Gold(I)-Catalysed Hydroarylation of 1,3-Disubstituted Allenes with Efficient Axial-to-Point Chirality Transfer

Article abstract of DOI:10.1002/chem.201800209

Hydroarylation of enantioenriched 1,3-disubstituted allenes has the potential to proceed with axial-to-point chirality transfer to yield enantioenriched allylated (hetero)aryl compounds. However, the gold-catalysed intermolecular reaction was previously reported to occur with no chirality transfer owing to competing allene racemisation. Herein, we describe the development of the first intermolecular hydroarylations of allenes to proceed with efficient chirality transfer and summarise some of the key criteria for achieving high regio- and stereoselectivity.

Full text of DOI:10.1002/chem.201800209

A Journal of
Accepted Article
Title: Gold(I)-Catalysed Hydroarylation of 1,3 Disubstituted Allenes with
Efficient Axial-to-Point Chirality Transfer
Authors: Daniel Sutherland, Luke Kinsman, Stuart M Angiolini,
Georgina M Rosair, and Ai-Lan Lee
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Gold(I)-Catalysed Hydroarylation of 1,3-Disubstituted Allenes with
Efficient Axial-to-Point Chirality Transfer
Daniel R. Sutherland, Luke Kinsman, Stuart M. Angiolini, Georgina M. Rosair and Ai-Lan Lee*[a]
Abstract: Hydroarylation of enantioenriched 1,3-disubstituted allenes
has the potential to proceed with axial-to-point chirality transfer to
yield enantioenriched allylated (hetero)aryl compounds. However, the
gold-catalysed intermolecular reaction was previously reported to
occur with no chirality transfer, due to competing allene racemisation.
In this full article, we describe the development of the first
intermolecular hydroarylations of allenes to proceed with efficient
chirality transfer, and summarise some of the key criteria for achieving
high regio- and stereoselectivities.
enantioselectivities were obtained (~35-63% e.e.). The limitations
on enantioinduction often posed by the linear geometry of Au(I)
catalysts is well documented.[
The lack of efficient asymmetric methods is therefore a clear
limitation in the field. We herein report the first successful
development of intermolecular hydroarylations of allenes with
efficient chirality transfer (Scheme 1c). A substrate scope is
presented, along with suggested prerequisites for achieving high
enantiomeric ratios.
25]
a) Initial Development by Widenhoefer (Racemic Studies):[15]
Introduction
H
R1 R3
(IPr)AuCl (5 mol%) R3
N
AgOTf (5 mol%)
N
R5
R4
The axial chirality present within some 1,3-disubstituted allenes
offers a useful opportunity for asymmetric synthesis: via axial-to-
point chirality transfer upon -Lewis acid catalysed nucleophilic
R4
R5
Dioxane
RT, 24 h
R2
H
R1
racemic
b) Previous Attempts at Chirality Transfer by Che:[21]
R2
1
2
3
[
1],[2]
[3]
addition.
Within this context, the ability of gold(I) catalysts to
racemic
[
4],[1a, 5],[6]
activate allenes
towards nucleophilic addition is well
documented. The intramolecular gold-catalysed hydroarylation[
of allenes, for example, has been utilised extensively for the
synthesis of cyclic systems,[8],[9] and includes examples of
7]
H
Ph Me
Various gold(I) cat. Me
(5 mol%)
N
N
[
10]
+
reactions with enantioselectivity
diastereoselectivity.
with chirality transfer have also been reported.[
as well as excellent
Intramolecular hydroarylation of allenes
Toluene or THF
RT, 6-12 h
[
8k]
Ph
H
11]
Ph
Ph
1
a
2a
3aa
-5% ee
While
the
intermolecular
addition
of
amines
98% ee
0
(
hydroamination) and alcohols (hydroalkoxylation) have been
c) This Work:
reported to proceed with efficient chirality transfer,[
efficient intermolecular asymmetric hydroarylation of allenes,
however, has proven more elusive. Racemic gold-catalysed
12],[13],[14]
3 6 4 3
(CF C H ) PAuCl
R1
H
R3
(10 mol%)
R3
N
N
AgNTf
2
(10 mol%)
R4
R4
R5
Toluene, 5 o
hydroarylation of allenes was first reported independently by Li
C
R2
H
R
5
with aryls)[15] in 2008, Widenhoefer (with indoles, Scheme 1a)
[16]
(
R2
R1
[
17]
in 2009.[18],[19],[20],[21]
1
2
and Gagné (with MeO-substituted aryls)
3
9
9
8:2 to
9:1 e.r.
(
or pyrroles
Two years later, Che and co-workers reported their attempts at
hydroarylations with chirality transfer, which resulted in racemic
products (Scheme 1b).[22] They attributed the lack of chirality
transfer to the competitive gold(I)-catalysed allene racemisation
reaction.[23] As a result, Che and co-workers ingeniously utilised
up to 98:2 e.r.
or e-rich ArH)
Scheme 1. a) Initial racemic studies by Widenhoefer. b) Previous attempts at
chirality transfer by Che. c) This work.
the aforementioned racemisation to develop
enantioselective dynamic resolution method[
a
catalytic
24]
using chiral Results and Discussion
dinuclear gold(I) phosphine complexes instead.[ While these
efforts let to good yields of desired product, only moderate
22]
We commenced our investigations with a few initial theories and
design criteria, based on our previous studies on chirality
transfer,[
13a, 26]
as to the type of allenes and nucleophiles required
[
a]
D. R. Sutherland, L. Kinsman, S. M. Angiolini, Dr G. M. Rosair,
Dr A.-L. Lee
Institute of Chemical Sciences,
School of Engineering and Physical Sciences,
Heriot-Watt University,
Edinburgh EH14 4AS
United Kingdom.
E-mail: A.Lee@hw.ac.uk
to achieve efficient chirality transfer. Firstly, if preventing gold-
catalysed allene racemization is the key to success, then any
substituents (such as aryls used by Che in 1a), which can
[23]
stabilize the key planar gold cation intermediate I (Scheme 2a),
should initially be avoided (see later: Table 2, Entry 13, which
[
13a],[27]
supports this criteria). Based on previous related work,
we
also predicted that regioselectivity on the allene will be influenced
by electronic rather than steric factors (see later: Table 2, Entry
14, which supports this criteria).We therefore intentionally
Supporting information for this article is given via a link at the end of
the document.
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planned to investigate 1,3-disubstituted allenes 1 with one
inductively withdrawing substituent (Scheme 2b). Such an
approach was designed with the dual aim of destabilizing
(Entry 7). Extending the reaction time to 3 days increases the yield
to 67% (Entry 8). Lower equivalents of nucleophile 5a (2 equiv.,
Entry 9) and lower concentration (0.4 M, Entry 10) was confirmed
to be detrimental to the reaction yields (58% and 55%
respectively).
intermediate
I
and hence disfavouring the competitive
racemization reaction, as well as electronically differentiating the
two π-bonds on the allene 1 for favourable regioselectivity.[13a]
The latter ensures that the gold(I) catalyst will activate the more
Table 1. Selected optimisation studies.
1
electron rich π -bond, thus favouring (hetero)aryl attack at
position b rather than a (Scheme 2b). Finally, if nucleophilic attack
vs. racemization is in competition, then the more electron-rich and
subsequently more nucleophilic (hetero)aryls should stand a
better chance of out-competing the racemization reaction. Lower
temperatures should also help with this competition to ensure
higher enantiomeric ratios. It is worth noting that the requirement
for an inductively withdrawing group in 1 is not necessarily a
limitation, as it allows for the inclusion of a variety of functional
groups (see Table 2) which are useful for further synthetic
elaboration.
Entry
Conc
(M)
T
Catalyst
3ba:
3ba
Yield
(%)[c]
3ba’[a]
e.r.[b]
(°C)
1[d][e]
2[d][e]
3[d][e]
4[d][e]
5[e][f]
6[d][e]
0.15
0.40
0.75
1.50
1.50
1.50
10
10
10
5
PPh
PPh
PPh
PPh
PPh
AuNTf
AuNTf
AuNTf
AuNTf
AuNTf
10:1
8:1
7:1
7:1
7:1
5:1
N.D.
N.D.
27
39
50
41
37
55
3
3
3
3
3
2
2
2
2
2
87:13
90:10
91:9
5
5
(IMes)AuCl/
AgNTf
77:23
2
7[d][e]
8[d][g]
9[f][g]
1.50
1.50
1.50
0.40
5
5
5
5
(CF
C
H
)
PAuCl/
11:1
11:1
10:1
12:1
93:7
93:7
94:6
60
67
59
55
3
6
4
3
AgNTf
2
(CF
3
C
6
H
4
)
3
PAuCl
2
/
AgNTf
(CF
3
3
C
6
H
4
)
3
PAuCl/
2
AgNTf
1
0[d][g]
(CF
C
6
H
4
)
3
PAuCl/
2
90:10
AgNTf
[
b] Determined by 1H NMR analysis. >20:1 E:Z by 1H NMR analysis. [b]
Determined by CSP-HPLC. [c] Isolated yields. [d] 4 Equiv. 2a. [e] 1 Day. [f]
Equiv. 2a. [g] 3 Days. N.D. = not determined.
Scheme 2. a) Competing allene racemization reaction. b) Initial Theory for
Design of Substrate.
2
With these initial design criteria in mind, our investigation
With optimised conditions in hand, we proceeded to
investigate the allene substrate scope (Table 2).[32] To our delight,
the next two allenes that were subjected to our optimised
conditions (1c and 1e) proceeded with excellent yield and chirality
transfer (94%, 97:3 e.r. 3ca and 95%, 97:3 e.r. 3ea, Entries 1 and
3). Pleasingly, replacing the Me in 1c with n-pentyl in 1d is not
detrimental to the reaction, with desired product 3da formed in
high regioselectivity (>20:1), good yield (81%) and excellent
chirality transfer (98:2 e.r., Entry 2). Given the excellent chirality
transfer obtained for the OBz containing allene 1e (Entry 3) a
range of protected allenols was investigated next (Entries 4-6).
Replacing Ph in 1e with alkyls (1f, 1g, Entries 4-5) does not seem
to significantly affect enantiomeric ratios of the products (97:3 3fa,
94:6 3gb). However, the regioselectivity of the reaction drops off
slightly with the pivaloyl protected allenol 1g (8:1 3:3′ vs. 15:1 3:3′
with 1e and 1f). Removing the carbonyl (1h) gives a similar drop
in regioselectivity (6:1 3:3′) but a decrease in chirality transfer is
also observed (85:15 e.r.), presumably due to the lower inductive
withdrawing ability of OBn (1h) vs. OBz (1e). Moving away from
protected allenols, the cyano-substituted allene 1i (Entry 7)
commenced with optimization studies on allene 1b and N-
[
28]
methylindole 2a, a selection of which is represented in Table 1.
Initial conditions using Gagosz catalyst[ PPh
29]
3 2
AuNTf at 10 °C
provided good regioselectivity for reaction at position b vs. a,
producing 3ba:3ba′ in 10:1 ratio, but in a poor 27% yield. A screen
of alternative counterions failed to improve the reaction yield,
however, higher concentrations successfully increases the yield
(
Entries 1-3). A reduction in temperature from 10 °C to 5 °C was
deemed necessary to improve the enantiomeric ratios (87:13 vs.
0:10 e.r., Entries 3-4). Reducing the equivalents of indole
9
nucleophile 5a from 4 to 2 equivalents was slightly detrimental to
the yield (41% vs. 37%, Entries 4-5). Next, the ligand on the
catalyst was varied in an attempt to improve yields and e.r.
(
(
Entries 5-7). While changing from PPh
3
to the NHC ligand IMes
1,3-dimesityl-1,3-dihydro-2H-imidazol-2-ylidene)[ provided an
30]
improved yield of 55%, regioselectivity and e.r. decreased to 5:1
and 77:23 respectively (Entry 6). Pleasingly, the use of
3 6 4 3 3
C H ) P instead of PPh
successfully increases the yield,[31]
(CF
regioselectivity as well as e.r. to 60%, 11:1 and 93:7 respectively
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performs very well under our conditions, giving perfect chirality
transfer (98:2 e.r. 1i →98:2 e.r. 3ia), yield (77%) and
8
9
67%
11:1 3:3′
2:8 e.r.[
b]
9
regioselectivity (>20:1). Inserting an extra CH
1j, Entry 9) or OBz group (1k, Entry 10) further from the allene
moiety causes a noticeable drop in chirality transfer for allene 1j
76:24 e.r. vs. 97:3 e.r. with 1c) and an expected drop in
regioselectivity in both (11:1 1j vs. >20:1 1c and 7:1 1k vs. 15:1
2
to place the NPhth
(
(
97%
11:1 3:3′ [b]
76:24 e.r.[
b]
1
e), although 3 is still the major product in all cases.
Table 2. Allene Scope
10
82%
7
9
:1 3:3′
2:8 e.r.[
b]
11
96%
8:1 3:3′
87:13 e.r.
1
[b]
Result[a]
Entry
1
Allene
Major product
94%
>
9
20:1 3:3’
7:3 e.r.
[
b]
12[c]
23% (RT)
>
20:1 3:3′
2
81%
>
9
20:1 3:3’
8:2 e.r.
8
1
3
3
6%
:3 3:3′
[
b]
13
’ 79:21 e.r.
53:47 e.r.
[
b]
3
4
5
95%
1
4
28%
1.4:1 3:3’
1
9
5:1 3:3′
7:3 e.r.
[
b]
74%
1
9
5:1 3:3′
7:3 e.r.
[
b]
1
[
a] Isolated yields, all >20:1 E:Z and reported regioselectivity determined by H
NMR analysis. 2b was used when the product using 2a could not be separated
by CSP-HPLC. [b] E.r. of major product determined by CSP-HPLC [c] Reaction
carried out at room temperature (trace product observed at 5 C).
58%
8
9
:1 3:3′
4:6 e.r.
[
b]
o
Pleasingly, the diester containing allene 1l (Entry 11) shows
good regioselectivity (18:1) and chirality transfer (87:13 e.r.)
despite the electron withdrawing esters being fairly distant from
the allene moeity. In contrast to moving the functionality further
away from the allene (1l vs. 1b), having the ester directly
conjugated to the allene (1m vs. 1b) is detrimental to the reaction.
The more electron poor allene 1m appears very unreactive
compared to allenes 1a-1l: the reaction proceeds very sluggishly,
6
7
74%
6
8
:1 3:3′
5:15 e.r.
[
b]
77%
20:1 3:3′
>
[
b]
98:2 e.r.
o
resulting in poor yield (trace product at 5 C), even when carried
out at room temperature (23% yield 3ma, Entry 12).
To our surprise, the aryl-substituted allene 1n, which was
expected to fully racemise under these conditions (via Ph
stabilising intermediate I, see Scheme 2a),[33] proceeded with
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moderate chirality transfer for the major regioisomer (Entry 13).
The regioselectivity is also reversed (1:3 ratio of 3:3′, 53:47 e.r.
for 3 and 79:21 e.r. for 3′). Therefore, although it does prove that
substituents capable of stabilising the cationic intermediate I is
detrimental to efficient chirality transfer, the effect is not quite as
drastic as originally predicted. The 1:3 regioselectivity under
8
9
84%
>20:1 3:3′
6:4 e.r.[
b]
9
these conditions, albeit modest, was also
a surprise as
98%
15:1 3:3′ [
b]
hydroarylation with allene 1n was previously reported to be non-
regioselective (1:1.2) under racemic conditions.[16] Finally, and as
82:18 e.r.[b]
predicted, the sterically differentiated dialkyl substituted allene 1o
provided very poor regioselectivity (1.4:1 3:3′). This result seems
to support our initial theory described in Scheme 2b, that it is
electronic rather than steric factors that influence the
regioselectivity of the gold-catalysed hydroarylation reaction.
10
92%
>20:1 3:3′
9
8:2 e.r. [
b]
Table 3. (Hetero)aryl Nucleophile Scope
11
48%
20:1 3:3′
8
>
2:18 e.r.[
b]
12[c]
58%
Entry
1
(Het)ArylH
Major product
Result[a]
94%
1
:1 α/
[
d]
selectivity
>
9
20:1 3:3’
7:3 e.r.
>20:1 3:3′
[
b]
2
3
4
5
6
7
99%
>
9
20:1 3:3′
5:5 e.r.
[
b]
41% or 48%[c]
1
3
4
>
9
20:1 3:3′
8:2 e.r.[
b]
32%
1
5
8:1 3:3′
5:45 e.r.
[
b]
40% major[e]
1
5
:1:1 α//′
[d]
selectivity
:1 3:3′
5
89%
>
9
20:1 3:3′
5:5 e.r.
[
b]
1
5[f]
98%
>
9
20:1 3:3′
0:10 e.r.[
b]
96%
5:1 3:3′ [
5:15 e.r.
b]
1
8
[
b]
16
97%
1
5
0:1 3:3′
7:43 e.r.[b]
90%
>
8
20:1 3:3′
9:11 e.r.
[
b]
[
1
a] Isolated yields, all >20:1 E:Z and reported regioselectivity determined by
H NMR analysis unless otherwise stated. 1e was used when the product
67%
using 1c could not be separated by CSP-HPLC. [b] E.r. of major product
determined by CSP-HPLC. [c] 15 mol% catalyst used. [d] Ratio determined
by 1H NMR. E.r. not determined due to inseparable mixtures. [e] Yield
1
9
1:1 3:3′
7:3 e.r.
[
b]
1
calculated by H NMR. [f] 6 equivalents of nucleophile used.
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The nucleophile scope was investigated next, commencing
with different groups on the nitrogen of the indole (Table 3). Both
N-methylindole as well as N-benzylindole (2a and 2c) reacted
smoothly in the reaction (Entries 1-2) as did unsubstituted indole
the competing allene racemization to occur. Based on the results
in Table 3, it is therefore of no surprise that less nucleophilic
(hetero)aryls such as benzofurans, 2-methylfuran,
2-
methoxythiophene, methoxybenzene and hexamethylbenzene do
not react under these conditions.
2
b
(Entry 4), to give excellent yields (94%, 99%, 89%
respectively), regioselectivities (all >20:1) and e.r. (97:3, 95:5,
5:5 respectively). Boc protected indole (2d, Entry 3), however,
It is worth noting that the gold-catalysed hydroarylation
reaction is highly stereoselective both in terms of chirality transfer
(providing the (hetero)aryl is sufficiently nucleophilic, vide supra),
9
reacted sluggishly due to the electron withdrawing nature of the
Boc group and thus less nucleophilic nature of the indole. It is
thought that the lower nucleophilicity of the N-Boc-indole allows
the competing allene racemisation to occur, resulting in a poor
enantiomeric ratio (55:45) of product 3cd. The same pattern is
observed with 5-substituted indoles (Entries 5-7), with more
electron rich methoxy[34] substituted 2g outpreforming the less
electron rich chloro- and fluoro-substituted indoles (2e and 2f) in
terms of chirality transfer efficiency (97:3 e.r. for 3eg vs. 85:15
and 89:11 e.r. for 3ce and 3cf). 7-Ethyl (2h, Entry 8) and 6-Cl (2i,
Entry 9) are also tolerated well in the reaction, again with the more
electron rich ethyl substituted indole (2h) providing better
enantiomeric ratios in the product (96:4 e.r. 3ch vs. 82:18 e.r.
1
as well as E selectivity (all >20:1 E:Z by H NMR analysis). A
plausible[36] mechanism to describe the observed selectivity is
provided in Scheme 3. As described in Scheme 2b, the
regioselectivity is thought to originate from the electronic
differentiation of the π-bonds on the allene 1, with the LAu+
catalyst preferring to coordinate to the more electron-rich π.
Within this context, the cationic gold catalyst can still coordinate
to either face of the allene (II and II′), and a low barrier of
interconversion exists between II and II′.[ Nucleophiles tend to
approach anti- to the gold(I),[1] so the arylation of II is expected to
37]
[
38]
be sterically and kinetically favoured over that of II′.
The
resulting intermediate III leads to the observed (R,E)-3 product
upon protodeauration. On the other hand, arylation onto II′ should
be kinetically unfavourable, which explains why (S,Z)-3 is never
observed experimentally.[
3
ci). 1,2-Methyl indole (2j, Entry 10) reacts smoothly with
excellent yield (92%), regioselectivity (>20:1) and chirality transfer
98:2 e.r.). However, when the most reactive 3-position of the
indole is blocked (2k, Entry 11), a drop in yield is observed (48%
ck). As before, this is accompanied by a drop in chirality transfer
39]
(
3
Less hindered face
(82:18 e.r.), presumably due to the less reactive nucleophile.
(Het)ArH
L
Next, pyrrole nucleophiles were investigated (Entries 12-14).
+
Au
H
H
low barrier
H
H
Although N-methylpyrrole 2l was reported to be unreactive under
Gagné’s original conditions,[
17]
the reaction proceeded with a
Au+
L
n
n
reasonable yield (58%), good allene regioselectivity (>20:1, Entry
2) and excellent chemoselectivity under the conditions shown in
X
X
Hindered
II'
face
(Het)ArH
II
1
Table 3. It should be noted that chemoselectivity is a well known
problem in gold-catalysed reactions with pyrroles, as the mono-
anti-
Lower energy anti-
Higher energy
barrier
attack barrier
attack
alkylated product is more nucleophilic than the starting pyrrole,
Ar
H
LAu
alkylations.[
35]
Remarkably,
this
leading
to
multiple
H
Me
n
chemoselectivity issue is not observed under our conditions. To
our surprise, however, no regioselectivity was observed between
reaction at the α and  position of the pyrrole (3cl:3cl′′ 1:1, Entry
n
Me
III AuL X
Ar
X
III'
protode-
auration
protode-
auration
1
2). As a result, an N-methylpyrrole, with the α-positions blocked,
Ar
H
was investigated next (2m, Entry 13). To our delight, 2m reacted
smoothly give 3cm with excellent regioselectivity (>20:1) and
chirality transfer (98:2 e.r.), albeit with a moderate yield (41%).
The yield could be improved slightly to 48% upon increasing the
catalyst loading to 15 mol% (Entry 13) but increasing the
equivalents of pyrrole has no effect on the yield. Encouraged by
the success of 2m a monosubstituted N-methylpyrrole 2n was
investigated next. As hoped, the reaction occurred preferentially
at the 4-position of the pyrrole albeit with only moderate selectivity
over the other two positions (5:1:1, Entry 14).
H
n
Me
Me
n
Ar
X
X
(S, Z)-3
(
R, E)-3
Observed product
Scheme 3. Postulated origin of stereoselectivity.
In order to prove that the chirality transfer in this reaction is
a kinetic phenomenon, the rate of allene 1 racemisation vs.
formation of product 3 was investigated next (Table 4). In the
absence of nucleophile 2, the allene 1b is fully racemised within
Finally, electron-rich aryls were investigated as nucleophiles
(Entries 15-16). To our delight, 2o reacted smoothly to give 3co
in excellent yield (98%), regioselectivity (>20:1) and good chirality
transfer (90:10 e.r., Entry 15). As predicted, removing one
methoxy group (2p, Entry 16), substantially reduced the efficiency
of chirality transfer (57:43 e.r. 3cp) even though the yield is still
excellent at 97%. This reduction in e.r. is once again thought to
be due to the reduced nucleophilicity of 2p vs. 2o, which allows
1
h (Entries 1-2). However, the racemisation of allene 1b is
significantly slower under our hydroarylation reaction conditions,
when nucleophile 2 is present (Entries 3-8). This could be due to
reversible coordination of the nucleophile to the cationic gold
catalyst.[40] As predicted, the gold-catalysed hydroarylation
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Chemistry - A European Journal
10.1002/chem.201800209
FULL PAPER
outcompetes the allene racemisation under our reaction
conditions, proving that the chirality transfer is indeed a kinetic
phenomenon (Table 4, Entries 3-8).
conditions as it outcompetes the rate of gold-catalysed allene
racemization.
Experimental Section
General Procedure
Table 4. Rate of reactions vs. racemisation studies.
Allene 1 (0.15 mmol, 1 equiv.), toluene (0.1 mL) and nucleophile 2 (0.6
mmol, 4 equiv.) were added to a 1 dram vial equipped with a small stirrer
bar and cooled to 5 oC. (4-CF
followed by AgNTf
PAuCl (0.015 mmol, 10 mol%)
(0.015 mmol, 10 mol%) were added in quick
3
6 4 3
C H )
2
succession and the reaction was allowed to stir at 5 oC for 3 days. The
reaction mixture was purified by column chromatography to give product
3. Full experimental procedures, characterisation for all new compounds
and copies of
NMR conv.[e]
Entry
Time (h)
Allene 1b
Product 3ba
e.r.[
c]
e.r.
[d]
1H and 13C NMR spectra are provided in the Supporting
Information.
1[a]
2[a]
3[b]
4[b]
5[b]
6[b]
7[b]
8[b]
0.25
1
55:45
50:50
95:5
-
-
-
-
0
-
-
Acknowledgements
0.25
1
94:6
-
<5%
26%
56%
78%
89%
We thank Heriot-Watt University (James Watt Scholarship for
DRS and ICS Undergraduate Summer Research Bursary for
SMA) for funding. Mass spectrometry data was acquired at the
EPSRC UK National Mass Spectrometry Facility at Swansea
University. We thank the EPSRC UK National Crystallography
Service at the University of Southampton for the collection of
the crystallographic data.[41]
93:7
92:8
92:8
91:9
90:10
6
90:10
87:13
83:17
16
24
[
a] In absence of nucleophile 2a. [b] 4 Equiv. nucleophile 2a. [c] Determined
by CSP-GC. [d] Determined by CSP-HLPC. [e] Determined by H NMR
analysis.
1
Keywords: gold • allene • chirality transfer • hydroarylation •
asymmetric
[
[
1]
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We have developed the first intermolecular hydroarylation of 1,3-
disubstituted allenes to proceed with efficient chirality transfer,
thereby providing access to functionalized, allylated indoles,
pyrroles and aryls (3) in up to 99% yields, >20:1 regioselectivity
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a ϭ-withdrawing
substituent not only disfavours racemization, but also ensures
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furnishing products with much higher enantiomeric ratios. For
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and unprotected indoles proceed with excellent chirality transfer,
greatly outperforming their less nucleophilic counterparts such as
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[
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Chemistry - A European Journal
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