Enantioselective cyclizations of silyloxyenynes catalyzed by cationic metal phosphine complexes

Article abstract of DOI:10.1021/ja210388g

The discovery of complementary methods for enantioselective transition metal-catalyzed cyclization with silyloxyenynes has been accomplished using chiral phosphine ligands. Under palladium catalysis, 1,6-silyloxyenynes bearing a terminal alkyne led to the desired five-membered ring with high enantioselectivities (up to 91% ee). As for reactions under cationic gold catalysis, 1,6-and 1,5-silyloxyenynes bearing an internal alkyne furnished the chiral cyclopentane derivatives with excellent enantiomeric excess (up to 94% ee). Modification of the substrate by incorporating an α,β- unsaturation led to the discovery of a tandem cyclization. Remarkably, using silyloxy-1,3-dien-7-ynes under gold catalysis conditions provided the bicyclic derivatives with excellent diastereo-and enantioselectivities (up to >20:1 dr and 99% ee).

Full text of DOI:10.1021/ja210388g

Article
pubs.acs.org/JACS
Enantioselective Cyclizations of Silyloxyenynes Catalyzed by Cationic
Metal Phosphine Complexes
Jean-Franco̧ is Brazeau, Suyan Zhang, Ignacio Colomer, Britton K. Corkey, and F. Dean Toste*
Department of Chemistry, University of California, Berkeley, California 94720, United States
S
* Supporting Information
ABSTRACT: The discovery of complementary methods for
enantioselective transition metal-catalyzed cyclization with
silyloxyenynes has been accomplished using chiral phosphine
ligands. Under palladium catalysis, 1,6-silyloxyenynes bearing a
terminal alkyne led to the desired five-membered ring with
high enantioselectivities (up to 91% ee). As for reactions under
cationic gold catalysis, 1,6- and 1,5-silyloxyenynes bearing an
internal alkyne furnished the chiral cyclopentane derivatives
with excellent enantiomeric excess (up to 94% ee). Modi-
fication of the substrate by incorporating an α,β-unsaturation
led to the discovery of a tandem cyclization. Remarkably, using silyloxy-1,3-dien-7-ynes under gold catalysis conditions provided
the bicyclic derivatives with excellent diastereo- and enantioselectivities (up to >20:1 dr and 99% ee).
gold-catalyzed enantioselective version of a 5-exo-dig cyclization
using 1,6-enynes in the presence of methanol.7 Moreover,
related enantioselective cycloisomerization reactions have been
INTRODUCTION
■
Enantioselective α-functionalization of enolates and enolate
derivatives serves as one of the most important methods for the
construction of enantioenriched carbonyl containing compounds.1
A wide range of electrophiles react with enolate derivatives, includ-
ing activated carbon−carbon π-bonds.2 In this context, alkynes are
potentially interesting electrophiles, as the product of the addition
reaction is an alkene that can be further elaborated. Therefore, a
number of addition reactions of silyl enol ethers to alkynes have
been reported.3,4 From these reports, two major reactivity para-
digms have emerged. The first, which follows from Conia’s seminal
report3a of mercury(II)-promoted addition of silyl enol ethers to
alkynes, involves nucleophilic addition to the triple bond that is
activated by a π-acidic transition metal complex or Lewis acid. The
second more recent approach proceeds through nucleophilic
addition of the enol ether to an electrophilic transition metal
vinylidene generated from a terminal alkyne.5 Despite recent
developments, enantioselective variants of this class of addition
reaction remain scarce. This paucity can perhaps be traced to
the fact that the majority of catalysts reported for this reaction
are either simple metal salts or transition metal carbonyl com-
pounds and therefore lack a readily tunable ancillary ligand.
The past decade has witnessed the development of cationic
late transition metal complexes as catalysts for addition to
alkynes.6 These complexes demonstrate the ability to catalyze
the addition of nucleophiles to alkynes, even when ligated with
Lewis basic phosphine ligands. For example, we reported that
cationic triphenylphosphinegold(I) efficiently promoted the
addition of β-ketoesters and silyl enol ethers to alkynes through
a π-activation pathway.4a
described by Mikami8 and Genet9
using catalysts based on
̂
cationic phosphinepalladium(II) and platinum(II) complexes,
respectively. More recently, we,10 Michelet,11 and Sanz12
showed that bisphosphinegold(I) complexes also effectively
catalyzed enantioselective polycyclization and cycloisomeriza-
tion reactions.13,14 On the basis of this work, we aimed to
develop a set of catalysts that would allow for enantioselective
5-endo-dig and 5-exo-dig addition reactions of enol ether
nucleophiles. In this context, we focused our attention on
cyclizations of 1,6- and 1,5-silyloxyenynes (eqs 1 and 2)
catalyzed by cationic (phosphine)platinum, palladium, and gold
complexes as catalysts.15Herein, we present a full account of our
studies employing chiral gold and palladium catalysts to promote
asymmetric 5-exo-dig and 5-endo-dig cyclizations. This work re-
sulted in the discoveries of complementary palladium(II)- and
gold(I)-catalyzed highly enantioselective silyloxyenyne cycloisomeriza-
tion reactions to yield synthetically useful exomethylencylopentane
Therefore, we envisioned that chiral phosphine analogues
could catalyze such cyclization reactions in an enantioselective
manner. In support of this hypothesis, Echavarren reported a
Received: November 4, 2011
Published: January 31, 2012
© 2012 American Chemical Society
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or cyclopentene derivatives. Furthermore, we also demonstrate
that silyloxy-1,3-dien-7-ynes are suitable substrates for diastereo-
and enantioselective cyclization reactions to form polysubstituted
bicyclo[3.3.0]octane derivatives.
silyloxyenyne 5 was synthesized and treated under the optimal
palladium conditions to generate the desired ketone 10 with
96% yield and 95% ee (entry 5). The utility of this reaction was
exemplified by the transformation of 10 into naturally occurring
RESULTS AND DISCUSSION
■
Palladium-Catalyzed Enantioselective Cyclization of
Silyloxy-1,6-enynes. We began our investigation with the
tetrasubstituted silyl enol ether 1 depicted in Table 1. We found
a
Table 1. Pd-Cyclizations of Silyloxy-1,6-enynes
dimeric sesquiterpene (−)-laurebiphenyl (eq 3).15 In addition,
trisubstituted silyloxyenyne 6 was reacted with catalyst
L3Pd(OTf)2 at 0 °C to furnish the cyclic ketone 11, having a
tertiary stereocenter with 85% enantioselectivity (entry 6).
The high enantioselectivity obtained with 1 and 2 suggests a
transition state where the chiral complex selects the face based
on the placement of the large (aryl/silyloxy portion) and the
small (methyl) groups of the silyl enol ether in the appropriate
quadrants of the chiral environment (Scheme 1). This
Scheme 1. Postulated Transition States
hypothesis is supported by the low impact of the alkene
geometry on the enantioselectivity (Table 1, entries 1 and 2).
We decided to extend this methodology to the preparation of
enantioenriched spirocyclic amides.17 However, L3Pd(OTf)2 with
substrate 12 proved to be problematic as lower enantioselectivity
was observed (Table 2, entry 1). A ligand screen was undertaken,
Table 2. Selected Optimization Experiments with Silyloxy-
a
1,6-Enynes 12
a
Reactions performed at 0.02 M in Et2O/AcOH (100/1) using
b
c
entry
ligand
conv (%)
ee (%)
b
1 equiv of substrate and 10 mol % L3Pd(OTf)2 for 16 h. Isolated
yields. Determined by chiral HPLC. At 0 °C.
d
c
d
1
(R)-DTBM-SEGPHOS (L3)
(R)-DTBM-SEGPHOS (L3)
(R)-SEGPHOS (L1)
(R,S)-SynPhos
15
>95
50
48
47
88
84
5
2
3
4
5
6
that palladium complex (R)-DTBM-SEGPHOSPd(OTf)2
[L3Pd(OTf)2] that was successful in our previously reported
enantioselective Conia-ene cyclization gave the best results
in terms of enantiomeric excess (ee).16 Indeed, (Z)-isomer 1
was treated with catalyst L3Pd(OTf)2 and cyclic product 7 was
isolated in 80% yield and 78% ee (entry 1). We were pleased to
observe that (E)-isomer 2 led to the desired aryl ketone with an
increase in enantioselectivity (91% ee, entry 2).
50
(R,S)-CyJosiPhos
>95
e
(R)-Binaphane (L4)
>95 (80)
98
a
Reactions performed at 0.02 M in Et2O/AcOH (100/1) using
b
1 equiv of substrate 12 and 10 mol % LPd(OTf)2 for 2 h. Determined
c
d
by 1H NMR. Determined by chiral HPLC. No actetic acid was
e
added. Isolated yield.
and we found that the SEGPHOS (L1) ligand gave higher
enantioselectivity with moderate conversion, since the hydrolysis
product (corresponding lactam) was also obtained in a significant
amount (entry 3). A number of bisphosphine ligands having the
biaryl atropisomeric backbone were tested with moderate success.
The scope of this reaction was studied, and we found that the
methyl substituent could also be modified. For example, allyl-
substituted ketone 8 was formed with high selectivity (88% ee,
entry 3). We also observed that the 1,4-dien-6-yne 4 led to the
desired cyclic ketone 9 with 73% ee (entry 4). The (Z)-1,6-
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We discovered that binaphane ligand (L4) was a highly effective
ligand with substrate 12 (entry 6). The reaction times were
generally shorter and catalyst loading could be decreased
substantially compared with the conditions with L3Pd(OTf)2.
Under the optimized conditions, the desired spirocyclic compound
13 was isolated with 80% yield and 98% ee.
Table 4. Selected Optimization Experiments with Silyloxy-
1,6-enynes
a
Next, we examined the scope of this cyclization with other
O-silylketene aminals. As shown in Table 3, 2-silyloxy indole 14
a
Table 3. Pd-Cyclizations of Silyloxy-1,6-enynes
b
c
entry
catalyst
additive
yield (%)
ee (%)
1
2
3
4
5
6
7
8
L3Pd(OTf)2
L4Pd(OTf)2
L3Pt(OTf)2
L3(AuCl)2
L3(AuCl)2
L5(AuCl)2
L5(AuCl)2
L6(AuCl)2
L6(AuCl)2
L6(AuCl)2
L7(AuCl)2
none
NR
ND
ND
ND
17
none
traces
NR
none
d
AgOTf
AgSbF6
AgSbF6
NaBARF
NaBARF
NaBARF
NaBARF
NaBARF
39
d
37
32
d
42
35
67
81
74
84
88
52
72
e
9
85
ef
,
10
11
93
ef
,
87
a
Reactions performed at 0.1 M using 1 equiv of 22, 5 mol % catalyst,
and 10 mol % additive for 16 h. NR and ND mean no reaction and
b
c
not determined, respectively. Isolated yields. Determined by chiral
d
HPLC. Determined 1H NMR versus using an internal standard
e
f
(diethyl phthalate). Reaction was performed at −30 °C. Using 1,2-
dichloroethane (DCE) as a solvent.
a
Reactions performed at 0.02 M in CH2Cl2/AcOH (100/1) using 1
b
equiv of substrate and 5 mol % L4Pd(OTf)2 for 120 min. Isolated
yields. Determined by chiral HPLC.
to trace amounts of acid formed under the reaction conditions with
silver salts.21 Performing the reaction at low temperature and using
sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaBARF)
as a chloride scavenger in combination with L5(AuCl)2 led to the
desired cyclized ketone 23 in 67% yield and 52% ee (entry 7).
Lowering the temperature and switching to L6(AuCl)2 was
promising in terms of enantioselectivity (entries 8 and 9). Upon
further optimization of the reaction parameters, the desired product
was isolated in 84% yield and 93% ee when the reaction was per-
formed at −30 °C using dichloroethane as the solvent (entry 10).
We explored the optimized conditions with substrates having
different substituents on the aryl moiety. As shown in Table 5, the
cyclization proceeded cleanly with substrates bearing methyl
substitution (24, 25, and 26) to give the desired products with
high enantiomeric excess (86−91% ee). Having a chlorine substit-
uent such as in 28 was deleterious to reactivity, and a higher
reaction temperature was required (entry 5). Finally, modifying
the position of the gem-diester as in substrate 29 had a significant
impact on the enantioselectivity, and the cyclic product 35 was
obtained with 50% ee (entry 6).
Gold-Catalyzed Enantioselective Cyclization of Sily-
loxy-1,5-enynes. Decreasing the tether length by one carbon
allowed us to examine the 5-endo-dig process in further detail.
We suspected that silyloxy-1,5-enynes such as 36 would be
suitable substrates and could favor only the product derived
from the 5-endo attack. We initially subjected 36 to palladium
and platinum catalysis; however reaction catalyzed by these
d8 metal complexes gave none of the desired product (Table 6,
entries 1 and 2). Treatment of the same substrate with gold
catalyst L6(AuCl)2 and NaBARF gave the desired product 37
but with low enantioselectivity (entry 3). The catalyst derived
from (R)-SEGPHOS(AuCl)2 [L1(AuCl)2] and NaBARF was
c
afforded the desired spiro-oxindole product 18 with 83% yield
and 91% ee (entry 1). The acyclic O-silylketene aminal 15 was
also reacted under similar conditions to obtain amide 19 with
satisfactory enantioselectivity (entry 2). The efficiency of this
catalyst is particularly noteworthy, as treatment of silyl enol ethers
16 and 17 with L4Pd(OTf)2 gave the corresponding cyclo-
pentane adducts with high enantioselectivity (entries 3 and 4),
while attempts at the L3Pd(OTf)2-catalyzed cyclization of these
substrates provided trace amounts of the desired products.18
Gold-Catalyzed Enantioselective Cyclization of Sily-
loxy-1,6-enynes. During the course of our study of this
enantioselective palladium-catalyzed 5-exo-dig cyclization re-
action, we found that substrates bearing an internal alkyne such
as 22 were not reactive with catalyst L3Pd(OTf)2 (Table 4,
entry 1). With the more reactive binaphane ligand (L4), the
ketone derived from the hydrolysis of the silyl enol ether was
obtained as the major product (entry 2). We also tested
substrate 22 under platinum catalysis with L3Pt(OTf)2, and no
reaction was observed (entry 3). Despite little success with
chiral cationic gold complexes and substrates bearing a terminal
alkyne,19 we decided to explore the reactivity of 22 with a
different set of ligands under gold catalysis. An initial screen
revealed that L3(AuCl)2 could promote the desired 5-exo-dig
cylization to give 23, albeit with low yield and enantioselectivity
(entries 4 and 5).20 We subjected 22 to previously reported
conditions for the 6-exo-dig cyclization10b (L5(AuCl)2 and
AgSbF6), and moderate yields (42%) of desired cyclized
product 23 were obtained with a slight improvement in the
enantioselectivity (entry 6). The low conversions were
associated with the hydrolysis of the enolsilane, probably due
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Table 5. Enantioselective Au(I)-Cyclizations with Silyloxy-
1,6-Enynes
Table 7. Enantioselective Au(I)-Cyclization with Silyloxy-
1,5-Enynes
a
a
a
Reactions performed at 0.1 M using 1 equiv of substrate, 5 mol % (R)-
MeO-DTBM-BIPHEP(AuCl)2 [L5(AuCl)2], and 10 mol % NaBARF for
b
c
16 h in DCE at −30 °C. Isolated yields. Determined by chiral HPLC.
d
e
Reaction was performed at −10 °C. Using dichloromethane as a
solvent. Isolated as an inseparable, 4:1 mixture of cyclic products.
f
Table 6. Selected Optimization Experiments with Silyloxy-
a
1,5-enynes
a
Reactions performed at 0.1 M using 1 equiv of substrate, 5 mol %
(R)-DTBM-SEGPHOS(AuCl)2 [L3(AuCl)2], and 10 mol % NaBARF
b
c
for 16 h at −30 °C. Isolated yields. Determined by chiral HPLC.
e
Using 1,2-dichloroethane as a solvent.
With these results in hand, we next sought to evaluate the
substrate scope of our optimized conditions (Table 7). Various
substituted phenyl derived silyl enol ethers (38−42) furnished
the cyclized products (45−49) in good yields (67−92%) and
high enantiomeric excess (91−94% ee) (entries 1−5). The
reactions with substrates bearing an electron-poor aryl
substituent showed lower reaction rates but still provided the
desired product in high enantiomeric purity. Similarly, 2-
naphthyl (43) and 2-thiophenyl (44) substituted substrates
reacted under these conditions to generate the desired ketones
in high yields and enantioselectivities (entries 6 and 7, 89 and
90% ee, respectively). The absolute stereochemistry of the
cyclopentene derivatives was assigned by analogy to an X-ray
structure obtained after recrystallization of aryl ketone 47.22
As depicted in Table 8, decreasing the size of the substituents
on the silyl group (52, TES and 53, TBDMS) was slightly
detrimental in terms of yields but still led to good
enantioselectivities (87% and 86% ee, respectively). Next, we
observed that substrate 54, having no substitution on the back-
bone, gave lower enantioselectivity (entry 4, 55% ee). Treatment
of malononitrile derivative 55 under the optimal conditions gave
58 with an increase in enantioselectivity (entry 5, 71% ee).
b
c
entry
catalyst
T (°C)
yield (%)
ee (%)
d
1
L3Pd(OTf)2
L3Pt(OTf)2
L6(AuCl)2
L1(AuCl)2
L2(AuCl)2
L3(AuCl)2
L3(AuCl)2
L3(AuCl)2
L3(AuCl)2
r.t.
NR
NR
76
69
72
74
79
81
75
ND
ND
24
4
d
2
r.t
3
4
5
6
7
8
9
r.t.
r.t.
r.t.
28
73
82
88
94
r.t.
−10
−30
−50
a
Reactions performed at 0.1 M using 1 equiv of 36, 5 mol % catalyst,
and 10 mol % additive for 16 h. Isolated yields. Determined by chiral
HPLC. No NaBARF was added during this reaction.
b
c
d
also tested and furnished the desired product with no significant
enantiomeric excess (entry 4). However, increasing the size of the
substituents on the phosphorus aryl moieties proved to be beneficial
for enantioselectivity and led to an encouraging 73% ee (entry 6).
Moreover, performing the cyclization using L3(AuCl)2 and
NaBARF at lower temperature (−50 °C) greatly improved the
selectivity, as 37 was isolated with 94% ee and 75% yield (entry 9).
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Table 8. Enantioselective Au(I)-Cyclization with Silyloxy-
1,5-Enynes
Table 9. Selected Optimization for Enantioselective Au(I)-
Cyclization with Silyloxy-1,3-dien-7-ynes
a
a
b
c
d
entry
ligand
solvent
dr
yield (%)
ee (%)
1
2
3
4
L3
L3
L1
L2
CH2Cl2
DCE
>20:1
>20:1
>20:1
>20:1
76
91
36
72
98
99
41
56
CH2Cl2
CH2Cl2
a
Reactions performed at 0.1 M using 1 equiv of 60, 5 mol %
b
L3(AuCl)2, and 10 mol % NaBARF for 16 h. The diastereoselectivity
was determined by H NMR of the crude reaction mixture. Isolated
yields. Determined by chiral HPLC.
c
1
d
(entry 2) gave 61 in a very impressive 99% ee, with excellent
yield (91%) and diastereoselectivity (>20:1). We noted that
both the electron density and steric hindrance associated with
bulky ligand L3 were essential to obtain excellent yields and
enantioselectivities (entries 3 and 4).
a
Reactions performed at 0.1 M using 1 equiv of substrate, 5 mol %
This tandem gold(I)-catalyzed process showed great compat-
ibility with the presence of a wide range of substrates (Table 10).
Tetrasubstituted diene 62 gave the desired bicyclic product
69 with high yield (76%) and enantioselectivity (95% ee,
entry 1). Modification of the terminal substituent of the alkyne to an
ethyl group gave the desired silyl enol ether 63 in a satisfactory yield
(61%) and enantioselectivity (96% ee, entry 2). The reactions were
faster with substrates 64 and 65 and resulted in the formation of the
bicyclic dienes71 and 72 with high enantioselectivities (98% and
89% ee, entries 3 and 4). However, substrate having a para-methoxy
substitution on the aryl ring gave a complex mixture of products.
We found that the reaction was efficient with a substrate bearing the
1-naphthyl group (66); the bicyclic product 73 was obtained with
high enantioselectivity (91% ee, entry 5). Finally, the reaction was
found to tolerate various alkyl substituents at R1 (c-hexyl and
n-butyl) and gave the bicyclic ketones 74 and 75 in good yield with
slightly lower enantioselectivites (73 and 81% ee, entries 6 and 7).
To exemplify the utility of this tandem cyclization, silyl
enol ether 61 was hydrolyzed in the presence of acid to give
the corresponding ketone 76 (eq 4). The absolute stereochemistry
was determined by X-ray analysis of this crystalline compound,
(R)-DTBM-SEGPHOS(AuCl)2 [L3(AuCl)2], and 10 mol % NaBARF
b
c
for 16 h at −30 °C. Isolated yields. Determined by chiral HPLC.
e
Using 1,2-dichloroethane as a solvent.
Finally, we were pleased to find that the gold-catalyzed
cyclization of 56 led to the desired dimethyl-substituted product
59 in 81% yield and 90% ee (entry 6).
Gold-Catalyzed Enantioselective Tandem Cyclization
of Silyloxy-1,3-dien-7-yne. Subsequently, as depicted in
Scheme 2, we explored the reactivity of the analogous 3-siloxy-1,
Scheme 2. Proposed Intermediates for Gold-Catalyzed
Tandem Cyclization of Silyloxy-1,3-dien-7-yne
3-diene-7-yne toward gold(I) catalysis, anticipating the formation
of bicyclo[3.3.0]octane derivatives. For this scenario to be
successful, the vinyl gold intermediate B obtained after the
cyclization would perform a conjugate addition on the activated
unsaturated ketone to form an additional carbon−carbon bond.23
Under this proposed mechanism, the carbene intermediate24
would undergo subsequent 1,2-hydrogen migration to give the
desired bicylic diene.25
To our delight, the reaction performed with substrate 60 and
L3(AuCl)2 gave the desired product 61 with excellent
diastereoselectivity and enantioselectivity (Table 9, entry 1).
In this case, the reaction was performed at room temperature
and dry molecular sieves were added to the reaction mixture in
order to avoid the formation of a complex mixture of ketones.
The optimized conditions using dichloroethane as a solvent
and the stereochemistry of the related bicyclo[3.3.0]octane
derivatives was assigned by analogy. Ketone 77, containing four
contiguous stereogenic centers, was obtained as a single
stereoisomer by treatment of 69 under similar conditions (eq 5).
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using palladium and gold complexes as catalysts. These
reactions showed excellent enantioselectivity and provided
entry into a wide range of cyclopentanoid structures. While
the palladium- and gold-catalyzed cyclization reactions are mecha-
nistically related, the two catalyst have complementary
limitations and advantages; the palladium(II) complexes were
generally limited to catalysis of 5-exo-dig cyclization reactions of
terminal alkynes, while the gold(I) catalysts showed preference
for cyclization reactions of nonterminal alkynes. Moreover, the
chiral phosphine gold complexes provided access to enantio-
selective 5-endo-dig cyclization reactions previously unachiev-
able through catalysis with cationic group 10 metal complexes.
Taken together, these results further highlight the great
potential of electrophilic late transition metal complexes to
serve as catalysts for enantioselective formation of carbon−
carbon bonds by alkyne activation.
Table 10. Enantioselective Au(I)-Cyclization with Silyloxy-
1,3-dien-7-ynes
a b
,
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures and compound characterization cif
data. This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
fdtoste@berkeley.edu
■
ACKNOWLEDGMENTS
We gratefully acknowledge NIHGMS (RO1 GM073932),
Amgen, and Novartis for financial support. J.-F.B. thanks the
■
́
Fonds Quebecois de la Recherche sur la Nature et les
Technologies (FQRNT) for a postdoctoral fellowship. S.Z.
and I.C. acknowledge the Groningen University Fund (GUF)
and the Spanish MCI, respectively. We would also like to thank
Dr. Antonio DiPasquale for his assistance in collecting and
analyzing crystallographic data. Solvias and Takasago are
acknowledged for the generous donation of phosphine ligands
and Johnson Matthey for a gift of AuCl3.
a
Reactions performed at 0.1 M using 1 equiv of substrate,
5 mol % (R)-DTBM-SEGPHOS(AuCl)2, and 10 mol % NaBARF
for 16 h. The diastereoselectivity was >20:1 as determined by H
NMR of the crude reaction mixture. Isolated yields. Determined by
chiral HPLC.
b
1
c
d
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Furthermore, bromination of 61 afforded the α-bromoketone
78 with high diastereoselectivity (>20:1, eq 6). The preference
for formation of the anti-substituted product may be explained
by increased steric repulsion between the β-substituent and
the methyl group in transition state 80, leading to the syn-substituted
adduct (Figure 1).
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Figure 1. Rationale for trans Diastereoselectivity.
CONCLUSION
■
In summary, we have described novel asymmetric metal-
catalyzed 5-exo and 5-endo-dig cyclizations of syliloxyenynes
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(22) See Supporting Information.
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