Catalytic Enantioselective Synthesis of C1- and C2-Symmetric Spirobiindanones through Counterion-Directed Enolate C-Acylation

Article abstract of DOI:10.1002/anie.201607731

A catalytic enantioselective route to C₁- and C₂-symmetric 2,2′-spirobiindanones has been realized through an intramolecular enolate C-acylation. This reaction employs a chiral ammonium counterion to direct the acylation of an in situ generated ketone enolate with a pentafluorophenyl ester. This reaction constitutes the first example of a direct catalytic enantioselective C-acylation of a ketone and provides an efficient and highly enantioselective route to axially chiral spirobiindanediones. These products can be diastereoselectively derivatized, offering access to a range of functionalized spirocyclic architectures.

Full text of DOI:10.1002/anie.201607731

Angewandte
Communications
Chemie
International Edition: DOI: 10.1002/anie.201607731
German Edition: DOI: 10.1002/ange.201607731
Counterion-Directed Catalysis
Catalytic Enantioselective Synthesis of C1- and C2-Symmetric
Spirobiindanones through Counterion-Directed Enolate C-Acylation
Benjamin F. Rahemtulla, Hugh F. Clark, and Martin D. Smith*
Abstract: A catalytic enantioselective route to C1- and C2-
symmetric 2,2’-spirobiindanones has been realized through an
intramolecular enolate C-acylation. This reaction employs
a chiral ammonium counterion to direct the acylation of an
in situ generated ketone enolate with a pentafluorophenyl ester.
This reaction constitutes the first example of a direct catalytic
enantioselective C-acylation of a ketone and provides an
efficient and highly enantioselective route to axially chiral
spirobiindanediones. These products can be diastereoselec-
tively derivatized, offering access to a range of functionalized
spirocyclic architectures.
b-dicarbonyl derivatives are versatile and valuable inter-
mediates for an enormous range of synthetic chemistry, and
can be synthesized in enantioenriched form by enantioselec-
tive 1,4-addition and alkylation reactions.[1] In comparison,
enantioselective methods for their synthesis by enolate C-
acylation are relatively limited.[2] Enolate C-acylation offers
a valuable strategic approach to such derivatives, but is often
limited by poor O- vs. C-regioselectivity.[3] One approach to
solving this problem employs silyl enol ethers or silyl ketene
acetals as enolate precursors,[4] and this has led to several
distinct strategies for enantioselective C-acylation
(Scheme 1).[5] Fu has demonstrated that planar chiral 4-
pyrrolidinopyridine derivative 1 is highly effective in promot-
ing the C-acylation of a-aryl ketene acetal derivatives with
high levels of enantioselectivity.[6] This reaction proceeds
through the in situ formation of a chiral acylpyridinium cation
Scheme 1. Previous work and strategy for enantioselective C-acylation.
and the generation of a silicon-free enolate. A related Lewis
base approach from Smith employs a chiral isothiourea[7] 2 to
mediate highly enantioselective C-acylation of a cyclic silyl
ketene acetal, most likely via an activated acyl-isothiouro-
nium ion.[8] Jacobsen has disclosed a distinct method that
utilizes a chiral thiourea 3 with a 4-pyrrolidinopyridine co-
catalyst to effect enantioselective C-acylation with acyl
fluoride derivatives.[9,10] This process likely proceeds through
the reaction of a thiourea-bound enolate and a catalyst-
associated acylpyridinium ion. A very recent approach from
Stoltz achieves the first intermolecular enantioselective C-
acylation of a carbonyl derivative that is not a ketene acetal.
This process utilizes a Ni-catalyzed three-component cou-
pling of lactam enolates, benzonitriles and aryl halides in the
presence of ligand 4 to produce b-imino lactams that afford b-
keto lactams upon hydrolysis.[11] We considered that an
alternative approach that did not utilize a preformed enolate
derivative could be extremely valuable, but also recognized
that this was likely to be challenging due to competitive O-
acylation, especially as the oxygen of an enolate is intrinsically
the most nucleophilic site;[12] to our knowledge no methods
for the direct catalytic enantioselective C-acylation of ketones
have been disclosed. We rationalized that intramolecular
acylation of a ketone enolate could geometrically disfavour
reaction on oxygen and favour the desired C-acylation. To
achieve this, we propose that an enolate generated from an
indanone[13] derivative 5 could be trapped in an intramolec-
ular fashion by an activated ester to generate chiral spiro-
biindanones 6. If the enolate were to be generated under
phase transfer conditions in the presence of a chiral counter-
[*] B. F. Rahemtulla, Prof. Dr. M. D. Smith
Chemistry Research Laboratory, University of Oxford
12 Mansfield Road, Oxford, OX1 3TA (UK)
E-mail: martin.smith@chem.ox.ac.uk
Homepage: http://msmith.chem.ox.ac.uk
H. F. Clark
GlaxoSmithKline Pharmaceuticals, Medicines Research Centre
Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY (UK)
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under http://dx.doi.org/10.
1002/anie.201607731.
Angew. Chem. Int. Ed. 2016, 55, 1 – 5
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!

Angewandte
Communications
Chemie
ion, a catalytic enantioselective route to spiro b-dicarbonyl
derivatives could be envisaged. Spiro compounds are valuable
intermediates in synthesis, materials and catalysis,[14] but
catalytic enantioselective routes for their synthesis are
relatively underdeveloped.[15] Catalytic enantioselective
methods for the generation of axially chiral spiro compounds
are particularly rare.[16]
We prepared a suitable substrate 7 in which the acyl group
was activated as a phenyl ester in three steps from indan-1-
one.[17] Upon exposure of 7 to tetrabutylammonium bromide
(TBAB) and 50% aqueous potassium carbonate in toluene at
room temperature, we observed smooth cyclization to the
racemic C2-symmetric spirobiindanone 9, with no trace of O-
acylation observed (Table 1, entry 1).
Use of N-benzyl cinchonidinium chloride 10 in place of
TBAB gave complete conversion to the desired product and
a modest e.r. of 56:44. We observed that the use of aqueous
hydroxide bases led to hydrolysis of the phenyl ester 7
(entry 3) and hence we switched to solid bases in order to
screen catalysts for higher enantioselectivity. This led to
a small increase in selectivity (to 59:41 e.r., entry 4) and under
these conditions no hydrolysis was observed. We subse-
quently screened a range of ammonium salts and under these
conditions, 11, which bears a urea as a Brønsted acidic group,
was found to give improved selectivity of 69:31 e.r. (entry 5).
We were concerned that the relatively low selectivities
observed were a consequence of a background reaction
mediated by the basic phenolate leaving group, and hence we
examined a reaction with a stoichiometric amount of sodium
phenolate in the presence of catalyst 11 (entry 6). This led to
very low enantioselectivity (51: 49 e.r.), which was consistent
with our hypothesis. Consequently, we changed our substrate
to pentafluorophenyl ester 8, rationalizing that the lower pKa
of pentafluorophenol to phenol (19.5 vs. 27.4 in MeCN)[18]
would limit this background reaction.[19] Subjecting this
substrate 8 to the same conditions (entry 7) led to a relatively
poor 42:58 e.r. but a significantly slower reaction time, and
hence we decided to reoptimize the catalyst for this sub-
strate.[17] Changing to quininium catalyst 12 led to a signifi-
cantly higher selectivity (79:21 e.r., entry 8), and pseudo-
enantiomer 13 led to a very similar 25:75 e.r. and the expected
reversal of absolute configuration (entry 9). We subsequently
examined a range of different N-substituents on the quinidi-
nium nucleus; N-pentafluorophenylbenzyl catalyst 14 gave
poorer selectivity (36:64 e.r., entry 10) but we observed that
selectivity improved with larger N-substituents (29:71 e.r.
with 3,5-di-tert-butyl derivative 15, and 17:83 e.r. with 9-
anthracenyl catalyst 16, entries 11 and 12 respectively).
Quininium catalyst 17 gave better e.r. (88:12), and a switch
to a weaker base with solid K3PO4 gave similar e.r. (89:11;
entry 13). Changing to aqueous K3PO4 led to an increase in
e.r. (to 97:3) without the issues of ester hydrolysis that
plagued our earlier attempts to use aqueous base. We believe
this to be a rare example of a catalytic enantioselective C-
acylation of an enolate.[20]
Table 1: Optimization: cation-directed enantioselective C-acylation.[a]
With an optimized procedure in hand, we examined the
scope and limitations of this reaction (Table 2). The unsub-
stituted C2-symmetric spirobiindanone 9 can be produced in
93% yield and 97:3 e.r. via this approach; this cyclization can
be performed on a gram scale without compromising yield or
enantioselectivity. The absolute configuration of this material
was confirmed to be (S)- through comparison with literature
data.[21a] Substitution is tolerated on both the indan-1-one and
benzoic acid sections of substrates; thus C2-symmetric
dimethyl 18 (92:8 e.r., 84% yield) and bistrifluoromethyl
spiro derivatives 19 (95:5 e.r., 95% yield) are both produced
with excellent enantioselectivity and yield. This represents
a novel method for the catalytic enantioselective synthesis of
these axially chiral motifs; other methods rely on resolution
or the use of chiral auxiliaries.[21] The reaction is not limited to
C2-symmetric products and we have explored substitution at
all sp2 positions on the 1-indanone ring. Cyclization of
substrates bearing substituents in the 5-position of the
indanone ring occured with high levels of enantioselectivity
to afford 20 (5-bromo) and 21 (5-fluoro) with consistently
high levels of enantioselectivity (96:4 e.r. in both cases). The
absolute configuration of bromide 20 was confirmed through
X-ray crystallography.[22] An indanone substrate substituted
with an electron-donating substituent in the 4-position
cyclized to afford methoxy derivative 22 in 99% yield and
94:6 e.r. Similarly, cyclization of a 4-bromo indanone to give
23 occurred in 93:7 e.r. We have also examined the formation
of spirobiindanones with different groups on each of the two
Entry
R1
Catalyst
Base
e.r.[b]
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Ph
Ph
C6F5
C6F5
C6F5
C6F5
C6F5
C6F5
C6F5
C6F5
C6F5
Bu4NBr
10
10
10
11
11
11
12
13
14
15
16
17
17
17
K2CO3 (aq.)[c]
K2CO3 (aq.)[c]
KOH (aq.)[c]
KOH (s)
KOH (s)
NaOPh (s)
KOH (s)
KOH (s)
KOH (s)
KOH (s)
KOH (s)
50:50
56:44
–
59:41
69:31
51:49
42:58
79:21
25:75
36:64
29:71
17:83
88:12
89:11
97:3
9
10
11
12
13
14
15
KOH (s)
KOH (s)
K3PO4 (s)
K3PO4 (aq.)[c]
[a] Conditions: substrate 7 or 8 (0.02 mmol), catalyst (10 mol%), solid
base (1.0 equiv.), PhMe ([substrate]=0.1 moldmÀ3), RT, 48 h. [b] e.r.
determined by chiral stationary phase HPLC. [c] base: 50% aq., w/w,
10.0 equiv.
2
www.angewandte.org
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2016, 55, 1 – 5
These are not the final page numbers!

Angewandte
Communications
Chemie
Table 2: Scope of cation-directed enantioselective direct C-acylation.
Scheme 2. Chemoselective derivatizations of the spirobindanone core.
Conditions: a) N-Bromosuccinimide (1.0 equiv.), AIBN (0.02 equiv.),
CCl4, 808C. b) DIBALH (1.0m in THF, 3.0 equiv.), t-BuLi (1.7m in
pentane, 3.0 equiv.), THF, À788C. c) DIBALH (1.0m in hexanes,
3.3 equiv.), t-BuLi (1.7m in pentane, 3 equiv.), THF, À788C. d) 4-
F(C6H4)B(OH)2 (1.5 equiv.), Pd(PPh3)4 (2 mol%), Na2CO3, Toluene/
H2O (2.3:1, v/v), reflux. e) B2Pin2 (1.2 equiv.), Pd(dppf)Cl2 (5 mol%),
KOAc (3.0 equiv.), 1,4-dioxane, reflux. e.r. determined by chiral sta-
tionary phase HPLC; d.r. determined by examination of the crude
1H NMR spectra. Yields refer to isolated materials.
28 as a single diastereoisomer in 83% yield and without any
loss of enantiopurity (at 97:3 e.r.). Stereoselective reduction
of spirobindanones has been reported previously on racemic
material.[21e] Under the reported conditions, of DIBALH and
t-BuLi in THF, reduction of the 1,3-diketone 9 to diol 29
proceeded with complete diastereoselectivity and without
compromising e.r. (97:3 e.r. (major), > 20:1:1 d.r., (S,S,S):-
(R,S,S):(R,S,R)). Temperature control in this transformation
is key; allowing the reaction to warm above À788C led to
significantly lower e.r., presumably through reversible retro-
aldol condensation on mono-reduced material. We also
observed that if an excess of DIBALH in hexane (rather
than THF) was employed, an enhancement of e.r. in the major
diastereoisomer was observed (from 97:3 to > 99:1 e.r.),
whilst a reduction in diastereoselectivity (to 7:1:0 d.r.,
(S,S,S):(R,S,S):(R,S,R)) was attained. We attribute this to
a modification of the reducing agent with enantioenriched
diol in situ, which leads to discrimination between the major
and minor enantiomer in 8 by a chiral non-racemic reducing
agent.[23] This leads to an augmentation of enantioselectivity
(for the major diastereoisomer) at the expense of overall
diastereoselectivity.
Conditions: substrate (0.10 mmol), catalyst (10 mol%), K3PO4 (50%
aq., w/w, 10.0 equiv.), PhMe ([substrate]=0.1 moldmÀ3), RT, 48 h. e.r.
determined by chiral stationary phase HPLC; yields refer to isolated
materials.
aromatic rings such as 24, which can be synthesized in 99%
yield and 95:5 e.r. Reaction of an indanone containing a 7-
trifluoromethyl group occurred smoothly under the optimized
conditions to give 25 (95:5 e.r. and 88% yield). Monosub-
stituted derivatives such as 26 and 27 can be made by the
reaction of precursors bearing a group on either the indanone
or the benzoic acid portion of the precursor. Consequently, we
investigated whether the enantioselectivity observed is differ-
ent via cyclization from these two distinct starting materials.
For the formation of trifluoromethyl substituted compound
26, there are small differences between the two approaches,
with higher selectivity observed with the substituent on the
indanone (95:5 e.r. vs. 93:7 e.r.). This small difference was also
observed in the formation of 27, where cyclization from the
precursor carrying the methyl group on the indanone cyclized
in 99:1 e.r. and 71% yield versus 96:4 e.r. and 99% yield from
the substituted benzoate derivative. The observed difference
in yield is likely a consequence of a significantly slower
cyclization from the 6-substituted indanone.
Ultimately this means that 29, which has been employed
as a building block in ligand design and construction,[21g] can
be isolated as a single diastereoisomer in 78% yield and
> 99:1 e.r. We have also demonstrated that non-symmetrical
spirobindanone 20, which contains an aryl bromide, can be
cross-coupled with 4-fluorophenylboronic acid to afford
biaryl 30 in 86% yield and 95:5 e.r.; similarly, the carbon-
bromine bond in 20 can be transformed to a carbon-boron
We subsequently examined whether these spirobiinda-
nones could be chemoselectively derivatized to afford access
to unrealized spirocyclic architectures (Scheme 2). Radical
bromination of unsubstituted spirobiindanone 9 with N-
bromosuccinimide in the presence of AIBN as initiator led
to clean monobromination in the benzylic position to afford
Angew. Chem. Int. Ed. 2016, 55, 1 – 5
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

Angewandte
Communications
Chemie
C. P. Johnston, C. Concellꢀn, C. Simal, D. Philp, A. D. Smith,
Angew. Chem. Int. Ed. 2009, 48, 8914 – 8918; Angew. Chem.
2009, 121, 9076 – 9080.
bond in good yield (70%) and without compromising
enantiointegrity (95:5 e.r.).
In conclusion, we have demonstrated an approach to
direct catalytic enantioselective C-acylation of a ketone using
a chiral counterion. This approach has been exemplified in the
synthesis of both C1- and C2-symmetric spirobiindanediones
but will likely be applicable to other highly functionalized
three-dimensional scaffolds. We have also shown that these
materials can be chemoselectively derivatized; in the case of
diastereoselective reduction this led to an increase in
enantioenrichment to > 99:1 e.r., offering a practical route
to a valuable scaffold for ligand and catalyst design.
[8] P. A. Woods, L. C. Morrill, R. A. Bragg, A. D. Smith, Chem. Eur.
J. 2011, 17, 11060 – 11067.
[9] J. A. Birrell, J.-N. Desrosiers, E. N. Jacobsen, J. Am. Chem. Soc.
2011, 133, 13872 – 13875.
[10] C. K. De, E. G. Klauber, D. Seidel, J. Am. Chem. Soc. 2009, 131,
17060 – 17061.
[11] M. Hayashi, S. Bachman, S. Hashimoto, C. C. Eichman, B. M.
Stoltz, J. Am. Chem. Soc. 2016, 138, 8997 – 9000.
[12] a) M. D. Brickhouse, R. R. Squires, J. Phys. Org. Chem. 1989, 2,
389 – 409; b) M. Breugst, H. Zipse, J. P. Guthrie, H. Mayr,
Angew. Chem. Int. Ed. 2010, 49, 5165 – 5169; Angew. Chem.
2010, 122, 5291 – 5295.
[13] U. H. Dolling, P. Davis, E. J. Grabowski, J. Am. Chem. Soc. 1984,
106, 446 – 447.
Acknowledgements
[14] a) G. B. Bajracharya, M. A. Arai, P. S. Koranne, T. Suzuki, S.
Takizawa, H. Sasai, Bull. Chem. Soc. Jpn. 2009, 82, 285 – 302;
b) For a review on the utility of C2 symmetric diols: K. C.
Bhowmick, N. N. Joshi, Tetrahedron: Asymmetry 2006, 17, 1901 –
1929.
The European Research Council has provided financial
support (FP7/2007-2013)/ ERC grant agreement no. 259056.
We are grateful to EPSRC and GlaxoSmithKline for a CASE
award (to B.F.R.). We gratefully acknowledge John Jolliffe for
help with X-ray crystallography.
[15] a) R. Rios, Chem. Soc. Rev. 2012, 41, 1060 – 1074; b) A. K. Franz,
N. V. Hanhan, N. R. Ball-Jones, ACS Catal. 2013, 3, 540 – 553.
[16] For catalytic enantioselective syntheses of axially chiral spiro
compounds see: a) K. Tamao, K. Nakamura, H. Ishii, S.
Yamaguchi, M. Shiro, J. Am. Chem. Soc. 1996, 118, 12469 –
12470; b) T. Takahashi, H. Tsutsui, M. Tamura, S. Kitagaki, M.
Nakajima, S. Hashimoto, Chem. Commun. 2001, 1604 – 1605;
c) J. Liu, Y. Tian, J. Shi, S. Zhang, Q. Cai, Angew. Chem. Int. Ed.
2015, 54, 10917 – 10920; Angew. Chem. 2015, 127, 11067 – 11070;
d) K. Takenaka, M. Sako, S. Takatani, H. Sasai, ARKIVOC
2015, (ii), 52 – 63; e) K. Takenaka, N. Itoh, H. Sasai, Org. Lett.
Keywords: axial chirality · C-acylation · counterion ·
enantioselective synthesis · organocatalysis · phase-transfer
[1] For catalytic enantioselective alkylations of b-keto esters:
a) B. M. Trost, R. Radinov, E. M. Grenzer, J. Am. Chem. Soc.
1997, 119, 7879 – 7880; b) T. Ooi, T. Miki, K. Fukumoto, K.
Maruoka, Adv. Synth. Catal. 2006, 348, 1539 – 1542; For catalytic
enantioselective Michael reactions of b-keto esters, see: c) Y.
Hamashima, D. Hotta, M. Sodeoka, J. Am. Chem. Soc. 2002, 124,
11240 – 11241; d) G. Bartoli, M. Bosco, A. Carlone, A. Cavalli,
M. Locatelli, A. Mazzanti, P. Ricci, L. Sambri, P. Melchiorre,
Angew. Chem. Int. Ed. 2006, 45, 4966 – 4970; Angew. Chem.
2006, 118, 5088 – 5092.
[2] a) D. A. Evans, M. D. Ennis, T. Le, N. Mandel, G, Mandel, J.
Am. Chem. Soc. 1984, 106, 1154 – 1156; b) Y. Ito, T. Katsuki, M.
Yamaguchi, Tetrahedron Lett. 1984, 25, 6015 – 6016.
[3] a) H. O. House, R. A. Auerbach, M. Gall, N. P. Peet, J. Org.
Chem. 1973, 38, 514 – 522; b) K. N. Houk, M. N. Paddon-Row, J.
Am. Chem. Soc. 1986, 108, 2659 – 2662; c) M. Zhong, J. I.
Brauman, J. Am. Chem. Soc. 1996, 118, 636 – 641.
ˇ
´
2009, 11, 1483 – 1486; f) I. Coric, B. List, Nature 2012, 483, 315 –
319.
[17] See the Supporting Information for an extended description of
experimental procedures, including catalyst, base and solvent
combinations examined.
[18] V. M. Vlasov, V. V. Aksenov, P. P. Rodionov, I. V. Beregovaya,
L. N. Shchegoleva, Russ. J. Org. Chem. 2002, 38, 115 – 125.
[19] For a C-acylation that employs a pentafluorophenyl ester
electrophile see: K. J. Hale, M. Grabski, J. T. Flasz, Org. Lett.
2013, 15, 370 – 373.
[20] For a highly enantioselective Steglich rearrangement using
a chiral ammonium betaine see: D. Uraguchi, K. Koshimoto, S.
Miyake, T. Ooi, Angew. Chem. Int. Ed. 2010, 49, 5567 – 5569;
Angew. Chem. 2010, 122, 5699 – 5701.
[21] For methods for the formation of chiral non-racemic 2,2’-
spirobiindanones and their derivatives see: a) H. Falk, W. Frçstl,
K. Schlçgl, Monatsh. Chem. 1974, 105, 574 – 597; b) N. Harada, T.
Ai, H. Uda, J. Chem. Soc. Chem. Commun. 1982, 232 – 233; c) K.
Kabuto, F. Yasuhara, S. Yamaguchi, Tetrahedron Lett. 1984, 25,
5801 – 5804; d) K. Naemura, I. Ebashi, M. Nakazaki, Bull. Chem.
Soc. Jpn. 1985, 58, 767 – 768; e) J. A. Nieman, B. A. Keay,
Tetrahedron: Asymmetry 1995, 6, 1575 – 1583; f) C. J. Boulton,
J. G. Finden, E. Yuh, J. J. Sutherland, M. D. Wand, G. Wu, R. P.
Lemieux, J. Am. Chem. Soc. 2005, 127, 13656 – 13665; g) Z. Guo,
X. Guan, Z. Chen, Tetrahedron: Asymmetry 2006, 17, 468 – 473.
[22] CCDC 1486386 (20) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre.
[23] a) N. Srivastava, A. Mital, A. Kumar, J. Chem. Soc. Chem.
Commun. 1992, 493 – 494; b) P. Daverio, M. Zanda, Tetrahedron:
Asymmetry 2001, 12, 2225 – 2259.
[4] a) T. Mukaiyama, A. Ishida, Chem. Lett. 1975, 4, 1201 – 1202;
b) I. Fleming, J. Goldhill, I. Paterson, Tetrahedron Lett. 1979, 20,
3205 – 3208.
[5] For enantioselective Lewis base mediated acyl transfer reactions
see: a) F. R. Dietz, H. Grçger, Synlett 2008, 663 – 666; b) J. C.
Ruble, G. C. Fu, J. Am. Chem. Soc. 1998, 120, 11532 – 11533;
c) S. A. Shaw, P. Aleman, E. Vedejs, J. Am. Chem. Soc. 2003, 125,
13368 – 13369; d) S. A. Shaw, P. Aleman, J. Christy, J. W. Kampf,
P. Va, E. Vedejs, J. Am. Chem. Soc. 2006, 128, 925 – 934; e) H. V.
Nguyen, D. C. D. Butler, C. J. Richards, Org. Lett. 2006, 8, 769 –
772; f) J. G. Seitzberg, C. Dissing, I. Søtofte, P.-O. Norrby, M.
Johannsen, J. Org. Chem. 2005, 70, 8332 – 8337; g) E. Busto, V.
Gotor-Fernandez, V. Gotor, Adv. Synth. Catal. 2006, 348, 2626 –
2632; h) Z. Zhang, F. Xie, J. Jia, W. Zhang, J. Am. Chem. Soc.
2010, 132, 15939 – 15941.
[6] A. H. Mermerian, G. C. Fu, J. Am. Chem. Soc. 2003, 125, 4050 –
4051.
[7] a) V. B. Birman, X. Li, Org. Lett. 2006, 8, 1351 – 1354; b) V. B.
Birman, X. Li, Org. Lett. 2008, 10, 1115 – 1118; c) C. Joannesse,
Received: August 9, 2016
Published online: && &&, &&&&
4
www.angewandte.org
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2016, 55, 1 – 5
These are not the final page numbers!

Angewandte
Communications
Chemie
Communications
Counterion-Directed Catalysis
B. F. Rahemtulla, H. F. Clark,
M. D. Smith*
&&&& — &&&&
Catalytic Enantioselective Synthesis of C1-
and C2-Symmetric Spirobiindanones
through Counterion-Directed Enolate C-
Acylation
Spirocyclic architectures: A catalytic
enantioselective route to C1- and C2-
symmetric 2,2’-spirobiindanones has
been realized through an intramolecular
enolate C-acylation. This reaction
employs a chiral counterion to direct the
acylation of an in situ generated enolate,
and constitutes the first example of an
enantioselective phase-transfer mediated
C-acylation.
Angew. Chem. Int. Ed. 2016, 55, 1 – 5
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!