Chiral Cyclopentadienyl Ligands Enable a Rhodium(III)-Catalyzed Enantioselective Access to Hydroxychromanes and Phthalides

Article abstract of DOI:10.1055/s-0034-1380765

The demand for efficient chiral cyclopentadienyl ligands (Cp^x) has increased significantly in recent years, partly because Cp?Rh(III) species have been developed as powerful catalysts for directed C-H functionalization reactions. However, a lac

Full text of DOI:10.1055/s-0034-1380765

SYNLETT
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© Georg Thieme Verlag Stuttgart · New York
2015, 26, 1490–1495
letter
1490
B. Ye, N. Cramer
Letter
Synlett
Chiral Cyclopentadienyl Ligands Enable a Rhodium(III)-Catalyzed
Enantioselective Access to Hydroxychromanes and Phthalides
Baihua Ye
O
Oi-Pr
Nicolai Cramer*
HN
Oi-Pr
OMOM
N
H
cat. (5 mol%), (BzO)2 (5 mol%)
DCE, 23 °C
O
Laboratory of Asymmetric Catalysis and Synthesis, Institute of
Chemical Sciences and Engineering, Ecole Polytechnique
Fédérale de Lausanne (EPFL), BCH 4305, 1015 Lausanne,
Switzerland
H
OH
OMOM
Rh
O
O
O
H
cat.
nicolai.cramer@epfl.ch
80% yield, 92:8 er
8 other examples
yields: 45–98%
Dedicated to K. Peter C. Vollhardt for his pioneering contribu-
tions to chiral cyclopentadienyl ligands.
er values 88:12 to 92.5:7.5
Received: 26.03.2015
Accepted after revision: 22.04.2015
Published online: 11.05.2015
strategies were developed by Ward and co-workers9 and by
us10 to provide a rhodium(III)-catalyzed enantioselective
route to dihydroisoquinolones. Our first generation of Cpx
rhodium(I) complexes contained C2-symmetric, cyclohex-
ane-fused, 1,2-disubstituted cyclopentadienyl (Cp) ligands,
among which ligand 1a showed the best performance (Fig-
ure 1). Subsequently, a second-generation catalyst 2a was
developed.11 Each ligand in this class of catalysts contain a
C2-symmetric 1,2-disubstituted cyclopentadienyl group
that draws its chirality from an atropoisomeric biaryl back-
bone.6 The ligand has proved versatile in a broad range of
rhodium(III)-catalyzed transformations12 and in a scandi-
um(III)-catalyzed process.13 However, only a few members
of each family of catalysts have been prepared. Access to
larger libraries of ligands having broadly variable steric de-
mands remains a task of high priority so as to permit adap-
tation to the specific needs of planned applications of the
resulting Cpx–metal complexes in synthesis. In this respect,
we have prepared a set of derivatives of both the first and
the second class of ligands, as well as their rhodium(I) com-
plexes. In addition, we have examined the potential of the
complexes in rhodium(III)-catalyzed asymmetric C–H func-
tionalization reactions involving enantioselective additions
across aldehydes.
DOI: 10.1055/s-0034-1380765; Art ID: st-2015-b0214-l
Abstract The demand for efficient chiral cyclopentadienyl ligands
(Cpx) has increased significantly in recent years, partly because
Cp*Rh(III) species have been developed as powerful catalysts for direct-
ed C–H functionalization reactions. However, a lack of suitable Cpx li-
gands has hampered the development of the corresponding enantiose-
lective processes. We report expansions of the libraries of two
generations of Cpx ligands and their corresponding rhodium(I) com-
plexes. The potential of the rhodium complexes as catalysts was evalu-
ated in enantioselective C–H functionalizations involving cyclizations
across tethered aldehydes. The mild reaction conditions permit the syn-
theses of hydroxychromanes and phthalides in good yields and high en-
antioselectivities.
Key words asymmetric catalysis, ligands, rhodium, cyclizations, het-
erocycles
Cyclopentadienyl-based complexes of metals are widely
used as homogeneous transition-metal catalysts.1 For in-
stance, half-sandwich rhodium(III) complexes bearing a
pentamethylcyclopentadienyl (Cp*) ligand have been ex-
ploited as powerful catalysts for a wide range of C–H func-
tionalization reactions over the past decade.2 Despite their
considerable potential, the corresponding enantioselective
processes remain largely underexplored because of a lack of
suitable and efficient chiral cyclopentadienyl (Cpx) ligands.
Historically, monosubstituted chiral Cpx ligands were re-
ported by Leblanc and Moise3 and by Kagan and co-work-
ers4 in the late 1970s. Halterman and Vollhardt5 and Colletti
and Halterman6 studied C2-symmetric 1,2-disubstituted
Cpx ligands, laying the structural foundations for our con-
temporary ligand systems. After an initial strong interest,7
the whole area remained relatively dormant for a long time,
with only scattered reports.8 In 2012, two complementary
OMe
O
O
OMe
Rh
Rh
1a
2a
2nd generation
1
st generation
Figure 1 Representative chiral Cpx rhodium(I) complexes containing
1,2-disubstituted C2-symmetric Cpx ligands of the first and second gen-
erations
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1490–1495

1491
B. Ye, N. Cramer
Letter
Synlett
For the first generation of Cpx ligands, several variations
on the acetonide bridge were tested in conjunction with
pseudoaxial methyl groups adjacent to the Cp ring. The size
of the steering group R was increased (Et or i-Bu instead of
Me) while the rigidifying trans-acetonide moiety was re-
tained. The required cyclic sulfates were prepared from D-
mannitol,14 and used in a subsequent double-alkylating
step for the preparation of the cyclohexane-fused Cpx li-
gand 3a and 3b (Scheme 1).10 The corresponding rhodi-
um(I) complexes 1b and 1c were isolated in high yields.
OH
OH
OMe
OMe
Ref. 11
5
4a
NaH, RX
CuI, PhI
35 %
1) Tf2O, Et3N
83%
2) cross-coupling
OPh
R
R
R
R
R
O
O
O
O
O
O
O
NaCp
NaH
1) TlOEt
O
O
S
Rh
R
2) [Rh(C2H4)2Cl]2
O
R
R
3a (R = Et), 49%
3b (R = i-Bu), 55%
1b (R = Et), 92%
1c (R = i-Bu), 91%
OPh
R
R
Scheme 1 Preparation of Cpx–rhodium(I) complexes based on cyclo-
4f (R = Me), 76%
4e
4b (R = OBn), 85%
hexane-fused chiral Cpx ligands
4g (R = Bn), 99%
4c (R = OMOM), 92%
4d (R = O(CH2)2Bn), 85%
4h (R = C≡CTIPS), 85%
Modulation of the 3- and 3′-positions of the biaryl scaf-
fold of the second generation of Cpx ligands has been shown
to have a marked effect on both their reactivity and selec-
tivity.11,12 For instance, methoxy, siloxy, or phenyl groups in
these positions have been shown to produce marked differ-
ences in performance. We therefore designed an expanded
set of 3,3′-substituted derivatives. To realize these modifi-
cations conveniently, we used binaphthol 5 as a key inter-
mediate (Scheme 2). The alkoxy-substituted derivatives 4b–
d were obtained in excellent yields by Williamson ether
synthesis. The phenyl ether derivative 4e was prepared by a
copper-catalyzed Ullmann coupling with iodobenzene. Al-
ternatively, the ether linkage was replaced by a C–C bond
through cross-coupling reactions of the bistriflate deriva-
tive of 5. In addition to a previously reported phenyl deriva-
tive,11 the spirocyclic dienes 4f–h bearing methyl, benzyl, or
(triisopropylsilyl)ethynyl groups, respectively, were suc-
cessfully prepared by this approach. All the spiro com-
pounds 4 thermally rearranged to the corresponding cyclo-
pentadienes 6. Subsequent complexation with bis[dichloro-
R
R
R
220 °C
1) TlOEt
4b– h
30–99%
2) [Rh(C2H4)2Cl]2
45–97%
R
Rh
6b–h
2b–h
Scheme 2 Preparation of a library of CpxRh(I) complexes based on
second-generation Cpx ligands
tions of arenes.17 A corresponding enantioselective reaction
remains elusive. Because of our longstanding interest in
asymmetric C–H functionalization processes,18 we decided
to attempt to use our rhodium(III)–Cpx system to prepare
chiral hydroxychromane structures 8 (Scheme 3, B). We
surmised that the problem of the low intrinsic reactivity of
aldehydes might be overcome by an intramolecular cycliza-
tion strategy in which the aldehyde moiety is brought near
the metal atom. On this basis, we evaluated the potential of
our enlarged portfolio of chiral Cpx ligands in the enantiose-
lective cyclization of aldehydes 7. We also hoped that a sub-
sequent lactonization step might expel the hydroxamate di-
recting group directly to give the corresponding phthalides
9, which are widely present as structural motifs in biologi-
cally active compounds.19
We chose the aryl hydroxamate 7a as a model substrate
for the evaluation of the performance of the various Cpx li-
gands. In 1,2-dichloroethane at 50 °C, the achiral complex
[Cp*Rh(OAc)2] gave a 5:1 mixture of hydroxychromane 8a
and phthalide 9a in good overall yield (Table 1, entry 1). Us-
ing this protocol, we investigated the corresponding enanti-
oselective process with our portfolio of CpxRh(I) complexes
after they had been subjected to oxidation in situ with ben-
bis(η2-ethene)rhodium]
corresponding rhodium(I) complexes 2b–h.
{[Rh(C2H4)2Cl]2}
gave
the
The carborhodation of olefins, alkynes, and allenes with
Cp*Rh(III)–C(sp2) species is well known.15 In addition, intra-
molecular reactions permit the use of more highly substi-
tuted and less reactive olefin coupling partners.12b,16 In this
respect, we have previously reported an enantioselective
rhodium(III)-catalyzed hydroarylation involving
a 1,1-
disubstituted alkene tethered through an ether bridge to an
arene core (Scheme 3, A).12b In contrast to olefins, the corre-
sponding addition across a carbonyl group is a rarer process
and there are only a few reported examples, with a limited
scope, of the use of aldehydes as coupling partners in rhodi-
um(III)–Cp* complex-catalyzed C–H functionalization reac-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1490–1495

1492
B. Ye, N. Cramer
Letter
Synlett
(entry 16). Further fine-tuning of the 3,3′-substituents on
the biaryl scaffold revealed that complex 2c bearing me-
thoxymethoxy groups gave the best reaction outcome (en-
tries 17–20). Complexes 2f and 2g, bearing methyl and ben-
zyl groups, respectively, gave similar enantioselectivities
but reduced chemical yields (entries 21 and 22). The phe-
nyl-containing complex 2k gave a slightly higher selectivity,
but resulted in incomplete conversion of the starting mate-
rial (entry 23). A considerably lower selectivity was ob-
served with complex 2h bearing flanking (triisopropylsi-
lyl)ethynyl groups (entry 24).
(A) alkenes as cyclization partners12b
O
OMe
O
HN
OMe
N
2a, (BzO)2
CH2Cl2, 23 °C
H
R1
R1
O
R2
*
R2
O
(B) this work: aldehydes as cyclization partners
O
OR3
HN
*
O
O
OR3
N
CpxRh(C2H4)2
H
O
– R3ONH2
OH
R2 R2
(BzO)2
With the optimized conditions,20 we evaluated the
scope of the reaction by varying the arene core and the
tether (Scheme 4). The reactivity of the substituted arenes
showed a degree of dependence on the structure. As ex-
pected, ortho-substitution decreased the reactivity. The
transformation of substrate 7e, bearing an ortho-methyl
group, required a higher reaction temperature of 50 °C. In
this case, subsequent lactonization gave phthalide 9e as the
major product. With respect to substitution at the position
meta to the hydroxamate directing group, substrates with
electron-rich or halo substituents were well tolerated, giv-
ing the corresponding hydroxychromanes 8f–h in high
yields and good enantioselectivities. A five-fold increase in
scale for 8g gave virtually identical results. Substituents in
the para-position also affected the reactivity, presumably
because of their proximity to the ether tether. Substrate 7k,
with a sterically hindered aldehyde adjacent to a quaterna-
ry carbon atom, readily cyclized to give 8k with no loss in
enantioselectivity. Notably, the transformation failed for
substrate 7l, in which the oxygen atom in the tether is shift-
ed by one position. The phenolic structural motif appears
to be crucial for C–H activation at the congested ortho-posi-
tion.
The versatility and synthetic importance of the phtha-
lide motif19 prompted us devise a one-pot procedure for the
synthesis of the tricyclic phthalide 9f (Scheme 5). When the
formation of hydroxychromane 8f from 7f was complete,
the mixture was heated to 100 °C to give phthalide 9f di-
rectly in 90:10 er. The absolute configuration of the major
enantiomer of 9f was determined to be S by X-ray crystallo-
graphic analysis.21 By analogy, this configuration was at-
tributed to all the major enantiomers of the phthalides and
their hydroxychromane precursors.
R1
R1
R1
*
R2
R2
X
O
X
R2
R2
X
Y
Y
Y
H
7
8
9
Scheme 3 Tethered cyclization partners for demanding enantioselec-
tive rhodium(III)-catalyzed C–H functionalization reactions
zoyl peroxide to give the corresponding rhodium (III) spe-
cies. The cyclohexane-fused complex 1a showed a similar
reactivity to the Cp*-containing complex, giving 8a and 9a
with a moderate enantioselectivity of 72:28 (Entry 2). The
negligible difference in the enantiomeric ratio of products
8a and 9a indicated that the phthalide 9a is formed after
the enantiodetermining step, and that the benzylic alcohol
is configurationally stable under the reaction conditions
used. Next, we evaluated the structurally related complexes
1b and 1c, which have larger substituents R2, but we ob-
served no improvement in the selectivity (entries 3 and 4).
The second-generation Cpx ligand complexes showed a
greater potential in this transformation. Complex 2a, which
has methoxy groups in the 3 and 3′ positions, gave 8a with
an increased enantioselectivity of 80:20 (Entry 5). An initial
inspection of the effect of changing the substituent in the 3-
and 3′-positions of the biaryl ligand scaffold showed that
complex 2i, containing isopropoxy groups, gave a superior
selectivity of 90:10 (entry 6). A further improvement in se-
lectivity was achieved by conducting the reaction at ambi-
ent temperature; this gave hydroxychromane 8a exclusively
in 93:7 er, without formation of the phthalide 9a (entry 8).
The low solubility of the substrate hampered the efficiency
of the reaction. To address this issue, we examined a range
of solvents; however, no better reaction outcomes were
achieved (entries 9–13). This prompted us to investigate the
effects of the nature of the substituent on the hydroxamate
directing group with the goal of improving the solubility
and enhancing the yield. In this respect, hydroxamate 7b,
which contains an N-isopropoxy fragment, resulted in a ho-
mogeneous reaction mixture and gave the corresponding
hydroxychromane 8b in good yield and high enantioselec-
tivity (entries 14 and 15). The phenyl-substituted deriva-
tive 7c failed to react because it was completely insoluble
In summary, we produced an enlarged library of two
families of chiral cyclopentadienyl ligands and their
CpxRh(I) complexes. A straightforward derivatization strat-
egy gave Cpx ligands with widely differing steric properties.
Moreover, we examined their potential in directed rhodi-
um(III)-catalyzed C–H functionalization reactions and sub-
sequent asymmetric additions across carbonyl groups of
tethered aldehydes. The developed protocol permits the
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1490–1495

1493
B. Ye, N. Cramer
Letter
Synlett
Table 1 Optimization of the Cyclizationa
OR1
O
HN
OR1
O
O
N
H
[Rh] (5 mol%)
(BzO)2 (5 mol%)
R2
R2
R2
O
O
O
+
OH
R2
Rh
O
O
Rh
O
O
H
7a (R1 = Me)
7b (R1 = i-Pr)
7c (R1 = Ph)
8a (R1 = Me)
8b (R1 = i-Pr)
8c (R1 = Ph)
9a
1a (R2 = Me)
1b (R2 = Et)
1c (R2 = i-Bu)
2a (R2 = OMe)
2b (R2 = OBn)
2c (R2
2g (R2 = Bn)
2h (R2 = C≡CTIPS)
2i (R2
= OMOM)
= Oi-Pr)
2d (R2 = O(CH2)2Bn) 2j (R2 = OTIPS)
2e (R2 = OPh)
2f (R2 = Me)
2k (R2 = Ph)
Entry
[Rh]
Substrate
Solvent
Temp (°C)
Yieldb (%) of 8
erc
–
Yieldb (%) of 9a
erc
–
1
Cp*Rh(OAc)2
7a
7a
7a
7a
7a
7a
7a
7a
7a
7a
7a
7a
7a
7b
7b
7c
7b
7b
7b
7b
7b
7b
7b
7b
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
PhCl
CCl4
THF
50
50
50
50
50
50
50
23
23
23
23
23
23
23
23
23
23
23
23
23
23
23
23
23
75
70
52
53
51
43
51
20
16
0
15
18
20
15
16
18
18
0
2
1a
1b
1c
2a
2i
71.5:28.5
72:28
3
n.d.d
n.d.
76:24
4
66:34
5
80:20
n.d.
81.5:18.5
6
90:10
7
2j
n.d.
86:14
8
2i
93:7
94.5:5.5
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
9
2i
0
10
11
12
13
14
15
16
17
18e
19
20
21
22
23
24
2i
0
2i
0
–
0
2i
iPrOH
0
–
0
2i
EtC(Me2)OH
DCE
0
–
0
2a
2i
74
74
0
86:14
91.5:8.5
–
0
DCE
0
2i
DCE
0
2b
2c
2d
2e
2f
2g
2k
2h
DCE
75
80f
71
79
70
75
55
53
92:8
92:8
88.5:11.5
88:12
91.5:8.5
92:8
93:7
68.5:31.5
0
DCE
0
DCE
0
DCE
0
DCE
0
DCE
0
DCE
0
DCE
0
a Reaction conditions: 7 (0.05 mmol), [Rh] (2.50 μmol), (BzO)2 (2.50 μmol), 0.10 M in the indicated solvent, r.t., 14 h.
b By 1H NMR spectroscopy with 1,3,5-trimethoxybenzene as the internal standard.
c Determined by HPLC on a chiral stationary phase.
d Not determined.
e 0.10 mmol scale.
f The isolated yield was also 80%.
synthesis of biologically relevant hydroxychromane and
phthalide structures with chiral secondary alcohol func-
tionalities in good yields and high enantioselectivities.
Acknowledgment
This work is supported by the European Research Council under the
European Community’s Seventh Framework Programme (FP7 2007–
2013)/ERC Grant Agreement No. 257891. We thank Dr. R. Scopelliti
for performing the X-ray crystallographic analysis of 9f.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1490–1495

1494
B. Ye, N. Cramer
Letter
Synlett
References and Notes
Oi-Pr
O
HN
O
O
2c (5 mol%)
(BzO)2 (5 mol%)
Oi-Pr
(1) (a) Hartwig, J. Organotransition Metal Chemistry: From Bonding
to Catalysis; University Science Books: Sausalito, 2010.
(b) Crabtree, R. H. The Organometallic Chemistry of the Transi-
tion Metals; 3rd ed, Wiley: New York, 2001.
(2) For selected reviews on Cp*Rh(III)-catalyzed C–H functionaliza-
tions, see: (a) Kuhl, N.; Schröder, N.; Glorius, F. Adv. Synth. Catal.
2014, 356, 1443. (b) Zhang, X.-S.; Chen, K.; Shi, Z.-J. Chem. Sci.
2014, 5, 2146. (c) Song, G.; Wang, F.; Li, X. Chem. Soc. Rev. 2012,
41, 3651. (d) Patureau, F. W.; Wencel-Delord, J.; Glorius, F. Aldri-
chimica Acta 2012, 45, 31. (e) Satoh, T.; Miura, M. Chem. Eur. J.
2010, 16, 11212.
(3) (a) Leblanc, J. C.; Moise, C. J. Organomet. Chem. 1976, 120, 65.
(b) Leblanc, J. C.; Moise, C.; Tirouflet, J. J. Am. Chem. Soc. 1975,
97, 6272.
(4) Cesarotti, E.; Kagan, H. B.; Goddard, R.; Krüger, C. J. Organomet.
Chem. 1978, 162, 297.
(5) Halterman, R. L.; Vollhardt, K. P. C. Tetrahedron Lett. 1986, 27,
1461.
(6) Colletti, S. L.; Halterman, R. L. Tetrahedron Lett. 1989, 30, 3513.
(7) Halterman, R. L. Chem. Rev. 1992, 92, 965.
(8) For selected examples, see: (a) Gutnov, A.; Heller, B.; Fischer, C.;
Drexler, H.-J.; Spannenberg, A.; Sundermann, B.; Sundermann,
C. Angew. Chem. Int. Ed. 2004, 43, 3795. (b) Gutnov, A.; Heller, B.;
Drexler, H.-J.; Spannenberg, A.; Oehme, G. Organometallics
2003, 22, 1550. (c) Li, Z.; Vasella, A. Helv. Chim. Acta 1996, 79,
2201. (d) Erker, G.; Schamberger, J.; van der Zeijden, A. A. H.;
Dehnicke, S.; Krüger, C.; Goddard, R.; Nolte, M. J. Organomet.
Chem. 1993, 459, 107.
N
H
O
or
OH
R2
R2
DCE, 23 °C, 14 h
R1
R1
R1
R2
X
O
X
R2
R2
X
Y
Y
Y
R2
7
8
9
H
Oi-Pr
Me
Oi-Pr
Br HN
O
O
HN
O
O
OH
OH
O
O
O
9e,a 61%, 89:11 er
8d, 45%, 92:8 er
Oi-Pr
8b, 80%, 92:8 er
Oi-Pr
Oi-Pr
HN
HN
HN
Ph
MeO
Br
O
O
O
OH
OH
OH
O
O
O
8g, 98%, 92:8 er
(97%, 91.5:8.5 er)b
8h, 82%, 91.5:8.5 er
8f, 91%, 90.5:9.5 er
Oi-Pr
Oi-Pr
Oi-Pr
Oi-Pr
HN
HN
HN
HN
O
O
O
O
O
O
OH
OH
OH
OH
Br
O
O
Me
O
O
Me
8i,a 54%, 88:12 er
8j, 48%, 92.5:7.5 er
8k, 79%, 87.5:12.5 er
8l, 0%
(9) Hyster, T. K.; Knörr, L.; Ward, T. R.; Rovis, T. Science 2012, 338,
500.
(10) Ye, B.; Cramer, N. Science 2012, 338, 504.
(11) Ye, B.; Cramer, N. J. Am. Chem. Soc. 2013, 135, 636.
(12) (a) Ye, B.; Cramer, N. Angew. Chem. Int. Ed. 2014, 53, 7896.
(b) Ye, B.; Donets, P. A.; Cramer, N. Angew. Chem. Int. Ed. 2014,
53, 507. (c) Zheng, J.; You, S.-L. Angew. Chem. Int. Ed. 2014, 53,
Scheme 4 Scope for the hydroxychromanes. Reagents and conditions: 7
(0.10 mmol), 2c (5.00 μmol), (BzO)2 (5.00 μmol), DCE (0.10 M), r.t.
Yields are of isolated pure products; er values were determined by chiral
HPLC. a Reaction conducted at 50 °C. b Reaction on a 0.5 mmol scale.
13244.
(d) Ye,
B.;
Cramer,
N.
Acc.
Chem.
Res.
2015,10.1021/acs.accounts.5b00092.
(13) Song, G.; O, W. W. N.; Hou, Z. J. Am. Chem. Soc. 2014, 136, 12209.
(14) (a) Li, W.; Zhang, Z.; Xiao, D.; Zhang, X. J. Org. Chem. 2000, 65,
3489. (b) See the Supporting Information for the preparation of
the isobutyl-substituted cyclic sulfate
(15) For selected examples, see: (a) Ueura, K.; Satoh, T.; Miura, M.
Org. Lett. 2007, 9, 1407. (b) Rakshit, S.; Grohmann, C.; Besset, T.;
Glorius, F. J. Am. Chem. Soc. 2011, 133, 2350. (c) Guimond, N.;
Gorelsky, S. I.; Fagnou, K. J. Am. Chem. Soc. 2011, 133, 6449.
(d) Zeng, R.; Fu, C.; Ma, S. J. Am. Chem. Soc. 2012, 134, 9597.
(16) For selected early examples, see: (a) Davis, T. A.; Hyster, T. K.;
Rovis, T. Angew. Chem. Int. Ed. 2013, 52, 14181. (b) Shi, Z.;
Arapinis-Boultadakis, M.; Koester, D. C.; Glorius, F. Chem.
Commun. 2014, 50, 2650.
(17) (a) Lian, Y.; Bergman, R. G.; Ellman, J. A. Chem. Sci. 2012, 3, 3088.
(b) Li, Y.; Zhang, X.-S.; Chen, K.; He, K.-H.; Pan, F.; Li, B.-J.; Shi,
Z.-J. Org. Lett. 2012, 14, 636. (c) Yang, L.; Correia, C. A.; Li, C.-J.
Adv. Synth. Catal. 2011, 353, 1269.
Scheme 5 Direct formation of phthalimide 9f and its absolute configu-
ration
(18) (a) Pedroni, J.; Boghi, M.; Saget, T.; Cramer, N. Angew. Chem. Int.
Ed. 2014, 53, 9064. (b) Tran, D. N.; Cramer, N. Angew. Chem. Int.
Ed. 2013, 52, 10630. (c) Saget, T.; Cramer, N. Angew. Chem. Int.
Ed. 2013, 52, 7865. (d) Saget, T.; Cramer, N. Angew. Chem. Int. Ed.
2012, 51, 12842. (e) Donets, P. A.; Cramer, N. J. Am. Chem. Soc.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1380765.
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© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1490–1495

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B. Ye, N. Cramer
Letter
Synlett
2013, 135, 11772. (f) Saget, T.; Lémouzy, S.; Cramer, N. Angew.
Chem. Int. Ed. 2012, 51, 2238. (g) Tran, D. N.; Cramer, N. Angew.
Chem. Int. Ed. 2011, 50, 11098.
1214, 1181, 1158, 1146, 1112, 1081, 1046, 1022, 980, 950, 906,
890, 840, 819, 803, 786, 760 cm–1; 1H NMR (400 MHz, acetone-
d6): δ = 10.66 (s, 1 H), 7.26–7.19 (m, 1 H), 7.08 (dd, J = 7.4, 1.2
Hz, 1 H), 6.95 (dd, J = 8.3, 1.2 Hz, 1 H), 4.71 (t, J = 3.1 Hz, 1 H),
4.35–4.18 (m, 3 H), 2.02 (q, J = 2.5 Hz, 1 H), 2.00 – 1.91 (m, 1 H),
1.29 (d, J = 6.2 Hz, 3 H), 1.26 (d, J = 6.2 Hz, 3 H); 13C NMR (100
MHz, acetone-d6): δ = 167.5, 155.0, 135.2, 128.7, 124.4, 120.0,
119.7, 77.4, 61.2, 59.7, 20.2, 20.1; HRMS (ESI): m/z [M +
H]+ calcd for C13H18NO4: 252.1230; found: 252.1230; HPLC: Chi-
ralpak IC (4.6 × 250 mm); 20% iPrOH–hexane (1.0 mL/min); 254
nm; tr(minor) = 17.7 min, tr(major) = 15.4 min; 92:8 er.
(19) (a) Beck, J. J.; Chou, S.-C. J. Nat. Prod. 2007, 70, 891. (b) Lin, G.;
Chan, S. S.-K.; Chung, H.-S.; Li, S.-L. Stud. Nat. Prod. Chem. 2005,
32, 611.
(20) (4S)-4-Hydroxy-N-isopropoxychromane-5-carboxamide
(8b): Typical Procedure
A solution of catalyst 2c (3.10 mg, 5.00 μmol) and (BzO)2 (1.20
mg, 5.00 μmol) in anhyd DCE (1.0 mL) was stirred for 15 min at
23 °C and then transferred to a vial containing 7b (26.0 mg, 0.10
mmol). The resulting solution was stirred at 23 °C for 14 h. Vol-
atiles were removed under reduced pressure and the residue
was loaded onto a silica gel column and subjected to gradient
elution with hexane–EtOAc (5:1 to 1:1) to give a colorless film;
yield: 21.0 mg (80%; 92:8 er); [α]D20 –123 (c 1.0, CH2Cl2); Rf =
0.30 (hexane–EtOAc, 1:1); IR (ATR): 3198, 2976, 2932, 2886,
1638, 1592, 1515, 1476, 1449, 1406, 1375, 1354, 1291, 1250,
(21) Crystallographic data for compound 9f have been deposited
with the accession number CCDC 1056306 and can be obtained
free of charge from the Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge CB2 1EZ, UK; Fax:
+44(1223)336033; E-mail: deposit@ccdc.cam.ac.uk; Web site:
www.ccdc.cam.ac.uk/conts/retrieving.html.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1490–1495