Photoredox-Catalyzed Ketyl-Olefin Coupling for the Synthesis of Substituted Chromanols

Article abstract of DOI:10.1021/acs.joc.6b01006

A visible light photoredox-catalyzed aldehyde olefin cyclization is reported. The method represents a formal hydroacylation of alkenes and alkynes and provides chromanol derivatives in good yields. The protocol takes advantage of the double role played by trialkylamines (NR₃) which act as (i) electron donors for reducing the catalyst and (ii) proton donors to activate the substrate via a proton-coupled electron transfer.

Full text of DOI:10.1021/acs.joc.6b01006

Brief Communication
pubs.acs.org/joc
Photoredox-Catalyzed Ketyl−Olefin Coupling for the Synthesis of
Substituted Chromanols
Eleonora Fava,†,‡ Masaki Nakajima,† Anh L. P. Nguyen,† and Magnus Rueping*,†,‡
†RWTH Aachen University, Institute of Organic Chemistry, Landoltweg 1, 52074, Aachen, Germany
‡King Abdullah University of Science and Technology (KAUST), KAUST Catalysis Center (KCC), Thuwal, 23955-6900, Saudi
Arabia
S
* Supporting Information
ABSTRACT: A visible light photoredox-catalyzed aldehyde
olefin cyclization is reported. The method represents a formal
hydroacylation of alkenes and alkynes and provides chromanol
derivatives in good yields. The protocol takes advantage of the
double role played by trialkylamines (NR3) which act as (i)
electron donors for reducing the catalyst and (ii) proton
donors to activate the substrate via a proton-coupled electron
transfer.
Knowles and co-workers reported a catalytic protocol in
arbon−carbon and carbon−heteroatom bond-forming
Creactions represent powerful transformations useful for which ketones are successfully reduced to ketyl radicals by the
concerted transfer of both a proton and an electron.11b This
the assembly of simple as well as sophisticated molecular
phenomenon is named proton-coupled electron transfer
(PCET).15
architectures. Among the variety of established methods
reported so far, the generation of ketyl radical species by the
reductive umpolung reaction of carbonyl derivatives and their
application in carbon−carbon bond-forming reactions repre-
sents an appealing route for the preparation of complex
molecules. The ketyl−olefin coupling, as first described by
Molander and Kenny,1 was promoted by samarium diiodide as
a stoichiometric single-electron reducing agent and enhanced
by its large reduction potential (up to −2.05 V in the presence
of HMPA).2 Alternatively, organotin compounds as reducing
agents have been used in either stoichiometric3,4 or catalytic
amounts,5 in this case requiring an additional metal hydride.
Other relevant procedures involve the use of zinc/trimethyl-
chlorosilane as reagent,6 or titanocene complexes,7 well-known
as pinacol-coupling promoters. Among the ketyl−olefin
couplings reported, the major protocols imply the use of
stoichiometric amounts of (transition) metals.8
In an attempt to demonstrate the active role of proton
donors in the reduction step, Knowles and co-workers also
reported an asymmetric aza-pinacol cyclization of ketones and
hydrazones where the binding effect of the chiral phosphoric
acids led to the formation of enantioenriched vicinal amino
alcohols.11c
Recently, our group described the photoredox-catalyzed
pinacol coupling of aldehydes, ketones, and aldimines through
hydrogen-bonding activation.12a With this work, we disclose the
possibility of generating a long-lived ketyl radical using tertiary
amines as the electron and proton source, replacing the
combination of Hantzsch ester and diphenyl phosphate (DPP).
Based on our previous work,12a we envisioned the possibility
of performing the ketyl radical addition on unsaturated bonds
triggered by visible light, which would initiate the single-
electron reduction from a photoexcited polypyridyl iridium
complex to a carbonyl group (aldehyde or ketone). We
postulated that the so-generated radical intermediate would be
able to undergo subsequent intramolecular addition to a
pendant alkene or alkyne moiety (Scheme 1).
Recently, the possibility of generating ketyl radicals by visible
light activation9−13 was shown to be a feasible alternative to the
common methods, avoiding the use of toxic and/or environ-
mentally unfriendly reducing reagents and yet enabling access
to a wide range of complex alcohols. However, the reduction of
Herein, we report the realization of this activation mode in
the context of a catalytic intramolecular reductive coupling of
aldehydes with alkenes and alkynes. This transformation allows
the synthesis of substituted 3-benzylchroman-4-ols (5),
containing a chroman unit, that exhibit anti picornavirus
red
aldehydes (E1/2 = −2.17 V vs Ag/AgNO3 for benzalde-
hydes),14 possessing an exceptionally negative redox potential,
represents an obstacle for the most commonly employed visible
light photocatalysts. In this context, Pandey reported the
visible-light-promoted one-electron reductive activation of
aldehydes and ketones and their intramolecular addition to
activated olefins (five examples) with a system consisting of
DCA (9,10-dicyanoanthracene) and PPh3 or DCA, DMN (1,5-
dimethoxynaphthalene) and ascorbic acid.11a
Special Issue: Photocatalysis
Received: April 30, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.6b01006
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Brief Communication
a c
−
Scheme 1. Photoredox-Catalyzed Reduction of Aldehydes
through PCET
Table 1. Scope of the Reaction
activity, commonly responsible for the upper respiratory tract
infections in humans.16
Remarkably, we observed that tertiary amines not only
provided the desired products in higher yields but also proved
to be crucial for the reaction to proceed.
We began our studies by evaluating conditions for the
cyclization of 2-(cinnamyloxy)benzaldehyde (1a) to chromanol
2a in the presence of Ir(ppy)2(dtb-bpy)PF6 (PC 3, 1 mol %),
trialkylamines 4a−c as reductive quencher (RQ), and
irradiation with a blue LED light source (11W, λmax = 450
nm). As shown in Table S1 (Supporting Information), the
reaction proceeded with good yield in the presence of 2.5 equiv
of tributylamine (4b, entry 5). Solvent evaluation confirmed
acetonitrile to be the best solvent, whereas aprotic (entries 1
and 2) and protic (entry 3) polar solvents were shown to be
unsuccessful as reaction media. Further screening of electron
donors in acetonitrile confirmed Hunig base (4c) to be the best
̈
among the trialkylamines tested, providing the desired product
in 80% yield (entry 6). As previously mentioned, the use of
Hantzsch esters 5a and 5b alone or in combination with 10 mol
% of DPP did not lead to the expected product (entries 7−10).
A series of control experiments demonstrated that the reaction
did not take place in the absence of light, catalyst, or 3. With
the optimized conditions in hand (acetonitrile, rt, 1 mol % PC
3), we began to evaluate a variety of substrates (Table 1).
As shown in Table 1, the reaction tolerates a wide variety of
substituents, confirming the ability of the ketyl radical to couple
to the olefin in the presence of both electron-withdrawing and
-donating groups on the aromatic aldehyde moiety.
Following the development of a successful formal hydro-
acylation we investigated the reaction in which the olefin was
replaced by an alkyne group (Table 2). Also in this case, the
reaction gave the expected products (2o and 2p) in good
yields.
a
All reactions of 1 (0.12 mmol) with DIPEA (0.3 mmol) were carried
out in the presence of PC 3 (1 mol %) in acetonitrile (3.0 mL) under
irradiation with blue LEDs (11 W, 450 nm) for 15 h at 25 °C.
Isolated yields are reported. The dr is given for anti/syn ratio.
Reaction performed using 2.5 mol % of photocatalyst.
b
c
Regarding the reaction mechanism, we propose the
following: Irradiation with visible light results in the formation
d
of the reductive species Ir2+. Hunig base (i-Pr NEt) acts as a
̈
2
CONCLUSIONS
sacrificial electron donor; therefore, the single-electron
oxidation weakens the adjacent C−H bond17 and the 1,2-H-
shift becomes energetically favored. The following deprotona-
tion through the tertiary amine provides the ammonium
derivative, which is now able to engage in a proton-coupled
electron transfer with the substrate, lowering its potential for
Ir2+ reduction and generation of a neutral ketyl intermediate.
Alternatively, the ammonium radical could also activate the
carbonyl functionality. The ketyl radical is able to add to the
unsaturated bond, forming the chroman ring and a benzyl
radical which upon hydrogen atom transfer leads to the final
product (Scheme 2).
■
In conclusion, we report a ketyl−olefin coupling for the
preparation of substituted 3-benzylchroman-4-ols, promoted by
visible light photoredox catalysis. Importantly, we uncovered
trialkylamines as a cheap and readily available alternative to the
previously reported electron−proton donor system consisting
of Hantzsch ester/Brønsted acid. By employing the trialkyl-
amine/photocatalyst system, we have been able to develop an
efficient intramolecular ketyl−olefin and ketyl−alkyne coupling
employing readily prepared substrates. The formal hydro-
acylation protocol provides the chromanol derivatives in good
yield under mild reaction conditions and with low catalyst
B
DOI: 10.1021/acs.joc.6b01006
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Brief Communication
δ. For the F-containing compound (2c), a simultaneously proton and
fluorine decoupled 13C NMR spectrum was recorded. Assignments are
aided by the use of DEPT-135, COSY and HMQC spectra where
necessary. IR spectra were recorded on a FTIR spectrometer. Low
resolution mass spectra (EI/CI) were recorded on a mass
spectrometer with (EI) or (CI) detectors. High-resolution mass
spectrometry (HRMS) was performed by EI using a double-focusing
mass spectrometer and by ESI using a hybrid ion-trap mass
spectrometer. Melting points were recorded at ambient pressure and
are uncorrected.
General Procedure for the Synthesis of Chromanols. A
Schlenk tube was charged with aldehyde 1 (1 equiv), catalyst PC 3 (1
or 2.5 mol %), and degassed DIPEA (2.5 equiv). It was capped,
evacuated, and backfilled with argon. Subsequently, degassed
acetonitrile (3 mL) was added via syringe. The vial was placed in a
100 mL beaker containing a blue LED strip glued on the inner wall,
and the reaction mixture was stirred for 15 h. After this time, the
solvent was evaporated, and the reaction mixture was purified on silica
gel (gradient pentane/EtOAc 95:5).
Table 2. Scope of the Intramolecular Ketyl−Alkyne
a
Cyclization
b
entry
product
yield (%)
E/Z
1
2
Ar = m-MePh (2o)
Ar = p-OMePh (2p)
57
59
1:1
1:1
a
All reactions of 1 (0.12 mmol) with DIPEA (0.3 mmol) were carried
out in the presence of PC 3 (2.5 mol %) in acetonitrile (3.0 mL) under
irradiation with blue LEDs (11 W, 450 nm) for 18 h at 25 °C.
b
Isolated yields are reported.
loadings. Efforts are currently underway to expand this concept
3-Benzylchroman-4-ol (2a).18 The title compound was synthesized
according to the general procedure employing 1a (0.12 mmol, 28.6
mg), 1 mol % (1.1 mg) of PC 3, and 2.5 equiv of DIPEA (38.8 mg).
The product was purified by flash column chromatography: yield 80%
(23 mg); anti/syn 1:1; 1H NMR (600 MHz, CDCl3) δ 7.34−7.18 (m,
14H), 6.96 (td, J = 7.5, 0.9 Hz, 1H), 6.90 (dd, J = 10.6, 4.2 Hz, 2H),
6.85 (d, J = 8.5 Hz, 1H), 4.51 (dd, J = 9.4, 3.1 Hz, 2H), 4.23 (dd, J =
11.1, 2.6 Hz, 1H), 4.14−4.05 (m, 2H), 3.98 (dd, J = 11.1, 4.2 Hz, 1H),
2.89 (dd, J = 13.8, 8.4 Hz, 1H), 2.75−2.64 (m, 2H), 2.54 (dd, J = 13.8,
9.3 Hz, 1H), 2.40−2.29 (m, 1H), 2.28−2.17 (m, 1H), 1.92 (bs, 1H),
1.74 (bs, 1H); 13C NMR (151 MHz, CDCl3) δ 154.3, 154.2, 139.2,
139.1, 130.2, 130.1, 129.9, 129.8, 129.1 (2C), 128.6, 128.5, 126.3 (2C),
124.1, 123.2, 120.9, 120.5, 116.9 (2C), 67.6, 64.9 (2C), 64.6, 41.5,
40.0, 34.6, 32.8; FT-IR νmax(ATR) cm−1 3372, 2922, 1582, 1485, 1450,
1302, 1264, 1222, 1119, 1074, 1039, 909, 748, 698; m/z (EI) 240
([M]+, 100), 91 ([PhCH2]+, 28); HRMS (ESI) calcd for [C16H16O2 +
Na]+ 263.10425, found 263.10419.
to further transformations.
EXPERIMENTAL SECTION
■
General Information. All reactions were performed with oven-
dried glassware and under an inert atmosphere (argon) unless
otherwise stated. Acetonitrile was distilled from calcium hydride and
stored over 4 Å molecular sieves under nitrogen/argon atmosphere.
Tetrahydrofuran was distilled from Solvona/benzophenone. Pentane
was distilled in a standard distillation apparatus. Other solvents were
used as purchased unless otherwise stated. Commercial reagents were
used as purchased without further purification. Organic solutions were
concentrated under reduced pressure on a rotary evaporator.
Chromatographic purification of products was carried out using silica
gel (230−400 mesh). Thin-layer chromatography was carried out
using aluminum plates coated with silica (230−400 mesh) which were
visualized under UV light (254 nm) or by staining with aqueous
1
potassium permanganate solutions or vanillin alcoholic solution. H
3-Benzyl-6-bromochroman-4-ol (2b). The title compound was
synthesized according to the general procedure employing 1b (0.12
mmol, 38.1 mg), 2.5 mol % (2.74 mg) of PC 3, and 2.5 equiv of
DIPEA (38.8 mg). The product was purified by flash column
NMR spectra were recorded in deuterated solvents on spectrometers
at 300, 400, or 600 MHz with residual protic solvent as the internal
standard. 13C NMR spectra were recorded in deuterated solvents on
spectrometers at 75, 101, or 151 MHz with the central peak of the
deuterated solvent as the internal standard. Chemical shifts (δ) are
given in parts per million (ppm), and coupling constants (J) are given
in hertz (Hz) rounded to the nearest 0.1 Hz. The 1H NMR spectra are
reported as δ downfield from tetramethylsilane (multiplicity, coupling
constant J, number of protons). The 13C NMR spectra are reported as
1
chromatography: yield 50% (19.1 mg); anti/syn 1.1:1; H NMR (400
MHz, CD3OD) δ 7.45 (d, J = 2.4 Hz, 1H, syn), 7.34 (d, J = 3.1 Hz, 1.1
× 1H, anti), 7.31−7.13 (m, 12.6H), 6.73−6.65 (m, 2.1H), 4.47 (d, J =
3.4 Hz, 1H, syn), 4.36 (d, J = 5.0 Hz, 1.1 × 1H, anti), 4.13 (dd, J =
11.2, 2.8 Hz, 1.1 × 1H, anti), 4.03−3.94 (m, 2H, syn), 3.89 (dd, J =
Scheme 2. Plausible Reaction Mechanism
C
DOI: 10.1021/acs.joc.6b01006
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Brief Communication
11.1, 5.5 Hz, 1.1 × 1H, anti), 2.87 (dd, J = 13.6, 7.1 Hz, 1H, syn), 2.76
(dd, J = 13.8, 6.1 Hz, 1H, syn), 2.55 (dd, J = 13.6, 8.3 Hz, 1.1 × 1H,
anti), 2.45 (dd, J = 13.7, 9.3 Hz, 1.1 × 1H, anti), 2.25−2.17 (m, 1H,
syn), 2.16−2.08 (m, 1.1 × 1H, anti); 13C NMR (101 MHz, CD3OD) δ
153.5 (2C), 139.4, 139.2, 132.4 (2C), 131.60 (2C), 128.8, 128.7, 128.1
(2C), 127.0, 126.1, 126.0, 125.8, 118.1 (2C), 111.9, 111.5, 66.4, 65.0,
64.8, 64.2, 41.5, 40.2, 34.2, 32.1; FT-IR νmax(ATR) cm−1 2926, 1479,
1407, 1260, 1224, 1191, 1085, 1055, 1021, 819, 748, 699; m/z (EI)
319 ([M]+, 9), 91 ([PhCH2]+, 100); HRMS (EI) calcd for
[C16H15O279Br]+ 318.02499, found 318.02492.
3-Benzyl-6-fluorochroman-4-ol (2c). The title compound was
synthesized according to the general procedure employing 1c (0.12
mmol, 30.8 mg), 1 mol % (1.1 mg) of PC 3 and 2.5 equiv of DIPEA
(38.8 mg). The product was purified by flash column chromatography:
yield 43% (13.2 mg); mp =102−104 °C; anti/syn 1.1:1; 1H NMR (600
MHz, CD3OD) δ 7.31−7.23 (m, 6.5 H), 7.21−7.15 (m, 4.3 H), 7.06
(dd, J = 9.0, 3.1 Hz, 1.1 × 1H, anti), 6.96 (dd, J = 8.9, 3.1 Hz, 1H, syn),
6.89 (dtd, J = 11.6, 8.5, 3.1 Hz, 2H), 6.78−6.71 (m, 2H), 4.48 (d, J =
3.5 Hz, 1H, syn), 4.37 (d, J = 5.1 Hz, 1.1 × 1H, anti), 4.12 (dd, J =
11.1, 2.8 Hz, 1.1 × 1H, anti), 4.01−3.94 (m, 2H, syn), 3.87 (dd, J =
11.1, 5.6 Hz, 1.1 × 1H, anti), 2.88 (dd, J = 13.6, 7.2 Hz, 1H, syn), 2.79
(dd, J = 13.8, 6.0 Hz, 1.1 × 1H, anti), 2.56 (dd, J = 13.6, 8.3 Hz, 1H,
syn), 2.46 (dd, J = 13.8, 9.4 Hz, 1.1 × 1H, anti), 2.24−2.17 (m, 1H,
syn), 2.16−2.11 (m, 1.1 × 1H, anti); 19F NMR (564 MHz, CD3OD) δ
−125.8, −126.4; 13C NMR (101 MHz, CD3OD) δ 156.9, 156.6, 150.4,
150.3, 139.5, 139.2, 128.8, 128.7, 128.1, 128.0, 125.9 (2C), 125.8,
125.0, 117.2, 117.1, 115.5, 115.4, 115.3 (2C), 66.8, 65.0, 64.7, 64.4,
41.6, 40.3, 34.2, 32.1; FT-IR νmax(ATR) cm−1 3370, 2926, 2493, 1488,
1436, 1251, 1201, 1027, 736, 698; m/z (EI) 258 ([M]+, 48), 91
([PhCH2]+, 100); HRMS (EI) calcd for [C16H15O2F]+ 258.10506,
found 258.10537.
Methyl 3-Benzyl-4-hydroxychroman-6-carboxylate (2d). The title
compound was synthesized according to the general procedure
employing 1d (0.12 mmol, 35.6 mg), 1 mol % (1.1 mg) of PC 3,
and 2.5 equiv of DIPEA (38.8 mg). The product was purified by flash
column chromatography: yield 51% (18.2 mg); anti/syn 1.3:1; 1H
NMR (400 MHz, CD3OD) δ 8.05 (d, J = 2.1 Hz, 1.3 × 1H, anti), 7.92
(d, J = 2.2 Hz, 1H, syn), 7.80 (ddd, J = 14.4, 8.6, 2.2 Hz, 2.3H), 7.32−
7.11 (m, 11.5H), 6.81 (dd, J = 14.4, 8.6 Hz, 2.3H), 4.52 (d, J = 3.2 Hz,
1H, syn), 4.42 (d, J = 4.9 Hz, 1.3 × 1H, anti), 4.21 (dd, J = 11.2, 2.9
Hz, 1.3 × 1H, anti), 4.11−3.99 (m, 2H, syn), 3.96 (dd, J = 11.1, 5.3 Hz,
1.3 × 1H, anti), 3.84 (s, 1.3 × 3H, anti), 3.81 (s, 3H, syn), 2.88 (dd, J =
13.6, 7.1 Hz, 1H, syn), 2.75 (dd, J = 13.7, 6.1 Hz, 1.3 × 1H, anti), 2.56
(dd, J = 13.6, 8.3 Hz, 1H, syn), 2.43 (dd, J = 13.7, 9.3 Hz, 1.3 × 1H,
anti), 2.26−2.13 (m, 2.3H); 13C NMR (101 MHz, CD3OD) δ 167.0
(2C), 158.6 (2C), 139.4, 139.1, 132.3, 132.2, 130.4, 130.3, 128.8,
128.7, 128.1 (2C), 126.0, 125.9, 124.8, 123.9, 122.1, 121.7, 116.3 (2C),
66.4, 65.4, 65.2, 64.2, 51.0, 50.9, 41.4, 40.2, 34.2, 32.2; FT-IR
νmax(ATR) cm−1 2949, 1711, 1611, 1496, 1436, 1253, 1192, 1125,
1012, 767, 700; m/z (EI) 298 ([M]+, 12), 91 ([PhCH2]+, 40); HRMS
(EI) calcd for [C18H18O4]+ 298.11996, found 298.12009.
tert-Butyl (3-Benzyl-4-hydroxychroman-6-yl)carbamate (2e). The
title compound was synthesized according to the general procedure
employing 1e (0.12 mmol, 42.4 mg), 1 mol % (1.1 mg) of PC 3, and
2.5 equiv of DIPEA (38.8 mg). The product was purified by flash
column chromatography: yield 44% (18.7 mg); anti/syn 1.6:1; 1H
NMR (600 MHz, CDCl3) δ 7.49−7.15 (m, 15.6H), 7.08 (dd, J = 8.8,
2.6 Hz, 1.6 × 1H, anti), 6.99 (dd, J = 8.8, 2.6 Hz, 1H, syn), 6.80 (d, J =
8.8 Hz, 1.6 × 1H, anti), 6.76 (d, J = 8.8 Hz, 1H, syn), 6.45−6.24 (m,
2.6H), 4.52−4.41 (m, 2.6H), 4.19 (dd, J = 11.0, 1.9 Hz, 1.6 × 1H,
anti), 4.12−4.01 (m, 2H, syn), 3.92 (dd, J = 11.0, 3.9 Hz, 1.6 × 1H,
anti), 2.86 (dd, J = 13.5, 8.6 Hz, 1H, syn), 2.73−2.61 (m, 2.6H), 2.51
(dd, J = 13.7, 9.5 Hz, 1.6 × 1H, anti), 2.31−2.26 (m, 1H, syn), 2.21−
2.17 (m, 1.6 × 1H, anti), 1.91−1.62 (overlapping of two bs, 2.6H)
1.51 (s, 1.6 × 9H, anti), 1.48 (s, 9H, syn); 13C NMR (151 MHz,
CDCl3) δ 153.2, 153.1, 150.3, 150.2, 139.2, 139.1, 131.4, 131.3, 131.0
(2C), 129.1 (2C), 128.5 (2C), 126.3 (2C), 124.4, 123.5, 121.2, 120.7,
117.2, 117.1, 80.4 (2C), 67.6, 65.1, 64.8, 64.6, 41.3, 40.0, 34.6, 32.7,
28.4, 28.3; FT-IR νmax(ATR) cm−1: 3350, 2981, 2932, 1696, 1499,
1454, 1367, 1309, 1241, 1218, 1163, 1023, 822, 733, 699; m/z (EI)
298 ([M − (CH3)3C]+, 100), 91 ([PhCH2]+, 67); HRMS (EI) calcd
for [C16H16O2N1]+ ([M − Boc]+) 254.11756, found 254.11706.
3-Benzyl-8-phenylchroman-4-ol (2f). The title compound was
synthesized according to the general procedure employing 1f (0.12
mmol, 37.7 mg), 1 mol % (1.1 mg) of PC 3, and 2.5 equiv of DIPEA
(38.8 mg). The product was purified by flash column chromatography:
1
yield 61% (23 mg); anti/syn 1.2:1; H NMR (600 MHz, CD3OD)
δ7.48−7.44 (m, 1.2 × 1H, anti), 7.44−7.40 (m, 1H, syn), 7.37−7.05
(m, 24.2H), 7.00−6.94 (m, 1.2 × 1H, anti), 6.92−6.86 (m, 1H, syn),
4.49 (d, J = 2.7 Hz, 1H, syn), 4.44 (d, J = 4.1 Hz, 1.2 × 1H, anti), 4.15
(dd, J = 11.0, 2.6 Hz, 1.2 × 1H, anti), 4.00 (t, J = 10.9 Hz, 1H, syn),
3.92 (dd, J = 10.6, 3.5 Hz, 1H, syn), 3.86 (dd, J = 11.0, 4.5 Hz, 1.2 ×
1H, anti), 2.85 (dd, J = 13.5, 7.5 Hz, 1H, syn), 2.70 (dd, J = 13.7, 6.4
Hz, 1.2 × 1H, anti), 2.55 (dt, J = 18.0, 9.0 Hz, 1H, syn), 2.51−2.44 (m,
1.2 × 1H, anti), 2.25−2.18 (m, 1H, syn), 2.17−2.12 (m, 1.2 × 1H,
anti); 13C NMR (151 MHz, CD3OD) δ 151.1 (2C), 139.6, 139.4,
138.5, 138.4, 130.2, 130.1, 129.8 (2C), 129.7 (2C), 129.2 (2C), 128.8,
128.7, 128.1 (2C), 127.5 (2C), 126.4 (2C), 125.9, 125.8, 125.1, 123.9,
120.2, 119.9, 67.1, 64.8, 64.6, 64.5, 41.5, 40.3, 34.3, 32.5; FT-IR
νmax(ATR) cm−1 1594, 1496, 1469, 1430, 1219, 1017, 754, 697; m/z
(EI) 316 ([M]+, 63%), 91 ([PhCH2]+, 27%); HRMS (ESI) calcd for
[C22H20O2 + Na]+ 339.13555, found 339.13525.
3-Benzyl-8-methylchroman-4-ol (2g). The title compound was
synthesized according to the general procedure employing 1g (0.12
mmol, 30.3 mg), 1 mol % (1.1 mg) of PC 3, and 2.5 equiv of DIPEA
(38.8 mg). The product was purified by flash column chromatography:
yield 56% (17.1 mg); anti/syn 1.4:1; 1H NMR (600 MHz, CD3OD) δ
7.30−7.21 (m, 7.5H), 7.20−7.12 (m, 5.5H), 7.05−7.02 (m, 2.4H),
6.99 (d, J = 7.3 Hz, 1.4 × 1H, anti), 6.80 (t, J = 7.5 Hz, 1H, syn), 6.73
(t, J = 7.5 Hz, 1.4 × 1H, anti), 4.45 (d, J = 3.2 Hz, 1.4 × 1H, anti), 4.38
(d, J = 4.2 Hz, 1H, syn), 4.19 (dd, J = 11.0, 2.6 Hz, 1H, syn), 4.06−4.02
(m, 1.4 × 2H, anti), 3.94 (dd, J = 11.0, 4.6 Hz, 1H, syn), 2.87 (dd, J =
13.7, 7.4 Hz, 1.4 × 1H, anti), 2.68 (dd, J = 13.7, 6.5 Hz, 1H, syn), 2.58
(dd, J = 13.6, 8.1 Hz, 1.4 × 1H, anti), 2.45 (dd, J = 13.7, 9.1 Hz, 1H,
syn), 2.16 (s, 3H, syn), 2.12 (s, 1.4 × 3H, anti) OH signals not
observed; 13C NMR (151 MHz, CD3OD) δ 152.3, 152.2, 139.7, 139.5,
129.9, 129.8, 128.8, 128.7, 128.1 (2C), 127.9, 127.8, 125.8 (2C), 125.2
(2C), 123.9, 122.7, 119.6, 119.3, 66.9, 64.7, 64.6, 64.4, 41.8, 40.6, 34.3,
32.6, 14.8 (2C); FT-IR νmax(ATR) cm−1 3352, 2919, 1598, 1472,
1258, 1210, 1092, 1023, 747, 698; m/z (EI) 254 ([M]+, 59), 253 ([M
− 1], 100), 91 ([PhCH2]+, 39); HRMS (EI) calcd for [C17H18O2]+
254.13013, found 254.13046.
3-Benzyl-6,8-di-tert-butylchroman-4-ol (2h). The title compound
was synthesized according to the general procedure employing 1h
(0.12 mmol, 42.1 mg), 1 mol % (1.1 mg) of PC 3, and 2.5 equiv of
DIPEA (38.8 mg). The product was purified by flash column
1
chromatography: yield 88% (37.5 mg); anti/syn 1.2:1; H NMR (400
MHz, CD3OD) δ 7.33−7.07 (m, 15.4H), 4.48 (d, J = 3.5 Hz, 1H, syn),
4.39 (d, J = 3.3 Hz, 1.2 × 1H, anti), 4.13 (dd, J = 10.9, 2.5 Hz, 1.2 ×
1H, anti), 4.03−3.94 (m, 2H, syn), 3.90 (ddd, J = 10.9, 4.0, 1.1 Hz, 1.2
× 1H, anti), 2.88 (dd, J = 13.5, 7.2 Hz, 1H, syn), 2.67 (dd, J = 13.6, 6.0
Hz, 1.2 × 1H, anti), 2.57 (dd, J = 13.5, 8.3 Hz, 1H, syn), 2.42 (dd, J =
13.6, 9.8 Hz, 1.2 × 1H, anti), 2.23−2.15 (m, 1H, syn), 2.14−2.08 (m,
1.2 × 1H, anti), 1.37 (s, 1.2 × 9H, anti), 1.33 (s, 9H, syn), 1.29 (s, 1.2
× 9H, anti), 1.25 (s, 9H, syn); 13C NMR (101 MHz, CD3OD) δ 150.6
(2C), 141.8, 141.5, 139.8, 139.6, 136.3, 136.1, 128.8 (2C), 128.0 (2C),
125.8, 125.7, 125.2, 124.7, 124.0, 123.1, 123.0, 122.4, 67.7, 65.5, 63.9,
63.0, 41.7, 40.6, 34.5, 34.5, 34.3, 33.7, 33.7, 32.5, 30.7 (2C), 28.9 (2C);
FT-IR νmax(ATR) cm−1 2956, 2870, 1479, 1450, 1361, 1229, 1171,
1130, 1028, 882, 749, 701, 532; m/z (EI) 352 ([M]+, 65), 91
([PhCH2]+, 15); HRMS (EI) calcd for [C24H32O2]+ 352.23968, found
352.23972.
3-Benzyl-8-ethoxychroman-4-ol (2i). The title compound was
synthesized according to the general procedure employing 1i (0.12
mmol, 33.8 mg), 1 mol % (1.1 mg) of PC 3, and 2.5 equiv of DIPEA
(38.8 mg). The product was purified by flash column chromatography:
1
yield 73% (25 mg); anti/syn 1:1; H NMR (600 MHz, CDCl3) δ
7.36−7.14 (m, 10H), 6.95−6.77 (m, 6H), 4.48−4.47 (m, 2H), 4.29
(dd, J = 11.1, 2.7 Hz, 1H), 4.22 (ddd, J = 10.7, 3.7, 1.2 Hz, 1H), 4.15−
4.04 (m, 6H), 2.88 (dd, J = 13.7, 8.4 Hz, 1H), 2.70 (dd, J = 14.0, 7.0
D
DOI: 10.1021/acs.joc.6b01006
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Brief Communication
Hz, 1H), 2.68 (dd, J = 13.7, 7.2 Hz, 1H), 2.59 (dd, J = 13.9, 8.5 Hz,
1H), 2.35−2.29 (m, 1H), 2.22 (dqd, J = 12.9, 4.3, 2.8 Hz, 1H), 1.97
(bs, 2H), 1.47−1.45 (m, 6H); 13C NMR (151 MHz, CDCl3) δ 147.6,
147.5, 144.1, 144.0, 139.2, 139.1, 129.1 (2C), 128.5 (2C), 126.3 (2C),
125.0, 124.0, 121.8, 121.6, 120.4, 120.1, 112.6 (2C), 67.4, 65.4, 65.2,
64.7, 64.4, 64.3, 41.3, 39.8, 34.6, 32.9, 14.8 (2C); FT-IR νmax(ATR)
cm−1 3506, 2921, 1585, 1478, 1391, 1315, 1255, 1214, 1080, 1030,
964, 900, 737; m/z (EI) 284 ([M]+, 23), 91 ([PhCH2]+, 100); HRMS
(EI) calcd for [C18H20O3]+ 284.14070, found 284.14077.
3-Benzhydrylchroman-4-ol (2m). The title compound was
synthesized according to the general procedure employing 1m (0.12
mmol, 37.7 mg), 1 mol % (1.1 mg) of PC 3, and 2.5 equiv of DIPEA
(38.8 mg). The product was purified by flash column chromatography:
1
yield 86% (32.7 mg); anti/syn 1.8:1; H NMR (600 MHz, CDCl3) δ
7.43 (d, J = 7.2 Hz, 2H), 7.39 (d, J = 7.2 Hz, 2H), 7.35−7.18 (m,
26.7H), 7.12−7.09 (m, 3H), 6.97−6.85 (m, 5.5H), 4.44 (bs, 1H, syn),
4.41 (bs, 1.8 × 1H, anti), 4.27 (dd, J = 11.2, 2.3 Hz, 1.8 × 1H, anti),
4.14−4.06 (m, 2H, syn), 4.00 (ddd, J = 10.8, 3.5, 1.5 Hz, 1H, syn),
3.96−3.93 (m, 1.8 × 1H, anti), 3.70 (d, J = 12.4 Hz, 1.8 × 1H, anti),
2.91 (ddd, J = 11.9, 7.5, 3.2 Hz, 1H, syn), 2.79 (dq, J = 12.4, 2.3 Hz, 1.8
× 1H, anti), 2.00 (bs, 1.8 × 1H, anti), 1.80 (bs, 1H, syn); 13C NMR
(151 MHz, CDCl3) δ 154.4 (2C), 142.6, 142.4, 142.3 (2C), 130.9,
130.5, 130.0, 129.9, 128.9 (2C), 128.8 (2C), 128.1 (2C), 127.9, 127.8,
126.8, 126.7, 126.6, 126.6, 124.0, 122.5, 121.0, 120.5, 117.1, 116.9,
65.8, 64.1, 64.0, 63.1, 49.6, 49.2, 43.0, 41.9; FT-IR νmax(ATR) cm−1:
3036, 2927, 1702, 1619, 1516, 1491, 1446, 1318, 1226, 1117, 1014,
972, 755; m/z (EI) 167 ([CHPh2]+, 59), 151 ([M − CPh2]+, 28);
HRMS (EI) calcd for [C22H20O2]+ 316.14578, found 316.14636.
2-Benzyl-2,3-dihydro-1H-inden-1-ol (2n). The title compound was
synthesized according to the general procedure employing 1n (0.12
mmol, 26.7 mg), 2.5 mol % (2.74 mg) of PC 3, and 2.5 equiv of
DIPEA (38.8 mg). The product was purified by flash column
3-Benzyl-6-methoxychroman-4-ol (2j). The title compound was
synthesized according to the general procedure employing 1j (0.12
mmol, 32.2 mg), 1 mol % (1.1 mg) of PC 3, and 2.5 equiv of DIPEA
(38.8 mg). The product was purified by flash column chromatography:
1
yield 65% (21 mg); mp = 112−113 °C; anti/syn 1:1; H NMR (400
MHz, CD3OD) δ 7.30−7.13 (m, 10H), 6.88 (d, J = 3.0 Hz, 1H),
6.80−6.63 (m, 5H), 4.46 (d, J = 3.5 Hz, 1H), 4.36 (d, J = 4.6 Hz, 1H),
4.09 (dd, J = 11.0, 2.7 Hz, 1H), 3.99−3.89 (m, 2H), 3.84 (ddd, J =
11.0, 5.1, 0.7 Hz, 1H), 3.73 (s, 3H), 3.70 (s, 3H), 2.87 (dd, J = 13.6,
7.2 Hz, 1H), 2.74 (dd, J = 13.7, 6.2 Hz, 1H), 2.56 (dd, J = 13.6, 8.3 Hz,
1H), 2.47 (dd, J = 13.7, 9.3 Hz, 1H), 2.23−2.15 (m, 1H), 2.14−2.07
(m, 1H); 13C NMR (101 MHz, CD3OD) δ 153.7, 153.4, 148.2, 148.1,
139.7, 139.5, 128.8, 128.7, 128.0 (2C), 125.8, 125.7, 124.9, 123.9,
116.7 (2C), 115.5 (2C), 113.9, 113.8, 67.1, 64.8, 64.5 (2C), 54.7 (2C),
42.0, 40.7, 34.3, 32.3; FT-IR νmax(ATR) cm−1 2923, 2471, 1490, 1430,
1265, 1205, 1161, 1037, 807, 703; m/z (EI) 270 ([M]+, 71), 91
([PhCH2]+, 33); HRMS (EI) calcd for [C17H18O3]+ 270.12505, found
270.12551.
1
chromatography: yield 68% (14.6 mg); anti/syn 2.5:1; H NMR (600
MHz, CDCl3) δ 7.41−7.35 (m, 4H), 7.35−7.29 (m, 10H), 7.28−7.21
(m, 14.5H), 7.19−7.15 (m, 3H), 5.00 (d, J = 5.4 Hz, 1H, syn), 4.95 (d,
J = 6.6 Hz, 2.5 × 1H, anti), 3.14−3.07 (m, 4.5H), 3.01 (dd, J = 15.3,
7.3 Hz, 3H), 2.87−2.83 (m, 2.5H), 2.81−2.75 (m, 4H), 2.68 (dq, J =
14.0, 7.9 Hz, 1H, syn), 2.62−2.48 (m, 6H), 1.62 (bs, 3.5H); 13C NMR
(151 MHz, CDCl3) δ 144.7, 144.5, 143.5, 141.5, 141.2, 140.6, 128.9
(2C), 128.7, 128.5, 128.4, 128.2, 126.8 (2C), 126.2, 125.9, 125.0,
124.8, 124.7, 123.9, 80.8, 76.3, 52.3, 46.9, 39.3, 35.9, 35.8, 35.0; FT-IR
νmax(ATR) cm−1 3363, 2932, 1487, 1454, 1257, 1102, 1026, 804, 745,
697; m/z (EI) 223 ([M − 1]+, 21), 132 (M − [PhCH2]+, 100) 91
([PhCH2]+, 80); HRMS (EI) calcd for [C16H16O]+ 224.11957, found
224.11989.
3-(3-Methylbenzylidene)chroman-4-ol (2o). The title compound
was synthesized according to the general procedure employing 1o
(0.12 mmol, 30 mg), 2.5 mol % (2.74 mg) of PC 3, and 2.5 equiv of
DIPEA (38.8 mg). The product was purified by flash column
chromatography: yield 59% (17.7 mg); E/Z 1:1; 1H NMR (400 MHz,
CDCl3) δ 7.41 (dd, J = 7.7, 1.6 Hz, 1H), 7.31−7.18 (m, 6H), 7.16−
7.07 (m, 2H), 7.06−7.00 (m, 2H), 7.03−6.8 (m, 6H), 6.77 (s, 1H),
5.32 (s, 1H), 5.19 (s, 1H), 4.97−4.86 (m, 3H), 4.57 (dd, J = 12.0, 0.9
Hz, 1H), 2.37 (s, 3H), 2.35 (s, 3H), 2.14 (bs, 1H), 2.05 (bs, 1H); 13C
NMR (101 MHz, CDCl3) δ 154.4, 154.3, 138.1 (2C), 135.5, 135.4,
134.4, 133.4, 131.6, 130.3, 130.0, 129.8, 129.5 (2C), 129.2, 129.0,
128.7, 128.4, 128.3 (2C), 125.9, 125.8, 124.9, 124.0, 121.1 (2C), 117.2,
116.9, 69.3, 68.1, 63.0, 62.8, 21.4 (2C); FT-IR νmax(ATR) cm−1 3391,
2922, 1737, 1590, 1479, 1370, 1224, 993, 921, 756, 702; m/z (EI) 252
([M]+, 17), 104 ([3-MePh]+, 25), 91 ([3-MePhCH]+, 32); HRMS
calcd for [C17H16O2]+ 252.11448, found 252.11402.
3-Benzyl-7-methoxychroman-4-ol (2k).19 The title compound was
synthesized according to the general procedure employing 1k (0.12
mmol, 32.2 mg), 2.5 mol % (2.74 mg) of PC 3, and 2.5 equiv of
DIPEA (38.8 mg). The product was purified by flash column
chromatography: yield 92% (29.8 mg); mp = 100−103 °C; anti/syn
1
1.7:1; H NMR (400 MHz, CD3OD) δ 7.42−7.21 (m, 7.2H), 7.20−
7.12 (m, 8H), 7.09 (d, J = 8.5 Hz, 1H), 6.51 (dd, J = 8.5, 2.5 Hz, 1.7 ×
1H, anti), 6.44 (dd, J = 8.5, 2.5 Hz, 1H, syn), 6.35 (d, J = 2.5 Hz, 1.7 ×
1H, anti), 6.30 (d, J = 2.5 Hz, 1H, syn), 4.41 (d, J = 3.1 Hz, 1H, syn),
4.34 (d, J = 3.9 Hz, 1.7 × 1H, anti), 4.15 (dd, J = 11.0, 2.6 Hz, 1.7 ×
1H, anti), 4.11−3.93 (m, 2H, syn), 3.89 (ddd, J = 11.0, 4.2, 0.9 Hz, 1.7
× 1H, anti), 3.72 (s, 3H, anti), 3.69 (s, 3H, syn), 2.85 (dd, J = 13.6, 7.4
Hz, 1H, syn), 2.66 (dd, J = 13.7, 6.6 Hz, 1.7 × 1H, anti), 2.57 (dd, J =
13.6, 8.0 Hz, 1H, syn), 2.46 (dd, J = 13.7, 9.1 Hz, 1.7 × 1H, anti),
2.23−2.14 (m, 1H, syn), 2.14−2.03 (m, 1.7 × 1H, anti); 13C NMR
(101 MHz, CD3OD) δ 160.7 (2C), 155.2 (2C), 139.6, 139.5, 131.1,
130.9, 128.8, 128.7, 128.0 (2C), 125.8, 125.7, 117.1, 115.6, 107.3,
106.8, 100.5 (2C), 66.3, 64.5, 64.2, 64.1, 54.3, 54.2, 42.0, 40.7, 34.2,
32.6; FT-IR νmax(ATR) cm−1: 3215, 2960, 1737, 1667, 1494, 1366,
1221, 1092, 1032, 734; m/z (EI) 270 ([M]+, 15), 91 ([PhCH2]+, 89);
HRMS (EI) calcd for [C17H18O3]+ 270.12505, found 270.12534.
3-(4-methoxybenzyl)chroman-4-ol (2l).20 The title compound was
synthesized according to the general procedure employing 1l (0.12
mmol, 32.2 mg), 2.5 mol % (2.74 mg) of PC 3, and 2.5 equiv of
DIPEA (38.8 mg). The product was purified by flash column
chromatography: yield 55% (17.7 mg); mp =121−126 °C; anti/syn
1.2:1; 1H NMR (600 MHz, CDCl3) δ 7.32 (dd, J = 7.6, 1.4 Hz, 1.2 ×
1H, anti), 7.25−7.17 (m, 5.4H), 7.11−7.08 (m, 1.2 × 1H, anti), 6.95
(td, J = 7.5, 0.9 Hz, 1.2 × 1H, anti), 6.91−6.82 (m, 7.4H), 4.50 (t, J =
3.5 Hz, 1H, syn), 4.48 (t, J = 4.1 Hz, 1.2 × 1H, anti), 4.21 (dd, J = 9.2,
4.6 Hz, 1.2 × 1H, anti) 4.11−4.06 (m, 2H, syn), 3.97 (dd, J = 11.0, 4.0
Hz, 1.2 × 1H, anti), 3.80 (s, 3H, syn), 3.79 (s, 1.2 × 3H, anti), 2.82
(dd, J = 13.8, 8.5 Hz, 1H, syn), 2.68−2.58 (m, 2.2H), 2.48 (dd, J =
14.0, 9.3 Hz, 1.2 × 1H, anti), 2.32−2.24 (m, 1H, syn), 2.21−2.14 (m,
1.2 × 1H, anti), 1.91 (bs, 1.2 × 1H, anti), 1.72 (bs, 1H, syn); 13C NMR
(151 MHz, CDCl3) δ 158.1 (2C), 154.3, 154.2, 131.1, 131.0, 130.1
(2C), 130.0 (2C), 129.9, 129.7, 124.2, 123.2, 120.9, 120.5, 116.9 (2C),
114.0, 113.9, 67.6, 65.0, 64.9, 64.6, 55.3 (2C), 41.6, 40.1, 33.7, 31.9;
FT-IR νmax(ATR) cm−1: 3392, 2928, 1609, 1582, 1510, 1486, 1450,
1298, 1246, 1176, 1031, 850, 813, 753; m/z (EI) 270 ([M]+, 27), 121
([4-MeOPhCH2]+, 100); HRMS (EI) calcd for [C17H18O3]+
270.12505, found 270.12548.
3-(4-Methoxybenzylidene)chroman-4-ol (2p).21 The title com-
pound was synthesized according to the general procedure employing
1p (0.12 mmol, 32 mg), 2.5 mol % (2.74 mg) of PC 3, and 2.5 equiv
of DIPEA (38.8 mg). The product was purified by flash column
chromatography: yield 57% (18.3 mg), E/Z 1:1; 1H NMR (600 MHz,
CDCl3) δ 7.46−7.43 (m, 2H), 7.42−7.39 (m, 1H), 7.30−7.28 (m,
1H), 7.24−7.20 (m, 2H), 7.20−7.16 (m, 2H), 6.99−6.84 (m, 9H),
6.76 (s, 1H), 5.33 (s, 1H), 5.18 (s, 1H), 4.99−4.89 (m, 2H), 4.87 (dd,
J = 12.0, 1.2 Hz, 1H), 4.59−4.55 (m, 1H), 3.83 (s, 3H), 3.82 (s, 3H),
2.20 (bs, 1H), 2.07 (bs, 1H); 13C NMR (151 MHz, CDCl3) δ 159.3,
159.1, 154.4, 154.3, 133.3, 133.2, 131.9, 131.3, 130.3, 130.2, 130.0,
129.8, 129.1, 128.8, 128.1, 128.0, 125.0, 124.1, 121.1 (2C), 117.3,
116.9, 113.9 (2C), 69.4, 68.2, 63.0, 62.8, 55.3 (2C); FT-IR νmax(ATR)
cm−1 3393, 2958, 2929, 1606, 1509, 1485, 1458, 1246, 1177, 1031,
995, 828, 755; m/z (EI) 268 ([M]+, 25), 120 ([3-MeOPhCH]+, 100).
E
DOI: 10.1021/acs.joc.6b01006
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Brief Communication
(13) For early examples of photochemical generation of ketyl radicals
and their intramolecular addition on carbon-carbon double bonds, see:
(a) Belotti, D.; Cossy, J.; Pete, J.-P.; Portella, C. Tetrahedron Lett.
1985, 26, 4591. (b) Belotti, D.; Cossy, J.; Pete, J.-P.; Portella, C. J. Org.
Chem. 1986, 51, 4196. For an overview for the photochemical
generation of ketyl radicals and their applications, see: (c) Cossy, J.;
Belotti, D. Tetrahedron 2006, 62, 6459.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.6b01006.
■
S
1H and 13C NMR spectra of products (PDF)
(14) Ishitani, O.; Yanagida, S.; Takamuku, S.; Pac, C. J. Org. Chem.
1987, 52, 2790.
(15) For a review on PCET, see: Huynh, M. H. V.; Meyer, T. J.
Chem. Rev. 2007, 107, 5004.
(16) Conti, C.; Desideri, N. Bioorg. Med. Chem. 2009, 17, 3720.
(17) Dinnocenzo, J. P.; Banach, T. E. J. Am. Chem. Soc. 1989, 111,
8646.
(18) Bentley, J.; Nilsson, P. A.; Parsons, A. F. J. Chem. Soc. Perkin
Trans. 1 2002, 12, 1461.
(19) Sangwan, N. K.; Rastogi, S. N. Indian J. Chem. B 1980, 19, 500.
(20) Gomis, M.; Kirkiacharian, B. S.; Likforman, J.; Mahuteau, J. Bull.
Soc. Chim. Fr. 1988, 3, 585.
(21) Pivnenko, N. S.; Orlov, V. D.; Nodel’man, O. A.; Mikhed’kina,
E. I.; Lavrushin, V. F. J. Org. Chem. USSR (Engl. Trans.) 1980, 16,
1657.
AUTHOR INFORMATION
Corresponding Author
*E-mail: magnus.rueping@rwth-aachen.de.
Notes
■
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The research leading to these results has received funding from
the European Research Council under the European Union’s
Seventh Framework Programme (FP/2007-2013)/ERC Grant
Agreement No. 617044 (SunCatChem).
REFERENCES
■
(1) (a) Molander, G. A.; Kenny, C. Tetrahedron Lett. 1987, 28, 4367.
(b) Molander, G. A.; Kenny, C. J. Am. Chem. Soc. 1989, 111, 8236.
(2) Values calculated vs Ag/AgNO3 as reference electrode in THF:
(a) Shabangi, M.; Flowers, R. A., II Tetrahedron Lett. 1997, 38, 1137.
(b) Flowers, R. A., II. Synlett 2008, 2008, 1427.
(3) Selected examples using stoichiometric amount of tributyltin:
(a) Beckwith, A. L. J.; Roberts, D. H. J. Am. Chem. Soc. 1986, 108,
5893. (b) Ardisson, J.; Ferezou, J. P.; Julia, M.; Pancrazi, A.
Tetrahedron Lett. 1987, 28, 2001. (c) Sugawara, T.; Otter, B. A.;
Ueda, T. Tetrahedron Lett. 1988, 29, 75.
(4) Enholm was the first to systematically explore the scope of this
reaction: (a) Enholm, E. J.; Prasad, G. Tetrahedron Lett. 1989, 30,
4939. (b) Enholm, E. J.; Burroff, J. A. Tetrahedron Lett. 1992, 33, 1835.
(5) Hays, D. S.; Fu, G. C. J. Org. Chem. 1996, 61, 4.
(6) Corey, E. J.; Pyne, S. G. Tetrahedron Lett. 1983, 24, 2821.
(7) Estev
́
ez, R. E.; Oller-Lop
́
ez, J. L.; Robles, R.; Melgarejo, C. R.;
Gansauer, A.; Cuerva, J. M.; Oltra, J. E. Org. Lett. 2006, 8, 5433.
̈
(8) (a) Molander, G. A.; Harris, C. R. J. Org. Chem. 1998, 63, 812.
(b) Corey, E. J.; Pyne, S. G. Tetrahedron Lett. 1983, 24, 2821.
(c) Streuff, J. Synthesis 2013, 45, 281.
(9) For selected reviews on photocatalysis, see: (a) Hoffmann, N.
Chem. Rev. 2008, 108, 1052. (b) Balzani, V.; Credi, A.; Venturi, M.
ChemSusChem 2008, 1, 26. (c) Ravelli, D.; Dondi, D.; Fagnoni, M.;
Albini, A. Chem. Soc. Rev. 2009, 38, 1999. (d) Ravelli, D.; Fagnoni, M.;
Albini, A. Chem. Soc. Rev. 2013, 42, 97.
(10) For selected reviews on photoredox catalysis, see: (a) Zeitler, K.
Angew. Chem., Int. Ed. 2009, 48, 9785. (b) Yoon, T. P.; Ischay, M. A.;
Du, J. Nat. Chem. 2010, 2, 527. (c) Narayanam, J. M. R.; Stephenson,
C. R. J. Chem. Soc. Rev. 2011, 40, 102. (d) Ravelli, D.; Fagnoni, M.
ChemCatChem 2012, 4, 169. (e) Prier, C. K.; Rankic, D. A.;
MacMillan, D. W. C. Chem. Rev. 2013, 113, 5322.
(11) (a) Pandey, G.; Hajra, S.; Ghorai, M. K.; Kumar, K. R. J. Org.
Chem. 1997, 62, 5966. (b) Tarantino, K. T.; Liu, P.; Knowles, R. R. J.
Am. Chem. Soc. 2013, 135, 10022. (c) Rono, L. J.; Yayla, H. G.; Wang,
D. Y.; Armstrong, M. F.; Knowles, R. R. J. Am. Chem. Soc. 2013, 135,
17735. (d) Petronijevic,
Chem. Soc. 2013, 135, 18323. (e) Griesbeck, A. G.; Reckenthaler, M.
Beilstein J. Org. Chem. 2014, 10, 1143. (f) Wang, C.; Qin, J.; Shen, X.;
Riedel, R.; Harms, K.; Meggers, E. Angew. Chem., Int. Ed. 2016, 55,
685.
́
F. R.; Nappi, M.; MacMillan, D. W. C. J. Am.
̈
(12) (a) Nakajima, M.; Fava, E.; Loescher, S.; Jiang, Z.; Rueping, M.
Angew. Chem., Int. Ed. 2015, 54, 8828. (b) Zhu, Z.; Das, A.; Bui, L.;
Zhou, H. Z.; Curran, D. P.; Rueping, M. J. Am. Chem. Soc. 2013, 135,
1823. (c) Nakajima, M.; Lefebvre, Q.; Rueping, M. Chem. Commun.
2014, 50, 3619. (d) Lefebvre, Q.; Hoffmann, N.; Rueping, M. Chem.
Commun. 2016, 52, 2493.
F
DOI: 10.1021/acs.joc.6b01006
J. Org. Chem. XXXX, XXX, XXX−XXX