Iron-Catalyzed Ligand Free α-Alkylation of Methylene Ketones and β-Alkylation of Secondary Alcohols Using Primary Alcohols

Article abstract of DOI:10.1021/acs.joc.9b01600

Herein, we demonstrate a general and broadly applicable catalytic cross coupling of methylene ketones and secondary alcohols with a series of primary alcohols to disubstituted branched ketones. A simple and nonprecious Fe₂(CO)₉ catalyst enables one-pot oxidations of both primary and secondary alcohols to a range of branched gem-bis(alkyl) ketones. A number of bond activations and formations selectively occurred in one pot to provide the ketone products. Coupling reactions can be performed in gram scale and successfully applied in the synthesis of an Alzehimer's drug. Alkylation of a steroid hormone can be achieved. A single catalyst enables sequential one-pot double alkylation to bis-hetero aryl ketones using two different alcohols. Preliminary mechanistic studies using an IR probe, deuterium labeling, and kinetic experiments established the participation of a borrowing-hydrogen process using Fe catalyst, and the reaction produces H₂ and H₂O as byproducts.

Full text of DOI:10.1021/acs.joc.9b01600

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Article
Iron-Catalyzed Ligand Free #-Alkylation of Methylene Ketones
and #-Alkylation of Secondary Alcohols Using Primary Alcohols
Anitha Alanthadka, Sourajit Bera, and Debasis Banerjee
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01600 • Publication Date (Web): 09 Aug 2019
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The Journal of Organic Chemistry
Iron-Catalyzed Ligand Free α-Alkylation of Methylene Ketones and
β-Alkylation of Secondary Alcohols Using Primary Alcohols
Anitha Alanthadka,ϯ Sourajit Bera,ϯ and Debasis Banerjee*
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Department of Chemistry, Laboratory of Catalysis and Organic Synthesis, Indian Institute of Technology Roorkee, Roorkee
247667, Uttarakhand, India. E-mail: dbane.fcy@iitr.ac.in
ABSTRACT: Herein, we demonstrated a general and broadly applicable catalytic cross coupling of methylene ketones and secondary
alcohols with a series of primary alcohols to di-substituted branched ketones. A simple and non-precious Fe2(CO)9 catalyst enables
one-pot oxidations of both primary and secondary alcohols to a range of branched gem-bis(alkyl) ketones. A number of bond activa-
tion and formation selectively happened in one pot to provide the ketone products. Coupling reactions could be performed in gram
scale and successfully applied in the synthesis of Alzehimer’s drug. Alkylation of steroid hormone could be achieve. A single catalyst
enables sequential one-pot double alkylation to bis-hetero aryl ketones using two different alcohols. Preliminary mechanistic studies
using IR-probe, deuterium labeling and kinetic experiments established the participation of borrowing-hydrogen process using Fe-
catalyst and the reaction produces H2 and H2O as by products.
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KEYWORDS. Iron • gem-Bis(alkyl) Ketones • α-Alkylation • Hydrogen Borrowing Strategy • Base Metal Catalysis• Renew-
able alcohols
INTRODUCTION
elusive.6 Surprisingly, till date, another important synthetic
route, alkylation of -substituted secondary alcohols using pri-
mary alcohols for the synthesis of α,α-di-substituted branched
ketones has not been realized using transition metal catalysts.
More specifically, herein for the first time we report a general
and broadly applicable Fe-catalyzed alkylation of methylene
ketones and -substituted secondary alcohols using primary al-
cohols following borrowing hydrogen approach.
Transition-metal catalyzed C-C bond formation represents one
of the most fundamental organic transformations. In this con-
text, enolate alkylation have been utilized as a convenient ap-
proach to access branched ketones.1 Though, several indirect
approaches have been established for such α,α-di-substituted
branched products, often required multi-step synthesis, expen-
sive alkyl halides in combination with highly acidic or basic
conditions and generates stoichiometric halide waste. However,
direct utilization of readily available biomass derived renewa-
ble alcohols for such alkylation process represents one of the
most sustainable approach releasing water as byproduct.2,3
Nevertheless, to date, often alkylation of ketone enolates using
alcohols are limited to the linear ketone products;4 however
direct access to branched ketones utilizing enolate alkylation re-
mains a challenging goal and much less developed (Scheme 1).
α,α-Di-substituted branched ketones are an integral part of
many bioactive molecules and used as important building
blocks in organic synthesis.1
Scheme 1: Motivation and synthetic strategy
Surprisingly, only a handful examples are known for such gem-
inal di-substituted ketones (Scheme 1b).5, 13b-c In this direction,
notable breakthrough by Donohoe and co-workers have re-
ported an iridium catalyzed phosphine ligated system, which in-
terrupt the HB process and enables addition of various pro-nu-
cleophiles to the intermediate enone to branched products.5a In-
terestingly, in a recent contribution they have also demonstrated
Ir-catalyzed strategy for alkylation of α-substituted methylene
ketones. However, use of ortho-substituted phenyl and cyclo-
propyl ketones in combination with KOH is the key to suc-
cess.5b More recently, Glorius and co-workers have reported an
impressive Ru/NHC-catalyzed system for α,α-di-substituted ke-
tones using primary alcohols in presence of lithium base.5c
Nevertheless, homogeneous Ru-,5d and Ir-based catalysts,5e as
well as reusable Pd-nano-catalysts,5f-h and Ag/Mo-oxide,5i are
known for α,α-di-substituted ketones using primary alcohols.
Notably, very recently, we have also demonstrated non-pre-
cious Ni-,13b and Mn-based catalysts,13c for the synthesis of
branched ketones using primary alcohols. However, to the best
of our knowledge, applications of the first row transition metals,
in particular, iron-based catalysts for such applications remain
(a) Iron-catalyzed synthesis of linear ketones. (b) Metal-catalyzed alkyla-
tion to methylene ketones. (c) Fe-catalyzed coupling of methylene ketones
and secondary alcohols with primary alcohols.
Since, last decades there has been significant drive for the utili-
zation of iron catalysts in cross-coupling reactions,7 transfer hy-
drogenations,8 Lewis acid catalyzed transformations,9 as well as
in kinetic resolutions and for cycloisomerizations.10 One such
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iron-catalyst widely used in catalytic transformations is
catalysts having variable oxidation states (0, II or III). Pleas-
Knölker-type catalyst (Scheme 1a).11 Active catalyst, could be
generated using trimethylamine N-oxide (Me3NO) as an activa-
tor. Nevertheless, such cyclopentadienyl-based iron-catalysts
required multi-step synthesis process and their highly expensive
nature are often major concern in comparison to the inexpensive
metal-salts. Further, special care are necessary for handling and
storing of these catalysts under standard laboratory conditions.
In this direction, recent report for enolate alkylation catalyzed
by Knölker-type complex Fe-1 is noteworthy (Scheme 1a).12
However, still there is a need to develop a more general, inex-
pensive and radially accessible catalytic system and their appli-
cations for challenging synthetic strategy to di-substituted
branched ketones using Fe-catalyst (Scheme 1c).
ingly, branched ketones 3a was obtained in 81% isolated yield
with >18:1 selectivity (Table 1, entries 1-3). Nevertheless,
small amount of reduced alcohol 1a’, enone 3a” and trace
amount of self-couple product of 1a was detected in GC-MS
analysis of the reaction mixture (Table 1). Under identical con-
ditions, efficiency of different bases such as, t-BuONa, Na2CO3,
K2CO3 and K3PO4 were examine and resulted only moderate to
poor product conversions (Table 1, entries 4-7). Further, influ-
ence of different solvents (xylene and t-amylalcohol) did not
improve any product yields and selectivity to 3a (Table 1, en-
tries 8-9 and SI Table S1-S5). Notably, control experiments in
absence of base and without catalyst as well as lowering reac-
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tion temperature to 130 C drastically diminished the product
yields, revealed the potential role of the individual component
to achieve higher yield and selectivity (Table 1, entries 10-12
and Supporting Information Table S1-S5). However, in absence
of catalyst we observed 24% conversion to product 3a. At this
point, we believe that, in the presence of a base, alkoxide might
RESULTS AND DISCUSSION
Recently, selective alkylation of ketones using primary alcohols
have been developed by our laboratory using commercially
available manganese and nickel-catalysts in combination with
bench stable nitrogen ligands.13b-d However, cross-couplings of
two different alcohols (secondary and primary alcohols) to
geminal-di-substituted ketones remain unknown. The major
challenges associated with cross-couplings of secondary alco-
hols are: i) self-Aldol-coupling to undesire side products and ii)
diminishes atom-economy of the process. More importantly,
synthesis of α,α-di-substituted branched ketones through cross-
couplings of secondary and primary alcohols comprises one pot
four steps transformations; dehydrogenation of alcohols to car-
bonyls, Aldol condensations of carbonyls to enones, hydro-
genation of enones and finally dehydrogenation to the desired
ketones. Herein, for the first time we demonstrated the catalytic
cross coupling of two different alcohols using highly abundant
and inexpensive Fe-catalyst. The catalytic process does not
need any special ligand and liberated water and dihydrogen as
side products.
form with alcohol,
followed by the reaction with corre-
sponding ketone or ketone enolate, and resulted the formation
of enone-intermediate. Nevertheless, as the reaction was per-
formed in the closed system, at higher temperature base-medi-
ated Meerwein–Ponndorf–Verley reduction might results the
formation of 24% conversion to product in absence of catalyst
along with others side reactions. However, a more detailed
mechanism could be the future scope of the work.
Scheme 2. Catalytic cross-coupling of methylene ketones
with primary alcohols.
Table 1. Optimization studies for Fe-catalyzed alkylationa
Entry
Deviations from standard
conditions
3a (%)
Ratio
3a/3a’
1
2
3
4
None
87 (81)
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35
47
6
>18:1
0.9:1
0.6:1
1.7:1
-
Fe(OAc)2 (5)
Fe(acac)3 (5)
t-BuONa
Na2CO3
5
K2CO3
9
-
6
K3PO4
5
-
7
p-Xylene
t-Amyl alcohol
No Base
No Catalyst
130 oC
43
62
8
24
67
1.3:1
2.5:1
-
0.6:1
2.6:1
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Reaction conditions: aPropiophenone 1a (0.5 mmol), benzyl alcohol 2a
(0.625 mmol), Fe2(CO)9 (2.5 mol%), t-BuOK (0.5 mmol), toluene (2.0 mL),
Schlenk tube under N2 atmosphere at 140 °C in oil bath for 24 h reaction
time. bIsolated yield in parenthesis (average of two run). Conversions were
determined using GC-MS.
Reaction conditions: aKetone 1 (0.5 mmol), primary alcohol 2 (0.625
mmol), Fe2(CO)9 (2.5 mol%), t-BuOK (0.5 mmol), toluene (2.0 mL),
Schlenk tube under N2 atmosphere, 140 °C oil bath, 24 h reaction time. Iso-
lated yield reported. b36 h reaction time. cFe2(CO)9 (5 mol%), t-BuOK (1.0
mmol), 36 h reaction time.
Our initial studies for the α-alkylation were perform using pro-
piophenone 1a with benzyl alcohol 2a in combination with iron
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Thereafter, having the optimized conditions, the scope of meth-
ylene ketones were tested using a range benzyl, hetero-aryl as
well as alkyl primary alcohols and presented in Scheme 2.
Primarily, propiophenone 1a subjected to the alkylation with
benzyl alcohols decorated with –OMe, Cl or F-substitution in
aryl ring and efficiently transformed to a series of di-substituted
ketones 3b-3d in up to 50% yield. Interestingly, when more
challenging cyclopropyl methanol 2e and cyclohexyl methanol
2f were employed, the desired α,α-di-alkyl ketones 3e-3f were
obtained in 73-75% yield respectively (Scheme 2). Notably, we
studied the performance of readily abundant n-butanol 2h,
n-heptanol 2i including renewable terpenoid intermediate
citronellol 2g with 1a, and the di-alkyl branched ketones 3g-3i
were obtained in up to 73% yield without affecting the reducible
double bond in 3g. Next, we investigated the scope of sterically
hindered 1,2-diphenylethanone 1b with benzyl alcohols having
electronically different (methoxy, alkyl, chloro as well as tri-
fluoromethyl) substituents at the aryl ring and the desired
branched ketones 3j-3p were isolated in 49-88% yield respec-
tively (Scheme 2). Gratifyingly, sterically demanding
2-methylbenzylalcohol 2n and 1-naphthyl methanol 2o effec-
tively participated to provide 3q and 3r in 64% and 73% yield
respectively. Notably, application of hetero-aryl alcohols, such,
as, 1,3-dioxolone substituted benzylalcohol 2p, 2-thiophene-
methanol 2q, 2-furfurylmethanol 2r as well as 2-pyridinemeth-
anol 2s resulted the desired hetero-aryl substituted ketones
3s-3v in moderate yields. It is to be noted that, tetralone 1c, 6-
methoxytetralone 1d, 1,3-diphenylpropiophenone 1e as well as
valerophenone 1f showed promising activity and converted to
the desired branched products 3w-3z and 3za in moderate to
excellent isolated yields (Scheme 2). Further, to establish the
general applicability, alkyl ketones, such as, cyclopentanone 1g
and cyclohexanone 1h were reacted with benzylalcohol 1a and
the desired 2-benzylketones 3zb and 3zc were obtain in up to
43% yield (Scheme 2). When using 2-cyclohene-1-one 1i as
coupling partner with 1a, 2,6-bis-alkylated ketone 3zd was
obtained in 35% yield (Scheme 2). Remarkably, cyclohep-
tanone 1j could efficiently couple with cyclohexyl methanol 2f
to the desire product 3ze. These examples, using alkyl ketones
with aryl as well as alkyl alcohols highlights the potential ap-
plications of the present methodology beyond aryl-methyl or
aryl-alkyl ketones reported till date.
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Reaction conditions: aSecondary alcohol 1’ (0.5 mmol), primary alcohol 2
(0.625 mmol), Fe2(CO)9 (5 mol%), t-BuOK (0.5 mmol), toluene (2.0 mL),
Schlenk tube under N2 atmosphere, 140 °C in an oil bath for 24 h reaction
time. Isolated yield reported.
Thereafter, we focused our studies for the one-pot sequential
double alkylation of acetophenone derivatives using primary
and secondary alcohols (Scheme 4). Initially, acetophenone and
4-methoxyphenyl acetophenone were examine using a range of
aryl, heteroaryl including alkyl primary alcohols to the linear
ketones products. Remarkably, our optimized catalytic protocol
was highly selective for mono-alkylation in the first step,
followed by in situ addition of another alcohol furnished the de-
sired di-substituted ketones in up to 87% yield (3y and 3aa-3ae)
(Scheme 4). Notably, cyclopropyl methanol 1e as well as 1-phe-
nylethanol, proceeded smoothly to the desired ketones 3za and
3af (Scheme 4).
Scheme 4. Sequential one-pot double alkylation.
Further, we turned our attention to establish the general applica-
bility of the catalytic protocol towards cross coupling between
secondary and primary alcohols. A one-pot four-step process
demonstrated the synthesis of α,α-di-substituted ketones in
moderate to excellent yields (Scheme 3). The alkylation worked
well when 1-phenyl-1-propanol 1a’ employed with electroni-
cally different benzyl alcohols and resulted 3a-3c in 58-83%
isolated yields (Scheme 3). Next, applications of aliphatic
primary alcohols, such as, cyclohexylmethanol 2f and n-hep-
tanol 2i proceeded equally well, giving 59-62% yield of 3f and
3i. Again, the reaction of 1,2-diphenylethanol 1b’, resulted
moderate product yields due to strong steric interaction
(Scheme 3, 3j, 3m, and 3t). 1-Tetralol 1c’ and 1-phenyl-1-pen-
tanol 1f’ were also employed with benzyl alcohol and resulted
3w and 3z in 68% and 42% yield respectively (Scheme 3).
Reaction conditions: aAcetophenone (0.5 mmol), alcohol 2 (0.5 mmol),
Fe2(CO)9 (2.5 mol%), t-BuOK (0.5 mmol), toluene (2.0 mL), Schlenk tube
under N2 atmosphere, 140 oC oil bath. After 2 h another alcohol 2 (0.5
mmol) was added under N2 atmosphere, 140 oC oil bath, 20 h, bSecond step
reaction was carried out for 24 h, cFirst step reaction was carried out for 4 h
and second step for 24 h. Isolated yield reported.
Scheme 3. Catalytic cross coupling of secondary alcohols
with primary alcohols.
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After witnessing the excellent efficiency, we focused to the
terminal alkene) represents the potential of the present catalytic
potential synthetic applications for the present Fe-catalyzed
process. For instance, alkylation of 4-cholesten-3-one 1k with
benzyl alcohol 2a resulted the alkylated product 4 in 38% yield
(Scheme 6). It is anticipated that, the condensation product was
not reduced under the reaction conditions, instead a double
bond isomerization took place. The resulted double bond isom-
erization product is more stable due to substituted quinone
framework and resist the reduction process, hence product 4 is
dominated. Notably, we have also observed trace amount of an-
other unidentified products. Again, when using fatty acid de-
rived oleyl alcohol as coupling partner with propiophenone 1a,
chain elongated di-alkylated ketone 5 was obtained in moderate
yield. Nevertheless, the catalytic process worked well for one-
pot synthesis of donepezil 6, extensively used for the treatment
of Alzheimer’s disease.14 These interesting chemo-selective ap-
plications represent the synthetic potential of the catalytic pro-
cess and sustained well without much affecting the reducible
cholestenone as well as fatty acid framework (Scheme 5). In all
these complex products (4-6) low yields were observe due to
the presence of unreacted starting materials (25-30%) along
with the undesired side products (20-30%).
protocol. For a practical utility the present Fe-catalyzed proto-
col worked efficiently when a gram scale reaction was per-
formed using deoxybenzoin 1b with benzylalcohol 2a. Gratify-
ingly, 3j was obtain in 69% yield (Scheme 6). However, appli-
cations of benzyl alcohols bearing nitro and cyano groups,
cinnamyl alcohol, propagyl alcohol, diols as well as amino al-
cohols were not successful and we observed only trace or no
product conversion to the desired products (SI, Scheme S12).
Again, in case of 2-indanone, isophorone as well as other linear
ketones we observed albeit with poor product conversions (SI,
Scheme S12).
Further, to interrogate the reaction mechanism and to gain
insight about the active Fe-species for the alkylation process,
initially we investigated the reaction using IR probe to analyze
the actual changes associated with CO ligand frequency during
the progress of the reactions. The pre-catalyst Fe2(CO)9 was
identified by two characteristic signals at 2015 cm-1 and 1823
cm-1 respectively, which could be attributed as terminal CO and
bridged CO ligand frequency.11a However, the CO ligand fre-
quency at 1823 cm-1 was disappeared when the pre-catalyst
Fe2(CO)9 was heated at 140 0C for 1 h using benzyl alcohol 2a
and t-BuOK in toluene. Nevertheless, one signal at 1635 cm-1,
characteristic peak for benzaldehyde, was detected using IR
probe (SI, Scheme S10). We anticipated that, under thermal
reaction pre-catalyst Fe2(CO)9 converted to a transient 16-elec-
tron species Fe(CO)4 with a vacant coordination site, which
thereafter bind with benzyl alcohol 2a and resulted the interme-
diate iron-alkoxy species Fe-2.8a Subsequently, base mediated
-hydride elimination of species Fe-2 resulted the formation of
benzaldehyde and H2Fe(CO)4, responsible for hydrogenation
process (Figure 1).11f
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Scheme 5. Synthetic utility.
Figure 1: IR-probe studies for the detection of intermediate
Fe-species.
a
Reaction conditions: Ketone 1 (0.25 mmol), primary alcohol 2 (0.3125
mmol), Fe2(CO)9 (2.5 mol%), t-BuOK (0.25 mmol), toluene (2.0 mL),
Schlenk tube under N2 atmosphere, 140 °C oil bath, 36 h reaction time. Iso-
lated yield reported.
Scheme 6. Practical utility: gram scale synthesis of 3j.
Reaction condition: aDeoxybenzoin 1b (1 g, 5.1 mmol), benzyl alcohol 2a
(0.69 g, 6.38 mmol), Fe2(CO)9 (47 mg, 2.5 mol%), t-BuOK (572 mg, 5.1
mmol), toluene (10 mL) in a Schlenk tube under N2 atmosphere at 140 °C
in an oil bath for 24 h.
Figure 2: Plausible mechanism for the Fe-catalyzed synthe-
sis of branched ketones and alcohols.
Notably, herein we established a general catalytic protocol
proceeded well in the presence of benzyl alcohols decorated
with halides (F and Cl), methoxy, alkyl, trifluoromethyl and
1,3-dioxolone moiety. Heteroaryl alcohols, such as, thiophene,
furan and pyridine groups is tolerated. Interestingly, more chal-
lenging, long chain, C4-C10 alkyl alcohols efficiently utilized
for the alkylation process. Similarly, a variety of methylene
ketones, having aryl-alkyl framework, secondary alcohols as
well as alkyl ketones efficiently participated under the opti-
mized protocol. Importantly, cholestenone and oleyl alcohol
having reducible functional group (steroid framework and
Scheme 7. Catalytic and mechanistic studies.
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was independently prepared and employed with 2a and 2a-d2
(92% D) under standard conditions of Table 1. As expected, 3a
and 3a-d3 were obtained in up to 91-93% yield respectively and
in case of 3a-d3 we observed 14-18% deuterium incorporation
(Scheme 7a and SI Scheme S1). However, when benzyl alcohol
2a-d1 reacted with 1a, no deuterium incorporation observed in
the desired α-alkylated product (Scheme 7b and SI Scheme S4).
When using 1:1 mixture of 2a and 2a-d2, we witnessed the for-
1
mation of H/D-scrambled products 3a-d3 using H-NMR and
9
GC-MS analysis (Scheme 7b and SI Scheme S2-S3). Interest-
ingly, α-alkylation of 1a-d2 (96% D) with 2a evident the par-
ticipation of the benzylic C-H bond of the ketones (Scheme 7b
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and SI Scheme S4). Furthermore, a
series of control exper-
iments using 1a with benzylalcohol 2a in presence and absence
of Fe-catalyst were perform (Scheme 7c). Nevertheless, when
4-methoxybenzaldehyde was use for the alkylation with 1a un-
der standard conditions of Table 1, 3b was obtain in 15% prod-
uct yield. However, in absence of catalyst resulted albeit with
poor product conversion (Scheme 7c). Thereafter, deuterium la-
belling experiments also strongly supports our present findings
for D/H exchange involving hydrogen auto-transfer strategy
(Scheme 7 and SI Schemes S1-S5).15
A time conversion plot for α-alkylation of propiophenone 1a
with benzylalcohol 2a was monitored using GC. It was ob-
served that, after a certain periods of time, intermediate product
alcohol 3a’ gradually dehydrogenated to the ketone product 3a
and at this point, selective control to alcohol is quite challenging
(SI Scheme S8 and Figure 2). Notably, concentration of alde-
hyde 2a’ remained constant during the process. Finally, kinetics
studies to determine the rate and order of the alkylation process
were perform and observed first order kinetics (SI Schemes S6-
S7).
Scheme 7c: Control experiments.
CONCLUSIONS
In summary, herein we demonstrated an unprecedented and
general Fe2(CO)9 catalyzed,16 synthesis of functionalized
branched ketones. A simple catalytic system used for a series of
alkyl ketones, symmetrical, and unsymmetrical methylene ke-
tones and secondary alcohols to couple with aromatic as well as
C4-C10 alkyl alcohols. A single catalyst successfully employed
for dehydrogenation of both primary and secondary alcohols,
broaden the scope of this catalytic protocol. We established a
sequential one pot double alkylation to hetero bis-alkylated ke-
tones using a single catalyst with two different alcohols. Suc-
cessful synthetic application to one-step synthesis of
Alzheimer’s drug and alkylation of steroid hormone highlight
the potential of this process. Initial mechanistic studies involv-
ing a series of kinetic and deuterium labelling experiments
revealed the involvement of hydrogen auto-transfer principle
for C-C bond formation. We established that, our protocol could
be applied to a complex steroid derivative irrespective to the
nature of the ketones and alcohols.
Reaction condition: All mechanistic studies were performed using 1a or 3a”
with (0.1 mmol).
Based on the initial findings through IR probe, NMR including
GC-MS studies (Figure 1) and related literature reports,8-9, 11f, 12
herein we proposed a plausible reaction mechanism for the syn-
thesis of branched ketones using Fe-catalyst (Figure 2). Primar-
ily, Fe-catalyzed dehydrogenation of primary alcohols 2a re-
sulted benzaldehyde 2a’. Next, base mediated condensation
with propiophenone 1a gave α,β-unsaturated ketone 3a”. There-
after, selective hydrogenation of enone 3a” by in situ generated
H2Fe(CO)4 species resulted the desired α,α-di-substituted ke-
tones 3a. However, 3a could also be produced via a reversible
process from alcohol intermediate 3a’. Additionally, when us-
ing secondary alcohol 1a’, Fe-catalyzed dehydrogenation re-
sulted propiophenone 1a and continued the general mechanism
to access various functionalized branched ketones (Figure 2).
Notably, during the progress of the reactions, hydrogen gas was
generated and we have experimentally detected the gaseous hy-
drogen using gas chromatography analysis (SI Scheme S14).
Additionally, to establish the hydrogen-borrowing process and
bi-functional nature of the Fe-catalyst, a series of deuterium-
labelling experiments were performed (Scheme 7). Enone 3a”
EXPERIMENTAL SECTION
General Experimental Details: All solvents and reagents
were used, as received from the suppliers. TLC was performed
on Merck Kiesel gel 60, F254 plates with the layer thickness of
0.25 mm. Column chromatography was performed on silica gel
(100-200 mesh) using a gradient of ethyl acetate and hexane as
1
mobile phase. H-NMR spectral data were collected at, 400
1
MHz (JEOL), and 13C-NMR were recorded at 100 MHz. H
NMR spectral data are given as chemical shifts in ppm followed
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by multiplicity (s- singlet; d- doublet; t- triplet; q- quartet; m-
Procedure for gram scale reaction: Gram Scale reaction was
multiplet), number of protons and coupling constants. 13C{H}
NMR chemical shifts are expressed in ppm. HRMS (ESI) spec-
tral data were collected using Bruker High Resolution Mass
Spectrometer. GC and GC-MS were recorded using Agilent
Gas Chromatography Mass Spectrometry. Elemental analysis
data were recorded using Vario Micro Cube elemental analyser.
All the reactions were performed in a closed system using
Schlenk tube. All Iron salts were purchased from Alfa Aesar.
Fe2(CO)9 (Assay- ≥94.0 to ≤106.0% by Fe, CAS Number
14024-58-9; MDL number: MFCD00000022). Potassium tert-
butoxide was purchased from Avra Synthesis Pvt. Ltd., India.
(Purity-98%, CAS No: 865-47-4, Catalog No- ASP2012).
General procedures for Fe-catalyzed synthesis of branched
ketones and alcohols:
performed using deoxybenzoin 1b (1.0 g, 5.1 mmol), benzyl al-
cohol 2a (0.69 g, 6.38 mmol), Fe2(CO)9 (47 mg, 2.5 mol%), t-
BuOK (572 mg, 5.1 mmol), toluene (10.0 mL) in a 100 mL
pressure tube under N2 atmosphere at 140 ºC in oil bath for 24
h. The reaction mixture was cooled to room temperature and
15.0 mL of ethyl acetate was added and concentrated in vacuo.
The residue was purified by column chromatography using a
gradient of hexane and ethyl acetate (eluent system) to afford
the pure product 3j (0.98 g, 69% yield).
Preparation of α,α-dideuteriobenzyl alcohol (PhCD2OH)
2a-d2: In a 50 mL round-bottom flask LiAlD4 (150 mg, 3.6
mmol) was taken in THF (20 mL) at 0ºC and then, a solution of
methyl benzoate (5 mmol, 680 mg) was taken in THF (10 mL).
The mixture was stirred for 2 hours at 0 ºC. The resulting solu-
tion was quenched with HCl 1N and extracted with ether (3×20
mL), followed by concentrating in vacuum and the residue was
purified by flash chromatography on a short silica gel to afford
100 mg (92% of D) of PhCD2OH.
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Procedure [A]: For the synthesis of 2-methyl-1,3-diphenylpro-
pan-1-one (3a): In a 15 mL oven dried Schlenk tube, propio-
phenone 1a (0.5 mmol, 67 mg), t-BuOK (0.5 mmol, 56.1 mg),
Fe2(CO)9 (2.5 mol%, 4.5 mg) and benzyl alcohol 2a (0.625
mmol, 1.25 equiv., 67.5 mg) were added followed by toluene
2.0 mL under an atmosphere of N2 and the reaction mixture was
refluxed in an oil bath at 140 oC for 24 h in closed system. The
reaction mixture was cooled to room temperature and 3.0 mL
of ethyl acetate was added and concentrated in vacuo. The res-
idue was purified by column chromatography using a gradient
of hexane and ethyl acetate (eluent system) to afford the pure
product 3a. This procedure was used as general procedure A.
Procedure [B]: In a 15 mL oven dried Schlenk tube, acetophe-
none (0.5 mmol, 60.2 mg), t-BuOK (0.5 mmol, 56.1 mg),
Fe2(CO)9 (2.5 mol%, 4.54 mg) and alcohols 2 (0.5 mmol, 1.0
equiv.) were added followed by toluene 2.0 mL under an atmos-
phere of N2 and the reaction mixture was refluxed in an oil bath
at 140 oC for 2 h in closed system. After 2 h another alcohol 2
(0.5 mmol) was added under N2 atmosphere and the reaction
mixture was heated at 140 oC in an oil bath for 20 h, The reac-
tion mixture was cooled to room temperature and 3.0 mL of
ethyl acetate was added and concentrated in vacuo. The residue
was purified by column chromatography using a gradient of
hexane and ethyl acetate (eluent system) to afford the pure prod-
uct.
Procedure [C]: In a 15 mL oven dried Schlenk tube, secondary
ketones 1 (0.25 mmol), t-BuOK (0.25 mmol, 28 mg), Fe2(CO)9
(2.5 mol%, 2.27 mg) and primary alcohols 2 (0.3125 mmol,
1.25 equiv.) were added followed by toluene 2.0 mL under an
atmosphere of N2 and the reaction mixture was refluxed at 140
oC in an oil bath for 24 h in closed system. The reaction mixture
was cooled to room temperature and 3.0 mL of ethyl acetate
was added and concentrated in vacuo. The residue was purified
by column chromatography using a gradient of hexane and ethyl
acetate (eluent system) to afford the pure product.
Procedure [D]: In a 15 mL oven dried Schlenk tube, secondary
alcohols 1a’ (0.5 mmol), t-BuOK (0.5 mmol, 56.1 mg),
Fe2(CO)9 (2.5 mol%, 4.54 mg) and primary alcohols 2 (0.625
mmol, 1.25 equiv.) were added followed by toluene 2.0 mL un-
der an atmosphere of N2 and the reaction mixture was refluxed
in an oil bath at 140 oC for 24 h in closed system. The reaction
mixture was cooled to room temperature and 3.0 mL of ethyl
acetate was added and concentrated in vacuo. The residue was
purified by column chromatography using a gradient of hexane
and ethyl acetate (eluent system) to afford the pure product.
Preparation of benzyl alcohol-OD (PhCH2OD) 2a-d1: In a
50 mL round-bottom flask benzyl alcohol 2a (4.63 mmol, 500
mg) was taken in 5 ml D2O. The mixture was stirred for 48
hours under room temperature. After concentrating in vacuum,
the residue was purified by flash chromatography on a short sil-
ica gel to afford 420 mg (98% of D) of PhCH2OD.
Preparation of (PhC(O)CD2CH3) 1a-d2: In a 100 mL round-
bottom flask 805 mg (6.0 mmol) of propiophenone was taken
and added 30 mL of CH3OD. Sodium methoxide (9.5 mmol)
was added slowly. The mixture was stirred for 48-60 hours at
ambient temperature and monitored the progress of the reaction.
Subsequently quenched with cold water (10 mL), and the or-
ganics were extracted with Et2O (3 × 40 mL). And then, con-
centrating in vacuum and the residue was purified by flash chro-
matography on a short silica gel to afford 200 mg (97% of D)
of PhC(O)CD2CH3.
2-Methyl-1,3-diphenylpropan-1-one (3a):13b Following the
general procedure A and D, the title product was obtained as a
colorless oil using silica-gel column chromatography eluting
with 1% ethyl acetate in hexane. Yield: 90 mg, 81% yield (Pro-
1
cedure A), 83% yield (Procedure D); H NMR (400 MHz,
CDCl3) δ 7.92 (dd, J = 8.7, 1.4 Hz, 2H), 7.56-7.52 (m, 1H), 7.44
(t, J = 7.8 Hz, 2H), 7.28-7.24 (m, 2H), 7.21-7.13 (m, 3H), 3.75
(dq, J = 13.9, 7.0 Hz, 1H), 3.16 (dd, J = 14.0, 6.5 Hz, 1H), 2.69
(dd, J = 14.0, 8.0 Hz, 1H), 1.20 (d, J = 7.1 Hz, 3H); 13C{1H}
NMR (100 MHz, CDCl3) δ 203.7, 139.9, 136.4, 132.9, 129.1,
128.6, 128.3, 128.2, 126.2, 42.7, 39.3, 17.4.
3-(4-Methoxyphenyl)-2-methyl-1-phenylpropan-1-one
(3b):13b Following the general procedure A and D, the title prod-
uct was obtained as a colorless oil using silica-gel column chro-
matography eluting with 5% ethyl acetate in hexane. Yield: 62
1
mg, 49% yield (Procedure A), 58% yield (Procedure D); H
NMR (400 MHz, (100 MHz, CDCl3) δ 7.91 (d, J = 7.3 Hz, 2H),
7.55-7.51 (m, 1H), 7.43 (t, J = 7.6 Hz, 2H), 7.10 (d, J = 8.6 Hz,
2H), 6.79 (d, J = 8.6 Hz, 2H), 3.76 (s, 3H), 3.72-3.66 (m, 1H),
3.09 (dd, J = 13.8, 6.4 Hz, 1H), 2.62 (dd, J = 13.8, 7.7 Hz, 1H),
1.17 (d, J = 6.9 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ
203.8, 157.9, 136.4, 132.9, 130.1, 129.8, 128.2, 113.6, 109.4,
55.1, 42.9, 38.6, 17.3.
3-(4-Chlorophenyl)-2-methyl-1-phenylpropan-1-one
(3c):13b Following the general procedure A and D, the title prod-
uct was obtained as a colorless liquid using silica-gel column
chromatography eluting with 1% ethyl acetate in hexane. Yield:
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64 mg, 50% yield (Procedure A), 78% yield (Procedure D); 1H
(m, 4H), 1.18 (d, J = 6.8 Hz, 3H), 0.86 (t, J = 6.9 Hz, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 204.6, 136.7 132.8, 128.6,
128.2, 40.5, 33.4, 29.6, 22.8, 17.2, 14.0.
NMR (500 MHz, CDCl3) δ 7.92 (d, J = 8.7 Hz, 2H), 7.57 (t, J
= 7.6 Hz, 1H), 7.47 (t, J = 8.3 Hz, 2H), 7.24 (d, J = 8.8 Hz, 2H),
7.15 (d, J = 8.9 Hz, 2H), 3.76-3.72 (m, 1H), 3.17 (dd, J = 14.4,
7.2 Hz, 1H), 2.71 (dd, J = 14.4, 7.6 Hz, 1H), 1.23 (d, J = 7.6 Hz,
3H); 13C{1H} NMR (125 MHz, CDCl3) δ 203.3, 138.4, 133.0,
132.0, 130.4, 128.7, 128.6, 128.5, 128.2, 42.7, 38.7, 17.6.
3-(4-Fluorophenyl)-2-methyl-1-phenylpropan-1-one
2-methyl-1-phenylnonan-1-one (3i):13b Following the general
procedure A, the title product was obtained as a colorless oil
using silica-gel column chromatography eluting with 1% ethyl
acetate in hexane. Yield: 63 mg, 55% yield (Procedure A), 59%
yield (Procedure D); 1H NMR (500 MHz, CDCl3) δ 7.98 (d, J =
7.3 Hz, 2H), 7.61-7.57 (m, 1H), 7.49 (t, J = 6.8 Hz, 2H), 3.49-
3.47 (m, 1H), 1.84-1.80 (m, 1H), 1.51-1.40 (m, 1H), 1.27-1.21
(s, 10H), 1.22 (d, J = 6.6 Hz, 3H), 0.88 (t, J = 6.7 Hz, 3H);
13C{1H} NMR (101 MHz, CDCl3) δ 204.6, 136.8, 132.8, 128.6,
128.2, 40.6, 33.7, 31.8, 29.7, 29.1, 27.4, 22.6, 17.2, 14.1.
1,2,3-Triphenylpropan-1-one (3j):13b Following the general
procedure A and D, the title product was obtained as a colorless
solid using silica-gel column chromatography eluting with 1%
ethyl acetate in hexane. Yield: 122 mg, 86% yield (Procedure
A), 36% yield (Procedure D); 1H NMR (400 MHz, CDCl3) δ
7.89 (dd, J = 8.3, 1.2 Hz, 2H), 7.44-7.42 (m, 1H), 7.33 (dd, J =
8.0, 7.3 Hz, 2H), 7.25-7.21 (m, 4H), 7.20-7.17 (m, 3H), 7.14-
7.12 (m, 1H), 7.08-7.06 (m, 2H), 4.80 (t, J = 7.3 Hz, 1H), 3.56
(dd, J = 13.7, 7.5 Hz, 1H), 3.06 (dd, J = 13.7, 7.0 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ 199.2, 139.8, 139.1, 136.8,
132.8, 129.1, 128.9, 128.7, 128.5, 128.3, 128.2, 127.1, 126.1,
55.9, 40.1.
(3d):13b Following the general procedure A, the title product
was obtained as a colorless oil using silica-gel column chroma-
tography eluting with 1% ethyl acetate in hexane. Yield: 44 mg,
37% yield (Procedure A); 1H NMR (400 MHz, CDCl3) δ 7.89
(d, J = 8.2 Hz, 2H), 7.53 (t, J = 7.6 Hz, 1H), 7.43 (t, J = 7.9 Hz,
2H), 7.13 (dd, J = 9.0, 5.6 Hz, 2H), 6.92 (t, J = 8.9 Hz, 2H),
3.70 (dd, J = 14.2, 7.1 Hz, 1H), 3.12 (dd, J = 14.1, 7.0 Hz, 1H),
2.67 (dd, J = 14.0, 7.5 Hz, 1H), 1.19 (d, J = 7.1 Hz, 3H);
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13C{1H} NMR (100 MHz, CDCl3) δ 199.0, 160.2 (d, JC-F
=
242.7 Hz), 136.9, 136.8, 133.1, 130.4 (d, JC-F = 8 Hz), 128.6,
128.0, 115.2 (d, JC-F = 20.8 Hz), 40.4, 37.5, 29.2.
3-cyclopropyl-2-methyl-1-phenylpropan-1-one (3e): Fol-
lowing the general procedure A, the title product was obtained
as a colorless oil using silica-gel column chromatography elut-
ing with 1% ethyl acetate in hexane. Yield: 68 mg, 73% yield
(Procedure A); 1H NMR (400 MHz, CDCl3) δ 7.98 (dd, J = 5.3,
3.3 Hz, 2H), 7.58-7.54 (m, 1H), 7.49-7.45 (m, 2H), 3.62 (h, J =
6.8 Hz, 1H), 1.70 (dd, J = 13.8, 6.9 Hz, 1H), 1.43-1.34 (m, 1H),
1.24 (d, J = 6.9 Hz, 3H), 0.72-0.67 (m, 1H), 0.44-0.35 (m, 2H),
0.04 (dd, J = 4.9, 1.6 Hz, 2H); 13C{1H} NMR (100 MHz,
CDCl3) δ 204.7, 136.8, 132.8, 128.6, 128.3, 41.1, 38.9, 17.3,
9.2, 4.9, 4.5. Elemental Analysis: C13H16O: C, 82.94; H, 8.57;
O, 8.50. Found: C, 82.81; H, 8.39; O, 8.38. HRMS (ESI-TOF)
m/z [M+Na]+ Calcd for C13H16O 211.1093, Found 211.1076.
3-cyclohexyl-2-methyl-1-phenylpropan-1-one (3f):17 Follow-
ing the general procedure A and D, the title product was ob-
tained as a colorless oil using silica-gel column chromatography
eluting with 1% ethyl acetate in hexane. Yield: 86 mg, 75%
3-(4-methoxyphenyl)-1,2-diphenylpropan-1-one
(3k):13c
Following the general procedure A, the title product was ob-
tained as a colorless solid using silica-gel column chromatog-
raphy eluting with 3% ethyl acetate in hexane. Yield: 77 mg,
1
49% yield (Procedure A); H NMR (400 MHz, CDCl3) δ 7.82
(d, J = 7.2 Hz, 2H), 7.37 (t, J = 7.4 Hz, 1H), 7.27 (t, J = 7.6 Hz,
2H), 7.21-7.13 (m, 5H), 6.92 (d, J = 8.6 Hz, 2H), 6.66 (d, J =
8.7 Hz, 2H), 4.70 (t, J = 7.3 Hz, 1H), 3.67 (s, 3H), 3.43 (dd, J =
13.8, 7.5 Hz, 1H), 2.93 (dd, J = 13.8, 7.0 Hz, 1H); 13C{1H}
NMR (100 MHz, CDCl3) δ 199.4, 158.0, 139.2, 136.8, 132.8,
131.9, 130.0, 128.9, 128.6, 128.4, 128.3, 127.1, 113.2, 56.2,
55.2, 39.3.
1
yield (Procedure A), 62% yield (Procedure D); H NMR (400
MHz, CDCl3) δ 7.96-7.93 (m, 2H), 7.56-7.52 (m, 1H), 7.45 (dd,
J = 8.0, 7.0 Hz, 2H), 3.58 (h, J = 6.8 Hz, 1H), 1.73-1.63 (m,
6H), 1.27 (dd, J = 12.4, 6.6 Hz, 2H), 1.16 (d, J = 6.8 Hz, 3H),
1.14-1.06 (m, 3H), 0.89-0.86 (m, 2H); 13C{1H} NMR (100
MHz, CDCl3) δ 204.6, 136.6, 132.8, 128.6, 128.2, 41.2, 37.6,
35.3, 33.8, 33.0, 26.5, 26.2, 26.2, 17.5.
1,2-diphenyl-3-(p-tolyl)propan-1-one (3l):13c Following the
general procedure A, the title product was obtained as a color-
less solid using silica-gel column chromatography eluting with
1% ethyl acetate in hexane. Yield: 123 mg, 82% yield (Proce-
dure A); 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 8.6 Hz, 2H),
7.38 (t, J = 7.4 Hz, 1H), 7.27 (t, J = 7.6 Hz, 2H), 7.20-7.16 (m,
5H), 6.94-6.89 (m, 4H), 4.72 (t, J = 7.2 Hz, 1H), 3.46 (dd, J =
13.8, 7.6 Hz, 1H), 2.95 (dd, J = 13.8, 6.9 Hz, 1H), 2.19 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 199.3, 139.2, 136.7, 136.6,
135.5, 132.8, 129.0, 129.0, 128.9, 128.7, 128.4, 128.3, 127.1,
55.9, 39.7, 21.0.
2,5,9-Trimethyl-1-phenyldec-8-en-1-one (3g):13b Following
the general procedure A, the title product was obtained as a pale
yellow oil using silica-gel column chromatography eluting with
1% ethyl acetate in hexane. Yield: 99 mg, 73% yield (Procedure
A); 1H NMR (400 MHz, CDCl3) δ 7.94 (d, J = 7.9 Hz, 2H), 7.54
(dd, J = 8.2, 6.5 Hz, 1H), 7.45 (t, J = 7.6 Hz, 2H), 5.06-5.04 (m,
1H), 3.42-3.40 (m, 1H), 1.97-1.73 (m, 3H), 1.65 (d, J = 4.2 Hz,
3H), 1.57 (d, J = 5.0 Hz, 2H), 1.35-1.24 (m, 5H), 1.18 (d, J =
6.9 Hz, 3H), 1.15-1.04 (m, 2H), 0.84 (t, J = 6.5 Hz, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 204.4, 136.7, 132.7, 131.0,
128.5, 128.1, 124.7, 40.9, 36.9, 36.7, 34.5, 32.4, 31.1, 25.4,
19.5, 17.4.
3-(4-ethylphenyl)-1,2-diphenylpropan-1-one (3m):13c Fol-
lowing the general procedure A and D, the title product was ob-
tained as a colorless solid using silica-gel column chromatog-
raphy eluting with 1% ethyl acetate in hexane. Yield: 138 mg,
1
88% yield (Procedure A), 32% yield (Procedure D); H NMR
(400 MHz, CDCl3) δ 7.83 (d, J = 8.0 Hz, 2H), 7.38 (t, J = 7.4
Hz, 1H), 7.27 (t, J = 7.6 Hz, 2H), 7.20-7.17 (m, 5H), 6.97-6.92
(m, 4H), 4.76-4.72 (m, 1H), 3.47 (dd, J = 13.8, 7.7 Hz, 1H),
2.95 (dd, J = 13.8, 6.7 Hz, 1H), 2.50 (q, J = 7.6 Hz, 2H), 1.11
(t, J = 7.6 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 199.3,
142.0, 139.3, 137.0, 136.8, 132.8, 129.0, 128.9, 128.7, 128.4,
128.3, 127.7, 127.1, 56.1, 39.6, 28.1, 15.4.
2-methyl-1-phenylhexan-1-one (3h):8e Following the general
procedure A, the title product was obtained as a pale yellow oil
using silica-gel column chromatography eluting with 1% ethyl
1
acetate in hexane. Yield: 60 mg, 64% yield (Procedure A); H
NMR (400 MHz, CDCl3) δ 7.94 (dd, J = 5.2, 3.4 Hz, 2H), 7.56-
7.53 (m, 1H), 7.45 (t, J = 7.5 Hz, 2H), 3.45 (h, J = 6.8 Hz, 1H),
1.81-1.77 (m, 1H), 1.42 (dd, J = 12.9, 6.3 Hz, 1H), 1.30-1.28
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3-(4-isopropylphenyl)-1,2-diphenylpropan-1-one
(3n):13c
Following the general procedure A, the title product was ob-
tained as a colorless solid using silica-gel column chromatog-
raphy eluting with 1% ethyl acetate in hexane. Yield: 119 mg,
3-(1,3-dihydroisobenzofuran-5-yl)-1,2-diphenylpropan-1-
one (3s):13c Following the general procedure A, the title product
was obtained as a colorless solid using silica-gel column chro-
matography eluting with 5% ethyl acetate in hexane. Yield: 100
1
1
73% yield (Procedure A); H NMR (400 MHz, CDCl3) δ 7.83
mg, 61% yield (Procedure A); H NMR (400 MHz, CDCl3) δ
5
(d, J = 7.1 Hz, 2H), 7.38 (t, J = 7.3 Hz, 1H), 7.27 (t, J = 7.6 Hz,
2H), 7.20-7.17 (m, 5H), 6.97 (q, J = 8.2 Hz, 4H), 4.75 (t, J = 7.2
Hz, 1H), 3.49 (dd, J = 13.9, 7.9 Hz, 1H), 2.95 (dd, J = 13.8, 6.5
Hz, 1H), 2.80-2.71 (m, 1H), 1.12 (d, J = 7.1 Hz, 6H); 13C{1H}
NMR (100 MHz, CDCl3) δ 199.3, 146.6, 139.3, 137.1, 136.7,
132.8, 129.0, 128.9, 128.7, 128.4, 128.3, 127.1, 126.3, 55.8,
39.7, 33.6, 24.0.
7.84 (dd, J = 8.4, 1.3 Hz, 2H), 7.39 (t, J = 7.4 Hz, 1H), 7.29 (t,
J = 7.6 Hz, 2H), 7.21-7.13 (m, 5H), 6.58-6.46 (m, 3H), 5.81 (s,
2H), 4.69 (t, J = 7.2 Hz, 1H), 3.41 (dd, J = 13.8, 7.6 Hz, 1H),
2.91 (dd, J = 13.8, 6.9 Hz, 1H); 13C{1H} NMR (100 MHz,
CDCl3) δ 199.1, 147.0, 145.6, 139.1, 136.6, 133.5, 132.9, 128.9,
128.7, 128.5, 128.2, 127.2, 122.0, 109.5, 108.0, 100.7, 55.9,
39.7.
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3-(4-chlorophenyl)-1,2-diphenylpropan-1-one (3o):13c Fol-
lowing the general procedure A, the title product was obtained
as a colorless solid using silica-gel column chromatography
eluting with 1% ethyl acetate in hexane. Yield: 139 mg, 87%
yield (Procedure A); 1H NMR (400 MHz, CDCl3) δ 7.89 (d, J =
7.1 Hz, 2H), 7.46 (t, J = 7.4 Hz, 1H), 7.35 (t, J = 7.6 Hz, 2H),
7.26 (t, J = 7.3 Hz, 3H), 7.21 (d, J = 7.3 Hz, 2H), 7.15 (d, J =
8.4 Hz, 2H), 7.00-6.98 (m, 2H), 4.75 (t, J = 7.3 Hz, 1H), 3.50
(dd, J = 13.8, 7.4 Hz, 1H), 3.03 (dd, J = 13.7, 7.2 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ 198.9, 138.7, 138.2, 136.6,
132.9, 131.9, 130.5, 129.0, 128.7, 128.5, 128.3, 128.2, 127.3,
55.7, 39.3.
1,2-diphenyl-3-(thiophen-2-yl)propan-1-one (3t):13c Follow-
ing the general procedure A and D, the title product was ob-
tained as a pale yellow solid using silica-gel column chroma-
tography eluting with 5% ethyl acetate in hexane. Yield: 70 mg,
1
48% yield (Procedure A), 28% yield (Procedure D); H NMR
(400 MHz, CDCl3) δ 7.92 (d, J = 8.6 Hz, 2H), 7.48-7.43 (m,
1H), 7.36 (t, J = 7.6 Hz, 2H), 7.27 (dd, J = 3.8, 3.3 Hz, 4H),
7.23-7.10 (m, 1H), 7.05 (d, J = 5.1 Hz, 1H), 6.82 (dd, J = 5.1,
3.4 Hz, 1H), 6.68 (d, J = 3.4 Hz, 1H), 4.84 (dd, J = 7.9, 6.6 Hz,
1H), 3.78 (dd, J = 14.5, 7.5 Hz, 1H), 3.27 (dd, J = 14.8, 6.6 Hz,
1H); 13C{1H} NMR (100 MHz, CDCl3) δ 198.8, 142.1, 138.6,
133.0, 133.0, 129.0, 128.7, 128.5, 128.2, 127.4, 126.6, 125.7,
123.6, 56.3, 34.1.
1,2-diphenyl-3-(4-(trifluoromethyl)phenyl)propan-1-one
(3p):13c Following the general procedure A, the title product
was obtained as a colorless solid using silica-gel column chro-
matography eluting with 1% ethyl acetate in hexane. Yield: 95
3-(furan-2-yl)-1,2-diphenylpropan-1-one (3u):5c Following
the general procedure A, the title product was obtained as a pale
yellow solid using silica-gel column chromatography eluting
with 5% ethyl acetate in hexane. Yield: 63 mg, 46% yield (Pro-
cedure A); 1H NMR (400 MHz, CDCl3) δ 7.93 (dd, J = 8.3, 1.2
Hz, 2H), 7.49-7.44 (m, 1H), 7.39-7.33 (m, 2H), 7.27-7.23 (m,
5H), 7.19 (ddd, J = 9.6, 5.1, 2.9 Hz, 1H), 6.17 (dd, J = 3.1, 1.9
Hz, 1H), 5.86 (dd, J = 3.1, 0.5 Hz, 1H), 4.98 (dd, J = 7.7, 6.9
Hz, 1H), 3.60-3.53 (m, 1H), 3.09 (dd, J = 15.1, 6.8 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ 198.7, 153.3, 141.1, 138.7,
136.4, 132.9, 128.9, 128.7, 128.5, 128.0, 127.2, 110.2, 106.5,
52.5, 32.4.
1
mg, 54% yield (Procedure A); H NMR (400 MHz, CDCl3) δ
7.89 (d, J = 7.4 Hz, 2H), 7.45 (t, J = 8.9 Hz, 3H), 7.34 (t, J =
7.7 Hz, 2H), 7.28-7.25 (m, 2H), 7.19 (dd, J = 12.8, 7.6 Hz, 5H),
4.78 (t, J = 7.3 Hz, 1H), 3.59 (dd, J = 13.7, 7.5 Hz, 1H), 3.11
(dd, J = 13.8, 7.1 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ
198.6, 143.9, 143.9, 138.5, 136.3, 133.0, 129.5, 129.1, 128.7,
128.5 (q, JF-C = 32 Hz), 128.2, 127.4, 125.1 (q, JF-C = 8 Hz),
124.2 (d, JF-C = 271 Hz), 55.6, 39.8.
1,2-diphenyl-3-(o-tolyl)propan-1-one (3q): Following the
general procedure A, the title product was obtained as a color-
less solid using silica-gel column chromatography eluting with
1% ethyl acetate in hexane. Yield: 96 mg, 64% yield (Procedure
A); 1H NMR (400 MHz, CDCl3) δ 7.89-7.87 (m, 2H), 7.46-7.42
(m, 1H), 7.35-7.32 (m, 2H), 7.27-7.17 (m, 6H), 7.08-6.96 (m,
3H), 4.81-4.78 (m, 1H), 3.58-3.52 (m, 1H), 3.06 (dd, J = 14.1,
7.0 Hz, 1H), 2.21 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ
199.3, 139.2, 137.8, 136.3, 132.8, 130.1, 129.7, 129.1, 128.9,
128.7, 128.5, 128.2, 127.1, 126.2, 125.7, 54.5, 37.1, 19.5. Ele-
mental Analysis: C22H20O: C, 87.96; H, 6.71; O, 5.33. Found:
C, 87.84; H, 6.59; O, 5.50; HRMS (ESI-TOF) m/z [M+Na]+
Calcd for C22H20O 323.1514, Found 323.1528.
1,2-diphenyl-3-(pyridin-2-yl)propan-1-one (3v):13c Follow-
ing the general procedure A, the title product was obtained as a
yellow oil using silica-gel column chromatography eluting with
7% ethyl acetate in hexane. Yield: 97 mg, 68% yield (Procedure
A); 1H NMR (400 MHz, CDCl3) δ 8.45-8.43 (m, 1H), 7.92-7.90
(m, 2H), 7.44-7.41 (m, 2H), 7.31 (t, J = 7.6 Hz, 2H), 7.26-7.21
(m, 4H), 7.16-7.11 (m, 1H), 7.01 (t, J = 6.2 Hz, 2H), 5.30 (dd,
J = 8.5, 6.3 Hz, 1H), 3.69 (dd, J = 14.1, 8.5 Hz, 1H), 3.18 (dd,
J = 14.1, 6.3 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ
199.4, 159.4, 149.1, 139.1, 136.7, 136.1, 132.7, 128.9, 128.8,
128.4, 128.3, 127.1, 124.1, 121.2, 53.2, 42.2.
2-Benzyl-3,4-dihydronaphthalen-1(2H)-one (3w):13c Follow-
ing the general procedure A and D, the title product was ob-
tained as a colorless oil using silica-gel column chromatography
eluting with 1% ethyl acetate in hexane. Yield: 108 mg, 92%
3-(naphthalen-1-yl)-1,2-diphenylpropan-1-one (3r):13c Fol-
lowing the general procedure A, the title product was obtained
as a colorless solid using silica-gel column chromatography
eluting with 1% ethyl acetate in hexane. Yield: 122 mg, 73%
yield (Procedure A); 1H NMR (400 MHz, CDCl3) δ 8.04 (d, J =
8.4 Hz, 1H), 7.85-7.82 (m, 3H), 7.66 (d, J = 8.2 Hz, 1H), 7.53-
7.47 (m, 2H), 7.41 (t, J = 7.4 Hz, 1H), 7.30 (d, J = 8.0 Hz, 2H),
7.25-7.20 (m, 6H), 7.10 (d, J = 6.8 Hz, 1H), 4.99 (t, J = 7.0 Hz,
1H), 4.09 (dd, J = 14.1, 7.3 Hz, 1H), 3.47 (dd, J = 14.1, 6.6 Hz,
1H); 13C{1H} NMR (100 MHz, CDCl3) δ 199.2, 139.4, 136.6,
135.5, 133.8, 132.8, 131.8, 129.0, 128.9, 128.7, 128.4, 128.3,
128.1, 127.6, 127.2, 127.0, 126.0, 125.3, 123.4, 54.5, 36.9.
1
yield (Procedure A), 68% yield (Procedure D); H NMR (400
MHz, CDCl3) δ 8.07 (dd, J = 7.9, 1.0 Hz, 1H), 7.48-7.43 (m,
1H), 7.33-7.28 (m, 3H), 7.25-7.19 (m, 4H), 3.49 (dd, J = 13.6,
3.9 Hz, 1H), 2.95-2.90 (m, 2H), 2.77-2.67 (m, 1H), 2.64 (dd, J
= 13.6, 9.6 Hz, 1H), 2.12-2.07 (m, 1H), 1.83-1.76 (m, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ 199.4, 144.0, 140.0, 133.3,
132.4, 129.2, 128.7, 128.4, 127.5, 126.6, 126.1, 49.4, 35.6, 28.6,
27.6.
2-Benzyl-7-methoxy-3,4-dihydronaphthalen-1(2H)-one
(3x):13c Following the general procedure A, the title product was
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obtained as a pale yellow oil using silica-gel column chroma-
J = 6.9, 5.2 Hz, 1H), 4.43-4.36 (m, 1H), 3.23 (dd, J = 14.1, 8.5
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tography eluting with 2% ethyl acetate in hexane. Yield: 85 mg,
64% yield (Procedure A); H NMR (400 MHz, CDCl3) δ 7.54
Hz, 1H), 3.08 (dd, J = 13.6, 7.6 Hz, 1H), 2.90 (dd, J = 14.1, 5.8
Hz, 1H), 2.74 (dd, J = 13.6, 6.6 Hz, 1H); 13C{1H} NMR (100
MHz, CDCl3) δ 203.5, 159.3, 149.2, 139.2, 137.3, 136.1, 136.1,
132.7, 129.1, 128.4, 128.3, 126.2, 123.9, 121.2, 47.9, 40.1, 38.4.
2-Benzyl-1-(4-methoxyphenyl)-3-phenylpropan-1-one
(3ad):13c Following the general procedure B, the title product
was obtained as a colourless oil using silica-gel column chro-
matography eluting with 3% ethyl acetate in hexane. Yield: 140
mg, 85% yield (Procedure B); 1H NMR (400 MHz, CDCl3) δ
7.73 (d, J = 9.2 Hz, 2H), 7.39-7.38 (m, 1H), 7.25-7.19 (m, 4H),
7.14-7.11 (m, 5H), 6.80 (d, J = 9.1 Hz, 2H), 4.00-3.93 (m, 1H),
3.80 (s, 3H), 3.12 (dd, J = 14.2, 8.1 Hz, 2H), 2.79 (dd, J = 14.1,
6.5 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 201.6, 163.2,
139.7, 130.4, 130.3, 129.0, 128.3, 126.2, 113.6, 55.4, 49.9, 38.3.
2-Benzyl-1-(4-methoxyphenyl)-3-(p-tolyl)propan-1-one
(3ae): 13c Following the general procedure B, the title product
was obtained as a colourless liquid using silica-gel column
chromatography eluting with 3% ethyl acetate in hexane. Yield:
122 mg, 71% yield (Procedure B); 1H NMR (400 MHz, CDCl3)
δ 7.75-7.72 (m, 2H), 7.25-7.17 (m, 3H), 7.13-7.11 (m, 3H), 7.01
(d, J = 3.0 Hz, 3H), 6.80 (d, J = 8.9 Hz, 2H), 3.96-3.91 (m, 1H),
3.80 (s, 3H), 3.10-3.04 (m, 2H), 2.79-2.74 (m, 2H), 2.25 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 201.7, 163.2, 139.8, 136.5,
135.6, 130.5, 130.4, 129.0, 128.9, 128.3, 127.6, 126.1, 113.6,
55.5, 50.0, 38.2, 37.9, 21.0.
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(d, J = 2.8 Hz, 1H), 7.32-7.28 (m, 2H), 7.25-7.19 (m, 3H), 7.12
(d, J = 8.4 Hz, 1H), 7.04 (dd, J = 8.4, 2.8 Hz, 1H), 3.83 (s, 3H),
3.47 (dd, J = 13.4, 3.8 Hz, 1H), 2.88-2.86 (m, 2H), 2.66-2.63
(m, 2H), 2.10-2.05 (m, 1H), 1.79-1.73 (m, 1H); 13C{1H} NMR
(100 MHz, CDCl3) δ 199.4, 158.3, 140.0, 136.6, 133.2, 129.9,
129.2, 128.4, 126.1, 121.7, 109.4, 55.5, 55.5, 49.3, 35.7, 27.7.
2-benzyl-1,3-diphenylpropan-1-one (3y):13c Following the
general procedure A and B, the title product was obtained as a
colorless oil using silica-gel column chromatography eluting
with 1% ethyl acetate in hexane. Yield: 64 mg, 43% yield (Pro-
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cedure A), 73% yield (Procedure B); H NMR (400 MHz,
CDCl3) δ 7.72 (d, J = 8.2 Hz, 2H), 7.45 (t, J = 7.5 Hz, 1H), 7.34-
7.30 (m, 2H), 7.22 (dd, J = 15.4, 7.1 Hz, 4H), 7.19-7.11 (m,
6H), 4.05 – 3.98 (m, 1H), 3.13 (dd, J = 14.2, 8.1 Hz, 2H), 2.80
(dd, J = 14.1, 6.5 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ
203.3, 139.5, 137.3, 132.8, 129.0, 128.4, 128.4, 128.1, 126.2,
50.4, 38.2.
2-benzyl-1-phenylpentan-1-one (3z):13c Following the general
procedure A, the title product was obtained as a colorless oil
using silica-gel column chromatography eluting with 1% ethyl
1
acetate in hexane. Yield: 51 mg, 41% yield (Procedure A); H
NMR (400 MHz, CDCl3) δ 7.86-7.84 (m, 2H), 7.53-7.49 (m,
1H), 7.41 (t, J = 7.6 Hz, 2H), 7.24-7.14 (m, 5H), 3.75-3.70 (m,
1H), 3.10 (dd, J = 13.5, 7.7 Hz, 1H), 2.77 (dd, J = 13.6, 6.5 Hz,
1H), 1.79-1.73 (m, 1H), 1.55-1.48 (m, 1H), 1.33-1.23 (m, 2H),
0.85 (t, J = 7.3 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ
204.0, 140.0, 137.5, 132.8, 129.0, 128.5, 128.3, 128.1, 126.1,
48.1, 38.2, 34.6, 20.6, 14.2.
2-benzyl-3-cyclopropyl-1-phenylpropan-1-one (3ee): Fol-
lowing the general procedure A and B, the title product was ob-
tained as a colourless liquid using silica-gel column chromatog-
raphy eluting with 1% ethyl acetate in hexane. Yield: 87 mg,
1
66% yield (Procedure A); 35% yield (Procedure B); H NMR
2-Benzyl-3-(4-methoxyphenyl)-1-phenylpropan-1-one
(3aa):13c Following the general procedure B, the title product
was obtained as a colorless oil using silica-gel column chroma-
tography eluting with 1% ethyl acetate in hexane. Yield: 143
(400 MHz, CDCl3) δ δ 7.90-7.87 (m, 2H), 7.54-7.50 (m, 1H),
7.43-7.39 (m, 2H), 7.26-7.11 (m, 5H), 3.93-3.82 (m, 1H), 3.12
(dd, J = 14.0, 7.9 Hz, 1H), 2.83 (dd, J = 13.9, 6.7 Hz, 1H), 1.80-
1.70 (m, 1H), 1.46-1.42 (m, 1H), 0.72-0.57 (m, 1H), 0.42-0.23
(m, 2H), 0.11-0.01 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3)
δ 204.3, 140.0, 137.7, 132.8, 129.0, 128.5, 128.3, 128.2, 126.1,
48.8, 38.3, 37.7, 9.3, 5.1, 4.8. Elemental Analysis: C19H20O: C,
86.32; H, 7.63; O, 6.05. Found: C, 86.14; H, 7.49; O, 5.90.
HRMS (ESI-TOF) m/z [M+Na]+ Calcd for C19H20O 287.1406;
Found 287.1423.
1
mg, 87% yield (Procedure B); H NMR (400 MHz, CDCl3) δ
7.71 (d, J = 7.5 Hz, 2H), 7.45 (t, J = 7.4 Hz, 1H), 7.32 (t, J =
7.7 Hz, 2H), 7.21-7.18 (m, 2H), 7.13-7.11 (m, 3H), 7.04 (d, J =
8.6 Hz, 2H), 6.74 (d, J = 8.6 Hz, 2H), 3.98-3.94 (m, 1H), 3.73
(s, 3H), 3.12-3.03 (m, 2H), 2.80-2.71 (m, 2H); 13C{1H} NMR
(100 MHz, CDCl3) δ 203.5, 158.0, 139.6, 137.4, 132.7, 131.5,
130.0, 129.0, 128.4, 128.4, 128.1, 126.2, 113.8, 55.2, 50.7, 38.1,
37.4.
2-Benzyl-1,3-diphenylbutan-1-one (3ag):13c Following the
general procedure B, the title product was obtained as a colour-
less liquid using silica-gel column chromatography eluting with
1% ethyl acetate in hexane. Yield: 94 mg, 60% yield (Procedure
B); 1H NMR (400 MHz, CDCl3) δ 7.93-7.90 (m, 2H), 7.53-7.52
(m, 1H), 7.43 (t, J = 7.6 Hz, 3H), 7.31-7.25 (m, 6H), 7.20-7.14
(m, 3H), 3.54-3.46 (m, 1H), 3.32-3.14 (m, 3H), 1.33 (d, J = 6.9
Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 199.1, 146.6,
137.2, 133.0, 129.0, 128.5, 128.5, 128.4, 128.2, 128.0, 128.0,
126.9, 126.3, 47.0, 35.6, 29.7, 21.8.
3-(Benzo[d][1,3]dioxol-5-yl)-2-benzyl-1-phenylpropan-1-
one (3ab):13c Following the general procedure B, the title prod-
uct was obtained as a colorless liquid using silica-gel column
chromatography eluting with 5% ethyl acetate in hexane. Yield:
146 mg, 85% yield (Procedure B); 1H NMR (400 MHz, CDCl3)
δ 7.72 (d, J = 8.0 Hz, 2H), 7.46 (dd, J = 11.9, 4.4 Hz, 1H), 7.34
(t, J = 7.9 Hz, 2H), 7.22-7.18 (m, 2H), 7.14-7.10 (m, 3H), 6.65-
6.58 (m, 3H), 5.86 (dd, J = 3.3, 1.5 Hz, 2H), 3.98-3.91 (m, 1H),
3.12-3.01 (m, 2H), 2.80-2.68 (m, 2H); 13C{1H} NMR (100
MHz, CDCl3) δ 203.3, 147.5, 145.9, 139.4, 137.5, 137.3, 133.2,
132.8, 129.0, 128.5, 128.4, 128.1, 126.3, 122.0, 109.4, 108.1,
100.8, 50.7, 38.2, 37.9.
2-benzylcyclopentanone (3ga):13b Following the general pro-
cedure A, the title product was obtained as a colourless oil using
silica-gel column chromatography eluting with 1% ethyl acetate
in hexane. Yield: 37 mg, 43% yield Procedure A), 33% yield
2-Benzyl-1-phenyl-3-(pyridin-2-yl)propan-1-one (3ac):13c
Following the general procedure B, the title product was ob-
tained as a pale yellow oil using silica-gel column chromatog-
raphy eluting with 5% ethyl acetate in hexane. Yield: 53.4 mg,
(Procedure D); H NMR (400 MHz, CDCl3) δ 7.32-7.25 (m,
1
3H), 7.20 (d, J = 7.4 Hz, 1H), 7.14-7.11 (m, 1H), 3.41 (dd, J =
14.0, 3.8 Hz, 1H), 3.22 (t, J = 7.4 Hz, 1H), 3.04-2.97 (m, 1H),
2.88-2.79 (m, 3H), 2.68-2.59 (m, 1H), 2.16-2.12 (m, 2H).
2-benzylcyclohexanone (3ha):13b Following the general proce-
dure A, the title product was obtained as a colourless oil using
silica-gel column chromatography eluting with 1% ethyl acetate
1
61% yield (Procedure B); H NMR (400 MHz, CDCl3) δ 8.37
(d, J = 4.0 Hz, 1H), 7.78 (dd, J = 8.1, 0.9 Hz, 2H), 7.40-7.36
(m, 2H), 7.27 (t, J = 7.6 Hz, 2H), 7.13-7.00 (m, 6H), 6.94 (dd,
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in hexane. Yield: 26 mg, 28% yield Procedure A), 33% yield
(Procedure D); H NMR (400 MHz, CDCl3) δ 7.27-7.20 (m,
Supporting Information. The Supporting Information is availa-
ble free of charge on the ACS Publications website
X-ray crystallographic data, CIF file and NMR data (PDF)
1
3H), 7.11-7.06 (m, 2H), 2.94 (d, J = 13.4 Hz, 1H), 2.77 (d, J =
13.4 Hz, 1H), 1.98-1.92 (m, 1H), 1.72-1.67 (m, 1H), 1.60-1.41
(m, 5H), 1.34-1.19 (m, 2H).
AUTHOR INFORMATION
2,6-dibenzylcyclohexanone (3iaa):18 Following the general
procedure A, the title product was obtained as a colourless oil
using silica-gel column chromatography eluting with 1% ethyl
Corresponding Author
* E-mail: dbane.fcy@iitr.ac.in
1
acetate in hexane. Yield: 48 mg, 35% yield; H NMR (500
Author Contributions
9
MHz, CDCl3) δ 7.35-7.24 (m, 5H), 7.21-7.18 (m, 3H), 7.09 (d,
J = 7.5 Hz, 2H), 2.81-2.74 (m, 2H), 2.51-2.48 (m, 2H), 1.89-
1.82 (m, 2H), 1.83-1.78 (m, 2H), 1.40-1.31 (m, 2H), 1.28-1.14
(m, 2H). 13C{1H} NMR (125 MHz, CDCl3) δ 216.9, 139.5,
129.2, 128.3, 126.2, 53.5, 38.4, 31.0, 28.5.
2,7-bis(cyclohexylmethyl)cycloheptanone (3jff): Following
the general procedure A, the title product was obtained as a col-
ourless oil using silica-gel column chromatography eluting with
1% ethyl acetate in hexane. Yield: 50 mg, 33% yield; 1H NMR
(400 MHz, CDCl3) δ 2.68-2.62 (m, 2H), 1.82-1.72 (m, 4H),
1.68-1.60 (m, 10H), 1.24-1.09 (m, 16H), 0.88-0.79 (m, 4H);
13C{1H} NMR (101 MHz, CDCl3) δ 218.8 48.1, 40.6, 35.0,
33.8, 33.1, 32.6, 28.5, 26.3. HRMS (ESI-TOF) m/z [M+Na]+
Calcd for C21H36O 327.2658; Found 327.2653.
ϯ These authors contributed equally to this work.
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ACKNOWLEDGMENT
The authors thank DAE-BRNS, India (Young Scientist Research
Award to D. B., 37(2)/20/33/2016-BRNS). IIT Roorkee (SMILE-
32) and FIST-DST are gratefully acknowledge for instrument fa-
cilities. A. A. and S. B. thank IIT-R and INSPIRE Fellowship
(DST/2017/IF170766) for financial support.
REFERENCES
(1) (a) Modern Carbonyl Chemistry (Ed.: J. Otera), Wiley-VCH, Wein-
heim, 2000. (b) Beletskaya, I. P.; Nájera, C.; Yus, M. Stereodivergent
Catalysis. Chem. Rev. 2018, 118, 5080-5200.
(2) (a) Barta, K.; Ford, P. C. Catalytic Conversion of Nonfood Woody
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(3) For recent selected reviews: (a) Irrgang, T.; Kempe, R. 3d-Metal
Catalyzed N- and C-Alkylation Reactions via Borrowing Hydrogen or
Hydrogen Autotransfer. Chem. Rev., 2019, 119, 2524-2549. (b)
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Transition Metal-Catalyzed Dehydrogenation. Chem. Soc. Rev. 2015,
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2-Benzyl-10,13-dimethyl-17-(6-methylheptan-2-yl)-
6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclo-
penta[a]phenanthren-3-one (4):13b Following the general pro-
cedure C, the title product was obtained as a yellow oil using
silica-gel column chromatography eluting with 1% ethyl acetate
1
in hexane. Yield: 44 mg, 38% yield (Procedure C); H NMR
(400 MHz, CDCl3) δ 7.29-7.25 (m, 2H), 7.18 (t, J = 6.6 Hz, 3H),
6.59 (s, 1H), 6.05 (s, 1H), 3.63 (s, 2H), 2.44-2.30 (m, 2H), 2.16
(s, 1H), 2.02-1.89 (m, 3H), 1.85-1.77 (m, 1H), 1.56-1.48 (m,
4H), 1.33-1.24 (m, 4H), 1.14-1.04 (m, 9H), 0.99-0.92 (m, 4H),
0.85 (dd, J = 6.4, 4.6 Hz, 9H), 0.68 (s, 3H);13C{1H} NMR (100
MHz, CDCl3) δ 186.0, 168.9, 152.4, 139.6, 137.1, 129.1, 128.3,
126.0, 123.6, 56.1, 55.4, 52.7, 43.5, 42.6, 39.5, 36.1, 35.7, 35.5,
35.2, 32.6, 32.5, 28.1, 28.1, 28.0, 24.4, 23.8, 22.9, 22.8, 22.5,
18.7, 18.7, 11.9.
2-methyl-1-phenylicos-11-en-1-one (5):13b Following the gen-
eral procedure C, the title product was obtained as a pale yellow
oil using silica-gel column chromatography eluting with 1%
ethyl acetate in hexane. Yield: 17 mg, 32% yield (Procedure C);
1H NMR (500 MHz, CDCl3) δ 7.38-7.29 (m, 5H), 5.38 (t, J =
3.7 Hz, 2H), 3.59-3.52 (m, 1H), 2.09-2.04 (m, 4H), 1.89-1.70
(m, 2H), 1.35-1.30 (m, 24H), 0.95-0.77 (m, 6H); 13C{1H} NMR
(125 MHz, CDCl3) δ 207.1, 143.9, 129.9, 128.1, 127.4, 126.7,
126.3, 115.0, 40.2, 33.1, 32.2, 31.9, 31.0, 30.0, 29.8, 29.6, 29.5,
29.3, 27.2, 27.0, 22.7, 15.7, 14.1.
2-((1-Benzylpiperidin-4-yl)methyl)-5,6-dimethoxy-2,3-di-
hydro-1H-inden-1-one (6):13b Following the general procedure
C, the title product was obtained as a yellow oil using silica-gel
column chromatography eluting with 50 % ethyl acetate in hex-
1
(4) For selected recent examples, see: (a) Peꢀa-Lꢁpez, M.; Piehl, P.;
Elangovan, S.; Neumann, H.; Beller, M. Manganese Catalyzed Hydrogen‐
Autotransfer C−C Bond Formation: α-Alkylation of Ketones with Primary
Alcohols. Angew. Chem., Int. Ed. 2016, 55, 14967-14971. (b) Zhang, G.;
Wu, J.; Zeng, H.; Zhang, S.; Yin, Z.; Zheng, S. Cobalt-Catalyzed α-Alkyl-
ation of Ketones with Primary Alcohols. Org. Lett. 2017, 19, 1080-1083.
(c) Manojveer, S.; Salahi, S.; Wendt, O. F.; Johnson, M. T. Ru-Catalyzed
Cross-Dehydrogenative Coupling between Primary Alcohols to Guerbet
Alcohol Derivatives: with Relevance for Fragrance Synthesis. J. Org.
Chem. 2018, 83, 10864-10870.
ane. Yield: 34 mg, 36% yield (Procedure C); H NMR (500
MHz, CDCl3) δ 7.55 (d, J = 7.2 Hz, 2H), 7.43-7.36 (m, 3H),
7.12 (s, 1H), 6.84 (s, 1H), 3.95 (s, 3H), 3.88 (s, 3H), 3.64 (s,
2H), 3.34-3.25 (m, 1H), 2.71-2.51 (m, 4H), 1.97-1.85 (m, 5H),
1.50-1.27 (m, 4H); 13C{1H} NMR (125 MHz, CDCl3) δ 207.0,
155.6, 149.4, 148.6, 137.4, 131.0, 129.3, 128.9, 127.0, 107.3,
104.2, 70.4, 56.2, 56.0, 52.1, 44.5, 33.6, 31.8, 29.6, 22.6, 14.0.
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(16) Fe2(CO)9 is extremely toxic and contact with skin and eyes are
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avoided. Proper protection should be taken while use and to circumvent in-
hale of dust particles from the chemical, wear respiratory mask. Fe2(CO)9
should be kept in cold place and avoid intact with ignition flames.
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