Synthesis of benzannulated spiroacetals using chiral gold-phosphine complexes and chiral anions

Article abstract of DOI:10.1016/j.tetlet.2013.08.077

The development of an asymmetric gold-catalysed dihydroalkoxylation strategy for the synthesis of the 3′H-spiro[chroman-2,1′- isobenzofuran] spiroacetal ring system 5 is described. Spiroacetal was generated in up to 87:13 enantiomeric ratio using chiral gold-phosphine complexes and chiral silver phosphate Ag(S)-TRIP.

Full text of DOI:10.1016/j.tetlet.2013.08.077

Tetrahedron Letters 54 (2013) 5865–5868
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of benzannulated spiroacetals using chiral gold–phosphine
complexes and chiral anions
⇑
Rachelle Quach, Daniel P. Furkert, Margaret A. Brimble
School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 16 June 2013
Revised 26 July 2013
Accepted 21 August 2013
Available online 31 August 2013
The development of an asymmetric gold-catalysed dihydroalkoxylation strategy for the synthesis of the
30H-spiro[chroman-2,10-isobenzofuran] spiroacetal ring system 5 is described. Spiroacetal was generated
in up to 87:13 enantiomeric ratio using chiral gold–phosphine complexes and chiral silver phosphate
Ag(S)-TRIP.
Crown Copyright Ó 2013 Published by Elsevier Ltd. All rights reserved.
Keywords:
Gold catalysis
Spiroacetals
Asymmetric synthesis
Chiral catalysts
The 5,6-benzannulated spiroacetal moiety is a key pharmaco-
phore found in a variety of natural products exhibiting interesting
biological activity, such as paecilospirone,1 berkelic acid2 and the
rubromycins3 (Fig. 1). In particular, paecilospirone, an antimitotic
agent isolated from the marine fungus Paecilomyces sp.,1 was re-
cently synthesised by our group.4 To date, there has been limited
work on the construction of the paecilospirone spiroacetal ring
system5 and the development of methods for the reagent-
controlled asymmetric catalytic synthesis of spiroacetals has only
recently emerged.
spirocyclisation of dihydroxyalkyne 2 to construct the spiroacetal
ring system 1 of paecilospirone. Herein we report an asymmetric
gold-catalysed dihydroalkoxylation strategy for the synthesis of
the 30H-spiro[chroman-2,10-isobenzofuran] ring system 5.
We envisaged that the spiroacetal would be generated via me-
tal-catalysed spirocyclisation of dihydroxyalkyne 2, accessible
from Sonogashira coupling of 3 and 4. Iodide 3 and alkyne 4 in turn
would be prepared easily from commercially available reagents
(Scheme 1). The cyclisation precursor, dihydroxyalkyne 2 was pre-
pared by Sonogashira coupling of iodide 314 with alkyne 414 using
Pd(OAc)2 and 1,10-bis(di-tert-butylphosphino)ferrocene (dtbpf)
followed by cleavage of both protecting groups with 20 mol %
p-toluenesulfonic acid (Scheme 2).
Gold catalysis has developed into a robust synthetic tool for the
addition of heteroatoms to carbon–carbon multiple bonds under
mild conditions.6 Whilst spiroacetals have been assembled using
gold catalysis,7 extension of this valuable synthetic method to the
enantioselective synthesis of spiroacetals has only recently been
reported. Ding and coworkers developed an Ir(I)/SpinPHOX-
catalysed asymmetric hydrogenation and spirocyclisation of
With dihydroxyalkyne 2 in hand, we focused our attention on the
gold-catalysed enantioselective spirocyclisation to form spiroacetal
1 (Table 1). Initially, various metal catalysts (Pd, Cu and Au) were
screened for their ability to effect the dihydroalkoxylation of 2.
a,
a0-bis(2-hydroxyarylidene) ketones for the formation of enantio-
enriched spiroacetals.8 List and Nagorny have independently
reported the chiral phosphoric acid catalysed enantioselective spi-
roacetalisation of enol ethers.9,10 In addition, Gong and coworkers
reported a gold(I)/Bronsted acid relay catalytic three-component
cascade reaction to generate highly enantioenriched spiroacetals.11
During the preparation of this manuscript, Hashmi et al. also
reported highly active NAC-gold catalysts for the synthesis of phe-
nols and spiroacetals.12 Our ongoing interest in the synthesis of
benzannulated spiroacetals4,5,13 prompted us to investigate the
use of chiral gold-ligand complexes to catalyse the enantioselective
HO 2C
O
OH
HO
C6H13
OH
O
O
O
O
MeO2C
O
C8H17
Me H O
Me Et
C5H11
berkelic acid
paecilospirone
MeO
O
HO
O
O
O
OH
CO2Me
O
O
γ-rubromycin
OH
⇑
Corresponding author.
E-mail address: m.brimble@auckland.ac.nz (M.A. Brimble).
Figure 1. Structures of 5,6-benzannulated spiroacetal natural products: paecilo-
spirone, berkelic acid and -rubromycin.
c
0040-4039/$ - see front matter Crown Copyright Ó 2013 Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.08.077

5866
R. Quach et al. / Tetrahedron Letters 54 (2013) 5865–5868
Table 1
spirocyclisation
OH
Asymmetric gold-catalysed spirocyclisation
OTBS
O
O
EOMO
HO
OH
O
O
+
I
O
conditions
O
HO
+
1
2
3
4
Sonogashira
2
1
5
paecilospirone core
O
I
HO
Entry Catalysta
Lb
AgXc Yieldd 1:5e
er(1)f
er(5)f
OH
1
2
3
4
5
6
7
8
PdCl2
—
—
—
—
—
—
—
rac-6
rac-6
rac-6
(S)-6
(R)-7
(S)-6
(R)-7
-
—
97
25
53
92
—
63:37
57:43
53:47
74:26
—
—
—
—
—
—
—
—
—
—
—
0
—
—
—
—
—
—
—
—
—
—
0
CuBrꢀSMe2
AgSbF6
AgSbF6
—
Scheme 1. Retrosynthetic strategy.
AuCl
AuCl3
AuPPh3Cl
AuPPh3Cl
AuPPh3Cl
AuPPh3Cl
AuPPh3Cl
AuCl3
AuPPh3Cl
AuPPh3Cl
AuPPh3Cl
AuPPh3Cl
AuPPh3Cl
AuClꢀSMe2
AuClꢀSMe2
AuClꢀSMe2
AuClꢀSMe2
—
—
A regioisomeric mixture of spiroacetals 1 and 5 resulted with all
the catalytic systems.15 Products 1 and 5 were separable by chro-
matography, however, the composition of mixtures could be deter-
mined by 1H NMR. The catalyst screen revealed that AuPPh3Cl in
the presence of AgSbF6 in dichloromethane was initially the most
effective for the spirocyclisation of 2 (entry 7). Good selectivity
for 1 was obtained with the inclusion of the racemic biaryl phos-
phine ligand, BINAP (6) (entry 8). Surprisingly, a change in selectiv-
ity in favour of 5 was observed following a change in solvent from
dichloromethane to 1,4-dioxane (entry 9) that was even more
pronounced upon changing from AuPPh3Cl to AuCl3 (entry 10)
indicating that both the nature of the gold catalyst and the solvent
influenced the regioselectivity of the spirocyclisation. AuClꢀSMe2
gave similar selectivity and yields to AuPPh3Cl and was therefore
used in subsequent experiments (entries 15 and 16).
AgOTf
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
75
99
83
72
81
98
76
—
82:18
77:23
85:15
48:52
10:90
87:13
83:17
—
9g
10g
11
12
13h
14h
15
16
17
18
19
20
21
22
0
0
—
0
—
0
96
94:6
Ag(S)-13 81
Ag(S)-13 83
Ag(S)-13 72
Ag(S)-13 99
88:12 54:46 82:18
75:25 54:46 86:14
84:16 51:49 87:13
(S)-6
(R)-7
(S)-11
93:7
53:47 87:13i
(R)-12 Ag(S)-13 99
68:32 53:47 86:14
68:32 53:47 84:16
—
(S)-6
(R)-6
Ag(S)-13 29
Ag(S)-13 83
Ag(S)-13 27
AuClꢀSMe2
96:4
100:0
55:45 86:14
50:50
AuClꢀSMe2
—
All reactions carried out in CH2Cl2 at rt (unless otherwise noted).
With the optimised conditions in hand (entry 8), a range of chi-
ral ligands were next investigated for their ability to influence the
chirality established in the spirocyclisation reaction (Fig. 2). The
use of chiral phosphine ligands (S)-BINAP (6) and (R)-MeO-BIPHEP
(7) resulted in a complete lack of asymmetric induction with only
racemic material obtained (entries 11 and 12). Disappointingly,
lowering the reaction temperature to ꢁ40 °C resulted in no reac-
tion (entry 13), but at this temperature the (R)-MeO-BIPHEP (7) li-
gand showed good reactivity and an increase in selectivity for
spiroacetal 1 (entry 14). This result suggests that the formation
of spiroacetal 1 may be kinetically favoured. Alternative chiral li-
gands such as (R,S)-Josiphos (8), IndaBOX (9) and Ph-pyBOX (10)
a
10 mol % catalyst except 2 mol % for entry 21.
Catalyst:L (2:1).
[M]:AgX (1:1) except entry 10 (1:3).
b
c
d
Isolated yield (%) of regioisomeric mixture.
Determined by 1H NMR.
e
f
er determined by chiral HPLC.
1,4-Dioxane as solvent.
g
h
Reaction at ꢁ40 °C.
Mixture gave ½a 2D5
ꢁ13 (c 1.0, CH3Cl).
ꢂ
i
also resulted in a lack of chiral induction.16 Based on the chiral
counterion approach reported by Toste and coworkers
PPh2 MeO
PPh2 MeO
PPh2
PPh2
P
17
Fe
P
we next
investigated the use of the chiral silver phosphate, Ag(S)-TRIP
(13), in the gold-catalysed spirocyclisation of 2. Surprisingly, spiro-
acetal 5 was obtained in 82:18 er while only 54:46 er was obtained
for spiroacetal 1 (entry 15). A range of chiral phosphine–gold com-
plexes were then used in combination with the chiral silver phos-
phate counterion. A slight improvement in enantioselectivity for 5
was observed using chiral ligands 6, 7, 11 and 12 (entries 16–19),
however, no significant enantioselectivity for spiroacetal 1 was
observed.
Our focus next turned to optimising the enantioselectivity for
spiroacetal 5. The chiral silver phosphate alone was found to also
facilitate the reaction with good enantioselectivity (84:16 er for
spiroacetal 5), but gave spiroacetals 1 and 5 in poor yield (29%)
even after extended reaction times (50 h, entry 20). The catalyst
loading could be reduced to 2 mol % without significant change
(R)-MeO-BIPHEP
(R)-7
(R,S)-Josiphos
(R,S)-8
(S)-BINAP
(S)-6
O
H
H
O
O
O
O
N
O
O
PPh2
PPh2
N
N
N
N
H
H
O
(S)-SEGPHOS
(S)-11
iPr
IndaBox
9
Ph-pyBOX
10
iPr
tBu
CH3
tBu
O
iPr
O
O
O
P
P
P
O
O
2
OAg
iPr
tBu
O
iPr
iPr
CH3
(R)-DTBM-SEGPHOS
(R)-12
tBu
OH
2
Ag(S)-TRIP (13)
OTBS
EOMO
i, ii
HO
Figure 2. Structures of chiral ligands and counterions.
+
I
3
4
2
in enantioselectivity or yield (entry 21). Matched and mismatched
pairing was not apparent in our studies with only a 7% difference in
er obtained for spiroacetal 1 when pairing Ag(S)-TRIP (13) with
Scheme 2. Synthesis of dihydroxyalkyne 2. Reaction conditions: (i) Pd(OAc)2, dtbpf,
K2CO3, NMP, 50 °C, 2 h, 66%; (ii) p-TSA (20 mol%), EtOH, 55 °C, 48 h, 77%.

R. Quach et al. / Tetrahedron Letters 54 (2013) 5865–5868
OH
5867
(S)- or (R)-BINAP (6) (entries 16 and 22). A number of solvents
were screened, with dichloromethane proving to be the most suit-
able solvent for the gold-catalysed spirocyclisation reactions. All
other solvents screened (MTBE, toluene and 1,4-dioxane) resulted
in lower enantioselectivity.16
O
O
i, ii
iii
O
OH
5
14
16
76:24 er (rt, 5 min)
85:15 er (-20°C, 19 h)
OTBDPS
A postulated mechanism for the gold-catalysed dihydroalkoxy-
lation is depicted in Scheme 3.18 Coordination of the gold activates
the alkyne facilitating nucleophilic attack by the more nucleophilic
benzylic alcohol to give a trans-alkenyl gold complex. The oxonium
ion thus generated is susceptible to nucleophilic attack by the less
nucleophilic phenol. Protodeauration then regenerates the gold
catalyst and yields the spiroacetal product. A 5-exo-dig cyclisation
followed by a 6-exo-trig cyclisation (blue arrows) would form the
paecilospirone spiroacetal 1. However a 6-endo-dig cyclisation
followed by a 5-exo-trig cyclisation (red arrows) would form the
isomeric spiroacetal 5.
Scheme 4. Synthesis of spiroacetal 5 from enol ether 15. Reaction conditions: (i)
AuPPh3Cl, AgSbF6, CH2Cl2, rt, 5 h, 30%; (ii) TBAF, THF, rt, 5 min; (iii) (S)-TRIP
(10 mol %), CH2Cl2.
silver phosphate, Ag(S)-TRIP (13). Spirocyclisation with chiral
gold–phosphine complexes alone did not induce chirality, how-
ever, with the addition of the chiral anion, Ag(S)-TRIP, spiroacetal
5 was obtained in 87:13 er.
Supplementary data
Intermediate 14 was isolated from the reaction which may re-
sult from the protodeauration of intermediate 15, suggesting that
the reaction may proceed through an enol ether intermediate. In
an attempt to deconvolute the mechanism, intermediate 14 was
synthesised from the monoprotected dihydroxyalkyne 16
(Scheme 4). Gold-catalysed cyclisation of 16 followed by cleavage
of the silyl group selectively yielded enol ether 14. Spirocyclisation
of 14 with 10 mol % (S)-TRIP yielded spiroacetal 5 with a pleasing
76:24 er at room temperature and 85:15 er on conducting the
reaction at ꢁ20 °C (Scheme 4).
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2013.08.
077.
References and notes
1. Namikoshi, M.; Kobayashi, H.; Yoshimoto, T.; Meguro, S. Chem. Lett. 2000, 29,
308.
2. Stierle, A. A.; Stierle, D. B.; Kelly, K. J. Org. Chem. 2006, 71, 5357.
3. Ueno, T.; Takahashi, H.; Oda, M.; Mizunuma, M.; Yokoyama, A.; Goto, Y.;
Mizushina, Y.; Sakaguchi, K.; Hayashi, H. Biochemistry 2000, 39, 5995.
4. Yuen, T.-Y.; Yang, S.-H.; Brimble, M. A. Angew. Chem., Int. Ed. 2011, 50, 8350.
5. (a) Marsini, M. A.; Huang, Y.; Lindsey, C. C.; Wu, K.-L.; Pettus, T. R. R. Org. Lett.
2008, 10, 1477; (b) Wilson, Z. E.; Hubert, J. G.; Brimble, M. A. Eur. J. Org. Chem.
2011, 3938; (c) Jay-Smith, M.; Furkert, D. P.; Sperry, J.; Brimble, M. A. Synlett
2011, 1395.
In conclusion, we have investigated the use of an asymmetric
gold-catalysed dihydroalkoxylation for the synthesis of benzannu-
lated spiroacetals using chiral phosphine ligands and the chiral
6. For recent reviews on gold catalysis, see: (a) Rudolph, M.; Hashmi, A. S. K. Chem.
Soc. Rev. 2012, 41, 2448; (b) Fürstner, A. Chem. Soc. Rev. 2009, 38, 3208; (c)
Hashmi, A. S. K. Chem. Rev. 2007, 107, 3180; (d) Li, Z.; Brouwer, C.; He, C. Chem.
Rev. 2008, 108, 3239; (e) Hashmi, A. S. K.; Rudolph, M. Chem. Soc. Rev. 2008, 37,
1766.
7. For examples of gold catalysis in the synthesis of spiroacetals, see: (a)
Antoniotti, S.; Genin, E.; Michelet, V.; Genêt, J.-P. J. Am. Chem. Soc. 2005, 127,
9976; (b) Aponick, A.; Li, C.-Y.; Palmes, J. A. Org. Lett. 2008, 11, 121; (c) Zhang,
Y.; Xue, J.; Xin, Z.; Xie, Z.; Li, Y. Synlett 2008, 940; (d) Liu, B.; De Brabander, J. K.
Org. Lett. 2006, 8, 4907; (e) Tlais, S. F.; Dudley, G. B. Org. Lett. 2010, 12, 4698; (f)
Li, Y.; Zhou, F.; Forsyth, C. J. Angew. Chem., Int. Ed. 2007, 46, 279; (g) Fang, C.;
Pang, Y.; Forsyth, C. J. Org. Lett. 2010, 12, 4528; (h) Trost, B. M.; O’Boyle, B. M.;
Hund, D. J. Am. Chem. Soc. 2009, 131, 15061; (i) Benson, S.; Collin, M.-P.; Arlt, A.;
Gabor, B.; Goddard, R.; Fürstner, A. Angew. Chem., Int. Ed. 2011, 50, 8739; (j)
Yeung, Y.-Y.; Corey, E. J. Org. Lett. 2008, 10, 3877.
O
O
O
O
14
OH
Au
L*
OH
5
minor
≤ 75% ee
5-exo-trig
OH
Au-L*
Au
L*
OH
15
8. Wang, X.; Han, Z.; Wang, Z.; Ding, K. Angew. Chem., Int. Ed. 2012, 51, 936.
9. Coric, I.; List, B. Nature 2012, 483, 315.
10. Sun, Z.; Winschel, G. A.; Borovika, A.; Nagorny, P. J. Am. Chem. Soc. 2012, 134,
8074.
11. Wu, H.; He, Y.-P.; Gong, L.-Z. Org. Lett. 2013, 15, 460.
12. Jaimes, M. C. B.; Böhling, C. R. N.; Seranno-Becerra, J. M.; Hashmi, A. S. K. Angew.
Chem., Int. Ed. 2013, 52, 7963.
13. Brimble, M. A., Stubbing, L. A.; Topics in Heterocyclic Chemistry; Springer-
Verlag: Berlin, Heidelberg, New York, 2013 in press.; Saturated Oxygen
Heterocyclic Compounds; (b) Brimble, M. A.; Haym, I.; Sperry, J.; Furkert, D.
P. Org. Lett. 2012, 14, 5820; (c) Brimble, M. A.; McLeod, M. C.; Rathwell, D. C. K.;
Wilson, Z. E.; Yuen, T.-Y. Pure Appl. Chem. 2012, 84, 1379; (d) Sperry, J.; Wilson,
Z. E.; Rathwell, D. C. K.; Brimble, M. A. Nat. Prod. Rep. 2010, 27, 1117; (e)
Rathwell, D. C. K.; Yang, S.-H.; Tsang, K. Y.; Brimble, M. A. Angew. Chem., Int. Ed.
2009, 121, 8140.
H
6-endo-dig
5-exo-dig
O
OH
Au L*
HO
2
OH
OH
14. The preparation of iodide
information.
15. General gold-catalysed reaction procedure: Under argon,
3
and alkyne
4
is detailed in the Supporting
Au-L*
OH
L* Au
a
solution of
chloro(dimethylsulfide)gold(I) (10 mol %) and (S)-BINAP (5 mol %) in CH2Cl2
(1 mL) was stirred at room temperature for 2 h. Meanwhile, in a separate vial,
to a solution of (S)-TRIP (10 mol %) in CH2Cl2 (0.20 mL) protected from light
was added Ag2CO3 (5 mol %) and distilled H2O (0.20 mL). The resulting mixture
was stirred vigorously for 1 h, diluted with CH2Cl2 (2 mL), washed with H2O
(3 ꢃ 1 mL) and concentrated in vacuo yielding Ag(S)-TRIP. The solution of gold
catalyst in CH2Cl2 was added to Ag(S)-TRIP and the resulting mixture was
stirred with light excluded for 30 min. A solution of diol 2 in CH2Cl2 (1 mL) was
then added dropwise to the catalyst mixture. The mixture was stirred with
light excluded until the reaction was complete as indicated by TLC, then
concentrated in vacuo. Purification by flash column chromatography on silica
(30:1 hexanes-EtOAc) afforded spiroacetal 1 and/or 5.
6-exo-trig
O
O
O
OH
1
L* Au
Major
racemic
Scheme 3. Proposed mechanism.

5868
R. Quach et al. / Tetrahedron Letters 54 (2013) 5865–5868
30H-spiro[chroman-2,10-isobenzofuran] (1) mp 78–82 °C (lit. oil); Rf = 0.67 (2:1
hexanes-EtOAc); vmax (neat)/cmꢁ1 3048, 2916, 1585, 1457, 1229, 1011 and
745; dH (400 MHz; CDCl3) 3.17 (1H, d, J = 17.6 Hz, H-3 or H-40), 3.31 (2H, s, H-3
or H-40), 3.35 (1H, d, J = 17.6 Hz, H-3 or H-40), 4.80 (1H, d, J = 14.9 Hz, H-10),
5.15 (1H, d, J = 14.9 Hz, H-10), 6.80 (1H, d, J = 8.0 Hz, ArH), 6.92 (1H, td, J = 7.5,
1.0 Hz, ArH), 7.07 (1H, m, 5.3 Hz, ArH), 7.12–7.18 (2H, m, ArH), 7.21–7.24 (3H,
m, ArH); dC(100 MHz; CDCl3) 36.6 (CH2, C-3 or C-40), 42.3 (CH2, C-3 or C-40),
63.6 (CH2, C-10), 108.6 (quat., C-2), 110.0 (CH, ArC), 121.1 (CH, ArC), 124.0 (CH,
ArC), 125.0 (CH, ArC), 125.8 (quat., ArC), 126.4 (CH, ArC), 126.8 (CH, ArC), 128.1
(CH, ArC), 128.8 (CH, ArC), 130.7 (quat., ArC), 133.0 (quat., ArC), 158.2 (quat.,
ArC); m/z (ESI+, %) 261 (MNa+, 100), 262 (23), 263 (5); Found MNa+, 261.0889.
hexanes-EtOAc); vmax (neat)/cmꢁ1 3043, 2942, 1582, 1488, 1230, 1001 and
745; dH (400 MHz; CDCl3) 2.20 (1H, ddd, J = 13.2, 5.8, 2.2 Hz, H-3), 2.44 (1H, td,
J = 13.3, 5.9 Hz, H-3), 2.87 (1H, ddd, J = 16.4, 5.9, 2.0 Hz, H-4), 3.24-3.36 (1H, m,
H-4), 5.06 (1H, dd, J = 12.7, 0.8 Hz, H-30), 5.29 (1H, dd, J = 12.7, 0.8 Hz, H-30),
6.79 (1H, dd, J = 8.1, 1.2 Hz, ArH), 6.90 (1H, td, J = 7.4, 1.2 Hz, ArH), 7.10 (1H, t,
J = 8.1 Hz, ArH), 7.13 (1H, d, J = 7.4 Hz, ArH), 7.32 (1H, dt, J = 7.2, 1.0 Hz, ArH),
7.37–7.44 (3H, m, ArH); dC (100 MHz; CDCl3) 21.7 (CH2, C-4), 30.2 (CH2, C-3),
71.7 (CH2, C-30), 108.2 (quat., C-2), 117.1 (CH, ArC), 120.8 (CH, ArC), 121.3 (CH,
ArC), 121.7 (quat., ArC), 122.0 (CH, ArC), 127.4 (CH, ArC), 127.9 (CH, ArC), 129.1
(CH, ArC), 129.4 (CH, ArC), 140.0 (2 ꢃ quat., ArC), 153.2 (quat., ArC); m/z (ESI+,
%) 261 (MNa+, 100), 262 (23), 263 (5); Found MNa+, 261.0890. C16H14NaO2
required 261.0886. The spectroscopic data were in agreement with that
reported in the literature.6
C16H14NaO2 required 261.0886.
16. See the table in the Supporting Information.
17. (a) Hamilton, G. L.; Kang, E. J.; Mba, M.; Toste, F. D. Science 2007, 317, 496; (b)
Hashmi, A. S. K. Nature 2007, 449, 292.
3H-spiro[benzofuran-2,30-isochroman] (5) mp 108–114 °C; Rf = 0.66 (2:1
18. Hashmi, A. S. K. Angew. Chem., Int. Ed. 2010, 49, 5232.