α,β-Unsaturated N-Acylindoles: An Alternative Class of Michael Acceptors and Their Application in Asymmetric Borylation

Article abstract of DOI:10.1021/acs.joc.8b00831

Copper(I)-catalyzed enantioselective borylation of α,β-unsaturated N-acylindoles as well as N-acylpyrroles was efficiently achieved by means of bis(pinacolato)diboron (B₂pin₂), affording the enantioenriched products in excellent yields with up to 99% ee. The present work provides an alternative class of Michael acceptors, that is, α,β-unsaturated N-acylindoles, for potential asymmetric transformations.

Full text of DOI:10.1021/acs.joc.8b00831

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Article
#,#-Unsaturated N-Acylindoles: an Alternative Class of Michael
Acceptors and Their Application in Asymmetric Borylation
Quanbin Jiang, Tenglong Guo, Runli Gao, Quannan Wang, Jiang Lou, and Zhengkun Yu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00831 • Publication Date (Web): 25 May 2018
Downloaded from http://pubs.acs.org on May 26, 2018
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α,β-Unsaturated N-Acylindoles: an Alternative Class of Michael Acceptors and
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Their Application in Asymmetric Borylation
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Quanbin Jiang,†,ǁ Tenglong Guo,†,ǁ Runli Gao,≠,ǁ Quannan Wang,†,‡ Jiang Lou,†,‡ and Zhengkun
Yu*,†,§
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† Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023,
People’s Republic of China
≠ State Key Laboratory of NBC Protection for Civilian, Yang Fang Town, Changping District, Beijing
102205, People’s Republic of China
‡ University of Chinese Academy of Sciences, Beijing 100049, People’s Republic of China
§ State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, 354 Fenglin Road, Shanghai 200032, People’s Republic of China
RECEIVED DATE (will be automatically inserted after manuscript is accepted).
_____________________________________________________________________
ABSTRACT: Copper(I)-catalyzed enantioselective borylation of α,β-unsaturated
N-acylindoles as well as N-acylpyrroles was efficiently achieved by means of
bis(pinacolato)diboron (B2pin2), affording the enantioenriched products in excellent
yields with up to 99% ee. The present work provides an alternative class of Michael
acceptors, that is, α,β-unsaturated N-acylindoles, for potential asymmetric
transformations.
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INTRODUCTION
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Enantioselective conjugate additions of nucleophiles to α,β-unsaturated carbonyl
compounds are among the most fundamental and important reactions in organic
synthesis.1 Numerous useful products bearing diverse functional groups can be
obtained due to the broad scopes of the acceptors and donors. As compared to
α,β-unsaturated ketones which have been widely used in asymmetric additions, the
corresponding α,β-unsaturated esters and amides usually exhibit relatively low
reactivities. Thus, a few functional groups have been brought in as ester and amide
surrogates in order to improve their reactivities. In this regard, α,β-unsaturated
oxazolidinones,2 acyl imidazoles,3 acyl pyrrazoles,4 and acyl pyrroles5 have been
reported as the surrogates of α,β-unsaturated esters and amides in asymmetric
transformations. Among the above-mentioned compounds, α,β-unsaturated
N-acylpyrroles are monodentate coordinative acceptors, others are bidentate
coordinative ones. The former has the LUMO energy similar to that of
α,β-unsaturated ketones due to the delocalization of the lone electron pair of the
nitrogen atom into the pyrrolyl ring and the reduced donation to the carbonyl group.6
Therefore, α,β-unsaturated N-acylpyrroles can exhibit reactivity similar to that of
α,β-unsaturated ketones, which is much higher than those of the corresponding esters
and amides. Accordingly, α,β-unsaturated N-acylpyrroles have been widely
investigated as the surrogates of α,β-unsaturated esters and amides in asymmetric
synthesis.5 Indole motifs are more abundant than pyrrole functionalities in bioactive
compounds and natural products, and indole derivatives have become more and more
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attractive in the research areas of materials, agricultural chemicals, and
pharmaceuticals.7 However, only one α,β-unsaturated N-acylindole, that is,
N-cinnamoylindole, has been documented for asymmetric spirannulation to date, and
such a N-acylindole substrate could not behave as an effective acceptor under the
stated conditions.8
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Chiral organoboron derivatives are versatile reagents in organic synthesis,9 and
have been widely used as precursors for the construction of chiral C-O, C-N, and C-C
bonds with the retention of enantiopurity.10 Enantioselective conjugate addition of
diboron reagents to α,β-unsaturated carbonyls and related compounds has emerged as
one of the most powerful tools for the preparation of chiral organoboron compounds
due to the high reactivity and broad applicability of the substrates.9,11 In this area,
copper catalysis12 has been widely applied for asymmetric borylation although other
transition-metal-catalyzed13 and organocatalytic14 methods have also been
documented. Herein, We disclose copper-catalyzed enantioselective borylation of
α,β-unsaturated N-acylindoles with bis(pinacolato)diboron (B2pin2), and
α,β-unsaturated N-acylpyrroles were also explored for the same transformations.
RESULTS AND DISCUSSION
Initially, the Witting5g and Horner–Wadsworth–Emmons (HWE)5f reactions were
utilized to prepare α,β-unsaturated N-acylpyrroles by the literature methods.
Unfortunately, these traditional methods usually suffer from obvious drawbacks such
as use of air- and moisture-sensitive organolithium reagents, anaerobic manipulations,
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time-consuming multistep procedures, and generation of stoichiometric wastes. In this
communication, we used a phase transfer catalysis procedure15 for the synthesis of
α,β-unsaturated N-acylpyrroles and N-acylindoles in the presence of n-Bu4NHSO4
catalyst and NaOH base (eq 1). This method features ready availability of the starting
materials and easy manipulations as compared to the Witting and HWE reactions.
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Then, the reaction of (E)-1-(1H-indol-1-yl)-3-phenylprop-2-en-1-one (1a) with
B2pin2 (2) in a 1.0:1.1 molar ratio was carried out to screen the reaction conditions
(Table 1). In the presence of 5 mol % CuI as the catalyst, and 10 mol % K3PO4 as the
base in t-AmOH at ambient temperature, a range of chiral ligands were tested for the
asymmetric borylation of 1a. In the case of using an axially chiral bisphosphine ligand
such as (R)-BINAP (L1), the target product 3a was obtained in a moderate yield
(41%) with a very low enantioselectivity (Table 1, entry 1). Use of both
(S,S)-Me-Duphos (L2) and (S,S,R,R)-Tangphos (L3) ligands led to 3a in 95% yield,
but the ee values were not satisfactory (Table 1, entries 2 and 3). To our delight, the
chiral ligand with a ferrocenyl backbone, that is, (R,S)-Josiphos (L4), promoted the
reaction to afford the target product in excellent yield (95%) with 95% ee (Table 1,
entry 4). Either of (R)-(S)-NMe2-PPh2-Mandyphos (L5) and (R,R)-Walphos (L6)
ligands did not work well for the reaction (Table 1, entries 5 and 6). Although use of
(R,R)-Taniaphos (L7) resulted in an excellent enantioselectivity (99% ee), the target
product was only formed in 16% yield (Table 1, entry 7). CuI acted as the most
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e cient catalyst as compared to CuCl and CuBr (Table 1, entries 8 and 9). Lowering
the loading of CuI catalyst to 2.5 mol % and the amount of (R,S)-Josiphos to 3.75
mol % obviously deteriorated the reaction e ciency (Table 1, entry 10).
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_____________________________________________________________________
Table 1. Screening of Reaction Conditionsa
entry
[Cu] cat.
ligand
yieldb
(%)
eec
(%)
L1
L2
L3
L4
L5
L6
L7
L4
L4
L4
1
CuI
CuI
41
95
-4
-50
-4
2
3
CuI
95
4
CuI
99 (95)d
22
95
5
CuI
-56
-19
99
6
CuI
25
7
CuI
16
8
CuCl
CuBr
CuI
0
9
79
95
93
10e
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a Conditions: 1a (0.2 mmol), 2 (0.22 mmol), [Cu] (5 mol %), ligand
(7.5 mol %), K3PO4 (10 mol %), t-AmOH (2 mL), 0.1 MPa N2, 25
c
oC, 20 h. b 1H NMR yield using CH2Br2 as the internal standard.
d
Determined by chiral HPLC analysis using an AD-H column.
e
Isolated yield given in parentheses. CuI, 2.5 mol %; ligand, 3.75
mol %; K3PO4, 5 mol %.
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Having established the optimized reaction conditions, we tested a variety of
α,β-unsaturated N-acylindoles (1) to probe into the substrate diversity (Table 2).
N-Acylindoles bearing a methyl group at 3- to 7-positions of the indole ring showed
good reactivities to react with 2, forming the target products 3c-3g in excellent yields
(94-96%) with 92-99% enantioselectivities. The steric hindrance from 2-methyl group
on the indole ring slightly lessened the enantioselectivity, leading to 3b in 96% yield
with 88% ee. 5-Methoxy-substituted N-acylindole (1h) efficiently reacted with 2 to
give 3h (95% yield, 92% ee). 5-Halo-bearing N-acylindoles (halo = F, Cl, Br) reacted
to produce 3i-3k in 93-95% yields with 94-95% ee, demonstrating no substituent
effect from the 5-substituent on the indole ring. Next, α,β-unsaturated N-acylindoles
with various substituents at β-position were investigated. Variation of the methyl
substituent at 4-, 3-, and 2-positions of the β-aryl functionality slightly lessened the
enantioselectivities of products 3l-3n from 93% to 90% ee with 94-96% yields.
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4-OMe, 4-F, and 4-Cl on the β-aryl ring ensured 94-95% ee for products 3o-3q.
Sterically hindered β-(1-naphthyl)-α,β-unsaturated N-acylindole reacted with 2 less
efficiently, affording 3r in 88% yield and 87% ee. β-(2-Thienyl), methyl, ethyl, and
propyl-functionalized substrates also reacted well with 2 to give 3s-3v (80-95% yields,
90-96% ee).
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Table 2. Enantioselective borylation of α,β-unsaturated N-acyl- indoles (1) with 2a,b,c
(S)-3a, 94%, 95% ee
(-)-3d, 96%, 95% ee
(+)-3g, 94%, 92% ee
(+)-3b, 96%, 88% ee
(+)-3e, 94%, 96% ee
(-)-3h, 95%, 92% ee
(-)-3c, 94%, 92% eee
(-)-3f, 96%, 99% ee
(-)-3i, 95%, 94% ee
(-)-3j, 93%, 95% ee
(-)-3k, 93%, 95% ee
(-)-3l, 94%, 93% ee
(-)-3m, 94%, 91% ee
(-)-3n, 96%, 90% eee
(-)-3o, 95%, 94% ee
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(-)-3p, 90%, 95% ee
(-)-3q,d 92%, 94% ee
(+)-3r, 88%, 87% eee
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(-)-3s, 91%, 96% ee
(-)-3t, 95%, 92% ee
(-)-3u, 80%, 92% ee
(-)-3v,d 95%, 90% ee
a Conditions: 1 (0.2 mmol), 2 (0.22 mmol), t-AmOH (2 mL), 25 C, 0.1 MPa N2, 20 h. Yield
refers to the isolated products. c The ee values were determined by chiral HPLC analysis using an
o
b
d
AD-H column. 60 oC. e Determined by chiral HPLC analysis of the corresponding β-hydroxy
compound by oxidation with sodium perborate.
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In a similar manner, α,β-unsaturated N-acylpyrroles (4) were investigated in the
asymmetric borylation with 2 (Table 3). β-Aryl-N-acylpyrroles could efficiently react
with 2 under the standard conditions, giving the target products 5a-5c, and 5e-5g in
83-95% yields with excellent enantioselectivities (94-96% ee). Only in the case of
using the substrate bearing a β-(2-methyl)phenyl moiety (4d), the reaction efficiency
was slightly deteriorated to form 5d (87%) with 90% ee. The lower
enantioselectivities of 3b, 3n, 3r, and 5d may be due to the steric hindrance of
substrates. A minor steric effect was also observed from β-(1-naphthyl) in product 5h.
The N-acylpyrroles containing a β-(2-thienyl) or β-methyl functionality efficiently
underwent the reactions to form 5i (92%, 96% ee) and 5j (93%, 92% ee), respectively.
However, β-ethyl and propyl obviously lessened the reaction efficiencies to afford 5k
(73%, 84% ee) and 5l (77%, 90% ee).
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Table 3. Enantioselective borylation of α,β-unsaturated N-acylpyrroles (4) with 2a,b,c
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5 mol % CuI
7.5 mol % (R,S)-Josiphos
O
O
Bpin
R3
B2pin2
R3
N
+
N
10 mol % K3PO4
t-AmOH, 25 oC, 20 h
2
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(S)-5a, 95%, 95% ee
(+)-5d, 87%, 90% eee
(+)-5g,d 83%, 94% ee
(-)-5j, 93%, 92% ee
(+)-5b, 93%, 94% ee
(+)-5c, 92%, 94% ee
(+)-5f, 94%, 96% ee
(-)-5i, 92%, 96% ee
(+)-5e, 93%, 96% ee
(+)-5h,d 86%, 91% ee
(-)-5k, 73%, 84% ee
O
Bpin
Pr
N
(-)-5l,d 77%, 90% ee
a Conditions: 4 (0.2 mmol), 2 (0.22 mmol), t-AmOH (2 mL), 25 C, 0.1 MPa N2, 20 h. Yield
refers to the isolated products. c The ee values were determined by chiral HPLC analysis using an
o
b
d
AD-H column. 60 oC. e Determined by chiral HPLC analysis of the corresponding β-hydroxy
compound by oxidation with sodium perborate.
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Because the enantiomers of products 3c, 3n, 3r, and 5d could not be separated
on the chiral HPLC columns, they were converted to the corresponding β-hydroxy
compounds through oxidation with sodium perborate in order to determine the ee
values. Retention of the enantiopurity during this transformation was confirmed by
oxidizing compounds 3a to 6a, and 5a to 6e (Table 4). Similar transformations were
thus conducted for 3c, 3n, 3r, and 5d, affording the corresponding deborylated chiral
products, that is, chiral β-hydroxy-amides 6b-6d and 6f, in good to excellent yields
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(76-90%) with retention of enantiopurities (88-92%). Additional transformations were
also conducted to demonstrate the utility of compounds 3 and 5 as ester and amide
surrogates. However, treatment of 3a or 5a with NaOMe only led to trace amount of
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1
the target methyl esters through H NMR analysis of the reaction mixtures, which is
presumably attributed to the unstability of the borylated products under the strong
basic conditions. To our delight, the reactions of 3a and 5a with pyrrolidine gave the
corresponding amide 7 in good yields (71-80%) with rentention of the
enantioselectivities (eq 2). Compound 7 was assigned to be (S)-configuration by
comparison of its optical rotation with the reported data.12j Thus, chiral 3a and 5a
were assigned to be (S)-configuration, and the configurations of other chiral products
were assigned by analogy.
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Table 4. Oxidative deborylation of compounds 3 and 5a,b,c
(-)-6a from (-)-3a, 90%, 95% ee
(-)-6b from (-)-3c, 89%, 92% ee
(-)-6c from (-)-3n, 76%, 90% ee
(-)-6d from (+)-3r, 90%, 87% ee
(-)-6e from (S)-5a, 89%, 94% ee (-)-6f from (+)-5d, 87%, 90% ee
a Conditions: 3 or 5 (0.2 mmol), THF (1 mL), H2O (1 mL), 25 oC, 2 h. b Yields refer to the isolated
products. c The ee values were determined by chiral HPLC analysis using an AD-H column.
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Control reactions were performed to determine the reactivity difference between
α,β-unsaturated N-acylindoles and N-acylpyrroles. An equimolar mixture of 1a and
4a was reacted with 2 under the standard conditions to give a mixture of 3a (39%)
and 5a (42%) (eq 3), revealing that the α,β-unsaturated N-acylindole and
N-acylpyrrole have a similar reactivity in the asymmetric borylation reaction.
Although 3a reacted with pyrrolidine to afford 7 in a relative high yield (80% vs 71%)
than the same reaction of 5a did under the standard conditions (eq 2), the competition
reactions of 3a and 5a with pyrrolidine suggested that compound 5a reacted much
faster than 3a (eq 4). The asymmetric borylation reactions of α,β-unsaturated ketone 8
and ester 9 with 2 were also conducted under the standard conditions (eq 5), forming
the target products 10 and 11 in 78-79% yields with 84-90% ee which are much lower
than those from the reactions of the corresponding N-acylindoles and N-acylpyrroles
(Tables 3 and 4). These results have demonstrated the unique reactivity of
N-acylindoles and N-acylpyrroles as Michael acceptors.
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A plausible mechanism is proposed in Scheme 1.16 The copper(I) salt initially
reacts with B2pin2 (2) in the presence of a chiral phosphine ligand to generate
Cu(I)-Bpin species A. Addition of A to α,β-unsaturated N-acylindole (1) or
N-acypyrrole (4) leads to the organocopper(I) intermediate B. Subsequent protonation
of B with the alcohol solvent t-AmOH affords the target product 3 or 5 with release of
copper(I) alkoxide C. Interaction of species C with 2 regenerates the catalytically
active species A to accomplish the catalytic cycle.
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Scheme 1. Proposed mechanism
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In conclusion, copper-catalyzed enantioselective borylation of α,β-unsaturated
N-acylindoles and N-acylpyrroles with bis(pinacolato)diboron has been developed.
Under the mild conditions, chiral organoboron compounds were obtained in high
yields and enantioselectivities. This work provides an alternative class of Michael
acceptors for conjugate additions.
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EXPERIMENTAL SECTION
General Considerations. The solvents were dried and distilled prior to use by the
literature methods. 1H and 13C spectra were recorded on a 400 MHz NMR
spectrometer.
In the 13C NMR data, for many of the B-containing compounds, the
signal to noise ratio was low for the carbon atom bound to Boron, which appear as
broad signals likely due to quadrupolar relaxation.12j As a result, we have not assigned
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a value for the chemical shift in the tabulated C NMR data below. HRMS data was
obtained by ESI on a Q-TOF mass spectrometer. Enantiomeric excess was determined
by chiral HPLC analysis. Optical rotations were measured by an olarimeter. All the
chemical reagents were purchased from commercial sources and used as received
unless otherwise indicated. Compounds 1a,17 1c,18 1e,17 1h-1k,17 1o,17 1t,19 4a,5g 4b,5g
4c,20 4d,20 4e,5g 4f,5e 4g,5g 4h,5g 4i,5g 4j,21 4k,22 4l,5f ,712j ,1023 ,1124 were known and
their spectroscopic features are in good agreement with those reported in the
literatures.
General Procedure for the Synthesis of α,β-unsaturated N-acylindoles 1 and
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pyrroles 4. Indole or pyrrole (2.0 mmol) and n-Bu4NHSO4 (340 mg, 1.0 mmol) were
dissolved in CH2Cl2 (10 mL). Powdered NaOH (200 mg, 5.0 mmol) was added, and
then α,β-unsaturated acyl chloride (3.0 mmol) in CH2Cl2 (5 mL) was introduced
dropwise to the vigorously stirring solution. Stirring was continued at ambient
temperature for 12 h. All the volatiles were evaporated under reduced pressure. The
resulting residue was purification by silica gel column chromatography to afford the
desired product 1 or 4.
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(E)-1-(2-Methyl-1H-indol-1-yl)-3-phenylprop-2-en-1-one (1b). 256 mg, 49% yield;
yellow solid, mp 112-114 °C; 1H NMR (400 MHz, CDCl3) δ 7.92 (d, J = 15.7 Hz, 1 H,
7.78-7.75 (m, 1 H), 7.65-7.63 (m, 2 H), 7.52-7.50 (m, 1 H), 7.47-7.45 (m, 3 H),
7.28-7.21 (m, 3 H), 6.42 (s, 1 H), 2.67 (s, 3 H); 13C NMR (100 MHz, CDCl3) δ 166.4,
145.7, 137.7, 136.2, 134.6, 130.9, 129.9, 129.2, 128.5, 123.1, 122.9, 121.4, 120.2,
114.4, 108.6, 16.3; HRMS (ESI) calcd for C18H16NO [M+H]+ 262.1226, found
262.1230.
(E)-1-(4-Methyl-1H-indol-1-yl)-3-phenylprop-2-en-1-one (1d). 256 mg, 49% yield;
yellow solid, mp 98-100 °C; 1H NMR (400 MHz, CDCl3) δ 8.53 (d, J = 8.3 Hz, 1 H),
7.99 (d, J = 15.4 Hz, 1 H), 7.62-7.60 (m, 3 H), 7.45-7.40 (m, 3 H), 7.37-7.33 (m, 1 H),
7.19 (d, J = 15.4 Hz, 1 H), 7.15 (d, J = 7.3 Hz, 1 H, aromatic CH), 6.71 (d, J = 3.5 Hz,
1 H), 2.57 (s, 3 H); 13C NMR (100 MHz, CDCl3) δ 164.0, 146.1, 135.5, 134.2, 130.5,
130.1, 128.8, 128.2, 124.9, 124.1, 124.0, 117.0, 114.3, 107.3, 18.4; HRMS (ESI) calcd
for C18H16NO [M+H]+ 262.1226, found 262.1232.
(E)-1-(6-Methyl-1H-indol-1-yl)-3-phenylprop-2-en-1-one (1f). 219 mg, 42% yield;
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yellow solid, mp 63-65 °C; H NMR (400 MHz, CDCl3) δ 8.48 (s, 1 H), 8.00 (d, J =
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15.4 Hz, 1 H), 7.64-7.62 (m, 2 H), 7.56 (d, J = 3.8 Hz, 1 H), 7.50 (d, J = 7.9 Hz, 1 H),
7.45-7.44 (m, 3 H), 7.22 (d, J = 15.4 Hz, 1 H), 7.17 (d, J = 7.9 Hz, 1 H), 6.66 (d, J =
3.7 Hz, 1 H), 2.55 (s, 3 H); 13C NMR (100 MHz, CDCl3) δ 164.2, 146.3, 136.3, 135.1,
134.4, 130.7, 129.0, 128.4, 125.3, 124.0, 120.5, 117.3, 117.1, 109.1, 22.0; HRMS
(ESI) calcd for C18H16NO [M+H]+ 262.1226, found 262.1235.
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(E)-1-(7-Methyl-1H-indol-1-yl)-3-phenylprop-2-en-1-one (1g). 282 mg, 54% yield;
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yellow solid, mp 105-107 °C; H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 15.6 Hz, 1
H), 7.65 (s, 2 H), 7.55-7.47 (m, 5 H), 7.30-7.26 (m, 1 H), 7.23-7.16 (m, 2 H), 6.69 (s,
1 H), 2.62 (s, 3 H ); 13C NMR (100 MHz, CDCl3) δ 164.3, 146.6, 135.2, 134.3, 132.2,
130.9, 129.1, 126.2, 128.5, 127.8, 126.8, 124.0, 119.4, 118.8, 108.4, 22.1; HRMS
(ESI) calcd for C18H16NO [M+H]+ 262.1226, found 262.1233.
(E)-1-(1H-indol-1-yl)-3-(p-tolyl)prop-2-en-1-one (1l). 480 mg, 92% yield; yellow
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solid, mp 120-122 °C; H NMR (400 MHz, CDCl3) δ 8.62 (d, J = 8.3 Hz, 1 H), 7.98
(d, J = 15.4 Hz, 1 H), 7.64-7.61 (m, 2 H), 7.52 (d, J = 8.0 Hz, 2 H), 7.41 (t, J = 7.4 Hz,
1 H), 7.33 (t, J = 7.4 Hz, 1 H), 7.23 (d, J = 7.9 Hz, 2 H), 7.18 (d, J = 15.4 Hz), 6.69 (d,
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J = 3.7 Hz), 2.40 (s, 3 H); C NMR (100 MHz, CDCl3) δ 164.4, 146.5, 141.3, 136.0,
131.7, 130.6, 129.8, 128.4, 124.9, 124.7, 123.7, 120.9, 116.9, 116.1, 109.0, 21.5;
HRMS (ESI) calcd for C18H16NO [M+H]+ 262.1226, found 262.1228.
(E)-1-(1H-indol-1-yl)-3-(m-tolyl)prop-2-en-1-one (1m). 433 mg, 83% yield; pale
yellow solid, mp 100-102 °C; 1H NMR (400 MHz, CDCl3) δ 8.65 (d, J = 8.2 Hz, 1 H),
7.98 (d, J = 15.4 Hz, 1 H) 7.65-7.62 (m, 2 H), 7.43-7.41 (m, 3 H), 7.33 (td, J = 7.5,
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2.6 Hz, 2 H), 7.26 (s, 1 H), 7.21 (d, J = 15.4 Hz, 1 H), 6.70 (d, J = 3.5 Hz, 1 H), 2.42
(s, 3 H); 13C NMR (100 MHz, CDCl3) δ 164.2, 146.6, 138.6, 135.9, 134.3, 131.6,
130.6, 129.0, 128.9, 125.6, 124.9, 124.7, 123.7, 120.9, 116.89, 116.86, 109.0, 21.3;
HRMS (ESI) calcd for C18H16NO [M+H]+ 262.1226, found 262.1232.
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(E)-1-(1H-indol-1-yl)-3-(o-tolyl)prop-2-en-1-one (1n). 277 mg, 53% yield; yellow
solid, mp 58-59 °C; 1H NMR (400 MHz, CDCl3) δ 8.58 (d, J = 8.3 Hz, 1 H), 8.31 (d, J
= 15.3 Hz, 1 H), 7.69 (d, J = 7.7 Hz, 1 H), 7.66 (d, J = 3.8 Hz, 1 H), 7.62 (d, J = 7.7
Hz, 1 H), 7.41 (t, J = 7.6 Hz, 1 H), 7.35-7.30 (m, 2 H), 7.27 (d, J = 7.2 Hz, 2 H), 7.17
(d, J = 15.3 Hz, 1 H), 6.71 (d, J = 3.7 Hz, 1 H), 2.52 (s, 3 H); 13C NMR (100 MHz,
CDCl3) δ 164.4, 144.4, 138.3, 136.1, 133.6, 131.1, 130.7, 130.6, 126.5, 125.2, 124.7,
123.9, 121.0, 118.5, 116.9, 109.3, 20.0; HRMS (ESI) calcd for C18H16NO [M+H]+
262.1226, found 262.1234.
(E)-3-(4-Fluorophenyl)-1-(1H-indol-1-yl)prop-2-en-1-one (1p). 445 mg, 84%
yield; white solid, mp 106-108 °C; 1H NMR (400 MHz, CDCl3) δ 8.56 (d, J = 8.1 Hz,
1 H), 7.93 (d, J = 15.4 Hz, 1 H), 7.62-7.57 (m, 4 H), 7.41-7.37 (m, 1 H), 7.31 (td, J =
7.6, 1.0 Hz, 1 H), 7.15-7.07 (m, 3 H), 6.68 (d, J = 3.6 Hz, 1 H); 13C NMR (100 MHz,
CDCl3) δ 164.2 (d, J = 250.6 Hz), 164.1 (Cq, C=O), 145.2, 136.0, 130.73 (d, J = 3.3
Hz), 130.69, 130.4 (d, J = 8.7 Hz), 125.1, 124.6, 123.9, 121.0, 116.9, 116.2 (d, J =
21.8 Hz), 109.3, 117.0 (d, J = 2.0 Hz); HRMS (ESI) calcd for C17H13FNO [M+H]+:
266.0976, found 266.0985.
(E)-3-(4-Chlorophenyl)-1-(1H-indol-1-yl)prop-2-en-1-one (1q). 337 mg, 60%
yield; white solid, mp 119-121 °C; 1H NMR (400 MHz, CDCl3) δ 8.49 (d, J = 8.2 Hz,
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1 H), 7.87 (d, J = 15.4 Hz, 1 H), 7.57-7.54 (m, 2 H), 7.50 (d, J = 8.4 Hz, 2 H),
7.36-7.32 (m, 3 H), 7.28-7.21 (m, 1 H), 7.15 (d, J = 15.4 Hz, 1 H), 6.65 (d, J = 3.8 Hz,
1 H); 13C NMR (100 MHz, CDCl3) δ 164.0, 145.1, 136.8, 136.0, 133.0, 130.7, 129.6,
129.4, 125.2, 124.6, 124.0, 121.1, 117.9, 116.9, 109.4; HRMS (ESI) calcd for
C17H13ClNO [M+H]+ 282.0680, found 282.0677.
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(E)-1-(1H-indol-1-yl)-3-(naphthalen-1-yl)prop-2-en-1-one (1r). 315 mg, 53%
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yield; yellow solid, mp 146-148 °C; H NMR (400 MHz, CDCl3) δ 8.85 (d, J = 15.2
Hz, 1 H), 8.63 (d, J = 8.2 Hz, 1 H), 8.28 (d, J = 8.3 Hz, 1 H), 7.96-7.86 (m, 3 H), 7.68
(d, J = 3.6 Hz, 1 H), 7.64-7.52 (m, 4 H), 7.43 (t, J = 7.7 Hz, 1 H), 7.35-7.26 (m, 2 H),
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6.72 (d, J = 3.6 Hz, 1 H); C NMR (100 MHz, CDCl3) δ 164.2, 143.7, 136.1, 133.8,
132.0, 131.7, 131.1, 130.8, 128.9, 127.2, 126.5, 125.5, 125.3, 125.2, 124.7, 124.0,
123.5, 121.1, 120.1, 117.0, 109.4; HRMS (ESI) calcd for C21H16NO [M+H]+
298.1226, found 298.1229.
(E)-1-(1H-indol-1-yl)-3-(thiophen-2-yl)prop-2-en-1-one (1s). 364 mg, 72% yield.
pale yellow solid, mp 107-109 °C; 1H NMR (400 MHz, CDCl3) δ 8.54 (d, J = 8.3 Hz,
1 H), 8.11 (d, J = 15.1 Hz, 1 H), 7.63-7.59 (m, 2 H), 7.45 (d, J = 5.0 Hz), 7.40-7.37
(m, 2 H), 7.30 (t, J = 7.4 Hz), 7.11 (t, J = 4.3 Hz), 7.03 (d, J = 15.1 Hz), 6.70 (d, J =
3.7 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ 164.1, 139.8, 139.1, 136.0, 132.2, 130.8,
129.1, 128.5, 125.1, 124.7, 123.9, 121.0, 117.0, 115.9, 109.2; HRMS (ESI) calcd for
C15H12NOS [M+H]+ 254.0634, found 254.0637.
(E)-1-(1H-indol-1-yl)pent-2-en-1-one (1u). 115 mg, 29% yield; yellow liquid; 1H
NMR (400 MHz, CDCl3) δ 8.39 (d, J = 8.3 Hz, 1 H), 7.45 (d, J = 7.7 Hz, 1 H), 7.41 (d,
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J = 3.7 Hz, 1 H), 7.26-7.13 (m, 3 H), 6.53-6.49 (m, 2 H), 2.29-2.22 (m, 2 H), 1.05 (t, J
= 7.4 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 164.5, 153.0, 136.0, 130.7, 125.0,
124.8, 123.8, 120.9, 120.0, 116.9, 109.0, 26.0, 12.4; HRMS (ESI) calcd for C13H14NO
[M+H]+ 200.1070, found 200.1074.
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(E)-1-(1H-indol-1-yl)hex-2-en-1-one (1v). 256 mg, 60% yield; colorless liquid; 1H
NMR (400 MHz, CDCl3) δ 8.53 (d, J = 8.3 Hz, 1 H), 7.60 (d, J = 7.7 Hz, 1 H), 7.57 (d,
J = 3.8 Hz, 1 H), 7.41-7.37 (m, 1 H), 7.33-7.28 (m, 2 H), 6.70-6.66 (m, 2 H), 2.37 (qd,
J = 7.2, 1.5 Hz, 2 H), 1.67-1.57 (m, 2H), 1.03 (t, J = 7.4 Hz, 3 H); 13C NMR (100
MHz, CDCl3) δ 164.4, 151.6, 136.0, 130.7, 125.0, 124.8, 123.8, 121.1, 120.9, 116.9,
109.0, 34.9, 21.6, 13.9; HRMS (ESI) calcd for C14H16NO [M+H]+ 214.1226, found
214.1222.
A typical procedure for the enantioselective borylation of α,β-unsaturated
N-acylindoles (1) and N-acylpyrroles (4) with B2pin2 (2) − Synthesis of (S)-3a.
Under a nitrogen atmosphere, a mixture of CuI (1.9 mg, 0.01 mmol), (R,S)-JosiPhos
(9.6 mg, 0.015 mmol), and K3PO4 (4.2 mg, 0.02 mmol) in t-AmOH (1 mL) was
stirred at ambient temperature for 30 min, followed by the addition of B2pin2 (2) (56
mg, 0.22 mmol) in t-AmOH (0.5 mL). After the mixture was stirred at ambient
temperature for 10 min, (E)-1-(1H-indol-1-yl)-3-phenylprop- 2-en-1-one (1a) (49 mg,
0.2 mmol) in t-AmOH (0.5 mL) was added. The resultant mixture was stirred at
ambient temperature for 20 h, filtered through a short pad of celite, and rinsed with 20
mL EtOAc. All the volatiles were removed under reduced pressure, the resulting
residue was purified by silica gel column chromatography (eluent: petroleum ether
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(60-90 oC)/EtOAc = 50:1, v/v) to afford (S)-3a as a white solid (71 mg, 95%).
(S)-1-(1H-indol-1-yl)-3-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pro
pan-1-one (3a). 71 mg, 95% yield; 95% ee, [α]20D = -23.4 (c 1.0 CHCl3); white solid,
mp 90-92 °C; 1H NMR (400 MHz, CDCl3) δ 8.53 (d, J = 8.2 Hz, 1 H), 7.59 (d, J = 7.7
Hz, 1 H), 7.46 (d, J = 3.5 Hz, 1 H), 7.40-7.25 (m, 7 H), 6.63 (d, J = 3.6 Hz, 1 H), 3.55
(dd, J = 17.2, 11.2 Hz, 1 H), 3.32 (dd, J = 17.2, 5.1 Hz, 1 H), 2.97 (dd, J = 11.1, 5.0
Hz, 1 H, CH), 1.32 and 1.24 (s each, 6:6 H); 13C NMR (100 MHz, CDCl3) δ 171.3,
141.2, 135.7, 130.4, 128.7, 128.5, 126.0, 125.0, 124.7, 123.6, 120.8, 116.6, 109.0,
83.7, 40.1, 24.7, 24.5; HRMS (ESI) calcd for C23H27BNO3 [M+H]+ 376.2079, found
376.2084; HPLC (AD-H, elute: Hexanes/i-PrOH = 98/2, detector: 220 nm, flow rate:
0.7 mL/min), t1 = 7.3 min (maj.), t2 = 8.0 min.
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(+)-1-(2-Methyl-1H-indol-1-yl)-3-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborola
n-2-yl)propan-1-one (3b). 75 mg, 96% yield; 88% ee, [α]20D = +5.0 (c 1.0 CHCl3);
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white solid, mp 100-102 °C; H NMR (400 MHz, CDCl3) δ 8.02-8.00 (m, 1 H),
7.47-7.45 (m, 1 H), 7.36-7.31 (m, 4 H), 7.24-7.21 (m, 3 H), 6.37 (s, 1 H), 3.59 (dd, J
= 17.0, 11.4 Hz, 1 H), 3.38 (dd, J = 17.0, 4.9 Hz, 1 H), 2.93 (dd, J = 11.3, 4.8 Hz, 1 H),
2.65 (s, 3 H), 1.27 and 1.20 (s each, 6:6 H); 13C NMR (100 MHz, CDCl3) δ 173.5,
141.3, 137.7, 136.4, 129.9, 128.7, 128.5, 125.9, 123.5, 123.0, 119.8, 115.6, 109.6,
83.5, 43.4, 24.6, 24.5, 17.9; HRMS (ESI) calcd for C24H29BNO3 [M+H]+ 390.2235,
found 390.2243; HPLC (AD-H, elute: Hexanes/i-PrOH = 99/1, detector: 254 nm, flow
rate: 0.5 mL/min), t1 = 13.2 min (maj.), t2 = 14.6 min.
(-)-1-(3-Methyl-1H-indol-1-yl)-3-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborola
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n-2-yl)propan-1-one (3c). 73 mg, 94% yield; 92% ee, [α]20D = -20.2 (c 1.0 CHCl3);
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white solid, mp 137-139 °C; H NMR (400 MHz, CDCl3) δ 8.48 (d, J = 7.5 Hz, 1 H),
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11.2 Hz, 1 H), 3.28 (dd, J = 17.2, 5.2 Hz, 1 H), 2.94 (dd, J = 11.1, 5.1 Hz, 1 H), 2.28
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(s, 3 H), 1.29 and 1.21 (s each, 6:6 H); C NMR (100 MHz, CDCl3) δ 170.9, 141.4,
136.0, 131.4, 128.7, 128.5, 125.9, 125.1, 123.3, 121.7, 118.8, 118.2, 116.7, 83.7, 40.2,
24.7, 24.6, 9.8; HRMS (ESI) calcd for C24H29BNO3 [M+H]+ 390.2235, found:
390.2238; enantioselectivity was determined by chiral HPLC analysis of the
corresponding β-hydroxy compound (-)-6a by oxidation of (-)-3c with sodium
perborate.
(-)-1-(4-Methyl-1H-indol-1-yl)-3-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborola
n-2-yl)propan-1-one (3d). 75 mg, 96% yield; 95% ee, [α]20D = -7.2 (c 1.0 CHCl3);
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white solid, mp 103-105 °C; H NMR (400 MHz, CDCl3) δ 8.32 (d, J = 8.3 Hz, 1 H),
7.47 (d, J = 3.8 Hz, 1 H), 7.37-7.19 (m, 6 H), 7.09 (d, J = 7.3 Hz, 1 H), 6.67 (d, J =
3.8 Hz, 1 H), 3.53 (dd, J = 17.2, 11.2 Hz, 1 H), 3.31 (dd, J = 17.2, 5.1 Hz, 1 H), 2.94
(dd, J = 11.2, 5.1 Hz, 1 H), 2.54 (s, 3 H), 1.28 and 1.20 (s each, 6:6 H); 13C NMR (100
MHz, CDCl3) δ 171.4, 141.3, 135.5, 130.3, 130.0, 128.8, 128.5, 126.0, 125.2, 124.2,
124.0, 114.2, 107.4, 83.7, 40.2, 24.7, 24.6, 18.6; HRMS (ESI) calcd for C24H29BNO3
[M+H]+ 390.2235, found 390.2239; HPLC (AD-H, elute: Hexanes/i-PrOH = 99.2/0.8,
detector: 254 nm, flow rate: 0.7 mL/min), t1 = 13.1 min, t2 = 14.3 min (maj.).
(+)-1-(5-Methyl-1H-indol-1-yl)-3-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborola
n-2-yl)propan-1-one (3e). 73 mg, 94% yield; 96% ee, [α]20D = +33.9 (c 1.0 CHCl3);
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white solid, mp 142-144 °C; 1H NMR (400 MHz, CDCl3) δ 8.37 (d, J = 8.2 Hz, 1 H),
7.43 (d, J = 3.2 Hz, 1 H), 7.36-7.32 (m, 5 H), 7.24-7.17 (m, 2 H), 6.55 (d, J = 3.6 Hz,
1 H), 3.52 (dd, J = 17.1, 11.2 Hz, 1 H), 3.30 (dd, J = 17.2, 5.1 Hz, 1 H), 2.95 (dd, J =
11.1, 5.0 Hz, 1 H), 2.47 (s, 3 H), 1.29 and 1.21 (s each, 6:6 H); 13C NMR (100 MHz,
CDCl3) δ 171.1, 141.3, 133.9, 133.1, 130.6, 128.8, 128.6, 126.4, 126.0, 124.8, 120.8,
116.3, 108.8, 83.7, 40.0, 24.7, 24.6, 21.5; HRMS (ESI) calcd for C24H29BNO3 [M+H]+
390.2235, found 390.2243; HPLC (AD-H, elute: Hexanes/i-PrOH = 99/1, detector:
254 nm, flow rate: 0.7 mL/min), t1 = 9.3 min (maj.), t2 = 11.0 min.
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(-)-1-(6-Methyl-1H-indol-1-yl)-3-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborola
n-2-yl)propan-1-one (3f). 75 mg, 96% yield; 99% ee, [α]20D = -3.0 (c 1.0 CHCl3);
white solid, mp 117-119 °C. 1H NMR (400 MHz, CDCl3) δ 8.32 (s, 1 H), 7.43 (d, J =
7.9 Hz, 1 H), 7.39 (d, J = 3.6 Hz, 1 H), 7.35-7.29 (m, 4 H), 7.22-7.18 (m, 1 H), 7.10
(d, J = 7.9 Hz, 1 H), 6.56 (d, J = 3.6 Hz, 1 H), 3.50 (dd, J = 17.1, 11.0 Hz, 1 H), 3.29
(dd, J = 17.2, 5.2 Hz, 1 H), 2.93 (dd, J = 10.9, 5.1 Hz, 1 H), 2.49 (s, 3 H), 1.27 and
1.19 (s each, 6:6 H); 13C NMR (100 MHz, CDCl3) δ 171.3, 141.3, 136.1, 135.1, 128.7,
128.5, 128.1, 126.0, 125.0, 124.1, 120.4, 116.9, 108.9, 83.7, 40.0, 24.7, 24.6, 22.0;
HRMS (ESI) calcd for C24H29BNO3 [M+H]+ 390.2235, found 390.2242; HPLC
(AD-H, elute: Hexanes/i-PrOH = 99/1, detector: 254 nm, flow rate: 0.7 mL/min), t1 =
10.0 min, t2 = 12.6 min (maj.).
(+)-1-(7-Methyl-1H-indol-1-yl)-3-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborola
n-2-yl)propan-1-one (3g). 73 mg, 94% yield; 92% ee, [α]20D = +7.8 (c 1.0 CHCl3);
white solid, mp 113-115 °C; 1H NMR (400 MHz, CDCl3) δ 7.44 (d, J = 3.7 Hz, 1 H),
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7.41 (d, J = 7.5 Hz, 1 H), 7.36-7.31 (m, 4 H), 7.24-7.14 (m, 3 H), 6.60 (d, J = 3.6 Hz,
1 H), 3.54 (dd, J = 16.8, 10.6 Hz, 1 H), 3.35 (dd, J = 16.8, 5.5 Hz, 1 H), 2.97 (dd, J =
10.5, 5.5 Hz, 1 H), 2.57 (s, 3 H), 1.28 and 1.23 (s each, 6:6 H); 13C NMR (100 MHz,
CDCl3) δ 170.6, 141.3, 135.3, 132.0, 128.8, 128.6, 128.1, 126.8, 126.2, 126.0, 124.0,
118.5, 108.9, 83.8, 40.6, 24.8, 24.5, 23.0; HRMS (ESI) calcd for C24H29BNO3 [M+H]+
390.2235, found 390.2243; HPLC (AD-H, elute: Hexanes/i-PrOH = 99/1, detector:
220 nm, flow rate: 0.7 mL/min), t1 = 14.4 min, t2 = 16.6 min (maj.).
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(-)-1-(5-Methoxy-1H-indol-1-yl)-3-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborol
an-2-yl)propan-1-one (3h). 77 mg, 95% yield; 92% ee, [α]20D = -35.2 (c 1.0 CHCl3);
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white solid, mp 156-158 °C; H NMR (400 MHz, CDCl3) δ 8.37 (d, J = 8.8 Hz, 1 H),
7.43 (d, J = 3.3 Hz, 1 H), 7.35-7.29 (m, 4 H), 7.22-7.19 (m, 1 H), 7.03 (d, J = 2.1 Hz,
1 H), 6.96 (dd, J = 9.0, 2.2 Hz, 1 H), 6.54 (d, J = 3.6 Hz, 1 H), 3.86 (s, 3 H), 3.49 (dd,
J = 17.1, 11.2 Hz, 1 H), 3.28 (dd, J = 17.1, 5.1 Hz, 1 H), 2.92 (dd, J = 11.1, 5.1 Hz, 1
H), 1.27 and 1.19 (s each, 6:6 H); 13C NMR (100 MHz, CDCl3) δ 171.1, 156.5, 141.3,
131.4, 130.5, 128.8, 128.5, 126.0, 125.4, 117.4, 113.5, 108.9, 103.6, 83.7, 55.8, 39.9,
24.7, 24.6; HRMS (ESI) calcd for C24H29BNO4 [M+H]+ 406.2184, found 406.2187;
HPLC (AD-H, elute: Hexanes/i-PrOH = 98/2, detector: 254 nm, flow rate: 0.7
mL/min), t1 = 10.4 min (maj.), t2 = 12.2 min.
(-)-1-(5-Fluoro-1H-indol-1-yl)-3-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborola
n-2-yl)propan-1-one (3i). 75 mg, 95% yield; 94% ee, [α]20D = -12.8 (c 0.5 CHCl3);
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white solid, mp 128-130 °C; H NMR (400 MHz, CDCl3) δ 8.43 (dd, J = 8.9, 4.7 Hz,
1 H), 7.50 (d, J = 3.7 Hz, 1 H), 7.34-7.29 (m, 4 H), 7.22-7.20 (m, 2 H), 7.08-7.03 (m,
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1 H), 6.57 (d, J = 3.7 Hz, 1 H), 3.50 (dd, J = 17.2, 11.1 Hz, 1 H), 3.29 (dd, J = 17.2,
5.2 Hz, 1 H), 2.91 (dd, J = 11.0, 5.1 Hz, 1 H), 1.26 and 1.18 (s each, 6:6 H); 13C NMR
(100 MHz, CDCl3) δ 171.1, 159.6 (d, J = 238.4 Hz), 141.1, 132.1, 131.3 (d, J = 10.0
Hz), 128.8, 128.5, 126.2, 126.0, 117.6 (d, J = 9.0 Hz), 112.7 (d, J = 24.6 Hz), 108.6 (d,
J = 3.9 Hz), 106.3 (d, J = 23.7 Hz), 83.7, 39.8, 24.6, 24.5; HRMS (ESI) calcd for
C23H26BFNO3 [M+H]+ 394.1984, found: 394.1989; HPLC (AD-H, elute:
Hexanes/i-PrOH = 98/2, detector: 220 nm, flow rate: 0.7 mL/min), t1 = 6.6 min (maj.),
t2 = 7.2 min.
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(-)-1-(5-Chloro-1H-indol-1-yl)-3-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborola
n-2-yl)propan-1-one (3j). 76 mg, 93% yield; 95% ee, [α]20D = -14.7 (c 1.0 CHCl3);
white solid, mp 121-123 °C; 1H NMR (400 MHz, CDCl3) δ 8.41 (d, J = 8.8 Hz, 1 H),
7.52 (d, J = 2.0 Hz, 1 H), 7.47 (d, J = 3.7 Hz, 1 H), 7.33-7.28 (m, 5 H), 7.23-7.19 (m,
1 H), 6.55 (d, J = 3.7 Hz, 1 H), 3.50 (dd, J = 17.2, 11.1 Hz, 1 H), 3.28 (dd, J = 17.3,
5.2 Hz, 1 H), 2.92 (dd, J = 11.0, 5.2 Hz, 1 H, CH), 1.27 and 1.19 (s each, 6:6 H); 13C
NMR (100 MHz, CDCl3) δ 171.3, 141.1, 134.1, 131.6, 129.2, 128.8, 128.5, 126.1,
126.0, 125.2, 120.5, 117.7, 108.3, 83.8, 40.0, 24.7, 24.6; HRMS (ESI) calcd for
C23H26BClNO3 [M+H]+ 410.1689, found 410.1698; HPLC (AD-H, elute:
Hexanes/i-PrOH = 99/1, detector: 254 nm, flow rate: 0.7 mL/min), t1 = 14.8 min
(maj.), t2 = 21.0 min.
(-)-1-(5-Bromo-1H-indol-1-yl)-3-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborola
n-2-yl)propan-1-one (3k). 84 mg, 93% yield; 95% ee, [α]20D = -15.9 (c 1.0 CHCl3);
white solid, mp 132-133 °C; 1H NMR (400 MHz, CDCl3) δ 8.35 (d, J = 8.8 Hz, 1 H),
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7.69 (d, J = 1.9 Hz, 1 H), 7.46 (d, J = 3.8 Hz, 1 H), 7.43 (dd, J = 8.8, 1.9 Hz, 1 H),
7.33-7.29 (m, 4 H), 7.20 (ddd, J = 8.5, 5.9, 2.9 Hz, 1 H), 6.55 (d, J = 3.7 Hz, 1 H),
3.49 (dd, J = 17.2, 11.0 Hz, 1 H), 3.28 (dd, J = 17.3, 5.2 Hz, 1 H), 2.91 (dd, J = 11.0,
5.2 Hz, 1 H), 1.26 and 1.18 (s each, 6:6 H); 13C NMR (100 MHz, CDCl3) δ 171.3,
141.1, 134.5, 132.1, 128.8, 128.5, 127.9, 126.1, 125.9, 123.6, 118.1, 116.9, 108.2,
83.8, 40.0, 24.7, 24.6; HRMS (ESI) calcd for C23H26BBrNO3 [M+H]+ 454.1184,
found 454.1187; HPLC (AD-H, elute: Hexanes/i-PrOH = 99/1, detector: 254 nm, flow
rate: 0.7 mL/min), t1 = 9.0 min (maj.), t2 = 10.6 min.
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(-)-1-(1H-indol-1-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(p-tolyl)pr
opan-1-one (3l). 73 mg, 94% yield; 93% ee, [α]20D = -8.3 (c 1.0 CHCl3); white solid,
mp 132-134 °C; 1H NMR (400 MHz, CDCl3) δ 8.52 (d, J = 8.2 Hz, 1 H), 7.59 (d, J =
7.6 Hz, 1 H), 7.47 (d, J = 3.8 Hz, 1 H), 7.39-7.35 (m, 1 H), 7.29-7.26 (m, 3 H), 7.16
(d, J = 7.8 Hz, 2 H), 6.63 (d, J = 3.6 Hz, 1 H), 3.52 (dd, J = 17.2, 11.1 Hz, 1 H), 3.30
(dd, J = 17.2, 5.2 Hz, 1 H), 2.93 (dd, J = 11.1, 5.1 Hz, 1 H), 2.36 (s, 3 H), 1.31 and
1.23 (s each, 6:6 H); 13C NMR (100 MHz, CDCl3) δ 171.4, 138.1, 135.8, 135.4, 130.4,
129.5, 128.4, 125.0, 124.7, 123.6, 120.9, 116.7, 109.0, 83.7, 40.3, 24.7, 24.6, 21.1;
HRMS (ESI) calcd for C24H29BNO3 [M+H]+ 390.2235, found 390.2237; HPLC
(AD-H, elute: Hexanes/i-PrOH = 99/1, detector: 254 nm, flow rate: 0.5 mL/min), t1 =
11.5 min (maj.), t2 = 12.9 min.
(-)-1-(1H-indol-1-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(m-tolyl)p
ropan-1-one (3m). 73 mg, 94% yield; 91% ee, [α]20D = -2.7 (c 1.0 CHCl3); white solid,
mp 104-105 °C; 1H NMR (400 MHz, CDCl3) δ 8.50 (d, J = 8.2 Hz, 1 H), 7.58 (d, J =
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7.6 Hz, 1 H), 7.48 (d, J = 3.8 Hz, 1 H), 7.38-7.34 (m, 1 H), 7.30-7.26 (m, 1 H),
7.25-7.21 (m, 1 H), 7.17-7.15 (m, 2 H), 7.04 (d, J = 7.4 Hz, 1 H), 6.63 (d, J = 3.8 Hz,
1 H), 3.52 (dd, J = 17.2, 11.3 Hz, 1 H), 3.30 (dd, J = 17.2, 5.1 Hz, 1 H), 2.91 (dd, J =
11.3, 5.1 Hz, 1 H), 2.37 (s, 3 H), 1.29 and 1.21 (s each, 6:6 H); 13C NMR (100 MHz,
CDCl3) δ 171.4, 141.1, 138.3, 135.8, 130.4, 129.4, 128.7, 126.8, 125.5, 125.1, 124.8,
123.6, 120.9, 116.7, 109.0, 83.7, 40.2, 24.7, 24.6, 21.6; HRMS (ESI) calcd for
C24H29BNO3 [M+H]+ 390.2235, found 390.2228; HPLC (AD-H, elute:
Hexanes/i-PrOH = 99/1, detector: 254 nm, flow rate: 0.7 mL/min), t1 = 8.1 min (maj.),
t2 = 8.9 min.
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(-)-1-(1H-indol-1-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(o-tolyl)pr
opan-1-one (3n). 75 mg, 94% yield; 90% ee, [α]20D = -8.8 (c 1.0 CHCl3); white solid,
mp 84-86 °C; 1H NMR (400 MHz, CDCl3) δ 8.51 (d, J = 8.2 Hz, 1 H), 7.58 (d, J = 7.7
Hz, 1 H), 7.47 (d, J = 3.7 Hz, 1 H), 7.38-7.34 (m, 2 H), 7.30-7.27 (t, J = 7.5 Hz, 1 H),
7.21-7.17 (t, J = 7.7 Hz, 2 H), 7.14-7.11 (t, J = 7.1 Hz, 1 H), 6.63 (d, J = 3.7 Hz, 1 H),
3.51 (dd, J = 17.0, 10.9 Hz, 1 H), 3.24 (dd, J = 17.0, 4.8 Hz, 1 H), 3.18 (dd, J = 10.9,
4.8 Hz, 1 H), 2.44 (s, 3 H), 1.29 and 1.21 (s each, 6:6 H); 13C NMR (100 MHz, CDCl3)
δ 171.5, 139.6, 136.6, 135.8, 130.8, 130.4, 127.9, 126.3, 125.9, 125.1, 124.8, 123.6,
120.9, 116.7, 109.0, 83.7, 39.5, 24.8, 24.6, 20.2. HRMS (ESI) calcd for C24H29BNO3
[M+H]+ 390.2235, found 390.2238; enantioselectivity was determined by chiral
HPLC analysis of the corresponding β-hydroxy compound (-)-6b by oxidation of
(-)-3n with sodium perborate.
(-)-1-(1H-indol-1-yl)-3-(4-methoxyphenyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaboro
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lan-2-yl)propan-1-one (3o). 77 mg, 95% yield; 94% ee, [α]20D = -12.5 (c 1.0 CHCl3);
White solid, mp 147-148 °C; 1H NMR (400 MHz, CDCl3) δ 8.50 (d, J = 8.2 Hz, 1 H),
7.57 (d, J = 7.7 Hz, 1 H), 7.46 (d, J = 3.7 Hz, 1 H), 7.37-7.33 (m, 1 H), 7.29-7.26 (m,
3 H), 6.88 (d, J = 8.6 Hz, 2 H), 6.61 (d, J = 3.7 Hz, 1 H), 3.80 (s, 3 H), 3.48 (dd, J =
17.2, 11.0 Hz, 1 H), 3.28 (dd, J = 17.2, 5.3 Hz, 1 H), 2.89 (dd, J = 10.9, 5.2 Hz, 1 H),
1.29 and 1.21 (s each, 6:6 H); 13C NMR (100 MHz, CDCl3) δ 171.4, 158.0, 135.7,
133.1, 130.4, 129.4, 125.0, 124.7, 123.5, 120.8, 116.7, 114.2, 108.9, 83.7, 55.3, 40.4,
24.7, 24.6; HRMS (ESI) calcd for C24H29BNO4 [M+H]+ 406.2184, found 406.2183;
HPLC (AD-H, elute: Hexanes/i-PrOH = 98/2, detector: 254 nm, flow rate: 0.5
mL/min), t1 = 13.8 min (maj.), t2 = 14.9 min.
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(-)-3-(4-Fluorophenyl)-1-(1H-indol-1-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborola
n-2-yl)propan-1-one (3p). 71 mg, 90% yield; 95% ee, [α]20D = -13.5 (c 0.2 CHCl3);
white solid, mp 130-132 °C; 1H NMR (400 MHz, CDCl3) δ 8.49 (d, J = 8.2 Hz, 1 H),
7.57 (d, J = 7.7 Hz, 1 H), 7.45 (d, J = 3.7 Hz, 1 H), 7.38-7.25 (m, 4 H), 7.04-6.99 (m,
4 H), 6.62 (d, J = 3.8 Hz, 1 H), 3.47 (dd, J = 17.2, 10.8 Hz, 1 H), 3.28 (dd, J = 17.2,
5.4 Hz, 1 H), 2.92 (dd, J = 10.7, 5.3 Hz, 1 H), 1.29 and 1.21 (s each, 6:6 H); 13C NMR
(100 MHz, CDCl3) δ 171.1, 161.4 (d, J = 242.3 Hz), 136.9 (d, J = 3.2 Hz), 135.7,
130.4, 129.9 (d, J = 7.7 Hz), 125.1, 124.7, 123.6, 120.9, 116.7, 115.5 (d, J = 21.0 Hz),
109.1, 83.8, 40.1, 24.7, 24.6; HRMS (ESI) calcd for C23H26BFNO3 [M+H]+ 394.1984,
found 394.1990; HPLC (AD-H, elute: Hexanes/i-PrOH = 99/1, detector: 254 nm, flow
rate: 0.7 mL/min), t1 = 8.7 min (maj.), t2 = 9.7 min.
(-)-3-(4-Chlorophenyl)-1-(1H-indol-1-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborola
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n-2-yl)propan-1-one (3q). 75 mg, 92% yield; 94% ee, [α]20D = -6.4 (c 0.5 CHCl3);
white solid, mp 135-137 °C; 1H NMR (400 MHz, CDCl3) δ 8.46 (d, J = 8.2 Hz, 1 H),
7.57 (d, J = 7.6 Hz, 1 H), 7.46 (d, J = 3.8 Hz, 1 H), 7.37-7.33 (m, 1 H), 7.30-7.26 (m,
5 H), 6.63 (d, J = 3.7 Hz, 1 H), 3.48 (dd, J = 17.2, 10.7 Hz, 1 H), 3.29 (dd, J = 17.2,
5.4 Hz, 1 H), 2.90 (dd, J = 10.7, 5.4 Hz, 1 H), 1.27 and 1.20 (s each, 6:6 H); 13C NMR
(100 MHz, CDCl3) δ 171.1, 139.8, 135.8, 131.8, 130.4, 129.9, 128.9, 125.2, 124.6,
123.7, 121.0, 116.7, 109.2, 83.9, 39.9, 24.7, 24.6; HRMS (ESI) calcd for
C23H26BClNO3 [M+H]+ 410.1689, found 410.1700; HPLC (AD-H, elute:
Hexanes/i-PrOH = 98/2, detector: 254 nm, flow rate: 0.7 mL/min), t1 = 16.0 min
(maj.), t2 = 18.0 min.
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(+)-1-(1H-indol-1-yl)-3-(naphthalen-1-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborol
an-2-yl)propan-1-one (3r). 75 mg, 88% yield; 87% ee, [α]20D = +18.9 (c 1.0 CHCl3);
white solid, mp 124-126 °C; 1H NMR (400 MHz, CDCl3) δ 8.57 (d, J = 8.2 Hz, 1 H),
8.30 (d, J = 8.3 Hz, 1 H), 7.90 (d, J = 7.8 Hz, 1 H), 7.77 (d, J = 8.1 Hz, 1 H),
7.60-7.46 (m, 5 H), 7.41-7.38 (m, 2 H), 7.32-7.28 (m, 1 H), 6.59 (d, J = 3.7 Hz, 1 H),
3.79 (dd, J = 10.9, 4.5 Hz, 1 H), 3.67 (dd, J = 17.0, 10.9 Hz, 1 H), 3.40 (dd, J = 17.0,
4.5 Hz, 1 H), 1.35 and 1.24 (s each, 6:6 H); 13C NMR (100 MHz, CDCl3) δ 171.4,
137.9, 135.8, 134.3, 132.1, 130.4, 129.0, 126.9, 126.1, 125.9, 125,74, 125,68 125.1,
124.7, 124.0, 123.6, 120.9, 116.7, 109.0, 83.9, 39.8, 24.8, 24.6; HRMS (ESI) calcd for
C27H29BNO3 [M+H]+ 426.2235, found 426.2238; enantioselectivity was determined
by chiral HPLC analysis of the corresponding β-hydroxy compound (-)-6c by
oxidation of (+)-3r with sodium perborate.
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2-yl)propan-1-one (3s). 69 mg, 91% yield; 96% ee, [α]20D = -56.0 (c 0.1 CHCl3);
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white solid, mp 99-101 °C; H NMR (400 MHz, CDCl3) δ 8.48 (d, J = 8.1 Hz, 1 H),
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7.57 (d, J = 7.6 Hz, 1 H), 7.47 (d, J = 3.4 Hz, 1 H), 7.37-7.34 (m, 1 H), 7.29-7.26 (m,
1 H), 7.14 (d, J = 4.7 Hz, 1 H), 6.97-6.95 (m, 2 H), 6.63 (d, J = 3.6 Hz, 1 H), 3.51 (dd,
J = 17.1, 10.6 Hz, 1 H), 3.41 (dd, J = 17.2, 5.1 Hz, 1 H), 3.22 (dd, J = 10.4, 5.1 Hz, 1
H), 1.31 and 1.25 (s each, 6:6 H); 13C NMR (100 MHz, CDCl3) δ 170.8, 143.9, 135.8,
130.4, 127.1, 125.2, 124.7, 123.7, 123.4, 120.9, 116.7, 109.2, 84.1, 40.9, 24.8, 24.6;
HRMS (ESI) calcd for C21H25BNO3S [M+H]+ 382.1643, found 382.1646; HPLC
(AD-H, elute: Hexanes/i-PrOH = 99/1, detector: 254 nm, flow rate: 0.7 mL/min), t1 =
9.5 min (maj.), t2 = 10.6 min.
(-)-1-(1H-indol-1-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butan-1-one
(3t). 59 mg, 95% yield; 92% ee, [α]20D = -27.5 (c 0.1 CHCl3); white solid, mp 96-97
°C; 1H NMR (400 MHz, CDCl3) δ 8.49 (d, J = 8.2 Hz, 1 H), 7.56 (d, J = 7.7 Hz, 1 H),
7.48 (d, J = 3.8 Hz, 1 H), 7.37-7.32 (m, 1 H), 7.28-7.24 (m, 1 H), 6.61 (d, J = 3.7 Hz,
1 H), 3.09-2.98 (m, 2 H), 1.63-1.53 (m, 1 H), 1.29 and 1.27 (s each, 6:6 H), 1.15 (d, J
= 7.5 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 171.7, 135.7, 130.4, 125.0, 124.8,
123.5, 120.8, 116.7, 108.7, 83.3, 39.8, 24.8, 24.7, 15.2. HRMS (ESI) calcd for
C18H25BNO3 [M+H]+ 314.1922, found 314.1926; HPLC (AD-H, elute:
Hexanes/i-PrOH = 99/1, detector: 254 nm, flow rate: 0.7 mL/min), t1 = 6.8 min (maj.),
t2 = 7.6 min.
(-)-1-(1H-indol-1-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pentan-1-one
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(3u). 52 mg, 80% yield; 92% ee, [α]20D = -37.3 (c 1.0 CHCl3); white solid, mp 75-77
°C. 1H NMR (400 MHz, CDCl3) δ 8.47 (d, J = 8.2 Hz, 1 H), 7.56 (d, J = 7.7 Hz, 1 H),
7.51 (d, J = 3.7 Hz, 1 H), 7.36-7.32 (m, 1 H), 7.28-7.24 (m, 1 H), 6.62 (d, J = 3.8 Hz,
1 H), 3.11-3.00 (m, 2 H), 1.69-1.58 (m, 1 H), 1.56-1.46 (m, 2 H), 1.28 and 1.26 (s
each, 6:6 H), 1.02 (t, J = 7.3 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 172.0, 135.8,
130.4, 125.0, 124.9, 123.5, 120.8, 116.7, 108.8, 83.3, 37.7, 24.9, 24.8, 23.6, 13.6;
HRMS (ESI) calcd for C19H27BNO3 [M+H]+ 328.2079, found 328.2087; HPLC (two
AD-H series, elute: Hexanes/i-PrOH = 99/1, detector: 254 nm, flow rate: 0.7 mL/min),
t1 = 22.1 min (maj.), t2 = 27.2 min.
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(-)-1-(1H-indol-1-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexan-1-one
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(3v). 65 mg, 95% yield; 90% ee, [α]20D = -38.2 (c 1.0 CHCl3); Colorless liquid; H
NMR (400 MHz, CDCl3) δ 8.48 (d, J = 8.2 Hz, 1 H), 7.57 (d, J = 7.7 Hz, 1 H), 7.51 (d,
J = 3.8 Hz, 1 H), 7.36-7.32 (m, 1 H), 7.28-7.24 (m, 1 H), 6.62 (d, J = 3.8 Hz, 1 H),
3.22-2.89 (m, 2 H), 1.63-1.51 (m, 2 H), 1.50-1.38 (m, 3 H), 1.28 and 1.25 (s each, 6:6
H), 0.95 (t, J = 7.1 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 172.0, 135.8, 130.4,
125.0, 124.9, 123.5, 120.8, 116.7, 108.8, 83.3, 37.9, 32.8, 24.9, 24.8, 22.2, 14.4.
HRMS (ESI) calcd for C20H29BNO3 [M+H]+ 342.2235, found 342.2230; HPLC
(AD-H, elute: Hexanes/i-PrOH = 98/2, detector: 254 nm, flow rate: 0.7 mL/min), t1 =
7.9 min (maj.), t2 = 9.2 min.
(+)-3-Phenyl-1-(1H-pyrrol-1-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)p
ropan-1-one (5a). 62 mg, 95% yield; 95% ee, [α]20D = +18.4 (c 0.5 CHCl3); white
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solid, mp 65-66 °C; H NMR (400 MHz, CDCl3) δ 7.32-7.27 (m, 6 H), 7.23-7.16 (m,
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