viability of the endo route when a carbonyl
group (X=Y is O=CR) is used as carbocation intercepting
unit. The reaction provides a straightforward, robust, and
versatile access to synthetically appealing oxa-bridged sys-
tems of type 6 (X = O, Y = carbon) containing seven-, eight-,
or even nine-membered carbocycles. Additionally, we also
disclose several examples of an enantioselective variant
promoted by chiral diphosphine/gold and/or phosphorami-
dite/gold catalysts that provides a practical asymmetric
[
8]
[9]
approach to 8-oxabicyclo[3.2.1]octanes, and the first direct
enantiocatalytic entry to oxygen-bridged eight-membered
[10]
carbocycles.
Our study began by assessing the viability of a cascade
cycloaddition between the bisalkene 4a and 1a. We reasoned
that the different nature of the alkenes in 4a could bias the
annulation to selectively give the tricarbocycle 5aa
[
+]
[+]
[
*] H. Faustino, I. Alonso, Prof. J. L. MascareÇas, Dr. F. Lꢀpez
Centro Singular de Investigaciꢀn en Quꢁmica Biolꢀgica y Materiales
Moleculares (CIQUS) and Departamento de Quꢁmica Orgꢂnica
Universidad de Santiago de Compostela
(Scheme 1, exo mode). However, treatment of these sub-
C/Jenaro de la Fuente, s/n, 15782 Santiago de Compostela (Spain)
E-mail: joseluis.mascarenas@usc.es
strates with several gold catalysts, under different reaction
conditions, failed to give 5aa, and always led to a relatively
complex mixture of products, among which we could identify
and even isolate the (2+2) adduct 3aa and the allenamide
Dr. F. Lꢀpez
Instituto de Quꢁmica Orgꢂnica General (CSIC)
Juan de la Cierva, 3, 28006 Madrid (Spain)
E-mail: fernando.lopez@csic.es
[11]
homodimer 7a. (Scheme 2).
+
[
] These authors contributed equally to this work.
Therefore, we explored an alternative cascade process
relying on the use of a carbonyl group as an internal
nucleophile. Interception of II’ by the carbonyl oxygen
might generate a cyclic oxocarbenium ion (III, X = O, Y =
CR; Scheme 1), susceptible of undergoing a Prins-like
[
**] This work was supported by the Spanish MINECO, (SAF2010-
0822-C02-01/02, and Consolider-Ingenio 2010 CSD2007-00006),
ERDF funds, and Xunta de Galicia (INCITE09209084PR, GRC2010/
2). H.F. acknowledges the Fundażo para a CiÞncia e Tecnologia
Portugal) and POPH/FSE for a PhD grant (SFRH/BD/60214/2009).
2
1
(
[
12]
terminal cyclization with the vinyl gold moiety. Gratify-
Johnson-Matthey and Takasago are acknowledged for a gift of
metals and segphos, respectively.
ingly, slow addition over 1 hour of a solution of allenamide 1a
to a mixture of 4b and [Ph PAuCl]/AgSbF (A) led to a 1.2:1
mixture of the Z- and E-configured 8-oxabicyclo[3.2.1]octane
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201302713.
3
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Table 2: Scope of the Au-catalyzed cascade cycloaddition between allena-
[
a]
mides (1) and carbonyl-tethered alkenes (4).
Entry
1
Oxoalkene (4)
Product
6
Yield
[
b]
[
%]
2
1
2
3
4
1a
1a
1a
1a
4b, R =Me
6ab 87
6ac 86
6ad 90
6ae 75
2
4c, R =Ph
2
4d, R =H
2
[c]
4e, R =OMe
Scheme 2. Preliminary experiments with 1a and bisalkene 4a.
3
[d,e]
[d,f]
5
6
1a
1a
4 f, R =H
6af 41
6ag 65
3
4g, R =Me
derivatives 6ab, which were isolated in 75% yield (Table 1,
[
13]
entry 1). Similar results, but with higher Z selectivity, were
achieved with gold catalysts B–E (Table 1, entries 3–6).
Significantly, by using the phosphite/gold complex E, the
catalyst loading could be lowered to 1 mol% (Table 1,
entry 7), and the allenamide can be added in one portion
5
1
7
1a
1a
4h
6ah d.r.
1:0
[
14]
77
(
Table 1, entry 8), to provide (Z)-6ab in 87% yield. The
4
i
8
9
6ai d.r.
:0
robustness and practicality of the method was further
demonstrated by performing the reaction on an 8 mmol
scale (1a), with a 0.5 mol% of catalyst, which produced 2.0 g
of (Z)-6ab (84% yield) after just 5 min (entry 9).
We next evaluated the scope of the method (Table 2). Not
only was a methyl ketone competent to productively intercept
intermediate II’, but the cycloaddition also worked with
a phenyl ketone (4c), an aldehyde (4d), and a methyl ester
E/Z=1.3:1
1
3
1a
1a
4j, R =Me
6aj 63
6ak 65
1
0
4k,
3
R =NMeCO Bn
2
3
11
1a
1b
1c
4l, R =N*
6al 75
57
6bb d.r.
1
2
3
4b
4b
(4e), to give the corresponding 8-oxabicyclo[3.2.1]octane
3
:1
derivatives (6ac–6ae) in good yields (Table 2, entries 1–4).
Also, substrates in which the alkene and the carbonyl moiety
[
g]
1
6cb 77
(4 f and 4g) are attached by a phenyl ring, provided the
[a] Allenamide 1 (1 equiv) was added to a mixture of oxoalkenes 4
(
>
1.5 equiv) and catalyst E (1%) in CH Cl (0.1m) at À158C; Conversion was
2
2
1
99%, as determined by H NMR spectroscopy, after 5–15 min. [b] Yield of
1
[
a]
isolated 6; Z/E ratios, as determined by H NMR spectroscopy of the crude
mixtures, are >20:1, unless otherwise noted. [c] Cyclobutane 3ae was also
obtained in 14% yield. [d] The allenamide dimer 7a was also obtained in
Table 1: Cascade cycloadditions with carbonyl-tethered alkene 4b.
30% yield. [e] Z/E=9:1. [f] Z/E=10:1. [g] Z/E=3:1.
[
b]
Entry
[Au]
Mol%
Z/E
Yield of 6ab [%]
1
2
3
4
5
6
7
Ph PAuCl/AgSbF (A)
5
5
5
5
5
5
1
1
1.2:1
3.2:1
5.5:1
7.5:1
50:1
15:1
22:1
22:1
22:1
75
70
75
79
75
76
74
87
84
3
6
[
c]
Ph PAuCl/AgSbF (A)
3
6
Ph PAuNTf (B)
3
2
corresponding oxa-tricyclic systems, 6af and 6ag, in 41% and
65% yields, respectively (Table 2, entries 5 and 6).
C
D
E
E
E
E
This strategy also enables the synthesis of 5,7-bicarbo-
cyclic systems such as 6ah, by using cyclopentanone precur-
sors like 4h (Table 2, entry 7). This reaction was completely
diastereoselective and the relative configuration of the
[
d]
8
9
[
d,e]
0.5
[
15]
[
[
a] 1a (1 equiv) added over one hour to a solution of 4b (1.5 equiv) and
Au] (mol%), in CH Cl at À158C, unless otherwise noted. Conversion
product was determined by X-ray diffraction analysis. The
effect of additional substituents at the styrene moiety was
investigated in the substrate 4i (E/Z = 1.3:1: Table 2, entry 8).
In agreement with previous results for (2+2) cycloaddi-
2
2
1
was >99%, as determined by H NMR spectroscopy, after 5 min. [b] Z/E
1
ratios determined by H NMR spectroscopy of the crude mixtures.
[c] Catalyst was filtered through Celite prior to its use. [d] 1a was added
[
5a]
tions, we only observed the reaction of the trans compound
in one portion. [e] Performed on an 8.0 mmol scale (1a). Tf=trifluoro-
methanesulfonyl.
[16]
((E)-4i), which efficiently afforded the oxabicylic system
6
ai (77% yield; Table 2, entry 8), featuring the oxygen bridge
[17]
and the methyl group in a syn disposition (Figure 1).
Importantly, the cascade cycloaddition is not restricted to
phenyl-substituted alkenes, which might be particularly
2
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4
also proceeds with more-substituted alkenes (4p, R = Me) or
disubstituted allenamides (1b), to provide the oxa-bridged
cyclooctanes 6ap and 6bm with complete diastereoselectivity.
Unambiguous confirmation of the stereochemistry of 6bm
[21]
was obtained by X-ray diffraction analysis (Figure 1). The
method also provides direct entry to 6,8-fused bicarbocycles
such as 6aq (78% yield) and, importantly, can be even be
used to make cyclononane derivatives such as 6ar (61%
yield).
Figure 1. X-Ray structures of 6ai and 6bm (thermal ellipsoids are set
at 50% probability).
Overall, these results highlight the great potential and
versatility of the method, which provides a direct and
practical access to highly valuable oxa-bridged seven-,
eight-, and even nine-membered carbocycles from readily
biased to participate in the transformation owing to the
generation of benzylic carbocation intermediates (e.g. II’, R =
Ph; Scheme 1). Indeed, the presence of a methyl substituent
[
22]
accessible starting materials.
Owing to the recent progress in asymmetric gold catal-
(
4j) is enough to warrant the annulation, with the product 6aj
[
18]
[23]
being isolated in a 63% yield (Table 2, entry 9). Oxoena-
mides are also effective precursors, producing amino deriv-
atives, such as 6ak and 6al, in good yields (Table 2, entries 10
and 11). Substituted allenamides, such as 1b and the N-
phenyl-N-tosylallenamide (1c), also provided the corre-
sponding bicyclic products, 6bb and 6cb, in moderate to
good yields (Table 2, entries 12 and 13).
ysis,
we were interested in exploring the viability of
achieving these annulations in an enantioselective manner.
Curiously, despite the synthetic value of oxa-bridged medium-
sized carbocycles, catalytic enantioselective approaches to
these systems are very scarce, and essentially limited to the
[
9,10]
seven-membered derivatives.
A preliminary screening of different types of chiral gold
complexes identified the dtbm-segphos complex (R)-F and
the phosphoramidite/gold complex (S,R,R)-G as suitable
catalysts to achieve the cycloaddition of 1a with several
oxoalkenes 4, in good yields and moderate-to-high levels of
The efficiency of the above transformation suggested that
the strategy might be used to construct eight- or even nine-
membered carbocycles, simply by using oxoalkenes featuring
longer carbon tethers. Assembling these medium-sized carbo-
cycles, which are present in a large number of relevant
products, continues to be a major challenge in organic
synthesis, owing to the well-known difficulties associated
[
24]
enantioselectivity (Table 3). In the case of the oxa-bridged
Table 3: Enantioselective cycloadditions of 1a and oxoalkenes 4.
[19,20]
with their construction.
Gratifyingly, the gold-catalyzed
[
a]
[b]
[c]
Entry
4
[Au] (5 mol%)
6
Yield [%]
e.r.
annulation of 1a with 4m–4o provided the desired 9-
oxabicyclo[3.3.1]nonanes 6am–6ao, in moderate to excellent
yields (Scheme 3). Moreover, and similarly to the cyclo-
additions leading to the seven-membered cycles, the reaction
[
[
d]
e]
1
2
4b
4c
4d
4i
4m
4o
4p
(S,R,R)-G
(S,R,R)-G
(S,R,R)-G
(S,R,R)-G
(R)-F
6ab
6ac
6ad
6ai
6am
6ao
6ap
63
69
83
83:17
82:18
84:16
90:10
95:5
[
f]
3
4
5
6
7
[
g]
72
[
[
[
h]
h]
h]
52
80
45
(R)-F
(R)-F
91:9
96:4
[
a] 1a (1 equiv), 4 (1.5–2 equiv) and [Au] (5 mol%) in CH Cl at À788C,
2
2
unless otherwise noted. Conversion was >99% after 10–180 min.
[
[
b] Yield of isolated 6; Z/E ratios are >20:1. [c] Determined by HPLC.
d] e.r.=95:5 after crystallization (iPrOH/hexane). [e] e.r.=98:2 after
crystallization. [f] At À78 to À608C, for 5 h. [g] d.r.=1:0. [h] At À78 to
À358C, for 4–12 h.
Scheme 3. Synthesis of 8- and 9-membered oxa-bridged carbocycles.
Reaction conditions: Allenamide 1 (1 equiv) was added to a mixture of
seven membered carbocycles, the best enantiomeric ratios
were obtained with (S,R,R)-G, and ranged from 82:18 to
4
>
(1.5 equiv) and E (1%) in CH Cl (0.1m) at À158C. Conversions are
2
2
1
99%, as determined by H NMR spectroscopy, after 5–15 min.
9
0:10. (Table 3, entries 1–4). Interestingly, these e.r. values
Yields are of the isolated products. Z/E ratios, as determined by
1
could be increased up to 98:2, by performing a partial
crystallization (Table 3, entries 1 and 2). In the case of the
cyclooctanes, although the phosphoramidite gold catalyst
(S,R,R)-G provided good enantioselectivity (e.r. from 87:13 to
H NMR spectroscopy of the crude mixtures, are >20:1, unless
otherwise noted. [a] The cyclobutane derivative 3ap (12% yield) was
also obtained. [b] 3bm (12% yield) was also obtained. [c] Carried out
at À788C for 6 h. 3ar (26% yield), was also obtained.
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Angewandte
Communications
[
24]
9
0:10),
adducts 6am, 6ao, and 6ap with higher enantiomeric ratios
between 91:9 and 96:4; Table 3, entries 5–7). Although there
the Segphos complex (R)-F provided the cyclo-
[3] a) B. Trillo, F. López, S. Montserrat, G. Ujaque, L. Castedo, A.
Lledós, J. L. MascareÇas, Chem. Eur. J. 2009, 15, 3336 – 3339;
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Castedo, A. Lledós, J. L. MascareÇas, J. Am. Chem. Soc. 2009,
(
is still room for improvement, these results represent the first
highly enantioselective syntheses of oxa-bridged eight-mem-
bered carbocycles and one of the very few enantiocatalytic
131, 13020 – 13030; c) I. Alonso, H. Faustino, F. López, J. L.
MascareÇas, Angew. Chem. 2011, 123, 11698 – 11702; Angew.
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Goddard, F. D. Toste, J. Am. Chem. Soc. 2011, 133, 5500 – 5507;
f) X. Huang, L. Zhang, J. Am. Chem. Soc. 2007, 129, 6398 – 6399;
g) M. R. Luzung, P. Mauleón, F. D. Toste, J. Am. Chem. Soc.
[
10]
approaches to cyclooctanes.
Finally, we also did a preliminary exploration of the
manipulability of the oxa-bridged carbocycles, and confirmed
that the presence of the exo-enamide enables a variety of
transformations (Scheme 4). Treatment of adduct 6ab with
2007, 129, 12402 – 12403; h) M. Alcarazo, T. Stork, A. Anoop, W.
Thiel, A. Fꢀrstner, Angew. Chem. 2010, 122, 2596 – 2600; Angew.
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8895 – 8901.
[
[
[
4] For (4+2) cycloadditions, see: a) H. Faustino, F. López, L.
Castedo, J. L. MascareÇas, Chem. Sci. 2011, 2, 633 – 637; b) J.
Francos, F. Grande-Carmona, H. Faustino, J. Iglesias-Sigꢀenza,
E. Diez, I. Alonso, R. Fernµndez, J. M. Lassaletta, F. López, J. L.
MascareÇas, J. Am. Chem. Soc. 2012, 134, 14322 – 14325; for
a related reaction using allenyl ethers, see: c) Q. R. Wang, G. A.
Wang, Y. Zou, Z. M. Li, A. Goeke, Adv. Synth. Catal. 2011, 353,
Scheme 4. Reaction conditions: a) RuO , NaIO , THF/H O, 70%.
2
4
2
b) H , Pd/C; 60%. c) i) HCl (aq); ii) NaBH ; 95%. d) TiCl , Et SiH,
2
4
4
3
CH Cl , À788C; 64%.
2
2
550 – 556.
5] For (2+2) cycloadditions, see: a) H. Faustino, P. Bernal, L.
Castedo, F. López, J. L. MascareÇas, Adv. Synth. Catal. 2012, 354,
RuO /NaIO cleanly afforded the ketone 8ab (70% yield).
2
4
1658 – 1664; b) X.-X. Li, L.-L. Zhu, W. Zhou, Z. Chen, Org. Lett.
Alternatively, the enamide group could be hydrogenated to
give 9ab (60% yield), or reduced to the epimeric alcohols
2012, 14, 1185 – 1185; c) S. Suµrez-Pantiga, C. Hernµndez-Díaz,
M. Piedrafita, E. Rubio, J. M. Gonzµlez, Adv. Synth. Catal. 2012,
54, 1651 – 1657; d) S. Suµrez-Pantiga, C. Hernµndez-Díaz, E.
1
0ab in 95% yield. Also, the presence of the methoxy group
3
in 6ae enabled a Lewis acid induced opening of the bridge to
yield cycloheptane 11ae.
Rubio, J. M. Gonzµlez, Angew. Chem. 2012, 124, 11720 – 11723;
Angew. Chem. Int. Ed. 2012, 51, 11552 – 11555.
6] The use of allenamides appears critical, probably because the
amide group facilitates the activation of the allene, while
stabilizing the resulting cationic intermediates. For a recent
review on allenamides, see: T. Lu, Z. Lu, Z.-X. Ma, Y. Zhang,
R. P. Hsung, Chem. Rev. 2013, DOI: 10.1021/cr400015d.
7] Cascade cycloaddition refers to a reaction that unites multiple
reaction partners to form a cyclic product through a cascade
process, in accord with the IUPAC Gold Book definition of
cycloaddition.
8] While this manuscript was under preparation, a related inter-
molecular reaction involving alkynes and 5-oxoalkenes, which
leads to 8-oxabicyclo[3.2.1]oct-3-enes, was reported: a) C. Obra-
dors, A. M. Echavarren, Chem. Eur. J. 2013, 19, 3547 – 3551; for
work of the same group on intramolecular cycloisomerizations
of oxoenynes, see: b) N. Huguet, A. M. Echavarren, Synlett 2012,
In summary, we have discovered a simple and highly
versatile cascade cycloaddition between allenamides and
carbonyl-tethered alkenes. The reaction can be performed
at mild temperatures with just 1 mol% of the catalyst, and
provides a straightforward entry to oxa-bridged seven-, eight-,
and even nine-membered rings. Moreover, we have also
demonstrated that by using chiral gold catalysts it is possible
to obtain the products with good to high enantioselectivities.
In particular, the method provides the first enantiocatalytic
entries to eight-membered carbocycles by means of a formal
intermolecular cycloaddition reaction.
[
[
Received: April 2, 2013
Published online: && &&, &&&&
49 – 53; c) A. Escribano-Cuesta, V. López-Carrillo, D. Janssen,
A. M. Echavarren, Chem. Eur. J. 2009, 15, 5646 – 5650; d) E.
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10900; h) D. B. Huple, R. S. Liu, Chem. Commun. 2012, 48,
10975 – 10977.
Keywords: annulation · cascade reactions ·
homogeneous catalysis · enantioselective · gold
.
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Angew. Chem. Int. Ed. 2013, 52, 1 – 6
These are not the final page numbers!

Angewandte
Chemie
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[16] The Z isomer, (Z)-4i, is recovered from the crude reaction
2
mixture.
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[17] CCDC 917327 (6ai) contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via www.
ccdc.cam.ac.uk/data_request/cif.
[18] The reaction of 1a with a non-substituted alkene partner
(Scheme 1, R = H), exclusively led to the homodimer 7a.
[19] For reviews about natural products containing eight-membered
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[
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lective approaches to oxa-bridged eight membered rings are
unknown. For selected enantioselective approaches based on
two-step methods, see: a) C. M. Yu, J. Y. Lee, B. So, J. Hong,
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[21] CCDC 930626 (6bm) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
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of eight-membered ring are also virtually unknown, see:
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2009, 131, 2056 – 2057; d) B. DeBoef, W. R. Counts, S. R.
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3251.
[22] There are very few catalytic methods for the construction of
different sizes of oxa-bridged medium-sized rings. For examples,
see: a) G. A. Molander, Acc. Chem. Res. 1998, 31, 603 – 609; b) F.
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Wang, Angew. Chem. 2012, 124, 4188 – 4192; Angew. Chem. Int.
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S. Liu, J. Am. Chem. Soc. 2010, 132, 12565 – 12567.
[
[
11] Other bisalkenes led exclusively to (2+2) adducts of type 3. See
the Supporting Information for more details.
12] For examples of Prins-like cyclizations involving vinyl gold
species, in the context of enyne cycloisomerizations, see
references [8a–g].
13] Slow addition of the allenamide is aimed to avoid the formation
of dimer 7a.
14] CCDC 917326 (6ab) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
[
[
[
15] CCDC 930627 (6ah) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
[23] V. Michelet, A. Pradal, P. Y. Toullec, Synthesis 2011, 1501 – 1514.
[24] See the Supporting Information for details.
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
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.
Angewandte
Communications
Communications
Gold Catalysis
H. Faustino, I. Alonso, J. L. MascareÇas,*
F. Lꢁpez*
&&&& — &&&&
Gold(I)-Catalyzed Cascade
Cycloadditions between Allenamides and
Carbonyl-Tethered Alkenes: An
Enantioselective Approach to Oxa-
Bridged Medium-Sized Carbocycles
Gold standard: Allenamides react with
aldehydes or ketones having g, d, or
e alkenyl groups, upon activation with
suitable gold catalysts, to provide oxa-
bridged systems containing seven- to
nine-membered carbocycles, in a formal
cascade cycloaddition. By using chiral
phosphoramidite/gold or bisphosphine/
gold catalysts it is possible to obtain the
oxa-bridged seven- and eight-membered
rings with good to high enantioselectivity.
6
www.angewandte.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
These are not the final page numbers!