A Mechanochemical Zinc-Mediated Barbier-Type Allylation Reaction under Ball-Milling Conditions

Article abstract of DOI:10.1021/acs.joc.9b02876

A ball-milling-enabled zinc-mediated Barbier-type allylation reaction is reported. Notably, running the reaction in this manner renders it effective irrespective of the initial morphology of the zinc metal. The process is operationally simple, does not re

Full text of DOI:10.1021/acs.joc.9b02876

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Article
A Mechanochemical Zinc-Mediated Barbier-Type Allylation Reaction
under Ball-Milling Conditions
JieXiang Yin, Roderick T. Stark, Ian A. Fallis, and Duncan L. Browne*
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ABSTRACT: A ball-milling-enabled zinc-mediated Barbier-type
allylation reaction is reported. Notably, running the reaction in this
manner renders it effective irrespective of the initial morphology of
the zinc metal. The process is operationally simple, does not
require inert atmospheres or dry solvents, and is reported over a
range of aldehyde and ketone substrates; a gram-scale process is
demonstrated.
Scheme 1. Context and Outline of Ball-Milled Zinc-
Mediated Barbier-Type Reaction
INTRODUCTION
■
The Barbier reaction features the use of base metals, in their
zero-valence form, to couple alkyl halides with carbonyl
compounds.1 Since the seminal publication by Barbier in
1899,2 the use of a variety of metals has been reported, such as
zinc,3a magnesium,3b samarium,3c aluminum,3d indium,3e
cadmium,3f antimony,3g lead,3h tin,3i bismuth,3j and mangane-
se,3k as well as asymmetric processes4 and even aqueous media
variants.5 Perhaps, the most studied Barbier-type reaction is
the allylation of carbonyl groups to deliver versatile homoallylic
alcohol products.1 A common feature of these processes is the
requirement of a base metal whose physical form, solubility,
and oxide surface layer can lead to variable outcomes. Indeed,
the use of chemical additives to circumvent these issues has
been well studied (Scheme 1A).6
Recently, we and others have been investigating the use of
mechanochemistry7 to impart impact and shear forces onto
reactants via ball-milling and thus mechanically activate, rather
than chemically activate, zinc metal in a variety of forms.8 In
addition to its ability to mechanically activating metals, ball-
milling often requires the use of no or very little solvent (for
the reaction portion at least) and can lead to interesting
reaction profiles and reduced sensitivity of reactions to oxygen
and/or water.9 To date, we have demonstrated, in the context
of zinc-mediated transformations, that a ball-milling approach
can deliver an improved protocol for the Negishi cross-
coupling and Reformatsky reactions (Scheme 1B). Under these
processes, it was found that the reactions were operable
irrespective of the morphology of the zinc starting material.
Thus, by simply adding the appropriate reagents to the
grinding jar under an air atmosphere followed by closing the
jar and milling on commercially available equipment led to the
desired products in good yields and across a range of
substrates.8a,b Herein, we report the application of ball-milling
mechanochemistry for the Barbier-type zinc-mediated coupling
of allyl halides to aldehydes and ketones (Scheme 1C).
RESULTS AND DISCUSSION
To begin, our investigations commenced with a model set of
substrates, tolualdehyde (1) and ally bromide (2) with zinc
■
Received: November 13, 2019
https://dx.doi.org/10.1021/acs.joc.9b02876
© XXXX American Chemical Society
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A

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flakes, a variety of stoichiometries, milling times, and ball sizes/
masses were investigated. We arrived at a molar ratio of
reagents of 1:1.5 (1:2) with 2 equiv. of zinc and milling in a 10
mL jar for 2 h with a single stainless steel ball of 9.25 g mass,
which afforded the target allyl alcohol in 81% yield (Table 1,
encumbered mesitylaldehyde (Scheme 2A). Notably, 2-
formylpyridine and the electron-rich 4-(dimethylamino)-
benzaldehyde were not competing substrates in this reaction.
A range of zinc sources were explored for the reaction of 4-
fluorobenzaldehyde with allyl bromide, and it was established
that, as well as zinc flake, zinc foil, zinc mesh, zinc wire, and
Table 1. Optimization of Model Ball-Milled Allylation
Reaction
Scheme 2. Scope of the Ball-Milling-Enabled Zinc-Mediated
a
Barbier Reaction
a
entry
variation from the standard conditions
yield of 3 (%)
1
2
3
4
5
6
7
8
9
none
81
85
91
99
85
45
51
69
24
+DMA (1.5 equiv.)
+DMF (1.5 equiv.)
+DMSO (1.5 equiv.)
+THF (1.5 equiv.)
+DCM (1.5 equiv.)
+hexane (1.5 equiv.)
+MeCN (1.5 equiv.)
2 (2.0 equiv.)
entries below this line contain DMSO (1.5 equiv.)
10
11
12
30 min
1 h
3 h
77
85
99
a
Isolated yields reported.
entry 1). With these conditions in hand, we looked to further
improve the conversion of starting materials and explored the
use of liquid-assisted grinding agents (LAG) to refine the
reaction outcome. Liquid-assisted grinding,10 a technique more
common in mechanochemical crystal engineering,11 is some-
what counterintuitive and requires the addition of a solvent-
type species to reactions that would otherwise be solvent-free.
Typically, the amount of LAG used is assigned a value, η,
which represents a liquid-to-reactant ratio; values between 0.1
and 1 describe reaction regimes within the LAG region as
opposed to those that are neat (η < 0.1) and those that are
slurries (η > 1) or solutions (typically when η > 10).10 The
precise role of a LAG agent appears to be situation-dependent:
some have been found to facilitate access to different crystal
polymorphic forms,11 while others have led to kinetic versus
thermodynamic product outcomes depending on the dielectric
constant of the LAG agent.12 Nonetheless, when screening a
small range of LAG agents, representing a range of
coordinating abilities and polarities, under the ball-milled
Barbier-type reaction, it was found that 1.5 equiv. of DMSO (η
= 0.44) afforded the desired product in 99% yield (Table 1,
entry 4). Indeed, there appears to be a general trend that more
coordinating liquid additives improve the reaction process,
presumably due to the breakup of aggregate organozinc species
and ready access to the exposed metal surface. Further
investigation of the reaction time (Table 1, entries 10−12)
with DMSO as LAG identified that 2 h was optimal.
Next, our attention turned to exploring the substrate scope
of the ball-milled-enabled zinc-mediated Barbier-type reaction.
Notably, the reaction proceeds effectively against a range of
aromatic aldehydes with halo substituents; iodo, bromo,
chloro, and fluoro were all tolerated under these conditions
as well as a range of electron-withdrawing groups and sterically
a
1H NMR yield with internal standard.
B
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zinc shot are all effective under milling conditions without any
pretreatment. The ball-milled process is not restricted to
aromatic aldehydes with phenylacetaldehyde (12; 47%),
cinnamaldehyde (13; 84%), 2-phenylpropanal (14; 69%, 3:1
anti:syn), hexanal (15; 69%), and cyclohexanecarboxaldehyde
(16; 70%), all converting to the desired homoallylic alcohol
products in moderate to good yields. Notably, however, crotyl
bromide and benzyl bromide were not effective substrates
under these conditions. A range of 14 acetophenone substrates
featuring electron-rich, electron-poor, and sterically encum-
bered derivatives participated effectively in this process
(Scheme 2B) and so did cyclohexenone (22; 71%), cyclo-
hexone (27; 82%), and cyclooctone (28; 94%). Imine
electrophiles also participated in this reaction process to afford
homoallylic amines in moderate to good yields (Scheme 2C).
Alternative allylic and propargylic substrates were also
investigated. It was found that allyl chloride could effectively
be used as a pronucleophile in a reaction with acetophenone to
furnish the corresponding tertiary allyl alcohol (20) in 85%
yield (Scheme 3A), although this reaction required 6 h of
and can be straightforwardly scaled to deliver gram quantities
of the materials. Furthermore, in comparison to earlier work by
Suzuki and co-workers using bismuth to mediate this process
by ball-milling,3j the present method offers an improved
substrate scope and greatly reduced loading of metal, albeit at
an increased reaction time.
EXPERIMENTAL SECTION
■
General Information. Unless otherwise stated, all reagents were
purchased from commercial sources and used without further
purification. DMSO was purchased from Fluorochem (99% purity).
Different zinc forms were purchased from different companies as
listed: (1) zinc granular (20−30 mesh, ACS reagent, ≥98.8%; Sigma-
Aldrich), (2) zinc flake (−325 mesh, 99.9%; Alfa Aesar), (3) zinc foil
(thickness 0.25 mm, 99.9% trace metals basis; Sigma-Aldrich), (4)
zinc shot (10 mm diameter × 2 mm thick, 99.99%, Alfa Aesar), and
(5) zinc wire (1.0 mm diameter, 99.95%, Alfa Aesar).
Thin layer chromatography (TLC) was carried out using Merck
TLC silica gel 60 sheet and visualized with ultraviolet light or
potassium permanganate stain. Flash column chromatography (FCC)
was performed with Sigma-Aldrich silica gel 40−60 Å as the stationary
phase, and solvents employed were analytical-grade. 1H NMR spectra
were recorded on a Bruker AVX500 (500 MHz) spectrometer at
ambient temperature. 13C NMR spectra were recorded on a Bruker
AVX500 (125 MHz) spectrometer at ambient temperature. 19F NMR
spectra were recorded on a Bruker AVX500 (471 MHz) spectrometer
at ambient temperature. Melting points were measured on a
Gallenkamp melting point apparatus and are reported corrected by
linear calibration to benzophenone (47−49 °C) and benzoic acid
(121−123 °C).
Scheme 3. Further Investigations
High-resolution mass spectroscopy (HRMS) data was obtained on
a Thermo Scientific LTQ Orbitrap XL by the EPSRC U.K. National
Mass Spectrometry Facility at Swansea University or on a Waters
MALDI-TOF MX in Cardiff University. Spectra were obtained using
electron impact ionization (EI), chemical ionization (CI), positive
electrospray (ES), pneumatically assisted electrospray (pNSI), or
atmospheric solids analysis probe (ASAP+). Infrared spectra were
recorded on a Shimadzu IR-Affinity-1S FTIR spectrometer.
The ball mill used was a Retsch MM 400 mixer mill. Unless
otherwise stated, mechanochemical reactions were performed in 10
mL stainless steel jars from Retsch with a 12 mm diameter stainless
steel ball (∼9.25 g). The longest time that this mill can be
programmed to run for is 99 min. In order to run longer reaction
times, the mill was started, and then additional time was added to the
timer in order to ensure that the mill was running continuously for the
desired reaction time.
General Procedure A for Reactions of Aldehydes and Allyl
Bromide. To a Retsch 10 mL stainless steel milling jar were added
the aldehyde (1.0 mmol, 1 equiv.), zinc (typically flake −325 mesh;
2.0 mmol, 131 mg, 2 equiv.), allyl bromide (1.5 mmol, 131 μL, 1.5
equiv.), and DMSO (1.5 mmol, 107 μL, 1.5 equiv.) under an air
atmosphere. A 12 mm stainless steel ball was added, and the mixture
was milled at 30 Hz for 2 h. After the reaction was finished, the
resulting black paste was rinsed, transferred with ethyl acetate (50
mL) into a 100 mL conical flask, quenched with 1 M HCl (50 mL),
and stirred for 20 min. The organic layer was separated and dried over
MgSO4, filtered, and concentrated under reduced pressure. The crude
material was then purified by silica gel flash chromatography.
General Procedure B for Reactions of Ketones and Allyl
Bromide. To a Retsch 10 mL stainless steel milling jar were added
the ketone (1.0 mmol, 1 equiv.), zinc (typically flake −325 mesh; 2.0
mmol, 131 mg, 2 equiv.), allyl bromide (1.5 mmol, 131 μL. 1.5
equiv.), and DMSO (1.2 mmol, 85 μL, 1.2 equiv.) under an air
atmosphere. A 12 mm stainless steel ball was added, and the mixture
was milled at 30 Hz for 2 h. After the reaction was finished, the
resulting black paste was rinsed, transferred with ethyl acetate (50
mL) into a 100 mL conical flask, quenched with distilled water (50
mL), and stirred for at least 30 min. The mixture was then filtered
through a pad of silica gel (1.5 cm) to remove insoluble materials.
milling to go to completion. Propargyl bromide underwent
transformation to afford a 4:1 mixture of the homopropargyl
tertiary alcohol (40a) and corresponding allenyl derivative
(40b) in 71% total yield.
By replacing the terminal alkyne C−H of propargyl bromide
with a terminal methyl group through the use of 1-
bromobutyne, 69% of the allenyl tertiary alcohol (42) could
be isolated. The ball-milling process can also be scaled up by
simply changing to a larger jar (25 mL rather than 10 mL), and
by increasing the reaction time from 2 to 6 h, we were able to
isolate 1.52 g of Barbier product 20.
To conclude, an operationally simple Barbier-type zinc-
mediated mechanochemical protocol has been developed with
a good substrate scope and is applicable across a range of
different zinc metal morphologies. The developed process,
irrespective of the potentially complex behavior of allyl zinc
species,13 does not require dry solvents or inert atmospheres
C
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1
The silica gel was then flushed with ethyl acetate (50 mL), dried over
MgSO4, filtered, and concentrated under reduced pressure. The crude
material was then purified by silica gel flash chromatography.
give the product (yield: 91%, 201 mg) as a clear oil. H NMR (500
MHz, CDCl3) δ 7.61 (d, J = 8.1 Hz, 2H), 7.48 (d, J = 8.0 Hz, 2H),
5.84−5.75 (m, 1H), 5.18 (d, J = 12.3 Hz, 2H), 4.82−4.80 (m, 1H),
2.58−2.53 (m, 1H), 2.50−2.44 (m, 1H), 2.13 (s, 1H). 13C{1H} NMR
(126 MHz, CDCl3) δ 147.9, 133.8, 129.9 (q, J = 33 Hz), 126.2, 125.5,
123.2, 119.4, 72.7, 44.1. 19F NMR (376 MHz, CDCl3) δ −62.5. Data
is consistent with literature values.14
1-(p-Tolyl)but-3-en-1-ol (3). The compound was prepared
according to general procedure A and purified by column
chromatography (ethyl acetate/hexane = 25:75) to give the product
(yield: 99%, 160 mg) as a clear oil. Note that 3 is volatile under
reduced pressure. 1H NMR (500 MHz, CDCl3) δ 7.22 (d, J = 8.1 Hz,
2H), 7.13 (d, J = 7.9 Hz, 2H), 5.81−5.73 (m, 1H), 5.15−5.08 (m,
2H), 4.67 (m, 1H), 2.49−2.45 (m, 2H), 2.31 (s, 3H), 1.96 (s, 1H).
13C{1H} NMR (126 MHz, CDCl3) δ 141.1, 137.4, 134.7, 125.9,
118.4, 73.3, 43.9, 21.3. Data is consistent with literature values.4b,14
1-Phenylbut-3-en-1-ol (4). The compound was prepared according
to general procedure A and purified by column chromatography
(ethyl acetate/hexane = 20:80) to give the product (yield: 67%, 99
4-(1-Hydroxybut-3-en-1-yl)benzonitrile (11). The compound was
prepared according to general procedure A and purified by column
chromatography (ethyl acetate/hexane = 15:85) to give the product
1
(yield: 75%, 130 mg) as a clear oil. H NMR (500 MHz, CDCl3) δ
7.61 (m, 2H), 7.46 (m, 2H), 5.80−5.71 (m, 1H), 5.16−5.12 (m, 2H),
4.80−4.76 (m, 1H), 2.54−2.48 (m, 2H), 2.46−2.39 (m, 1H).
13C{1H} NMR (126 MHz, CDCl3) δ 149.3, 133.5, 132.3, 126.6,
119.4, 119.0, 111.1, 72.5, 43.9. Data is consistent with literature
values, but the NMR data indicates the presence of minor
impurities.4b
1-Phenylpent-4-en-2-ol (12). The compound was prepared
according to general procedure A and purified by column
chromatography (ethyl acetate/hexane = 15:85) to give the product
(yield: 47%, 76 mg) as a clear oil. Note that 12 is volatile under
1
mg) as a clear oil. Note that 4 is volatile under reduced pressure. H
NMR (500 MHz, CDCl3) δ 7.25−7.24 (m, 4H), 7.20−7.16 (m, 1H),
5.74−5.66 (ddt, J = 17.2, 10.2, 7.1 Hz, 1H), 5.07−5.02 (m 2H), 4.61
(dd, J = 7.4, 5.6 Hz, 1H), 2.45−2.36 (m, 2H), 2.18 (app. s, 1H).
13C{1H} NMR (126 MHz, CDCl3) δ 144.0, 134.6, 128.5, 127.6,
125.9, 118.4, 73.4, 43.9. Data is consistent with literature values.4b,14
1-Mesitylbut-3-en-1-ol (5). The compound was prepared accord-
ing to general procedure A and purified by column chromatography
(ethyl acetate/hexane = 15:85) to give the product (yield: 99%, 188
1
reduced pressure. H NMR (500 MHz, CDCl3) δ 7.25−7.21 (m,
2H), 7.17−7.13 (m, 3H), 5.84−5.73 (m, 1H), 5.10−5.05 (m, 2H),
3.83−3.77 (m, 1H) or 3.80 (tt, 7.7, 4.8 Hz, 1H), 2.74 (dd, J = 13.6,
4.9 Hz, 1H), 2.64 (dd, J = 13.6, 7.9 Hz, 1H), 2.29−2.18 (m, 1H),
2.16−2.08 (m, 1H), 1.66 (s, 1H). 13C{1H} NMR (126 MHz, CDCl3)
δ 138.5, 134.8, 129.5, 128.6, 126.6, 118.2, 71.8, 43.4, 41.3. Data is
consistent with literature values.16
1
mg) as a clear oil. H NMR (500 MHz, CDCl3) δ 6.85 (app. s, 3H),
5.91−5.83 (m, 1H), 5.22−5.14 (m, 3H), 2.77−2.70 (m, 1H), 2.54−
2.49 (m, 1H), 2.44 (s, 6H), 2.28 (s, 3H), 1.97 (s, 1H). 13C{1H}
NMR (126 MHz, CDCl3) δ 136.6, 136.1, 135.4, 130.2, 117.8, 70.8,
40.4, 20.9. Data is consistent with literature values.14
(E)-1-Phenylhexa-1,5-dien-3-ol (13). The compound was prepared
according to general procedure A and purified by column
chromatography (ethyl acetate/hexane = 15:85) to give the product
1-(3-Iodophenyl)but-3-en-1-ol (6). The compound was prepared
according to general procedure A and purified by column
chromatography (ethyl acetate/hexane = 15:85) to give the product
1
(yield: 84%, 146 mg) as a clear oil. H NMR (500 MHz, CDCl3) δ
1
7.28 (m, 2H), 7.22−7.19 (m, 2H), 7.15−7.12 (m, 1H), 6.50 (d, J =
15.6 Hz, 1H), 6.14 (dd, J = 15.9, 6.4 Hz, 1H), 5.76 (ddt, 17.2, 10.2,
7.1 Hz, 1H), 5.10−5.04 (m, 2H), 4.25 (q, J = 5.9 Hz, 1H), 2.31−2.25
(m, 2H), 2.05 (s, 1H). 13C{1H} NMR (126 MHz, CDCl3) δ 136.7,
134.2, 131.7, 130.4, 128.6, 127.7, 126.6, 118.4, 71.8, 42.1. Data is
consistent with literature values.14
2-Phenylhex-5-en-3-ol (14). The compound was prepared
according to general procedure A and purified by column
chromatography (ethyl acetate/hexane = 20:80) to give the product
(yield: 69%, 122 mg) as a clear oil. Note that data is reported here as
a mixture of syn and anti diastereomers. 1H NMR (500 MHz, CDCl3)
δ 7.25−7.11 (m, 5H, syn and anti), 5.84−5.77 (m, 1H, syn), 5.76−
5.67 (m, 1H, anti), 5.06−4.98 (m, 2H, syn and anti), 3.65−3.60 (m,
1H, syn and anti), 2.75−2.64 (m, 1H, syn and anti), 2.31−2.27 (m,
1H, syn), 2.13−2.07 (m, 1H, anti), 2.06−1.97 (m, 1H, syn), 1.96−
1.91 (m, 1H, anti), 1.69 (s, 1H, anti), 1.60 (s, 1H, ant), 1.26 (d, J =
7.0 Hz, 3H, anti), 1.21 (d, J = 7.1 Hz, anti). 13C{1H} NMR (126
MHz, CDCl3) δ 144.5, 143.4, 135.2, 135.1, 128.6, 128.6, 128.3, 127.9,
126.7, 126.5, 118.0, 117.8, 75.1, 75.1, 45.5, 45.5, 39.6, 39.0, 17.8, 16.5.
Data is consistent with literature values.17,18
(yield: 72%, 197 mg) as a clear oil. H NMR (500 MHz, CDCl3) δ
7.58 (s, 1H), 7.48 (d, J = 7.8 Hz, 1H), 7.16 (d, J = 7.7 Hz, 1H), 6.95
(t, J = 7.8 Hz, 1H), 5.68−5.60 (m, 1H), 5.03 (m, 2H), 4.49 (dd, J =
7.6, 5.3 Hz, 1H), 2.53 (broad s, 1H), 2.37−2.27 (m, 2H). 13C{1H}
NMR (126 MHz, CDCl3) δ 146.2, 136.5, 134.8, 133.9, 130.1, 125.1,
118.7, 94.5, 72.4, 43.7. IR (CH2Cl2 film): 1639, 1591, 1566, 1472,
1423, 1192, 1061, 995, 918, 781, 696 cm−1. HRMS (TOF-EI+) m/z:
[M]+ calcd for C10H11OI 273.9855; found 273.9846.
1-(4-Chlorophenyl)but-3-en-1-ol (7). The compound was pre-
pared according to general procedure A and purified by column
chromatography (ethyl acetate/hexane = 15:85 → 20:80) to give the
1
product (yield: 69%, 126 mg) as a clear oil. H NMR (500 MHz,
CDCl3) δ 7.33−7.28 (m, 4H), 5.82−5.74 (m, 1H), 5.18−5.15 (m,
2H), 4.74−4.71 (m, 1H), 2.53−2.42 (m, 2H), 2.06 (s, 1H). 13C{1H}
NMR (126 MHz, CDCl3) δ 142.4, 134.1, 133.3, 128.7, 127.3, 119.0,
72.7, 44.0. Data is consistent with literature values.4b
1-(4-Bromophenyl)but-3-en-1-ol (8). The compound was pre-
pared according to general procedure A and purified by column
chromatography (ethyl acetate/hexane = 10:90 → 20:80) to give the
1
product (yield: 70%, 158 mg) as a clear oil. H NMR (500 MHz,
CDCl3) δ 7.48 (d, J = 7.2 Hz, 2H), 7.25 (m, 2H), 5.82−5.74 (m, 1H),
5.18−5.15 (m, 2H), 4.71 (s, 1H), 2.53 (m, 2H), 2.05 (s, 1H).
13C{1H} NMR (126 MHz, CDCl3) δ 143.0, 134.1, 131.6, 127.7,
121.4, 119.1, 72.7, 44.0. Data is consistent with literature values.15
1-(4-Fluorophenyl)but-3-en-1-ol (9). The compound was pre-
pared according to general procedure A and purified by column
chromatography (ethyl acetate/hexane = 15:85 → 20:80) to give the
product (yield: 73%, 121 mg) as a clear oil. Note that 9 is volatile
under reduced pressure. 1H NMR (500 MHz, CDCl3) δ 7.33 (dd, J =
8.2, 5.7 Hz, 2H), 7.03 (t, J = 8.6 Hz, 2H), 5.79 (m, 1H), 5.18−5.14
(m, 2H), 4.73 (dd J = 6.8, 6.0 Hz, 1H), 2.54−2.44 (m, 2H), 2.05 (s,
1H). 13C{1H} NMR (126 MHz, CDCl3) δ 162.3 (d, J = 246 Hz),
139.7 (d, J = 2.5 Hz), 134.3, 127.6, 118.9, 115.6 (d, J = 21.4 Hz),
72.8, 44.1. 19F NMR (376 MHz, CDCl3) δ −115.2. Data is consistent
with literature values.15
Non-1-en-4-ol (15). The compound was prepared according to
general procedure A and purified by column chromatography (ethyl
acetate/hexane = 10:90) to give the product (yield: 69%, 98 mg) as a
1
clear oil. Note that 15 is volatile under reduced pressure. H NMR
(500 MHz, CDCl3) δ 5.86−5.78 (m, 1H), 5.13−5.10 (m, 2H), 3.65−
3.61 (m, 1H), 2.31−2.26 (m, 1H), 2.16−2.10 (m, 1H), 1.71 (broad s,
1H), 1.45−1.25 (m, 8H), 0.88 (t, J = 6.9 Hz, 3H). 13C{1H} NMR
(126 MHz, CDCl3) δ 135.1, 118.1, 70.8, 42.1, 36.9, 32.0, 25.5, 22.8,
14.2. Data is consistent with literature values, but the NMR data
indicates the presence of minor impurities.14
1-Cyclohexylbut-3-en-1-ol (16). The compound was prepared
according to general procedure A and purified by column
chromatography (ethyl acetate/hexane = 20:80) to give the product
(yield: 70%, 108 mg) as a clear oil. Note that 16 is volatile under
1
reduced pressure. H NMR (500 MHz, CDCl3) δ 5.87−5.77 (m,
1H), 5.14−2.09 (m, 2H), 3.39−3.35 (m, 1H), 2.34−2.28 (m, 1H),
2.15−2.07 (m, 1H), 1.86−1.64 (m, 6H), 1.35−0.98 (m, 6H).
13C{1H} NMR (126 MHz, CDCl3) δ 135.6, 117.9, 74.84, 43.2, 38.9,
1-(4-(Trifluoromethyl)phenyl)but-3-en-1-ol (10). The compound
was prepared according to general procedure A and purified by
column chromatography (ethyl acetate/hexane = 10:90 → 20:80) to
D
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29.2, 28.2, 26.6, 26.4, 26.2. Data is consistent with literature
values.4b,14
CDCl3) δ 150.1 (dd, J = 16.4, 247.0 Hz), 149.1 (dd, J = 13.9, 248.2
Hz), 145.0 (t, J = 44.0 Hz), 133.1, 120.9 (q, J = 33.6 Hz), 120.1, 116.9
(d, J = 17.6 Hz), 114.4 (d, J = 17.6 Hz), 73.3, 48.5, 29.9. IR (CH2Cl2
film): 2984, 1609, 1514, 1418, 1379, 1277, 1153, 1117, 947, 922, 818,
775 cm−1. HRMS (TOF-EI+) m/z: [M−H2O]+ calcd for C11H10F2
180.0751; found 180.0747.
2-(p-Tolyl)pent-4-en-2-ol (19). The compound was prepared
according to general procedure B and purified by column
chromatography (ethyl acetate/hexane = 20:80) to give the product
(yield: 85%, 150 mg) as a clear oil. Note that 19 is volatile under
reduced pressure. 1H NMR (500 MHz, CDCl3) δ 7.34 (d, J = 8.1 Hz,
2H), 7.17 (d, J = 8.0 Hz, 2H), 5.69−5.60 (m, 1H), 5.17−5.11 (m,
2H), 2.71−2.67 (m, 1H), 2.53−2.48 (m, 1H), 2.35 (s, 3H), 2.08 (s,
1H), 1.54 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3) δ 144.8, 136.3,
133.9, 129.0, 124.8, 119.4, 73.6, 48.6, 30.1, 21.1. Data is consistent
with literature values.19
2-Phenylpent-4-en-2-ol (20). The compound was prepared
according to general procedure B and purified by column
chromatography (ethyl acetate/hexane = 20:80) to give the product
(yield: 81%, 131 mg) as a clear oil. Note that 20 is volatile under
reduced pressure. 7% unreacted acetophenone was present by purified
NMR. 1H NMR (500 MHz, CDCl3) δ 7.50−7.47 (m, 2H), 7.41−7.37
(m, 2H), 7.30−7.26 (m, 1H), 5.71−5.63 (m, 1H), 5.20−5.14 (m,
2H), 2.76−2.70 (m, 1H), 2.58−2.52 (m, 1H), 2.26 (broad s, 1H),
1.59 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3) δ 147.1, 133.8,
128.2, 126.7, 124.9, 119.4, 73.7, 48.6, 29.9. Data is consistent with
literature values.19
2-(4-(Trifluoromethyl)phenyl)pent-4-en-2-ol (26). The compound
was prepared according to general procedure B and purified by
column chromatography (ethyl acetate/hexane = 15:85) to give the
1
product (yield: 44%, 101 mg) as a clear oil. H NMR (500 MHz,
CDCl3) δ 7.61−7.55 (m, 4H), 5.64−5.55 (m, 1H), 5.17−5.13 (m,
2H), 2.68 (dd, J = 13.8, 6.4 Hz,1H), 2.52 (dd, J = 13.8, 8.3 Hz, 1H),
2.24 (s, 1H), 1.56 (s, 3H). 13C NMR (126 MHz, CDCl3) δ 151.8 (d,
J = 1.0 Hz), 133.1, 129.0 (q, J = 32.4 Hz), 125.4, 125.3 (q, J = 3.8
Hz), 124.4 (q, J = 271.8 Hz), 120.2, 73.7, 48.4, 30.0. 13C{1H} NMR
(126 MHz, CDCl3) δ 147.9, 133.8, 129.9 (q, J = 32.4 Hz), 126.2,
125.5 (q, J = 3.8 Hz), 124.3 (q, J = 271.9 Hz), 119.4, 72.7, 44.1. IR
(CH2Cl2 film): 1379, 1327, 1165, 1125, 1070, 1015, 955, 939, 843
cm−1. HRMS (TOF-EI+) m/z: [M−H2O]+ calcd for C12H9F3
212.0813; found 212.0805.
1-Allylcyclohexan-1-ol (27). The compound was prepared
according to general procedure B and purified by column
chromatography (ethyl acetate/hexane = 15:85) to give the product
1
2-(2-Bromophenyl)pent-4-en-2-ol (21). The compound was
prepared according to general procedure B and purified by column
chromatography (ethyl acetate/hexane = 15:85) to give the product
(yield: 82%, 115 mg) as a clear oil. H NMR (500 MHz, CDCl3) δ
5.89 (ddt, J = 17.7, 10.2, 7.5 Hz), 5.16−5.09 (m, 2H), 2.22 (d, J = 7.5
Hz, 2H), 1.64−1.40 (m, 13H), 1.30−1.25 (m, 2H). 13C{1H} NMR
(126 MHz, CDCl3) δ 133.9, 118.8, 71.1, 46.8, 37.5, 25.9, 22.3. Data is
consistent with literature values.19
1
(yield: 76%, 182 mg) as a clear oil. H NMR (500 MHz, CDCl3) δ
7.71 (dd, J = 8.0, 1.7 Hz, 1H), 7.58 (dd, J = 7.9, 1.3 Hz, 1H), 7.30 (dt,
J = 7.4, 1.3 Hz, 1H), 7.09 (dt, J = 7.4, 1.7 Hz, 1H), 5.57 (dddd, J =
17.1, 10.1, 8.4, 6.4 Hz, 1H), 5.19−5.07 (m, 2H), 3.33−3.23 (m, 1H),
2.70 (s, 1H), 2.69−2.63 (m, 1H), 1.73 (s, 3H). 13C{1H} NMR (126
MHz, CDCl3) δ 145.1, 135.1, 133.7, 128.6, 128.3, 127.5, 120.0, 119.4,
74.7, 45.1, 27.4. Data is consistent with literature values.20
1-Allylcyclooctan-1-ol (28). The compound was prepared
according to general procedure B and purified by column
chromatography (ethyl acetate/hexane = 20:80) to give the product
1
(yield: 94%, 158 mg) as a clear oil. H NMR (500 MHz, CDCl3) δ
5.83 (ddt, 17.7, 10.2, 7.5 Hz, 1H), 5.09−5.02 (m, 2H), 2.15 (d, J =
7.5 Hz), 1.59−1.35 (m, 19H). 13C{1H} NMR (126 MHz, CDCl3) δ
134.2, 118.7, 74.5, 46.1, 36.3, 28.4. 25.1, 22.3. Data is consistent with
literature values.
1-Allylcyclohex-2-en-1-ol (22). The compound was prepared
according to general procedure B and purified by column
chromatography (ethyl acetate/hexane = 15:85) to give the product
(yield: 71%, 98 mg) as a clear oil. Note that 22 is volatile under
2-(3-Chloro-4-fluorophenyl)pent-4-en-2-ol (29). The compound
was prepared according to general procedure B and purified by
column chromatography (ethyl acetate/hexane = 20:80) to give the
product (yield: 86%, 184 mg) as a clear oil. Note that trace 3′-chloro-
4′-fluoroacetophenone was observed by purified NMR. 1H NMR
(500 MHz, CDCl3) δ 7.52−7.50 (m, 1H), 7.31−7.27 (m, 1H), 7.10
(t, J = 8.7 Hz, 1H), 5.62 (m, 1H), 5.17−5.13 (m, 2H), 2.63 (dd, J =
13.8, 6.6 Hz, 1H), 2.49 (dd, J = 13.8, 8.1 Hz, 1H), 2.22 (s, 1H), 1.53
(s, 3H). 13C{1H} NMR (126 MHz, CDCl3) δ 156.8 (d, J = 248.2
Hz), 144.8, 132.9, 127.4, 124.8, 120.1, 116.2, 116.2, 73.2, 48.4, 29.9.
IR (CH2Cl2 film): 1684, 1639, 15.91, 1497, 1391, 1263, 1244, 1076,
1057, 920, 880, 820, 729, 714 cm−1 HRMS (TOF-ES+) m/z: [M−
H2O + H]+ calcd for C11H11ClF 197.0533; found 197.0540.
2-(2-Chloro-4-fluorophenyl)pent-4-en-2-ol (30). The compound
was prepared according to general procedure B and purified by
column chromatography (ethyl acetate/hexane = 20:80) to give the
1
reduced pressure. H NMR (500 MHz, CDCl3) δ 5.93−5.80 (m,
2H), 5.65−5.61 (m, 1H), 5.16−5.13 (m, 2H), 2.31 (m, 2H), 2.11−
1.86 (m, 2H), 1.76−1.63 (m, 5H). 13C{1H} NMR (126 MHz,
CDCl3) δ 133.8, 132.3, 130.4, 118.8, 69.3, 46.9, 35.7, 35.7, 19.9, 25.3,
19.1. Data is consistent with literature values.21
2-(4-Chlorophenyl)pent-4-en-2-ol (23). The compound was
prepared according to general procedure B and purified by column
chromatography (ethyl acetate/hexane = 20:80) to give the product
1
(yield: 91%, 178 mg) as a clear oil. H NMR (500 MHz, CDCl3) δ
7.38−7.36 (m, 2H), 7.31−7.29 (m, 2H), 5.60 (dddd, J = 20.2, 9.5,
8.2, 6.5 Hz, 1H), 5.13 (dd, J = 14.0, 1.3 Hz, 2H), 2.64 (dd, J = 13.8,
6.5 Hz, 1H), 2.48 (dd, J = 13.8, 8.3 Hz, 1H), 2.13 (s, 1H), 1.52 (s,
3H). 13C{1H} NMR (126 MHz, CDCl3) δ 146.3, 133.3, 132.5, 128.4,
126.5, 120.0, 73.5, 48.5, 30.0. Data is consistent with literature
values.19
2-(4-Bromophenyl)pent-4-en-2-ol (24). The compound was
prepared according to general procedure B and purified by column
chromatography (ethyl acetate/hexane = 20:80) to give the product
(yield: 87%, 209 mg) as a clear oil. Note that trace 4′-
bromoacetophenone was observed by purified NMR. 1H NMR
(500 MHz, CDCl3) δ 7.44−7.42 (d, J = 8.8 Hz, 2H), 7.33−7.31 (d, J
= 8.8 Hz, 2H), 5.61−5.51 (m, 1H), 5.11 (d, J = 12.4 Hz, 2H), 2.63
(dd, J = 13.7, 6.5 Hz, 1H), 2.49 (dd, J = 13.7, 8.2 Hz, 1H), 2.11 (s,
1H), 1.52 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3) δ 146.8, 133.3,
131.3, 126.9, 120.7, 120.0, 73.5, 48.4, 30.0. Data is consistent with
literature values.20
1
product (yield: 79%, 169 mg) as a clear oil. H NMR (500 MHz,
CDCl3) δ 7.69 (dd, J = 8.9, 6.4 Hz, 1H), 7.11 (dd, J = 8.4, 2.7 Hz,
1H), 6.97 (ddd, J = 8.9, 7.7, 2.7 Hz, 1H), 5.59−5.48 (m, 1H), 5.18−
5.06 (m, 2H), 3.18 (dd, J = 14.0, 6.4 Hz, 1H), 2.61 (dd, J = 14.0, 8.4
Hz, 1H), 2.46 (s, 1H), 1.68 (s, 3H). 13C{1H} NMR (126 MHz,
CDCl3) δ 161.4 (d, J = 312.5 Hz), 139.8 (d, J = 5.0 Hz), 133.5, 131.3
(d, J = 12.6 Hz), 129.4 (d, J = 10.1 Hz), 119.8, 118.5 (d, J = 31.5 Hz),
113.8 (d, J = 25.2 Hz), 74.1, 45.3, 27.6. IR (CH2Cl2 film): 1601, 1578,
1483, 1389, 1377, 1271, 1258, 1215, 1078, 1032, 999, 918, 897, 860,
820 cm−1. HRMS (TOF-ES+) m/z: [M−H2O + H]+ calcd for
C11H11ClF 197.0533; found 197.0540.
2-(3,4-Difluorophenyl)pent-4-en-2-ol (25). The compound was
prepared according to general procedure B and purified by column
chromatography (ethyl acetate/hexane = 15:85) to give the product
1,1,1-Trifluoro-2-phenylpent-4-en-2-ol (31). The compound was
prepared according to general procedure B and purified by column
chromatography (ethyl acetate/hexane = 15:85) to give the product
1
1
(yield: 95%, 188 mg) as a clear oil. H NMR (500 MHz, CDCl3) δ
(yield: 76%, 164 mg) as a clear oil. H NMR (500 MHz, CDCl3) δ
7.31−7.27 (m, 1H), 7.15−7.09 (m, 2H), 5.62 (m, 1H), 5.16−5.13
(m, 2H), 2.63 (dd, J = 13.8, 6.6 Hz, 1H), 2.49 (dd, J = 13.8, 8.2 Hz,
1H), 2.22 (broad s, 1H), 1.53 (s, 3H). 13C{1H} NMR (126 MHz,
7.58 (d, J = 7.7 Hz, 2H), 7.38 (m, 3H), 5.56 (td, J = 17.0, 7.7 Hz,
1H), 5.27−5.17 (m, 2H), 2.98 (dd, J = 14.3, 6.5 Hz, 1H), 2.85 (dd, J
= 14.3, 8.0 Hz, 1H), 2.68 (s, 1H). 13C{1H} NMR (126 MHz, CDCl3)
E
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Article
δ 137.0, 130.5, 128.7, 128.5, 126.6 (d, J = 1.3 Hz), 124.3, 122.1, 75.9
(q, J = 30.0 Hz), 40.4 (d, J = 0.7 Hz). Data is consistent with literature
values.4b,21
B with propargyl bromide (1.0 mmol, 167 μL, 80 wt % in PhMe). The
reaction mixture was milled for 6 h and then purified by column
chromatography (ethyl acetate/hexane = 15:85) to give an
inseparable mixture of 40a and 40b (a:b = 4.2:1, yield: 71%, 114
mg) as a clear oil. Note that product mixture 40 is volatile under
reduced pressure.1H NMR (500 MHz, CDCl3) δ 7.42−7.39 (m, 2H, a
and b), 7.28−7.24 (m, 1H, a and b), 7.19−7.15 (m, 2H, a and b),
5.47 (t, J = 6.6 Hz, 1H, b), 4.90−4.83 (m, 1H, b), 2.64 (dq, J = 16.7,
1.8 Hz, 2H, a), 2.41 (s, 1H, a), 2.19 (s, 1H, b), 1.96 (s, 1H, a), 1.57 (s,
3H, b), 1.55 (s, 3H, a). 13C{1H} NMR (126 MHz, CDCl3) δ 206.0,
171.3, 147.2, 146.4, 128.3, 128.3, 127.2, 127.1, 125.0, 124.8, 100.3,
80.5, 79.2, 73.3, 73.1, 71.8, 60.5, 34.7, 30.5, 21.1, 14.3. Data is
consistent with literature values.25,26
2-(o-Tolyl)pent-4-en-2-ol (32). The compound was prepared
according to general procedure B and purified by column
chromatography (ethyl acetate/hexane = 15:85) to give the product
(yield: 78%, 137 mg) as a clear oil. Note that 32 is volatile under
1
reduced pressure. H NMR (500 MHz, CDCl3) δ 7.27−7.26 (m,
1H), 6.98 (app. s, 3H), 5.49 (td, J = 17.4, 7.3 Hz, 1H), 4.99−4.93 (m,
2H), 2.69 (dd, J = 13.9, 6.6 Hz, 1H), 2.42−2.37 (m, 4H), 1.94 (s,
1H), 1.44 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3) δ 144.6, 135.4,
134.0, 132.7, 127.1, 126.1, 125.8, 119.4, 74.9, 46.7, 29.0, 22.6. Data is
consistent with literature values.19
3-Methyl-2-phenyl-4λ5-penta-3,4-dien-2-ol (42). The compound
was prepared according to general procedure B with 1-bromobut-2-
yne (1.0 mmol, 88 μL). The reaction mixture was milled for 6 h and
then purified by column chromatography (ethyl acetate/hexane =
20:80) to give product 42 (yield: 69%, 120 mg). Note that this
product is volatile under reduced pressure. 1H NMR (500 MHz,
CDCl3) δ 7.47 (d, J = 8.0 Hz, 2H), 7.34 (t, J = 7.5 Hz, 2H), 7.27−
7.24 (m, 1H), 4.91−4.86 (m, 2H), 2.01 (s, 1H), 1.67 (s, 3H), 1.57 (d,
J = 2.7 Hz, 3H). 13C{1H} NMR (126 MHz, CDCl3) δ 205.3, 146.1,
128.2, 127.0, 125.4, 106.0, 77.2, 75.1, 30.3, 14.8. Data is consistent
with literature values.27
Scale-Up Reaction. The reaction was carried out using
acetophenone (1.5 g, 1.46 mL, 12.5 mmol, 1.0 equiv.) according to
general procedure B. The reaction mixture was milled for 6 h in a 25
mL jar and purified by Kugelrohr distillation to give the product
(yield: 75%, 1.52 g) as a clear oil. The characterization data of the
product was in accordance with 20.
2-(Naphthalen-2-yl)pent-4-en-2-ol (33). The compound was
prepared according to general procedure B and purified by column
chromatography (ethyl acetate/hexane = 15:85) to give the product
1
(yield: 92%, 195 mg) as a clear oil. H NMR (500 MHz, CDCl3) δ
7.93 (s, 1H), 7.86−7.83 (m, 3H), 7.56 (dd, J = 8.6, 1.1 Hz, 1H),
7.51−7.46 (m, 2H), 5.64 (m, 1H), 5.15 (dd, J = 23.2, 13.6 Hz, 2H),
2.82 (dd, J = 13.8, 6.3 Hz, 1H), 2.61 (dd, J = 13.8, 8.4 Hz, 1H), 2.23
(s, 1H), 1.65 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3) δ 145.1,
133.7, 133.3, 132.4, 128.3, 128.0, 127.6, 126.2, 125.8, 123.7, 123.3,
119.7, 73.9, 48.4, 30.1. Data is consistent with literature values.19
2-(2-Fluorophenyl)pent-4-en-2-ol (34). The compound was
prepared according to general procedure B and purified by column
chromatography (ethyl acetate/hexane = 15:85) to give the product
(yield: 84%, 151 mg) as a clear oil. Note that 34 is volatile under
reduced pressure. 1H NMR (500 MHz, CDCl3) δ 7.56 (t, J = 7.7 Hz,
1H), 7.24 (m, 1H), 7.13 (t, J = 7.5 Hz, 1H), 7.04−7.00 (dd, J = 12.2,
8.1, 1H), 5.60 (dt, J = 16.8, 9.2 Hz), 5.13 (m, 2H), 2.91 (dd, J = 13.8,
6.3 Hz, 1H), 2.57 (dd, J = 13.8, 8.5 Hz, 1H), 2.42 (s, 1H), 1.63 (s,
3H). 13C{1H} NMR (126 MHz, CDCl3) δ 159.5 (d, J = 245.7 Hz),
134.1 (d, J = 11.3 Hz), 133.7, 128.8 (d, J = 8.8 Hz), 127.5 (d, J = 5.0
Hz), 124.1 (d, J = 2.5 Hz), 119.6, 116.0 (d, J = 23.9 Hz), 72.8, 46.7,
28.4. Data is consistent with literature values.22
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.9b02876.
■
sı
2-(2-Methoxyphenyl)pent-4-en-2-ol (35). The compound was
prepared according to general procedure B and purified by column
chromatography (ethyl acetate/hexane = 30:70) to give the product
Assessment of different zinc sources and the spectral
data (PDF)
1
(yield: 85%, 163 mg) as a clear oil. H NMR (500 MHz, CDCl3) δ
7.46 (m, 1H), 7.16 (app. s, 3H), 5.68 (m, 1H), 5.15 (m, 2H), 2.88
(dd, J = 13.9, 6.5 Hz, 1H), 2.60−2.55 (m, 4H), 2.09 (s, 1H), 1.63 (s,
3H). 13C{1H} NMR (126 MHz, CDCl3) δ 144.7, 135.4, 134.1, 132.8,
127.1, 126.2, 125.8, 119.4, 74.9, 46.7, 29.1, 22.6. IR (CH2Cl2 film):
2984, 1489, 1458, 1375, 1256, 1152, 1094, 1072, 1055, 997, 932, 914,
760, 727 cm−1. Note that HRMS analysis of 35 was unsuccessful, with
unidentifiable fragmentation of the compound.
AUTHOR INFORMATION
Corresponding Author
■
Duncan L. Browne − Cardiff University, Cardiff, U.K.;
orcid.org/0000-0002-8604-229X;
Email: duncan.browne@ucl.ac.uk
N-(1-Phenylbut-3-en-1-yl)benzenesulfonamide (36). The com-
pound was prepared according to general procedure A and purified by
column chromatography (ethyl acetate/hexane = 30:70) to give the
Other Authors
JieXiang Yin − Cardiff University, Cardiff, U.K.
Roderick T. Stark − Cardiff University, Cardiff, U.K.
Ian A. Fallis − Cardiff University, Cardiff, U.K.
1
product (yield: 69%, 129 mg) as white solids. H NMR (500 MHz,
CDCl3) δ 7.66 (m, 2H), 7.45 (t, J = 7.4 Hz, 1H), 7.33 (t, J = 7.7 Hz,
2H), 7.16−7.15 (m, 3H), 7.07−7.05 (m, 2H), 5.57−5.47 (m, 1H),
5.08−4.99 (m, 3H), 4.42 (q, J = 6.7 Hz, 1H), 2.52−2.42 (m, 2H).
13C{1H} NMR (126 MHz, CDCl3) δ 140.6, 140.3, 133.2, 132.5,
128.8, 128.5, 127.6, 127.2, 126.7, 119.5, 57.3, 42.0. Data is consistent
with literature values.23
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.9b02876
Notes
The authors declare no competing financial interest.
N-(1-Phenylbut-3-en-1-yl)aniline (37). The compound was
prepared according to general procedure A and purified by column
chromatography (ethyl acetate/hexane = 8:92) to give the product
(yield: 46%, 103 mg) as white solids. Note that a mixture of rotamers
(5.7:1) was observed by purified NMR. Only the major rotamer is
ACKNOWLEDGMENTS
■
We gratefully acknowledge the School of Chemistry, Cardiff
University for generous support. I.A.F. and D.L.B. are grateful
to the European Union, Tenovus Cancer Charity, and the
National Research Network Wales. R.S. and J.Y. are thankful to
Cardiff University for a Knowledge Economy and Skills
Scholarship (KESS2) and Fellowship, respectively.
1
reported here. H NMR (500 MHz, CDCl3) δ 7.28−7.19 (m, 4H),
7.15−7.12 (m, 1H), 7.00−6.96 (m, 2H), 6.57−6.52 (m, 1H), 6.41−
6.39 (m, 2H), 5.72−5.61 (m, 1H), 5.11−5.03 (m, 2H), 4.29 (dd, J =
8.0, 5.1 Hz, 1H), 4.04 (broad s, 1H), 2.54−2.47 (m, 1H), 2.43−2.36
(m, 1H). 13C{1H} NMR (126 MHz, CDCl3) δ 147.4, 143.7, 134.8,
129.2, 128.7, 127.1, 126.4, 118.4, 117.5, 113.6, 57.2, 43.4. Data is
consistent with literature values.24
REFERENCES
■
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(40b). The compounds were prepared according to general procedure
F
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Article
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