Chemoselectivity in the Kosugi-Migita-Stille coupling of bromophenyl triflates and bromo-nitrophenyl triflates with (ethenyl)tributyltin

Tetrahedron xxx (2018) 1e14

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Chemoselectivity in the Kosugi-Migita-Stille coupling of bromophenyl

triﬂates and bromo-nitrophenyl triﬂates with (ethenyl)tributyltin

*

€

Nurul N. Ansari, Matthew M. Cummings, Bjorn C.G. Soderberg

C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV 26506-6045, USA

a r t i c l e i n f o

a b s t r a c t

Article history:

Kosugi-Migita-Stille cross coupling reactions of (ethenyl)tributyltin with all isomeric permutations of

bromophenyl triﬂate and bromo-nitrophenyl triﬂate were examined in order to determine the chemo-

selectivity of carbon-bromine versus carbon-triﬂate bond coupling under different reaction conditions. In

general, highly selective carbon-bromine bond cross couplings were observed using for example bis(-

triphenylphosphine)palladium dichloride (2 mol-%) in 1,4-dioxane at reﬂux. In contrast, reactions using

the same pre-catalyst but in the presence of a three-fold excess of lithium chloride in N,N-dime-

thylformamide at ambient temperature were in most cases selective for coupling at the carbon-triﬂate

bond. Overall, isolated yields and the selectivity for carbon-bromine bond coupling were signiﬁcantly

higher compared to carbon-triﬂate bond coupling.

Received 5 January 2018

Received in revised form

20 February 2018

Accepted 21 February 2018

Available online xxx

Keywords:

Palladium catalyzed

Kosugi-Migita-Stille coupling

Bromo-nitrophenyl triﬂates

Chemoselectivity

1. Introduction

Echavarren and Stille thus established the overall reactivity or-

der for cross coupling reactions of organotin reagents in the

The reactivity order usually observed in palladium catalyzed

coupling reactions of aromatic halides is I > Br ~ OTf > Cl > F^1,2and

it parallels the rate of oxidative addition of tetrakis(-

triphenylphosphine)palladium (Pd(PPh₃)₄) to aromatic halides as

established by Fitton and Rick in 1971.³In Echavarren and Stille's

seminal work on palladium catalyzed cross coupling reactions of

organotin reagents with aromatic triﬂates, the chemoselectivity of

carbon-bromine (C-Br) versus carbon-triﬂate (C-OTf) coupling of 4-

bromophenyl triﬂate (1) with (ethenyl)tributyltin was dramatically

modulated by proper choice of reaction conditions and additives.⁴

For example, treatment of 4-bromophenyl triﬂate (1) with

(ethenyl)tributyltin in 1,4-dioxane in the presence of Pd(PPh₃)₄at

reﬂux gave product 2 derived from a highly selective oxidative

addition to the C-Br bond (Scheme 1).⁵In contrast, using bis(-

triphenylphosphine)palladium dichloride (PdCl₂(PPh₃)₂) as the

catalyst precursor, in the presence of a three-fold excess of lithium

chloride in N,N-dimethylformamide (DMF) at 24 ^ꢀC, afforded

selectively product 3 derived from oxidative addition to the C-OTf

bond (Scheme 1).⁶Furthermore, a completely selective cross

coupling at the iodine bearing carbon was observed for 4-

iodophenyl triﬂate even in the presence of lithium chloride.⁷

absence of LiCl as I > Br > OTf > Cl and in the presence of LiCl as

I > OTf > Br > Cl. This reactivity order should be used with some

caution since the catalyst system can be tailored so that C-Cl

coupling dominates over C-OTf. For example, treatment of 4-

chlorophenyl triﬂate with (phenyl)tributyltin in the presence of

tris(dibenzylideneacetone)dipalladium

-

bis(tri-tert-butylphos-

phine)palladium and cesium ﬂuoride in 1,4-dioxane, at ambient

temperature, gave exclusively the C-Cl coupling product 2.^8,9

The change in selectivity in the presence of added LiCl is most

likely due to more than one factor. An increase in the rate of

oxidative addition has been observed upon addition of LiCl. The

apparent rate (K_app) of oxidative addition of Pd(PPh₃)₄to phenyl

triﬂate in DMF at 20 ^ꢀC was shown to increase nineteen-fold going

from 0 to 150 equivalents of LiCl.¹⁰In contrast, less than a two-fold

change in K_appwas observed using the more reactive 4-nitrophenyl

triﬂate under the same reaction conditions. Thus, added LiCl ac-

celerates the rate of oxidative addition but the magnitude of ac-

celeration depends on additional functional groups present in the

molecule.¹¹

In addition to an increased rate of oxidative addition, the effect

of added chloride ions has been attributed to a chloride e triﬂate

metathesis of the intermediate Ar-Pd-OTf complex, i.e. Ar-Pd-OTf to

Ar-Pd-Cl, followed by a rapid transmetallation and reductive

elimination.¹²For example, Jutand and Maes et al. have shown that

transmetallation of tin reagents are faster for pyridyl-Pd-Cl

* Corresponding author.

€

E-mail address: bjorn.soderberg@mail.wvu.edu (B.C.G. Soderberg).

https://doi.org/10.1016/j.tet.2018.02.051

Please cite this article in press as: Ansari NN, et al., Chemoselectivity in the Kosugi-Migita-Stille coupling of bromophenyl triﬂates and bromo-

nitrophenyl triﬂates with (ethenyl)tributyltin, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.02.051

2

N.N. Ansari et al. / Tetrahedron xxx (2018) 1e14

activated for oxidative addition by the two electron withdrawing

nitro groups. In addition, the steric environments should be more

or less equivalent since both sites have an ortho-nitro group and

they are separated by an unsubstituted position. Thus, the absence

of any apparent reaction at ambient temperature and the failure to

obtain the expected C-OTf bond coupling product from 5, under the

reaction conditions reported to be selective for triﬂate coupling,

were puzzling.

To the best of our knowledge, there is no reported systematic

study on the chemoselectivity in Kosugi-Migita-Stille couplings of

substituted bromophenyl triﬂates.

Herein is described a detailed study of the selectivity observed

in palladium catalyzed coupling reactions of (ethenyl)tributyltin

with all possible isomeric permutations of bromophenyl triﬂate

and bromo-nitrophenyl triﬂate. Each isomeric compound was

examined under bromide and triﬂate selective reaction conditions.

Scheme 1. Kosugi-Migita-Stille cross coupling of 1 with (ethenyl)tributyltin.

complexes compared to pyridyl-Pd-I complexes.¹³In a similar

fashion, Casado and Espinet reported that transmetallation e

reductive elimination from isolated trans-[3,5-dichloro-2,4,6-

triﬂuorophenyl-Pd-X(AsPh₃)₂] complexes were in the order

X ¼ Cl > Br > I.¹⁴

In addition to the group being replaced, the rate of reaction

depends on the electronic nature of additional substituents on the

aromatic ring. Milstein and Stille reported an almost ninety-fold

difference in the relative reaction rate in reactions of tetrame-

thyltin with 4-methoxy-1-bromobenzene (1) < 4-methyl-1-

bromobenzene (1.46) < bromobenzene (2.18) < 4-triﬂuoromethyl-

1-bromobenzene (19.5) < 3-nitro-1-bromobenzene (87.9) in hex-

amethylphophoramide (HMPA) at 63 ^ꢀC using BnPd(PPh₃)₂Cl as the

pre-catalyst.¹⁵These results clearly demonstrate the signiﬁcant rate

accelerating effect of the electron withdrawing nitro group even

when not in conjugation with the site of the oxidative addition. In a

similar fashion, the usually unreactive aryl ﬂuorides can participate

in Kosugi-Migita-Stille couplings in the presence of two electron

withdrawing groups. For example, cross couplings of 4-ﬂuoro-3-

2. Results and discussion

In an attempt to corroborate the results reported by Echavarren

and Stille, cross coupling reactions of 4-bromophenyl triﬂate (1)

and (ethenyl)tributyltin were performed (Table 1). Under bromine

selective conditions, a 33:1 ratio of C-Br to C-OTf (2:3) bond

coupling was reported by the authors based on ¹H NMR of the

crude reaction mixture (Table 1, entry 1). This reaction was

repeated and in our hands only compound 2 was observed by ¹H

NMR at 600 MHz (entry 2). The catalyst, Pd(PPh₃)₄, used in the

initial study is not air stable and handling and extended storage of

this compound often results in diminished catalytic activity. In

order to minimize problems associated with Pd(PPh₃)₄, a combi-

nation of the signiﬁcantly more stable precursor bis(dibenzylide-

neacetone)palladium (Pd(dba)₂) and triphenylphosphine (PPh₃)

was used to generate Pd(PPh₃)₄in situ. In the event, the same

exclusive selectivity was observed using 2 mol% Pd(dba)₂and 8 mol

% PPh₃in 1,4-dioxane at reﬂux (entry 3). Since the latter conditions

gave the same selectivity as Pd(PPh₃)₄, the more convenient cata-

lyst precursor Pd(dba)₂-PPh₃was used in all subsequent reactions.

It is unclear why two different palladium catalyst precursors

were used by Echavarren and Stille (Scheme 1). We found that

PdCl₂(PPh₃)₂without any added PPh₃not only gave the same

chemoselectivity as Pd(PPh₃)₄in a reaction of 1 with (ethenyl)

tributyltin and in the absence of LiCl, but this catalyst precursor also

afforded a superior yield of product (entry 4). Under triﬂate se-

lective conditions, employing PdCl₂(PPh₃)₂in the presence of a

three-fold excess of LiCl in DMF at 24 ^ꢀC, Echavarren and Stille re-

ported exclusive coupling derived from oxidative addition to the C-

OTf bond (entry 5). In our hands, employing the same reaction

conditions, a much lower selectivity C-Br/C-OTF ¼ 1:6.7 (entry 6)

was observed. This product ratio is similar to the ratio reported by

Echavarren and Stille at a higher reaction temperature either in 1,4-

dioxane (at reﬂux, entry 7) or DMF (70 ^ꢀC, entry 8).¹⁸It should be

noted that products 2e3 decompose/polymerize to varying extent

upon chromatographic puriﬁcation on silica gel.

nitrobenzaldehyde

and

4-ﬂuoro-3-nitrobenzonitrile

with

(ethenyl)tributyltin have been reported.^16,17

A chemoselective sequential introduction of two different al-

kenes was of interest to us for the synthesis of dinitro-

dialkenylbenzenes, substrates suitable for a palladium catalyzed

double reductive cyclization en route to pyrroloindoles. It was

envisioned that the chemoselectivity observed by Echavarren and

Stille would enable us to prepare a variety of cyclization precursors

containing two different alkenes. Thus, 2,4-dinitro-5-bromophenyl

triﬂate (5) was prepared in good yield by dinitration of 3-

bromophenyl triﬂate (4) (Scheme 2). Treatment of

5 with

(ethenyl)tributyltin under the Echavarren-Stille conditions

described above that should result in oxidative addition to the C-

OTf bond did not afford any identiﬁable coupling product. The

solvent was changed from DMF to toluene in order to simplify the

work up and the analysis of the crude ¹H NMR spectrum. A small

amount of 2,6-di-tert-butyl-4-methylphenol (DTBMP) was added

as a radical inhibitor. No reaction occurred at ambient temperature,

however the starting material was completely consumed within

17 h when the reaction temperature was increased to 80 ^ꢀC. The ¹H

NMR spectrum of the resulting crude reaction mixture contained

three alkenyl proton resonances suggesting a single coupling

product. Surprisingly,

a

quartet resonance in the ¹³C NMR

(J ¼ 320 Hz) spectrum and a resonance at ꢁ72.9 ppm in the ¹⁹F NMR

spectrum indicated the presence of an intact triﬂate group. The

crude product was puriﬁed by chromatography to afford 6 in good

isolated yield.

In contrast to cross coupling of 1 with (ethenyl)tributyltin, car-

bonylative reactions of 1 with (2-phenylethenyl)tributyltin in the

The site selectivity of palladium catalyzed coupling reactions of

benzenes having two electrophilic centers depends on the position

of additional functional groups present in the substrate. However,

the two potential coupling sites in 5 should be similar if not equally

presence

of

1,1⁰-bis(diphenylphosphinoferrocene)-palladium

dichloride (PdCl₂(dppf)) was reported to afford exclusive C-OTf

bond coupling with or without added LiCl (Scheme 3).^19,20A C-OTf

selectivite carbonylation of 1 using Pd(OAc)₂- dppf in DMF to give

an amide was very recently reported by Jiao and Wu et al.²¹

Interestingly, switching the ligand to Xantphos and the solvent to

toluene completely reversed the selectivity to C-Br. We assumed

that the difference in site selectivity observed in the absence of LiCl

when comparing Schemes 1 and 3 was the result of the PdCl₂(dppf)

pre-catalyst and not the difference in tin reagents. Thus, 1 was

Scheme 2. Preparation and Kosugi-Migita-Stille reaction of 5.

Please cite this article in press as: Ansari NN, et al., Chemoselectivity in the Kosugi-Migita-Stille coupling of bromophenyl triﬂates and bromo-

nitrophenyl triﬂates with (ethenyl)tributyltin, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.02.051

N.N. Ansari et al. / Tetrahedron xxx (2018) 1e14

3

Table 1

Reaction of bromophenyl triﬂates with ethenyl tributyltin.

slower and a signiﬁcant amount of starting material was recovered

after 24 h. It should be noted that cross-coupling of 8 with (ethenyl)

tributyltin using PdCl₂(dppp) as the pre-catalyst has been described

(entry 15).²³Although only C-OTf coupling was reported in 25%

yield after 39 h, it is unclear if the reported selectivity is based on

the crude product or after puriﬁcation.

Scheme 3. Kosugi-Migita-Stille reaction of 1 using PdCl₂(dppf).

The following conclusions can be made based on the results

presented in Table 1; a) a high selectivity for C-Br coupling is

observed for all three substrates (1, 7e8). b) PdCl₂(PPh₃)₂and

treated with (ethenyl)tributyltin in the presence of PdCl₂(dppf) in

DMF at ambient temperature in the absence of LiCl. The starting

material was almost completely consumed after 24 h and an

exclusive formation of 3 was observed in the ¹H NMR of the crude

reaction mixture. However, only a low isolated yield of product was

obtained after chromatographic puriﬁcation. Based on the result

depicted in Scheme 3, it is plausible that other palladium catalysts

and/or reaction conditions can be developed for selective C-OTf

bond Kosugi-Migita-Stille cross-couplings even in the absence of

added LiCl.²²

To determine if the relative position of the bromide and the

triﬂate would alter the chemoselectivity of the coupling reaction,

the isomeric 2-bromophenyl and 3-bromophenyl triﬂates 7 and 8

were examined. Reactions of both 7 and 8 displayed the same high

selectivity for C-Br coupling and a similar selectivity for C-OTf

coupling as was observed in the reactions of 1 (Table 1, entries

10e14). In comparison to bromo-triﬂates 1 and 7, reaction of 8 was

Pd(dba)₂

e PPh₃are convenient, air stable, alternatives to

Pd(PPh₃)₄. c) Although we were unable to repeat the results by

Echavarren and Stille, a signiﬁcantly lower but still synthetically

very useful C-OTf selectivity can be realized. d) Reactions wherein

the two substituents were either ortho or para to each other were

faster.

Having established the general trends for cross coupling of

bromophenyl triﬂates, the inﬂuence of a nitro group on the che-

moselectivity of C-Br versus C-OTf coupling of the Kosugi-Migita-

Stille reaction was examined next. All ten possible bromo-

nitrophenyl triﬂate permutations (13e22) were prepared from

the corresponding bromo-nitrophenols using triﬂic anhydride and

pyridine. Compounds 13e22 were treated with (ethenyl)tributyltin

under three different reaction conditions A - C. Conditions A con-

sisted of a bis(dibenzylideneacetone)palladium (2-mol%) and tri-

phenylphosphine (8-mol%) pre-catalyst system and the reactions

Please cite this article in press as: Ansari NN, et al., Chemoselectivity in the Kosugi-Migita-Stille coupling of bromophenyl triﬂates and bromo-

nitrophenyl triﬂates with (ethenyl)tributyltin, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.02.051

4

N.N. Ansari et al. / Tetrahedron xxx (2018) 1e14

were performed in 1,4-dioxane at reﬂux temperature. Conditions B,

employed bis(triphenylphosphine)palladium dichloride (2 mol%)

in 1,4-dioxane at reﬂux temperature. Finally, for Condition C bis(-

triphenylphosphine)palladium dichloride (2 mol%) and lithium

chloride (300 mol%) was used and the reactions were performed in

DMF at ambient temperature. Conditions A and B were anticipated

to be bromo-selective conditions and Conditions C to be triﬂate-

selective conditions. The reaction time was in all cases ~24 h

regardless if all starting material had been consumed or not. The

crude reaction mixtures were analyzed by ¹H NMR (400 or

600 MHz) to give the ratio of products prior to chromatographic

puriﬁcation. Unreacted starting material was observed in the crude

reaction mixtures in some of the reactions. Although not seen prior

to chromatography, phenols derived from hydrolysis of the triﬂate

of the starting material were also obtained after puriﬁcation. Since

the aim of this study was to determine the chemoselectivity of the

coupling reaction, i.e. C-Br versus C-OTf bond coupling, no attempts

were made to optimize the yield of a given product for a particular

substrate. The observed crude product ratios and the isolated yields

of products after puriﬁcation are seen in Table 2. Tin impurities may

at times be problematic to remove by chromatography on silica gel.

However, no trace of metal impurities was observed using a com-

bination of silica gel and potassium carbonate (9:1 ratio) as

described by Harrowven et al.⁶

Treatment of 2-bromo-3-nitrophenyl triﬂate (13) with (ethenyl)

tributyltin under Conditions A gave the expected C-Br coupling

product 23 in relatively low yield but with excellent chemo-

selectivity (Table 2, entry 1). The low yield can in part be explained

by the observation of a fair amount of starting material. Under

Conditions B, the isolated yield of 23 was more than doubled and

the chemoselectivity remained the same (entry 2). The C-OTf

coupling product was not observed by ¹H NMR in either of the

reaction. It should be noted that cross coupling of 13 with (ethenyl)

tributyltin in the presence of Pd(PPh₃)₄in toluene at reﬂux has

been reported to give C-Br coupling in 91% yield (entry 3).²⁴While

the reactions under Conditions A-B exhibited excellent chemo-

selectivities, a very disappointing 1:1.6 ratio of C-Br/C-OTf coupling

was obtained under Conditions C (entry 5). In addition to the low

Table 2

Cross-coupling of 13e22 with (ethenyl)tributyltin.

Please cite this article in press as: Ansari NN, et al., Chemoselectivity in the Kosugi-Migita-Stille coupling of bromophenyl triﬂates and bromo-

nitrophenyl triﬂates with (ethenyl)tributyltin, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.02.051

N.N. Ansari et al. / Tetrahedron xxx (2018) 1e14

5

selectivity, the reaction did not go to completion.

bidentate ligand 1,3-bis(diphenylphosphino)propane (dppp),

a

Kamikawa and Hayashi have shown that the chemoselectivity of

the oxidative addition of palladium(0) to 4-bromophenyl triﬂate (1)

can be controlled by the proper choice of ligand.²⁵Using the

95:5 C-OTf/C-Br ratio of oxidative addition products was observed

in a stoichiometric reaction. In contrast, using PPh₃as the ligand

gave an almost reversed 15:85 ratio. When a catalytic amount of

Please cite this article in press as: Ansari NN, et al., Chemoselectivity in the Kosugi-Migita-Stille coupling of bromophenyl triﬂates and bromo-

nitrophenyl triﬂates with (ethenyl)tributyltin, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.02.051

6

N.N. Ansari et al. / Tetrahedron xxx (2018) 1e14

PdCl₂(dppp) was employed in a cross coupling of 1 with phenyl-

magnesium bromide, a rapid and highly triﬂate selective reaction

was observed at 0 ^ꢀC in diethyl ether. Based on this report, it may be

possible to improve the C-OTf/C-Br coupling ratio of 13 by simply

replacing PPh₃with dppp as the ligand in Kosugi-Migita-Stille re-

actions. In the event, no reaction of 13 with (ethenyl)tributyltin was

observed in DMF at ambient temperature in the presence of a

catalytic amount of PdCl₂(dppp) (entry 4). The starting material

was recovered in 75% yield. In contrast, reaction of 13 using

of interest to examine if a nitro group in a similar fashion activates

the ortho position of 47 for cross coupling reactions using a tin

reagent. Treatment of 47 under the published reaction conditions,²⁸

replacing 1-heptyne with (ethenyl)tributyltin, resulted in a 98%

recovery of the starting material. In a second experiment, com-

pound 47 was subjected to Conditions B. The starting material was

completely consumed affording 36 and an inseparable mixture of

24 and 25, all in similar yields (Scheme 4). Although cross-coupling

at the ortho-position of 47 was slightly favored (1.3:1), it appears

that the nitro group has only a very small effect on the site-

selectivity in this case, in sharp contrast to the Sonagashira

reaction.

Aryl iodides undergo Kosugi-Migita-Stille coupling reactions

signiﬁcantly faster compared to aryl triﬂates even in the presence of

a large excess of LiCl. Cross couplings of 4-iodo-2-nitrophenyl tri-

ﬂate (48) under conditions A-C were examined to determine if a

nitro group is sufﬁciently ortho-activating for a triﬂate to react in

the presence of an iodide in a less activated meta-position (Scheme

5). Compound 48 is the iodo-analog of 19 for which a relatively low

C-Br selectivity and an excellent C-OTf selectivity were observed

(Table 2, entry 25e27). In all three experiments employing 48, the

major product 39 was derived from oxidative addition to the C-I

bond. In addition to 39, di-coupled product 30 and compounds 49

and 51 derived from loss of triﬂate from 39 and 48, respectively,

were also isolated. Comparing the two pre-catalysts Pd(dba)₂-PPh₃

and PdCl₂(PPh₃)₂, the latter again proved to be superior, affording

an excellent overall yield of coupling products (95%). The results

shown in Scheme 5 illustrate the signiﬁcantly higher reactivity of

the carbon-iodide bond. Only under Conditions C was a small

amount of the C-OTf coupling product 50 isolated. Although the

yield of 50 was unimpressive it represents, to the best of our

knowledge, the only example of a Kosugi-Migita-Stille coupling

reaction wherein even a small fraction of C-Br or C-OTf coupling

occurred on a benzene ring also containing an iodide.^29,30

PdCl₂(dppp) under Conditions

C was faster compared to

PdCl₂(PPh₃)₂and the starting material was completely consumed

after 24 h at ambient temperature (entry 6). Unfortunately, only a

slight improvement of the product ratio was observed in addition

to a fair amount of product derived from coupling at both positions

(25). Excellent yield of 25 can be realized by treatment of 13 with a

three-fold excess of (ethenyl)tributyltin in the presence of

PdCl₂(PPh₃)₂and LiCl in 1,4-dioxane at reﬂux (entry 7). It should be

noted that di-coupling affording di(ethenyl)-nitrobenzenes was

observed in several of the reactions seen in Table 2.

The results obtained from reactions of 14 and 15 parallels the

cross couplings described above employing 13 as the starting ma-

terial. A pre-catalyst system consisting of 2-mol% palladium diac-

etate (Pd(OAc)₂) and 4-mol% PPh₃was also examined in reactions

of (ethenyl)tributyltin with substrates 14 and 15. Compared to the

reactions using Conditions A-B, cross coupling experiments in the

presence of Pd(OAc)₂-PPh₃afforded similar yields of 26 and 29

(Table 2, entries 8e10 and 12e14). Not only were the isolated yields

more or less the same, the crude ratios of 26/28 and of 29/31 were

comparable using either Pd(OAc)₂or PdCl₂(PPh₃)₂. Thus, there is a

very minor, if any, effect on the C-Br/C-OTf selectivity from the

chloride present when using PdCl₂(PPh₃)₂as the catalyst.

The remaining seven substrates were only treated with

(ethenyl)tributyltin under Conditions A-C. Some general trends can

be discerned from the result depicted in Table 2. For all substrates

13e22, the C-Br/C-OTf coupling ratios were similar or better under

Conditions B compared to Conditions A. The ratios under the

former reaction conditions ranged from 12:1 to >30:1. Not only did

the reactions under Conditions B exhibit better chemoselectivities,

the isolated yields of C-Br cross coupling products were also su-

perior. The yields under Conditions B ranged from 66 to 94%

(average 77%) for the ten substrates and were in all but one case

(compound 14, Table 2) signiﬁcantly higher compared to the yields

obtained under Conditions A, which ranged from 22 to 82%

(average 50%). Results from experiments employing Conditions C

were inferior compared to Conditions A-B. The C-Br/C-OTf coupling

ratios ranged from 4:1 to >1:30. It should be noted that cross

coupling of compound 21 actually favored C-Br coupling under

conditions presumed to favor C-OTf coupling (entry 33-C, Table 2).

In addition to a lower chemoselectivity under Conditions C, the

isolated yields of products were also lower ranging from 7 to 78%

(average 44%).

In order to examine if a similar chemoselectivity can be

extended to benzene rings substituted with other electron with-

drawing

groups,

5-bromo-2-

triﬂuoromethanesulfonylacetophenone (52) was prepared and

treated with (ethenyl)tributyltin (Scheme 6). Under all reaction

Scheme 4. Kosugi-Migita-Stille reaction of 47.

For half of the substrates, compounds 16e17, 19e20, and 22,

highly selective C-OTf coupling reactions were observed under

conditions C with C-Br/C-OTf ratios of >1:30. These substrates

either have the bromide in an “unactivated” meta-position relative

to the nitro group (entries 21, 27, and 30) or the triﬂate and the

bromide were both ortho or meta to the nitro group (entries 18 and

36). For the other ﬁve substrates having the bromide ortho or para

relative to the nitro group, compounds 13e15,18, and 21, a reversed

or mediocre C-Br/C-OTf ratio (4:1e1:3) was observed (entries 5e6,

11, 15, 24, and 33).

Scheme 5. Kosugi-Migita-Stille cross-coupling of 48 with (ethenyl)tributyltin.^a.

Palladium catalyzed Sonogashira reactions of 3,4-dibromo-1-

nitrobenzene and 2,3-dibromo-1-nitrobenzene (47) with 1-

heptyne have been reported to occur exclusively at the more

electrophilic site, that is ortho or para to the nitro group.^26,27It was

Scheme 6. Kosugi-Migita-Stille cross-coupling of 52.

Please cite this article in press as: Ansari NN, et al., Chemoselectivity in the Kosugi-Migita-Stille coupling of bromophenyl triﬂates and bromo-

nitrophenyl triﬂates with (ethenyl)tributyltin, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.02.051

N.N. Ansari et al. / Tetrahedron xxx (2018) 1e14

7

conditions (A-C), a single coupling product was observed in each

case as determined by ¹H NMR (>30:1 ratio) of the crude reaction

mixtures. The C-Br bond selectivity under Conditions A and B was

signiﬁcantly higher starting from 52 relative to the selectivity

observed for the nitro substituted compound 19 (Table 3, entry

25e26) having the same relative substituent conﬁguration. It is

plausible, that the electron-withdrawing keto-functionality acti-

vates the ring toward oxidative addition of palladium(0) but does

not sufﬁciently activate the ortho-position bearing the triﬂate to

override the exclusive C-Br selectivity observed for the

bromophenyl-triﬂate (1). As observed previously (Table 2), a

signiﬁcantly higher yield of cross-coupling product 53 was isolated

using Conditions B in comparison to Conditions A.

SiMe₄(0.0 ppm, ¹H and ¹³C) or CDCl₃(77.0 ppm, ¹³C) internal

standards. HRMS data were obtained via ESI with an orbitrap mass

analyzer.

Anhydrous N,N-dimethylformamide was used as received.

Hexanes and ethyl acetate were distilled prior to use. 1,4-Dioxane

was puriﬁed/dried via two consecutive columns composed of

activated alumina and Q5 catalyst on a Glass Contours solvent

puriﬁcation system. Dichloromethane and toluene was puriﬁed/

dried via two consecutive columns composed of activated alumina

on a Glass Contours solvent puriﬁcation system. Chemicals pre-

pared according to literature procedures have been footnoted the

ﬁrst time used; all other reagents were obtained from commercial

sources and used as received. All reactions were performed under a

nitrogen atmosphere in oven-dried glassware. Solvents were

removed from reaction mixtures and products on a rotary evapo-

rator at water aspirator pressure unless otherwise stated. Chro-

Finally, the site-selectivity of

a

bromophenyl tri-

ﬂuoromethanesulfonate having an electron donating substituent

on the aromatic ring was examined. Only a very limited number of

palladium catalyzed coupling reactions of this type of substrate

have been reported.^31e33In no case was the effect of an electron

donating group on the C-Br/C-OTf selectivity examined in detail.

The known triﬂate 55 was selected as the starting material in order

to minimize the effect of steric interactions between the bromide

and triﬂate with the methoxy group. Two reactions were per-

formed one under Conditions A and one under Conditions C

(Scheme 7). The reactions were more sluggish and only low yields

of products were obtained after puriﬁcation. However, the site-

selectivity remained the same, a selective C-Br bond coupling was

seen under Conditions A and a relatively selective C-OTf bond

coupling (~10:1 ratio) was realized under Conditions C. From these

two experiments it appears that the only effect of the electron-

donating group for this substrate is a somewhat lower reactivity.

matography was performed on silica gel (SiO_2,40e63 mm) if not

otherwise stated. Melting points (uncorrected) were recorded from

the pure products obtained by chromatography.

4.1.1. 2,4-Dinitro-5-bromophenyl triﬂuoromethanesulfonate (5)

To a solution of fuming HNO₃(4.2 mL) in H₂SO₄(4.2 mL) was

added 3-bromophenyl triﬂuoromethanesulfonate (4)³⁴(1.52 g,

4.98 mmol) and the mixture was heated at 60 ^ꢀC for 15 h. The

resulting mixture was poured onto ice, the ice was allowed to melt,

and the resulting mixture was extracted with EtOAc (3 ꢂ 20 mL).

The combined organic phases were dried (MgSO₄), ﬁltered, and the

solvents were removed under reduced pressure. The crude product

was puriﬁed by chromatography (hexane/EtOAc, 9:1) affording 5

(1.82 g, 4.60 mmol, 92%) as a pale yellow oil that solidiﬁed upon

standing. Mp ¼ 33e35 ^ꢀC; ¹H NMR (400 MHz, CDCl₃)

d 8.72 (s, 1H),

d 148.2, 142.7, 140.2, 131.2,

7.90 (s, 1H); ¹³C NMR (150 MHz, CDCl₃)

3. Conclusions

124.0, 122.1, 118.5 (q, J^C-F¼ 320 Hz); IR (ATR) 1591, 1541, 1436, 1337,

1213, 1130 cm^ꢁ1

; HRMS (ESI, negative ion mode) calcd for

We have examined the chemoselectivity of carbon-bromine

versus carbon-triﬂate bond coupling in Kosugi-Migita-Stille re-

actions of (ethenyl)tributyltin with bromophenyl triﬂates and

bromo-nitrophenyl triﬂates. In general, highly selective carbon-

bromine bond cross couplings were observed using bis(-

triphenylphosphine)palladium dichloride in 1,4-dioxane at reﬂux.

In contrast, reactions using the same pre-catalyst but in the pres-

ence of a three-fold excess of LiCl, in DMF at ambient temperature,

were in most cases selective for coupling at the carbon-triﬂate

bond. However, both isolated yields and the selectivity for

carbon-bromine bond coupling were signiﬁcantly higher compared

to carbon-triﬂate bond coupling reactions.

C₇HBrF₃N₂O₇S (M-H^-) 392.8640; found 392.8654.

4.1.2. 5-Ethenyl-2,4-dinitro triﬂuoromethanesulfonate (6)

A

mixture of 5 (238 mg, 0.60 mmol), (ethenyl)tributyltin

(187 mg, 0.59 mmol), 2,6-di-t-butyl-4-methylphenol (22 mg,

0.10 mmol), LiCl (87 mg, 2.05 mmol), PPh₃(25.2 mg, 0.098 mmol),

and PdCl₂(PPh₃)₂(33.7 mg, 0.048 mmol) in toluene (4 mL) was

heated at 80 ^ꢀC for 17 h. The solvent was removed at reduced

pressure and the crude product was puriﬁed by chromatography

(hexane/EtOAc, 9:1) to give 6 (160 mg, 0.468 mmol, 78%) as a faint

brown oil. ¹H NMR (600 MHz, CDCl₃)

d 8.81 (s, 1H), 7.69 (s, 1H), 7.26

(dd, J ¼ 16.8, 10.8 Hz, 1H), 5.96 (d, J ¼ 17.4 Hz, 1H), 5.86 (d,

J ¼ 10.8 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃)

d 145.3, 143.6, 140.5,

4. Experimental Section

139.7, 129.8, 125.0, 124.4, 123.9, 118.5 (q, J^C-F¼ 321 Hz); ¹⁹F NMR

(376 MHz, CDCl₃)

d

ꢁ72.9; IR (ATR) 1614, 1590, 1539, 1437, 1345,

4.1. General procedures

1223, 1134 cm^ꢁ1

;

HRMS (ESI, negative ion mode) calcd for

C₉H₅F₃NO₇S (M^ꢁ) 341.9770; found 341.9787.

NMR spectra were recorded in CDCl₃at 400 and 600 MHz (¹H

NMR), 100 and 150 MHz (¹³C NMR), and 376 and 565 MHz (¹⁹

F

4.1.3. 4-Bromo-3-nitrophenyl triﬂuoromethanesulfonate (15)

NMR). The chemical shifts are expressed in

d values relative to

To a solution of 4-bromo-3-nitrophenol³⁵(269 mg, 1.23 mmol)

in CH₂Cl₂(5 mL) at 0 ^ꢀC was added pyridine (200

and triﬂuoromethanesulfonic anhydride (Tf₂O, 250

m

L, 2.48 mmol)

L, 1.48 mmol).

The mixture was removed from the cold bath and allowed to stir at

ambient temperature for 30 min. The resulting mixture was ﬁltered

through a small plug of silica gel and the solvent was removed

under reduced pressure from the ﬁltrate. Puriﬁcation by chroma-

tography (hexane/EtOAc, 9:1) afforded 15 (391 mg, 1.12 mmol, 90%)

as a yellow oil. ¹H NMR (400 MHz, CDCl₃)

d

7.88 (d, J ¼ 8.4 Hz, 1H),

7.81 (d, J ¼ 2.8 Hz, 1H), 7.41 (dd, J ¼ 8.8, 2.8 Hz, 1H); ¹³C NMR

(100 MHz, CDCl₃)

d

150.1, 147.9, 136.8, 126.3, 119.3, 118.6 (q, J^C-F

¼

Scheme 7. Kosugi-Migita-Stille cross-coupling of 55.

319 Hz), 114.6; IR (ATR) 3103, 1541, 1428, 1208, 1132 cm^ꢁ1; HRMS

Please cite this article in press as: Ansari NN, et al., Chemoselectivity in the Kosugi-Migita-Stille coupling of bromophenyl triﬂates and bromo-

nitrophenyl triﬂates with (ethenyl)tributyltin, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.02.051

8

N.N. Ansari et al. / Tetrahedron xxx (2018) 1e14

(ESI) calcd for C₇H₃BrNNaO₅F₃S (M þ Na^þ) 371.8765; found

triﬂuoromethanesulphonate (1)⁴(102 mg, 0.34 mmol) followed by

(ethenyl)tributyltin (128 mg, 0.40 mmol). The solution was heated

at reﬂux for 24 h. The solvent was removed under reduced pressure

and the residue was dissolved in EtOAc (10 mL) and washed with

NH₄OH (10% aqueous, 3 ꢂ 20 mL), H₂O (20 mL), and brine (20 mL).

The organic phase was dried (MgSO₄), ﬁltered, and solvents were

removed under reduced pressure. The crude product was puriﬁed

by chromatography (hexane/EtOAc, 97:3) to give 2 (25.2 mg,

0.10 mmol, 30%) as a colorless oil. Only 2 was observed by ¹H NMR

(600 MHz, CDCl₃) of the crude reaction mixture.

371.8760.

4.1.4. 3-Bromo-2-nitrophenyl triﬂuoromethanesulfonate (16)

Treatment of 3-bromo-2-nitrophenol³⁶(298 mg, 1.37 mmol) in

CH₂Cl₂(5 mL) with pyridine (250 mL, 3.10 mmol) and Tf₂O (300 mL,

1.77 mmol), as described for 15, gave after chromatography (hex-

ane/EtOAc, 8:2) 16 (394 mg, 1.13 mmol, 80%) as a red solid. Mp

52e53 ^ꢀC; ¹H NMR (400 MHz, CDCl₃)

d

7.73 (dd, J ¼ 6.6, 3.0 Hz, 1H),

7.49 (m, 2H); ¹³C NMR (150 MHz, CDCl₃)

d 140.6, 136.2, 133.4, 132.1,

121.6, 118.3 (q, J^C-F¼319 Hz), 115.2; ¹⁹F NMR (376 MHz, CDCl₃)

d

ꢁ73.2; IR (ATR) 3099, 1538, 1434, 1360, 1219, 1132 cm ^ꢁ1; HRMS

4.3. Conditions B

(ESI) calcd for C₇H₃BrNNaO₅F₃S (M þ Na^þ) 371.8765; found

371.8767.

4.3.1. Entry 4. 4-Ethenylphenyl triﬂuoromethanesulfonate (2)

To a solution of PdCl₂(PPh₃)₂(4.3 mg, 0.007 mmol) in dioxane

(4 mL), stirred for 5 min under an atmosphere of N₂, was added 1

(310 mg, 1.02 mmol) followed by (ethenyl)tributyltin (340 mg,

1.07 mmol). The solution was heated at reﬂux for 24 h. The solvent

was removed under reduced pressure and the resulting residue was

puriﬁed by chromatography (SiO₂/K₂CO₃¼ 9:1, hexane/EtOAc,

98:2) to give 2 (231 mg, 0.917 mmol, 90%) as a colorless oil. Only 2

was observed by ¹H NMR (600 MHz, CDCl₃) of the crude reaction

mixture.

4.1.5. 2-Bromo-6-nitrophenyl triﬂuoromethanesulfonate (17)

Treatment of 2-bromo-6-nitrophenol³⁷(189 mg, 0.87 mmol) in

CH₂Cl₂(5 mL) with pyridine (150 mL, 1.85 mmol) and Tf₂O (200 mL,

1.18 mmol), as described for 15, gave after chromatography (hex-

ane/EtOAc, 7:3) 17 (299 mg, 0.85 mmol 98%) as a colorless oil. ¹H

NMR (400 MHz, CDCl₃)

d

8.04 (dd, J ¼ 8.4, 1.6 Hz, 1H), 7.99 (dd,

J ¼ 8.4,1.6 Hz,1H), 7.45 (t, J ¼ 8.6 Hz,1H); ¹³C NMR (150 MHz, CDCl₃)

d 143.6, 139.4, 139.1, 129.3, 125.6, 119.1, 118.4 (q, J^CꢁF¼319 Hz);¹⁹

F

NMR (376 MHz, CDCl₃)

d

ꢁ73.2; IR (ATR) 3093, 1588, 1540, 1431,

1347, 1207 cm^ꢁ1; HRMS (ESI) calcd for C₇H₃BrNNaO₅F₃S (M þ Na^þ)

4.4. Conditions C

371.8765; found 371.8761.

4.4.1. Entry 6. 4-Ethenylphenyl triﬂuoromethanesulfonate (2) and

4-ethenyl-1-bromobenzene (3).⁴

4.1.6. 4-Bromo-2-nitrophenyl triﬂuoromethanesulfonate (19).³⁸

Treatment of 4-bromo-3-nitrophenol³⁹(353 mg, 1.60 mmol) in

To a solution of LiCl (45.5 mg, 1.07 mmol) and Pd(PPh₃)₂Cl₂

(4.7 mg, 0.007 mmol) in DMF (1.5 mL), under an atmosphere of N₂,

was added 1 (108 mg, 0.35 mmol) followed by (ethenyl)tributyltin

(141 mg, 0.44 mmol). After stirring at ambient temperature for 24 h,

the solvent was removed by bulb-to-bulb distillation. The resulting

residue was dissolved in EtOAc (15 mL) and washed with NH₄OH

(10% aqueous, 3 ꢂ 20 mL) and brine (20 mL). The organic phase was

dried (MgSO₄), ﬁltered, and solvents were removed under reduced

pressure. The terminal cis-alkene protons were clearly resolved in

the ¹H NMR spectrum at 600 MHz and these signals were used to

CH₂Cl₂(5 mL) with pyridine (260 mL, 3.22 mmol) and Tf₂O (330 mL,

1.95 mmol), as described for 15, gave after chromatography (hex-

ane/EtOAc, 7:3) 19 (540 mg, 1.54 mmol, 97%) as a yellow oil. ¹H NMR

(600 MHz, CDCl₃)

d

8.30 (d, J ¼ 2.4 Hz, 1H), 7.88 (dd, J ¼ 9.0, 2.4 Hz,

1H), 7.36 (d, J ¼ 9.0 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃)

d 141.9,

140.5, 138.2, 129.7, 125.6, 122.3, 118.5 (q, J^C-F¼ 319 Hz); IR (ATR)

3105, 1540, 1431, 1207, 1131 cm^ꢁ1

.

4.1.7. 2-Bromo-5-nitrophenyl triﬂuoromethanesulfonate (21)

Treatment of 2-bromo-5-nitrophenol⁴⁰(119 mg, 0.55 mmol) in

determine the ratio of 2 (

J ¼ 10.8 Hz, 1H). A 6.7:1 ratio of 3/2 was observed by NMR. The

d

5.35, d, J ¼ 10.8 Hz, 1H) to 3 (

d 5.27, d,

CH₂Cl₂(5 mL) with pyridine (90 mL, 1.12 mmol) and Tf₂O (120 mL,

0.71 mmol), as described for 15, gave without further puriﬁcation

products decomposed upon attempted puriﬁcation on silica gel.

21 (188 mg, 0.54 mmol, 98%) as a brown oil. ¹H NMR (400 MHz,

CDCl₃)

d

8.22 (d, J ¼ 2.8 Hz, 1H), 8.16 (dd, J ¼ 8.4, 2.4 Hz, 1H), 7.93 (d,

4.4.2. Entry 10. 2-Ethenylphenyl triﬂuoromethanesulfonate (9).⁴²

Cross coupling of 2-bromophenyl triﬂuoromethanesulphonate

(7)⁴³(95.6 mg, 0.31 mmol) with (ethenyl)tributyltin (121 mg,

0.38 mmol) in the presence of PPh₃(6.9 mg, 0.026 mmol) and

Pd(dba)₂(3.8 mg, 0.007 mmol) in dioxane (1.5 mL) was performed

as described under Conditions A. Extractive work up and chroma-

tography (hexane/EtOAc, 9:1) gave 9 (4.1 mg, 0.016 mmol, 5%) as a

colorless oil. Only 9 was observed by ¹H NMR (600 MHz, CDCl₃) of

the crude reaction mixture after work up.

J ¼ 8.8 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃)

d 147.6, 146.9.0, 135.2,

124.0,123.9,118.5 (q, J^C-F¼ 320 Hz), 118.3; IR (ATR) 3104,1534, 1431,

1348, 1211, 1134 cm^ꢁ1; HRMS (ESI) calcd for C₇H₃BrNNaO₅F₃S

(M þ Na^þ) 371.8765; found 371.8740.

4.1.8. 3-Bromo-5-nitrophenyl triﬂuoromethanesulfonate (22)

Treatment of 3-bromo-5-nitrophenol⁴¹(329 mg, 1.51 mmol) in

CH₂Cl₂(10 mL) with pyridine (250 mL, 3.10 mmol) and Tf₂O (300 mL,

1.78 mmol), as described for 15, gave after chromatography (hex-

ane/EtOAc, 7:3) 22 (316 mg, 0.90 mmol, 60%) as a red oil. ¹H NMR

(400 MHz, CDCl₃)

d

8.44 (t, J ¼ 1.8 Hz, 1H), 8.11 (t, J ¼ 2.0 Hz, 1H),

4.4.3. Entry 11. 2-Ethenylphenyl triﬂuoromethanesulfonate (9) and

2-ethenyl-1-bromobenzene (10).⁴⁴

7.80 (t, J ¼ 2.0 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃)

d 149.2, 130.8,

126.8,123.9,118.6 (q, J^C-F¼ 320 Hz),116.0; IR (ATR) 3097,1732,1542,

1427, 1344, 1210, 1134 cm^ꢁ1; HRMS (ESI) calcd for C₇H₃BrNNaO₅F₃S

(M þ Na^þ) 371.8765; found 371.8764.

Cross coupling of 7 (88.3 mg, 0.25 mmol) with (ethenyl)tribu-

tyltin (98.0 mg, 0.31 mmol) in the presence of LiCl (32.2 mg,

0.76 mmol) and Pd(PPh₃)₂Cl₂(3.8 mg, 0.005 mmol) in DMF (1.0 mL)

was performed as described under Conditions C. A 5.9:1 ratio of 10/

9 was observed by ¹H NMR (600 MHz, CDCl₃) of the crude reaction

mixture after extractive work up. The products decomposed upon

attempted puriﬁcation on silica gel. The terminal cis-alkene protons

were clearly resolved in the ¹H NMR spectrum at 600 MHz and

4.2. Table 1 - conditions A

4.2.1. Entry 3. 4-Ethenylphenyl triﬂuoromethanesulfonate (2).⁴

To a solution of PPh₃(7.5 mg, 0.029 mmol) and Pd(dba)₂(4.3 mg,

0.007 mmol) in dioxane (1.5 mL), stirred for 5 min under an atmo-

these signals were used to determine the ratios of 9 (

d 5.49, d,

sphere

of

N₂,

was

added

4-bromophenyl

J ¼ 11.1 Hz, 1H) to 10 ( 5.37, dd, J ¼ 10.9, 1.0 Hz, 1H).

d

Please cite this article in press as: Ansari NN, et al., Chemoselectivity in the Kosugi-Migita-Stille coupling of bromophenyl triﬂates and bromo-

nitrophenyl triﬂates with (ethenyl)tributyltin, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.02.051

N.N. Ansari et al. / Tetrahedron xxx (2018) 1e14

9

4.4.4. Entry 12. 3-Ethenylphenyl triﬂuoromethanesulfonate (11)

4.5.3. Entry 5. 2-Ethenyl-3-nitrophenyl triﬂuoromethanesulfonate

(23), 2-bromo-3-nitrophenol, and 2-bromo-3-ethenyl-nitrobenzene

(24)

and 3-Ethenylphenyl-1-bromobenzene (12).⁵⁰

Cross coupling of 3-bromophenyl triﬂuoromethane sulphonate

(8) (105 mg, 0.34 mmol) with (ethenyl)tributyltin (127 mg,

0.40 mmol) in the presence of PPh₃(7.6 mg, 0.03 mmol) and

Pd(dba)₂(4.0 mg, 0.007 mmol) in dioxane (1.5 mL) was performed

as described under Conditions A. Extractive work up and chroma-

tography (hexane/EtOAc, 9:1) to give an inseparable mixture of 8

and 11 (49.2 mg, calculated from ¹H NMR spectrum: 20.2 mg 8 and

28.8 mg 11, 34%) as a colorless oil. A ~30:1 ratio of 11/12 was

observed by ¹H NMR (600 MHz, CDCl₃) of the crude reaction

mixture. The terminal cis-alkene protons were clearly resolved in

the ¹H NMR spectrum at 600 MHz and these signals were used to

Cross coupling of 13 (110 mg, 0.32 mmol) with (ethenyl)tribu-

tyltin (123 mg, 0.39 mmol) in the presence of LiCl (40.9 mg,

0.96 mmol) and Pd(PPh₃)₂Cl₂(4.8 mg, 0.007 mmol) in DMF (1.5 mL)

was performed as described under Conditions C. Extractive work up

and chromatography (hexane/EtOAc, 97:3) gave, in order of elution,

23 (18.5 mg, 0.06 mmol, 20%), 24 (27.6 mg, 0.12 mmol, 38%) as a

colorless oil and an impure mixture of 13 and 2-bromo-3-

nitrophenol (38.2 mg). Analytical data for 24: ¹H NMR (600 MHz,

CDCl₃)

d

7.70 (d, J ¼ 7.8 Hz, 1H), 7.58 (d, J ¼ 7.8 Hz, 1H), 7.42 (t,

J ¼ 7.8 Hz,1H), 7.10 (dd, J ¼ 16.8,11.4 Hz,1H), 5.76 (d, J ¼ 17.4 Hz,1H),

determine the ratios of 11 (

J ¼ 10.8 Hz, 1H).

d

5.38, d, J ¼ 11.4 Hz, 1H) to 12 (

d

5.30, d,

5.52 (d, J ¼ 10.8 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃)

d 147.2, 128.9,

128.3, 126.2, 125.7, 124.8, 123.8, 119.5; IR (ATR) 3110, 1533, 1423,

1358, 1210, 1135 cm^ꢁ1

; HRMS (ESI) calcd for C₈H₆NNaO₂Br

(M þ Na^þ) 249.9479; found 249.9473.

4.4.5. Entry 13. 3-Ethenylphenyl triﬂuoromethanesulfonate (11)

Cross coupling of 8 (310 mg, 1.02 mmol) with (ethenyl)tribu-

tyltin (490 mg,1.54 mmol) in the presence of Pd(PPh₃)₂Cl₂(13.3 mg,

0.019 mmol) in dioxane (4 mL) was performed as described under

Conditions B (50 h). A ~10:1:4 ratio of 11/12:ethenyltributyltin was

observed in the crude ¹H NMR spectrum. Solvent removal and

chromatography (SiO₂/K₂CO₃¼ 9:1, hexane/EtOAc, 98:2) gave 11

(121 mg, 0.480 mmol, 47%) as a colorless oil. ¹H NMR (600 MHz,

4.5.4. Entry 6. 2-Ethenyl-3-nitrophenyl triﬂuoromethanesulfonate

(23), 1-bromo-2-ethenyl-nitrobenzene (24), and 2,3-diethenyl-

nitrobenzene (25)

Cross coupling of 13 (143 mg, 0.41 mmol) with (ethenyl)tribu-

tyltin (123 mg, 0.39 mmol) in the presence of LiCl (53.8 mg,

1.27 mmol) and 1,3-bis(diphenylphosphino)propanepalladium

dichloride (5.3 mg, 0.009 mmol) in DMF (2 mL) was performed as

described under Conditions C. Extractive work up and chroma-

tography (hexane/EtOAc, 97:3) gave in order of elution, 25 (7.0 mg,

0.04 mmol, 10%), 23 (22.9 mg, 0.077 mmol, 19%), and 24 (45.7 mg,

0.20 mmol, 49%) as a colorless oil. Spectral data for 25: ¹H NMR

CDCl₃)

d

7.42e7.40 (m, 2H), 7.29 (br s, 1H), 7.16 (dt, J ¼ 6.4, 2.4 Hz,

1H), 6.70 (dd, J ¼ 17.2, 10.8 Hz, 1H), 5.80 (d, J ¼ 17.6 Hz, 1H), 5.38 (d,

J ¼ 10.8 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃)

d 149.9, 140.3, 135.0,

130.3, 126.1, 120.2, 118.8, 118.7 (q, J^C-F¼ 319 Hz), 116.5; IR (ATR)

1574, 1420, 1205, 1136, 1117, 924, 825 cm^ꢁ1; HRMS (ESI) calcd for

C₉H₈F₃O₃S (M þ H^þ) 253.0146; found 253.0146.

(400 MHz, CDCl₃)

d

7.79 (d, J ¼ 8.0 Hz, 1H), 7.71 (dd, J ¼ 8.0, 1.2 HZ,

1H), 7.37 (t, J ¼ 7.6 Hz, 1H), 6.96 (dd, J ¼ 17.2, 11.2 Hz, 1H), 6.88 (dd,

J ¼ 17.6, 11.2 Hz, 1H), 5.71 (dd, J ¼ 17.6, 0.8 Hz, 1H), 5.63 (dd, J ¼ 11.2,

1.2 Hz, 1H), 5.37 (dd, J ¼ 11.2, 0.8 Hz, 1H), 5.32 (d, J ¼ 18.0, 1.2 Hz,

4.4.6. Entry 14. 3-Ethenylphenyl triﬂuoromethanesulfonate (11)

and 3-Ethenylphenyl-1-bromobenzene (12)

1H); ¹³C NMR (100 MHZ, CDCl₃)

d 149.8, 138.7, 134.5, 131.4, 130.5,

Cross coupling of 8 (108 mg, 0.36 mmol) with (ethenyl)tribu-

tyltin (140 mg, 0.44 mmol) in the presence of LiCl (45.6 mg,

1.08 mmol) and Pd(PPh₃)₂Cl₂(5.4 mg, 0.008 mmol) in DMF (1.5 mL)

was performed as described for 3 under Conditions C. A 5.3:6.3:1

ratio of 8/12/11 was observed by ¹H NMR (600 MHz, CDCl₃) of the

crude reaction mixture after extractive work up. The products

decomposed upon attempted puriﬁcation on silica gel or basic

alumina.

130.0, 127.6, 122.8, 122.6, 117.3; IR (ATR) 1521, 1348, 985, 921, 810,

774, 753, 735 cm^ꢁ1; HRMS (ESI) calcd for C₁₀H₁₀NO₂(M þ H^þ)

176.0711; found 176.0709.

4.5.5. Entry 7. 2,3-Diethenyl-nitrobenzene (25)

Treatment of 13 (70.2 mg, 0.201 mmol) with (ethenyl)tributyltin

(203 mg, 0.641 mmol) in the presence of Pd(PPh₃)₂Cl₂(6.0 mg,

0.008 mmol) and LiCl (6.0 mg, 0.008 mmol) in dioxane (1 mL,

reﬂux, 24 h) was performed as described under Conditions B. Sol-

vent removal and chromatography (SiO₂/K₂CO₃¼ 9:1; hexane/

EtOAc, 98:2) gave 25 (33.7 mg, 0.192 mmol, 96%) as a faint yellow

oil.

4.5. Table 2

4.5.1. Entry 1. 2-Ethenyl-3-nitrophenyl triﬂuoromethanesulfonate

(23).²⁷

4.5.6. Entry 8. 3-Ethenyl-4-nitrophenyl triﬂuoromethanesulfonate

(26) and 2,4-diethenyl-nitrobenzene (27)

Cross

coupling

of

2-bromo-3-nitrophenyl

tri-

ﬂuoromethanesulfonate (13)²⁷(105 mg, 0.30 mmol) with (ethenyl)

tributyltin (119 mg, 0.38 mmol) in the presence of in the presence

of PPh₃(6.5 mg, 0.03 mmol) and Pd(dba)₂(3.7 mg, 0.006 mmol) in

dioxane (1.5 mL) was performed as described under Conditions A.

Extractive work up and chromatography (hexane/EtOAc, 97:3) gave,

in order of elution, 23 (32.3 mg, 0.11 mmol, 36%) as a white solid

and impure 2-bromo-3-nitrophenol⁵⁰(41 mg).

Cross

coupling

of

3-bromo-4-nitrophenyl

tri-

ﬂuoromethanesulfonate (14)⁴⁵(67.6 mg, 0.19 mmol) with (ethenyl)

tributyltin (72.8 mg, 0.23 mmol) in the presence of in the presence

of PPh₃(4.5 mg, 0.02 mmol) and Pd(dba)₂(2.2 mg, 0.004 mmol) in

dioxane (1 mL) was performed as described under Conditions A.

Extractive work up and chromatography (hexane/EtOAc, 97:3), gave

in order of elution, 27 (3.0 mg, 0.02 mmol, 9%) and 26 (47.3 mg,

0.16 mmol, 82%) as a colorless oil. Analytical data for 26: ¹H NMR

4.5.2. Entry 2. 2-Ethenyl-3-nitrophenyl triﬂuoromethanesulfonate

(23)

(600 MHz, CDCl₃)

d

8.06 (d, J ¼ 9.0 Hz, 1H), 7.52 (d, J ¼ 2.4 Hz, 1H),

7.34 (dd, J ¼ 9.0, 3.0 Hz, 1H), 7.18 (dd, J ¼ 16.8, 10.8 Hz, 1H), 5.81 (d,

Cross coupling of 13 (127 mg, 0.362 mmol) with (ethenyl)trib-

utyltin (149 mg, 0.471 mmol) in the presence of Pd(PPh₃)₂Cl₂

(5.1 mg, 0.007 mmol) in dioxane (1 mL) was performed as

described under Conditions B. Solvent removal and chromatog-

raphy (SiO₂/K₂CO₃¼ 9:1, hexane/EtOAc, 98:2) gave 23 (83 mg,

0.28 mmol, 77%) as a yellow oil.

J ¼ 17.4 Hz, 1H), 5.63 (d, J ¼ 10.8 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃)

d

151.7, 146.6, 136.4, 131.1, 127.0, 121.4, 121.3, 121.1, 118.7 (q, J^C-

¼ 319 Hz); IR (ATR) 3118, 1530, 1424, 1350, 1207, 1131 cm^ꢁ1; HRMS

F

(ESI) calcd for C₉H₆NNaO₅F₃S (M þ Na^þ) 319.9816; found 319.9809.

Analytical data for 27: ¹H NMR (600 MHz, CDCl₃)

d 7.96 (d,

J ¼ 8.4 Hz, 1H), 7.57 (d, J ¼ 1.8 Hz, 1H), 7.44 (dd, J ¼ 9.0, 1.8 Hz, 1H),

Please cite this article in press as: Ansari NN, et al., Chemoselectivity in the Kosugi-Migita-Stille coupling of bromophenyl triﬂates and bromo-

nitrophenyl triﬂates with (ethenyl)tributyltin, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.02.051

10

N.N. Ansari et al. / Tetrahedron xxx (2018) 1e14

7.23 (dd, J ¼ 17.4, 11.4 Hz, 1H), 6.75 (dd, J ¼ 17.4, 10.8 Hz, 1H), 5.92 (d,

J ¼ 17.4 Hz, 1H), 5.75 (dd, J ¼ 17.4, 0.6 Hz, 1H), 5.50 (dd, J ¼ 10.8,

0.6 Hz, 1H), 5.49 (d, J ¼ 10.8 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃)

4.5.11. Entry 13. 4-Ethenyl-3-nitrophenyl triﬂuoromethanesulfonate

(29) and 2,5-diethenyl-nitrobenzene (30).⁵⁶

Cross coupling of 15 (406 mg, 1.16 mmol) with (ethenyl)tribu-

tyltin (489 mg,1.54 mmol) in the presence of Pd(PPh₃)₂Cl₂(16.3 mg,

0.023 mmol) in dioxane (2.5 mL) was performed as described under

Conditions B., Solvent removal and chromatography (SiO₂/K₂CO₃¼

9:1; hexane/EtOAc, 97:3) gave, in order of elution, 30 (5.4 mg,

0.031 mmol, 3%) and 29 (280 mg, 0.942 mmol, 81%) both as a

colorless oil.

d

146.6, 142.4, 134.9, 134.1, 133.0, 126.5, 125.5, 125.1, 118.9, 118.2; IR

(ATR) 1600, 1575, 1509, 1337, 914, 835 cm^ꢁ1; HRMS (ESI) calcd for

C

₁₀H₁₀NO₂(M þ H^þ) 176.0711; found 176.0709.

4.5.7. Entry 9. 3-Ethenyl-4-nitrophenyl triﬂuoromethanesulfonate

(26)

Cross coupling of 14 (399 mg, 1.14 mmol) with (ethenyl)tribu-

tyltin (480 mg, 1.52 mmol) in the presence of Pd(PPh₃)₂Cl₂(16 mg,

0.023 mmol) in dioxane (2.5 mL) was performed as described under

Conditions B. Solvent removal and chromatography (SiO₂/

K₂CO₃¼ 9:1; hexane/EtOAc, 97:3) gave 26 (232 mg, 0.781 mmol,

68%) as a faint yellow oil.

4.5.12. Entry 14. 4-Ethenyl-3-nitrophenyl

triﬂuoromethanesulfonate (29) and 2,5-diethenyl-nitrobenzene

(30)

Cross coupling of 15 (221 mg, 0.630 mmol) with (ethenyl)trib-

utyltin (245 mg, 0.773 mmol) in the presence of Pd(OAc)₂(2.8 mg,

0.012 mmol) and PPh₃(6.6 mg, 0.025 mmol) in dioxane (2 mL) was

performed as described under Conditions B (31 h). Solvent removal

and chromatography (SiO₂/K₂CO₃¼ 9:1, hexane/EtOAc, 97:3) gave,

in order of elution, 30 (2.4 mg, 0.014 mmol, 2%) and 29 (139 mg,

0.468 mmol, 74%) both as a colorless oil.

4.5.8. Entry 10. 3-Ethenyl-4-nitrophenyl triﬂuoromethanesulfonate

(26) and 2,4-diethenyl-nitrobenzene (27)

Cross coupling of 14 (206 mg, 0.587 mmol) with (ethenyl)trib-

utyltin (248 mg, 0.782 mmol) in the presence of Pd(OAc)₂(2.6 mg,

0.012 mmol) and PPh₃(6.2 mg, 0.024 mmol) in dioxane (2 mL) was

performed as described under conditions B. Solvent removal and

chromatography (SiO₂/K₂CO₃¼ 9:1; hexane/EtOAc, 97:3) gave, in

order of elution, 27 (4.3 mg, 0.024 mmol, 4%) as a colorless oil and

26 (120.4 mg, 0.405 mmol, 69%) as a faint yellow oil.

4.5.13. Entry 15. 4-Ethenyl-3-nitrophenyl

triﬂuoromethanesulfonate (29), 2,5-diethenyl-nitrobenzene (30),

and 2-bromo-5-ethenyl-nitrobenzene (31).⁴⁷

Cross coupling of 15 (120 mg, 0.34 mmol) with (ethenyl)tribu-

tyltin (135 mg, 0.43 mmol) in the presence of LiCl (48.2 mg,

1.13 mmol) and Pd(PPh₃)₂Cl₂(4.8 mg, 0.007 mmol) in DMF (1.5 mL)

was performed as described under Conditions C. Extractive work up

and chromatography (hexane/EtOAc, 97:3) gave, in order of elution,

30 (1.7 mg, 0.0097 mmol, 3%), 31 (27.8 mg, 0.12 mmol, 36%) as a

colorless oil and a mixture of 29 and 15 (42 mg, calculated from ¹H

NMR spectrum: 29 22 mg, 23% and 15 20 mg, 17%). Spectral data for

31 were in accordance with literature values.

4.5.9. Entry 11. 3-Ethenyl-4-nitrophenyl triﬂuoromethanesulfonate

(26), 2,4-diethenyl-nitrobenzene (27), and 2-bromo-4-ethenyl-

nitrobenzene (28)

Cross coupling of 14 (75.2 mg, 0.22 mmol) with (ethenyl)tribu-

tyltin (85.5 mg, 0.27 mmol) in the presence of LiCl (28.1 mg,

0.66 mmol) and Pd(PPh₃)₂Cl₂(3.6 mg, 0.005 mmol) in DMF (1 mL)

was performed as described under Conditions C. Extractive work up

and chromatography (hexane/EtOAc, 97:3) gave, in order of elution,

27 (5.5 mg, 0.03 mmol, 15%) followed by a mixture of 28 and 26

(23.8 mg, calculated from ¹H NMR spectrum: 18.0 mg of 28, 37%,

5.8 mg of 26, 9%) as a yellow oil. Spectral data for 28 from the

4.5.14. Entry 16. 3-Ethenyl-2-nitrophenyl

triﬂuoromethanesulfonate (32), 2-bromo-6-ethenyl-nitrobenzene

(33), and 2,6-diethenyl-nitrobenzene (34)

Cross coupling of 16 (104 mg, 0.30 mmol) with (ethenyl)tribu-

tyltin (121 mg, 0.38 mmol) in the presence of in the presence of

PPh₃(6.7 mg, 0.03 mmol) and Pd(dba)₂(3.7 mg, 0.006 mmol) in

dioxane (1.5 mL) was performed as described under Conditions A.

Extractive work up and chromatography (hexane/EtOAc, 97:3) gave,

in order of elution, 34 (16.0 mg, 0.09 mmol, 30%) as a colorless oil,

33 (2.3 mg, 0.01 mmol, 3%) and 32 (52.9 mg, 0.18 mmol, 60%) as

faint yellow solids.

mixture: ¹H NMR

d

7.86 (d, J ¼ 7.8 Hz, 1H), 7.74 (d, J ¼ 1.2 Hz, 1H),

7.45 (dd, J ¼ 8.4, 1.8 Hz, 1H), 6.69 (dd, J ¼ 18.0, 11.4 Hz, 1H), 5.90, (d,

J ¼ 17.4 Hz, 1H), 5.52 (d, J ¼ 10.8 Hz, 1H); ¹³C NMR

d 142.9, 136.4,

133.7, 132.6, 126.1, 125.5, 119.3, 115.1; IR (ATR) 3095, 1573, 1526,

1346, 1217, 1139 cm^ꢁ1

; HRMS (ESI) calcd for C₈H₆NNaO₂Br

(M þ Na^þ) 249.9480; found 249.9478.

Analytical data for 32: Mp ¼ 38e39 ^ꢀC; ¹H NMR (600 MHz,

4.5.10. Entry 12. 4-Ethenyl-3-nitrophenyl

CDCl₃)

d

7.67 (d, J ¼ 8.4 Hz, 1H), 7.57 (t, J ¼ 8.4 Hz, 1H), 7.41 (dd,

triﬂuoromethanesulfonate (29) and 2,5-diethenyl-nitrobenzene

J ¼ 8.4,1.2 Hz,1H), 6.68 (dd, J ¼ 17.4,10.8 Hz,1H), 5.91 (d, J ¼ 17.4 Hz,

(30).⁴⁶

1H), 5.61 (d, J ¼ 11.4 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃)

d 142.0,

Cross coupling of 15 (110 mg, 0.32 mmol) with (ethenyl)tribu-

tyltin (134 mg, 0.42 mmol) in the presence of in the presence of

PPh₃(6.9 mg, 0.03 mmol) and Pd(dba)₂(3.6 mg, 0.006 mmol) in

dioxane (1.5 mL) was performed as described under Conditions A.

Extractive work up and chromatography (hexane/EtOAc, 97:3) gave,

in order of elution, 30 (1.2 mg, 0.0068 mmol, 2%) and 29 (63.3 mg,

0.21 mmol, 68%) both as colorless oils. Spectral data for 30 were in

accordance with literature values. Analytical data for 29: ¹H NMR

140.2, 133.2, 131.6, 128.6, 126.4, 121.9, 121.4, 118.4 (q, J^C-F¼ 321 Hz);

IR (ATR) 3090, 1533, 1427, 1361, 1211, 1138 cm^ꢁ1; HRMS (ESI) calcd

for C₉H₆NNaO₅F₃S (M þ Na^þ) 319.9816; found 319.9809.

Analytical data for 33: Mp ¼ 42e44 ^ꢀC; ¹H NMR

d 7.57 (d,

J ¼ 7.8 Hz, 1H), 7.56 (d, J ¼ 7.8 Hz, 1H), 7.33 (t, J ¼ 7.8 Hz, 1H), 6.57

(dd, J ¼ 16.8, 11.4 Hz, 1H), 5.85 (d, J ¼ 16.8 Hz, 1H), 5.51 (d,

J ¼ 10.8 Hz, 1H); ¹³C NMR

d 150.1, 132.6, 131.6, 130.9, 129.0, 125.6,

120.8, 112.9; IR (ATR) 3077, 1557, 1521, 1460, 1365, 1187 cm¹; HRMS

(600 MHz, CDCl₃)

d

7.90 (d, J ¼ 2.4 Hz, 1H), 7.74 (d, J ¼ 9.0 Hz, 1H),

(ESI) calcd for C₈H₆NNaO₂Br (M þ Na^þ) 249.9479; found 249.9454.

7.53 (dd, J ¼ 9.0, 2.4 Hz, 1H), 7.18 (dd, J ¼ 17.4, 10.8 Hz, 1H), 5.79 (d,

Analytical data for 34: ¹H NMR (600 MHz, CDCl₃)

d 7.54 (d,

J ¼ 16.8 Hz, 1H), 5.61 (d, J ¼ 10.8 Hz, 1H); ¹³C NMR (600 MHz, CDCl₃)

J ¼ 7.1 Hz, 2H), 7.43 (dd, J ¼ 8.6, 6.7 Hz, 1H), 6.62 (dd, J ¼ 17.2,

d

148.0, 147.7, 133.8, 131.1, 130.5, 126.2, 121.0, 118.6 (q, J^C-F¼ 319 Hz),

10.9 Hz, 2H), 5.83 (d, J ¼ 17.2 Hz, 2H), 5.47 (d, J ¼ 10.9 Hz, 2H); ¹³C

118.0; ¹⁹F NMR (565 MHz, CDCl₃)

d

ꢁ72.7; IR (ATR) 3110,1533, 1426,

NMR (150 MHz, CDCl₃) d 148.9, 130.4, 130.1, 129.8, 126.1, 119.8; IR

1351, 1208, 1133 cm^ꢁ1

;

HRMS (ESI) calcd for C₉H₆NNaO₅F₃S

(ATR) 1513, 1365, 926, 850, 809, 731 cm^ꢁ1; HRMS (ESI) calcd for

(M þ Na^þ) 319.9816; found 319.9810.

C

₁₀H₁₀NO₂(M þ H^þ) 176.0711; found 176.0709.

Please cite this article in press as: Ansari NN, et al., Chemoselectivity in the Kosugi-Migita-Stille coupling of bromophenyl triﬂates and bromo-

nitrophenyl triﬂates with (ethenyl)tributyltin, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.02.051

N.N. Ansari et al. / Tetrahedron xxx (2018) 1e14

11

4.5.15. Entry 17. 3-Ethenyl-2-nitrophenyl

triﬂuoromethanesulfonate (32), 2-bromo-6-ethenyl-nitrobenzene

(33), and 2,6-diethenyl-nitrobenzene (34)

Cross coupling of 16 (105 mg, 0.300 mmol) with (ethenyl)trib-

utyltin (140 mg, 0.442 mmol) in the presence of Pd(PPh₃)₂Cl₂

(4.2 mg, 0.006 mmol) in 1,4-dioxane (1 mL) was performed as

described under Conditions B. Solvent removal and chromatog-

raphy (SiO₂/K₂CO₃¼ 9:1 hexane/EtOAc, 19:1) gave, in order of

elution, 34 (11.9 mg, 0.068 mmol, 23%) a colorless oil, 33 (0.9 mg,

0.004 mmol, 1%) and 32 (60.6 mg, 0.204 mmol, 68%).

triﬂuoromethanesulfonate (18)⁴⁹(100 mg, 0.29 mmol) with

(ethenyl)tributyltin (95.1 mg, 0.30 mmol) in the presence of in the

presence of (6.0 mg, 0.02 mmol) and Pd(dba)₂(3.3 mg, 0.006 mmol)

in dioxane (1.5 mL) was performed as described under Conditions

A. Extractive work up and chromatography (hexane/EtOAc, 97:3)

gave, in order of elution, a mixture of 18 and dba (17.2 mg) followed

by 37 (34.6 mg, 0.12 mmol, 41%) as a yellow oil. Analytical data for

37: ¹H NMR (600 MHz, CDCl₃)

d

8.16 (d, J ¼ 8.4 Hz, 1H), 7.55 (dd,

J ¼ 8.4, 1.8 Hz, 1H), 7.41 (d, J ¼ 1.8 Hz, 1H), 6.76 (dd, J ¼ 17.4, 10.8 Hz,

1H), 5.97 (d, J ¼ 17.4 Hz, 1H), 5.63 (d, J ¼ 10.8 Hz, 1H); ¹³C NMR

d

145.2, 141.9, 140.1, 133.4, 127.1, 126.2, 121.4, 120.9, 118.6 (q, J^C-

¼ 319 Hz); IR (ATR) 3114, 1587, 1529, 1429, 1341, 1209 cm^ꢁ1; HRMS

F

4.5.16. Entry 18. 2-Bromo-6-ethenyl-nitrobenzene (33)

Cross coupling of 16 (119 mg, 0.34 mmol) with (ethenyl)tribu-

tyltin (138 mg, 0.44 mmol) in the presence of LiCl (45.6 mg,

1.08 mmol) and Pd(PPh₃)₂Cl₂(5.0 mg, 0.007 mmol) in DMF (1.5 mL)

was performed as described under Conditions C. Extractive work up

and chromatography (hexane/EtOAc, 97:3) gave 33 (47.1 mg,

0.21 mmol, 61%) as an off-white solid.

(ESI) calcd for C₉H₇NO₅F₃S (M þ H^þ) 297.9997; found 297.9994.

4.5.21. Entry 23. 5-Ethenyl-2-nitrophenyl

triﬂuoromethanesulfonate (37), 4-bromo-2-ethenyl-nitrobenzene

(38),⁵⁰and 2,4-diethenyl-nitrobenzene (27)

Cross coupling of 18 (96.8 mg, 0.277 mmol) with (ethenyl)trib-

utyltin (114 mg, 0.360 mmol) in the presence of Pd(PPh₃)₂Cl₂

(4.0 mg, 0.006 mmol) in 1,4-dioxane (0.7 mL) was performed as

described under Conditions B. Solvent removal and chromatog-

raphy (SiO₂/K₂CO₃¼ 9:1, hexanes/EtOAc, 19:1) gave, in order of

elution, a 6:1 mixture of 27 and 38 (5.1 mg, 0.024 mmol, 9% of 27

and 0.9 mg, 0.004 mmol, 14% of 38, calculated from ¹H NMR spec-

trum) and 37 (60.9 mg, 0.205 mmol, 74%).

4.5.17. Entry 19. 6-Ethenyl-2-nitrophenyl

triﬂuoromethanesulfonate (35), 3-bromo-6-ethenylnitrobenzene

(36), and 2,3-diethenyl-nitrobenzene (25)

Cross coupling of 17 (135 mg, 0.39 mmol) with (ethenyl)tribu-

tyltin (129 mg, 0.41 mmol) in the presence of in the presence of

PPh₃(8.2 mg, 0.03 mmol) and Pd(dba)₂(4.5 mg, 0.008 mmol) in

dioxane (2 mL) was performed as described under Conditions A.

Extractive work up and chromatography (hexanes/EtOAc, 97:3)

gave, in order of elution, 36 and 25 (8.5 mg, 1:1 mixture), 2-bromo-

6-nitrophenol²⁷(22.7 mg mixed with dba), and a mixture of 17 and

35 (95.1 mg). The latter fraction was repuriﬁed by chromatograhy

(hexane/EtOAc, 97:3) to give in order of elution, 35 as a colorless oil

(27.8 mg, 0.09 mmol, 24%) and 17 (12.3 mg, 0.04 mmol, 9%).

4.5.22. Entry 24. 5-Ethenyl-2-nitrophenyl

triﬂuoromethanesulfonate (37) and 4-bromo-2-ethenyl-

nitrobenzene (38)

Cross coupling of 18 (99.5 mg, 0.29 mmol) with (ethenyl)tribu-

tyltin (98.1 mg, 0.31 mmol) in the presence of LiCl (37.0 mg,

0.87 mmol) and Pd(PPh₃)₂Cl₂(4.0 mg, 0.006 mmol) in DMF (1.5 mL)

was performed as described under Conditions C. Extractive work up

and chromatography (hexane/EtOAc, 9:1) gave, in order of elution,

38 (11.0 mg, 0.05 mmol, 17%) as an off-white solid, 18 (22.9 mg,

0.07 mmol, 22%) and 37 (19.4 mg, 0.07 mmol, 23%). Spectral data for

38 were in accordance with literature values.

Analytical data for 35: ¹H NMR (600 MHz, CDCl₃)

d

7.98 (dd, J ¼ 8.4,

1.8 Hz, 1H), 7.91 (dd, J ¼ 8.4, 1.8 Hz, 1H), 7.48 (t, J ¼ 8.4 Hz, 1H), 6.99

(dd, J ¼ 17.4, 10.8 Hz, 1H), 5.95 (d, J ¼ 17.4 Hz, 1H), 5.67 (d,

J ¼ 10.8 Hz,1H); ¹³C NMR (150 MHz, CDCl₃)

d 143.0,137.8,134.4,132,

128.5, 128.0, 125.5, 121.4, 118.3 (q, J^C-F¼ 319 Hz); IR (ATR) 3103,

1539, 1429, 1351, 1210, 1131 cm^ꢁ1

; HRMS (ESI) calcd for

C₉H₆NNaO₅F₃S (M þ Na^þ) 319.9816; found 319.9808.

4.5.23. Entry 25. 4-Ethenyl-2-nitrophenyl

triﬂuoromethanesulfonate (39)

4.5.18. Entry 20. 3-Ethenyl-6-nitrophenyl

triﬂuoromethanesulfonate (35), 3-bromo-6-ethenylnitrobenzene

(36), and 2,3-diethenyl-nitrobenzene (25)

Cross coupling of 19 (103 mg, 0.29 mmol) with (ethenyl)tribu-

tyltin (112 mg, 0.35 mmol) in the presence of in the presence of

(6.8 mg, 0.03 mmol) and Pd(dba)₂(3.4 mg, 0.006 mmol) in dioxane

(1.5 mL) was performed as described under Conditions A. Extractive

work up and chromatography (hexane/EtOAc, 9:1) gave, in order of

elution, a mixture of 19 and 5-bromo-2-nitrophenol (11.3 mg) fol-

lowed by 39 as a yellow oil mixed with dibenzylideneacetone

(34.6 mg, 0.12 mmol, 41% of 39, calculated from ¹H NMR spectrum).

Cross coupling of 17 (117 mg, 0.334 mmol) with (ethenyl)tribu-

tyltin (159 mg, 0.501 mmol) in the presence of Pd(PPh₃)₂Cl₂

(5.1 mg, 0.007 mmol) in 1,4-dioxane (1 mL) was performed as

described under Conditions B. Solvent removal and chromatog-

raphy on (SiO₂/K₂CO₃¼ 9:1, hexane/EtOAc, 97:3) gave, in order of

elution, a mixture of 36 and 25 (16.1 mg, 1:2 mixture, 8% and 4%

respectively calculated from ¹H NMR spectrum) and 35 (65.3 mg,

0.220 mmol, 66%) as a yellow oil.

4.5.24. Entry 26. 4-Ethenyl-2-nitrophenyl triﬂate (39), 5-bromo-2-

ethenyl-nitrobenzene (40), and 2,5-diethenyl-nitrobenzene (30)

Cross coupling of 19 (122 mg, 0.348 mmol) with (ethenyl)trib-

utyltin (162 mg, 0.512 mmol) in the presence of Pd(PPh₃)₂Cl₂

(4.9 mg, 0.007 mmol) in 1,4-dioxane (2.5 mL) was performed as

described under Conditions B. Solvent removal and chromatog-

raphy (SiO₂/K₂CO₃¼ 9:1, hexane/EtOAc, 98:2) gave, in order of

elution, an inseparable 1:1.4 mixture of 40 and 30 (7.0 mg; calcu-

lated from ¹H NMR spectrum: 2.4 mg of 40, 3%; 4.6 mg of 30, 8%), 20

(11.1 mg, 0.032 mmol, 9%), and 39 (69.6 mg, 0.236 mmol, 67%) as a

4.5.19. Entry 21. 3-Bromo-2-ethenyl-nitrobenzene (36).⁴⁸

Cross coupling of 17 (99.8 mg, 0.29 mmol) with (ethenyl)tribu-

tyltin (97.5 mg, 0.31 mmol) in the presence of LiCl (36.6 mg,

0.86 mmol) and Pd(PPh₃)₂Cl₂(4.1 mg, 0.006 mmol) in DMF (1.5 mL)

was performed as described under Conditions C. Extractive work up

and chromatography (hexane/EtOAc, 9:1) gave, in order of elution,

36 as

a yellow oil (28.3 mg, 0.12 mmol, 43%), 2-bromo-6-

nitrophenol (7.4 mg, 0.03 mmol, 12%), and 17 (5.0 mg, 0.01 mmol,

5%). Spectral data for 35 were in accordance with literature values.

colorless oil. Analytical data for 39: ¹H NMR (CDCl₃, 400 MHz)

d 8.15

(d, J ¼ 2.2 Hz, 1H), 7.72 (dd, J ¼ 8.6, 2.6 Hz, 1H), 7.41 (d, J ¼ 8.5 Hz,

1H), 6.74 (dd, J ¼ 17.5, 10.9 Hz, 1H), 5.92 (d, J ¼ 17.6 Hz, 1H), 5.55 (d,

4.5.20. Entry 22. 5-Ethenyl-2-nitrophenyl

triﬂuoromethanesulfonate (37)

J ¼ 10.9 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃)

d 141.7, 140.3, 139.2,

133.1, 132.2, 124.3, 123.8, 119.1, 118.5 (q, J^C-F¼ 319 Hz); IR (ATR)

Cross

coupling

of

5-bromo-1-nitrophenyl

1526, 1425, 1345, 1209, 1134, 944, 836 cm ^ꢁ1; HRMS (ESI) calcd for

Please cite this article in press as: Ansari NN, et al., Chemoselectivity in the Kosugi-Migita-Stille coupling of bromophenyl triﬂates and bromo-

nitrophenyl triﬂates with (ethenyl)tributyltin, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.02.051

12

N.N. Ansari et al. / Tetrahedron xxx (2018) 1e14

C₉H₇NO₅F₃S (M þ H^þ) 297.9997; found 297.9994.

4.6.3. Entry 31. 2-Ethenyl-5-nitrophenyl triﬂuoromethanesulfonate

(43)

Cross coupling of 21 (74.7 mg, 0.21 mmol) with (ethenyl)tribu-

tyltin (83.2 mg, 0.26 mmol) in the presence of in the presence of

PPh₃(5.0 mg, 0.02 mmol) and Pd(dba)₂(2.7 mg, 0.005 mmol) in

dioxane (1.5 mL) was performed as described under Conditions A.

Extractive work up and chromatography (hexane/EtOAc, 97:3) gave,

in order of elution, 21 (14.8 mg, 0.04 mmol, 20%) and 43 (30.2 mg,

0.10 mmol, 48%) as a yellow oil. Analytical data for 43: ¹H NMR

4.5.25. Entry 27. 5-Bromo-2-ethenyl-nitrobenzene (40)

Cross coupling of 20 (111 mg, 0.32 mmol) with (ethenyl)tribu-

tyltin (131 mg, 0.41 mmol) in the presence of LiCl (44.5 mg,

0.86 mmol) and Pd(PPh₃)₂Cl₂(4.2 mg, 0.006 mmol) in DMF (1.5 mL)

was performed as described under Conditions C. Extractive work up

and chromatography (hexane/EtOAc, 9:1) gave 40 as a yellow solid

(56.3 mg, 0.25 mmol, 78%). Analytical data for 40: Mp ¼ 40e41 ^ꢀC;

(600 MHz, CDCl₃)

d

8.25 (dd, J ¼ 8.4, 1.8 Hz, 1H), 8.17 (d, J ¼ 1.8 Hz,

¹H NMR (600 MHz, CDCl₃)

d

8.07 (d, J ¼ 2.4 Hz, 1H), 7.70 (dd, J ¼ 8.4,

1H), 7.83 (d, J ¼ 8.4 Hz, 1H), 6.98 (dd, J ¼ 17.4, 10.8 Hz, 1H), 6.05 (d,

J ¼ 17.4 Hz, 1H), 5.75 (d, J ¼ 10.8 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃)

2.4 Hz, 1H), 7.51 (d, J ¼ 8.4 Hz, 1H), 7.11 (dd, J ¼ 17.4, 11.4 Hz, 1H),

5.76 (d, J ¼ 17.4 Hz, 1H), 5.55 (d, J ¼ 11.4 Hz, 1H); ¹³C NMR (150 MHz,

d

147.4, 145.9, 137.4, 127.8, 127.5, 123.2, 122.9, 118.5 (q, J^CꢁF¼319 Hz),

117.7; IR (ATR) 3118, 1528, 1425, 1346, 1210, 1132 cm^ꢁ1; HRMS (ESI)

CDCl₃)

d

148.0, 136.1, 132.2, 131.5, 129._ꢁ7,₁127.3, 121.4, 119.7; IR (ATR)

calcd for C₉H₆NNaO₅F₃S (M þ Na^þ) 319.9816; found 319.9809.

3097, 1552, 1514, 1341, 1149 cm

; HRMS (ESI) calcd for

C₈H₆NNaO₂Br (M þ Na^þ) 249.9479; found 249.9455.

4.6.4. Entry 32. 2-Ethenyl-5-nitrophenyl triﬂuoromethanesulfonate

(43)

4.5.26. Entry 28. 2-Ethenyl-4-nitrophenyl

triﬂuoromethanesulfonate (41)

A solution of 21 (162 mg, 0.463 mmol) in dioxane (2 mL) was

treated with (ethenyl)tributyltin (191 mg, 0.602 mmol) in the

presence of PdCl₂(PPh₃)₂(13.0 mg, 0.019 mmol), was performed as

described under Conditions B. Solvent removal and chromatog-

raphy (SiO₂/K₂CO₃¼ 9:1, hexane/EtOAc, 19:1) 43 (122 mg,

0.412 mmol, 89%) as a pale yellow oil.

Cross

coupling

of

2-bromo-4-nitrophenyl

tri-

ﬂuoromethanesulfonate (20)⁵¹(102 mg, 0.29 mmol) with (ethenyl)

tributyltin (116 mg, 0.37 mmol) in the presence of in the presence of

PPh₃(6.5 mg, 0.03 mmol) and Pd(dba)₂(4.1 mg, 0.007 mmol) in

dioxane (1.5 mL) was performed as described under Conditions A.

Extractive work up and chromatography (hexane/EtOAc, 8:2) gave,

in order of elution, a mixture of 20 and 41 (45.1 mg) followed by 2-

bromo-4-nitrophenol⁴⁰(5.2 mg, 0.02 mmol, 7%). The mixture was

repuriﬁed by chromatographed (hexane/EtOAc, 97:3) to afford, in

order of elution, 41 (19.3 mg, 0.06 mmol, 22%) as a light pink oil and

20 (7.0 mg, 0.02 mmol, 7%). Analytical data for 41: ¹H NMR

4.6.5. Entry 33. 2-Ethenyl-5-nitrophenyl triﬂuoromethanesulfonate

(43) and 4-bromo-3-ethenyl-nitrobenzene (44)

Cross coupling of 21 (85.9 mg, 0.25 mmol) with (ethenyl)tribu-

tyltin (98.2 mg, 0.31 mmol) in the presence of LiCl (32.2 mg,

0.76 mmol) and Pd(PPh₃)₂Cl₂(3.6 mg, 0.005 mmol) in DMF (1.5 mL)

was performed as described under Conditions C. Extractive work up

and chromatography (hexane/EtOAc, 97:3) gave, in order of elution,

44 (3.8 mg, 0.02 mmol, 7%) as an off-white solid, 21 (27.0 mg,

0.08 mmol, 31%) and 43 (22.4 mg, 0.08 mmol, 31%). Analytical data

(600 MHz, CDCl₃)

d

8.53 (d, J ¼ 3.0 Hz, 1H), 8.21 (dd, J ¼ 9.0, 2.4 Hz,

1H), 7.48 (d, J ¼ 9.0 Hz, 1H), 6.94 (dd, J ¼ 17.4, 11.4 Hz, 1H), 6.04 (d,

J ¼ 17.4 Hz, 1H), 5.70 (d, J ¼ 11.4 Hz, 1H); ¹³C (150 MHz, CDCl₃)

d

149.9, 147.2, 132.7, 127.3, 124.0, 122.9, 122.7, 121.7, 118.5 (q, J^C-

¼ 319 Hz); IR (ATR) 3107,1536, 1424, 1347,1209,1134 cm ^ꢁ1; HRMS

for 44: Mp ¼ 38e40 ^ꢀC; ¹H NMR

d

8.39 (d, J ¼ 2.4 Hz, 1H), 7.97 (dd,

F

J ¼ 8.4, 2.4 Hz, 1H), 7.74 (d, J ¼ 9.0 Hz, 1H), 7.06 (dd, J ¼ 17.4, 10.8 Hz,

(ESI) calcd for C₉H₇NO₅F₃S (M þ H^þ) 297.9997; found 297.9994.

1H), 5.99 (d, J ¼ 17.4 Hz, 1H), 5.56 (d, J ¼ 10.8 Hz, 1H); ¹³C NMR (150

MHz, CDCl₃)

d 143.5, 139.1, 134.2, 133.9, 131.4, 123.1, 121.5, 119.7; IR

(ATR) 3099, 2926, 1525, 1341, 1030 cm¹; HRMS (ESI) calcd for

4.6. Entry 29 e conditions B

C₈H₆NNaO₂Br (M þ Na^þ) 249.9479; found 249.9452.

4.6.1. 2-Ethenyl-4-nitrophenyl triﬂuoromethanesulfonate (41)

Cross coupling of 20 (89.1 mg, 0.255 mmol) with (ethenyl)trib-

utyltin (105 mg, 0.331 mmol) in the presence of Pd(PPh₃)₂Cl₂

(3.6 mg, 0.005 mmol) in 1,4-dioxane (0.8 mL) was performed as

described under Conditions B. Solvent removal and chromatog-

raphy (SiO₂/K₂CO₃¼ 9:1; hexane/EtOAc, 98:2) gave 41 (71.4 mg,

0.240 mmol, 94%) as a yellow oil.

4.6.6. Entry 34. 3-Ethenyl-5-nitrophenyl triﬂuoromethanesulfonate

(45)

Cross coupling of 22 (106 mg, 0.30 mmol) with (ethenyl)tribu-

tyltin (130 mg, 0.41 mmol) in the presence of in the presence of

(6.4 mg, 0.02 mmol) and Pd(dba)₂(3.4 mg, 0.006 mmol) in dioxane

(1.5 mL) was performed as described under Conditions A. Extractive

work up and chromatography (hexane/EtOAc, 97:3) gave, in order

of elution, 22 (4.1 mg, 0.01 mmol, 4%) and 45 (70.0 mg, 0.24 mmol,

78%) as a colorless oil. Analytical data for 45: ¹H NMR (600 MHz,

4.6.2. Entry 30. 3-Bromo-4-ethenyl-nitrobenzene (42)

Cross coupling of 20 (110 mg, 0.32 mmol) with (ethenyl)tribu-

tyltin (138 mg, 0.43 mmol) in the presence of LiCl (42.6 mg,

1.0 mmol) and Pd(PPh₃)₂Cl₂(4.5 mg, 0.006 mmol) in DMF (1.5 mL)

was performed as described under Conditions C. Extractive work up

and chromatography (hexane/EtOAc, 85:15) gave a mixture of 20

and 42. The mixture was repuriﬁed by chromatography (hexanes/

EtOAc, 97:3) to afford in order of elution, 42 (40.7 mg, 0.18 mmol,

57%) as a yellow oil, 20 (8.7 mg, 0.02 mmol, 8%), and 3-bromo-4-

nitrophenol (11.1 mg, 0.05 mmol, 16%). Analytical data for 42: ¹H

CDCl₃)

d

8.30 (t, J ¼ 1.8 Hz, 1H), 8.02 (t, J ¼ 1.8 Hz, 1H), 7.61 (t,

J ¼ 1.8 Hz, 1H), 6.78 (dd, J ¼ 17.4, 10.8 Hz, 1H), 5.98 (d, J ¼ 17.4 Hz,

1H), 5.61 (d, J ¼ 10.8 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃)

d 149.4,

149.2, 141.7, 133.2, 124.6, 120.6, 119.8, 118.6 (q, J^C-F¼ 319 Hz), 115.6;

IR (ATR) 3103, 1540, 1425, 1348, 1213, 1132 cm ^ꢁ1; HRMS (ESI) calcd

for C₉H₇NO₅F₃S (M þ H^þ) 297.9997; found 297.9997.

4.6.7. Entry 35. 3-Ethenyl-5-nitrophenyl triﬂuoromethanesulfonate

(45)

NMR

d

8.43 (d, J ¼ 2.4 Hz,1H), 8.14 (ddd, J ¼ 8.4, 2.4, 0.6 Hz,1H), 7.69

Cross coupling of 22 (104 mg, 0.296 mmol) with (ethenyl)trib-

utyltin (122 mg, 0.385 mmol) in the presence of Pd(PPh₃)₂Cl₂

(4.3 mg, 0.006 mmol) in 1,4-dioxane (1 mL) was performed as

described under Conditions B. Solvent removal and chromatog-

raphy (SiO₂/K₂CO₃¼ 9:1, hexane/EtOAc, 98:2) gave 45 (78.5 mg,

0.264 mmol, 89%) as a yellow oil.

(d, J ¼ 9.0 Hz, 1H), 7.09 (dd, J ¼ 17.4, 11.4 Hz, 1H), 5.88 (d, J ¼ 18.0 Hz,

1H), 5.60 (dd, J ¼ 10.8, 0.6 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃)

d

147.2, 143.7, 134.3, 128.2, 127.1, 123.4, 122.4, 120.9; IR (ATR) 3099,

1520, 1342, 1116, 1035 cm ^ꢁ1; HRMS (ESI) calcd for C₈H₆NNaO₂Br

(M þ Na^þ) 249.9479; found 251.9456.

Please cite this article in press as: Ansari NN, et al., Chemoselectivity in the Kosugi-Migita-Stille coupling of bromophenyl triﬂates and bromo-

nitrophenyl triﬂates with (ethenyl)tributyltin, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.02.051

N.N. Ansari et al. / Tetrahedron xxx (2018) 1e14

13

4.6.8. Entry 36. 3-Bromo-5-ethenyl-nitrobenzene (46)

142.0, 133.0, 132.8, 131.6, 129.8, 119.7, 91.8; IR (ATR) 3094, 2925,

1519, 1341, 1261, 1086 cm^ꢁ1; HRMS (ESI) calcd for C₈H₆NNaO₂I

(M þ Na^þ) 297.9341; found 297.9333.

Cross coupling of 22 (109 mg, 0.31 mmol) with (ethenyl)tribu-

tyltin (139 mg, 0.44 mmol) in the presence of LiCl (45.0 mg,

1.1 mmol) and Pd(PPh₃)₂Cl₂(4.7 mg, 0.007 mmol) in DMF (1.5 mL)

was performed as described under Conditions C. Extractive work up

and chromatography (hexane/EtOAc, 97:3) gave 46 (47.1 mg,

0.21 mmol, 66%) as an off-white solid. Analytical data for 46:

4.6.13. 5-Bromo-2-triﬂuoromethanesulfonylacetophenone (52).⁵⁴

To a solution of 5-bromo-1-hydroxyacetophenone⁵⁰(381 mg,

1.77 mmol) in CH₂Cl₂(10 mL) at 0 ^ꢀC was added pyridine (275

mL,

Mp ¼ 37e39 ^ꢀC; ¹H NMR (600 MHz, CDCl₃)

d

8.23 (t, J ¼ 1.8 Hz, 1H),

3.41 mmol) and Tf₂O (325 mL, 1.92 mmol). The mixture was

8.17 (t, J ¼ 1.8 Hz, 1H), 7.83 (t, J ¼ 1.8 Hz, 1H), 6.71 (dd, J ¼ 17.4,

removed from the cold bath and allowed to stir at ambient tem-

perature for 1 h. The resulting mixture was ﬁltered through a small

plug of silica gel and the solvent was removed under reduced

pressure from the ﬁltrate to give 52 (590 mg, 1.70 mmol, 96%) as a

pale orange oil. The compound was used as such without further

10.8 Hz, 1H), 5.91 (d, J ¼ 17.4 Hz, 1H), 5.50 (d, J ¼ 11.4 Hz, 1H); ¹³C

NMR (150 MHz, CDCl₃)

d 149.0, 140.8, 134.8, 133.6, 125.3, 122.9,

119.6, 118.5; IR (ATR) 3079, 1531, 1339, 1301, 1214 cm¹; HRMS (ESI)

calcd for C₈H₆NNaO₂Br (M þ Na^þ) 249.9479; found 249.9452.

puriﬁcation. ¹H NMR (600 MHz, CDCl₃)

d

7.89 (d, J ¼ 2.3 Hz, 1H),

4.6.9. 2-Bromo-3-ethenyl-nitrobenzene (24), 2,3-Diethenyl-

nitrobenzene (25), 3-bromo-2-ethenyl-nitrobenzene (36)

Cross coupling of 2,3-dibromo-1-nitrobenzene (47)²⁹(83.0 mg,

0.296 mmol) with (ethenyl)tributyltin (126 mg, 0.397 mmol) in the

presence of Pd(PPh₃)₂Cl₂(0.004 mg, 0.006 mmol) in dioxane (2 mL)

was performed as described under Conditions B. Solvent removal

and chromatography (SiO₂/K₂CO₃¼ 9:1, hexane/EtOAc, 98:2) gave,

in order of elution, an inseparable 1.0:0.9 mixture of 25 and 36

(23.2 mg, calculated from ¹H NMR spectrum: 10.2 mg 25, 20% and

13.0 mg 36,18%) as a colorless oil and 24 (10.0 mg, 0.040 mmol,14%)

as a colorless oil.

7.69 (dd, J ¼ 8.8 Hz, 2.3 Hz, 1H), 7.21 (d, J ¼ 8.8 Hz, 1H), 2.60 (s, 3H);

¹³C NMR NMR (150 MHz, CDCl₃)

d 195.1, 145.5, 136.4, 133.5, 133.4,

124.3, 122.0, 118.4 (d, J^C-F¼ 319 Hz) 29.2; IR (ATR) 1701, 1424, 1202,

1133, 879, 796 cm^ꢁ1; HRMS (ESI) calcd for C₉H₇BrO₄F₃S (M þ H^þ)

346.9200; found 346.9177.

4.6.14. 5-Ethenyl-2-triﬂuoromethanesulfylacetophenone (53)

Cross coupling of 52 (101 mg, 0.29 mmol) with (ethenyl)tribu-

tyltin (116 mg, 0.37 mmol) in the presence of in the presence of

PPh₃(6.4 mg, 0.02 mmol) and Pd(dba)₂(3.8 mg, 0.007 mmol) in

dioxane (1.5 mL) was performed as described under Conditions A.

Extractive work up and chromatography (hexane/EtOAc, 9:1) gave

4.6.10. 4-Ethenyl-2-nitrophenyl triﬂuoromethanesulfonate (39), 4-

Ethenyl-2-nitrophenol (49),⁵²and 2,5-diethenyl-1-nitrobenzene

(30)

53 (11.6 mg, 0.04 mmol, 14%) as a colorless oil. ¹H NMR

d 7.78 (d,

J ¼ 2.4 Hz, 1H), 7.61 (dd, J ¼ 8.4, 2.4 Hz, 1H), 7.30 (d, J ¼ 8.4 Hz, 1H),

6.73 (dd, J ¼ 17.4, 10.8 Hz, 1H), 5.83 (d, J ¼ 17.4 Hz, 1H), 5.44 (d,

Cross coupling of 4-iodo-6-nitrophenyl triﬂuoromethane

sulfonate (48)⁵³(102 mg, 0.26 mmol) with (ethenyl)tributyltin

(106 mg, 0.33 mmol) in the presence of in the presence of PPh₃

(5.8 mg, 0.02 mmol) and Pd(dba)₂(3.5 mg, 0.006 mmol) in dioxane

(1.5 mL) was performed as described under Conditions A. Extractive

work up and chromatography (hexane/EtOAc, 97:3) gave, in order

of elution, a mixture of 49 and 30 (8.2 mg; 5.8 mg, 0.035 mmol, 14%

of 49 and 2.4 mg, 0.014 mmol, 5% of 30, calculated from ¹H NMR

spectrum) followed by 39 (29.5 mg, 0.099 mmol, 38%) as a yellow

oil.

J ¼ 10.8 Hz, 1H), 2.65 (s, 3H); ¹³C NMR (150 MHz, CDCl₃)

d 196.6,

145.9, 138.1, 134.3, 132.3, 130.7, 128.3, 122.9, 118.5 (q, J^C-F¼ 319 Hz),

117.3, 29.6; IR (ATR) 3096, 1698, 1421, 1202, 1134 cm ^ꢁ1; HRMS (ESI)

calcd for C₁₁H₁₀F₃O₄S (M þ H^þ) 295.0252; found 295.0249.

4.6.15. 5-Ethenyl-2-triﬂuoromethanesulfonylacetophenone (53)

Cross coupling of 52 (70.2 mg, 0.202 mmol) with (ethenyl)trib-

utyltin (83.4 mg, 0.263 mmol) in the presence of PdCl₂(PPh₃)₂

(3.0 mg, 0.004 mmol) in dioxane (0.6 mL) was performed as

described under Conditions B. Solvent removal and chromatog-

raphy (SiO₂/K₂CO₃

0.115 mmol, 57%) as a colorless oil.

¼

9:1, hexane/EtOAc, 19:1) 53 (33.8 mg,

4.6.11. 4-Ethenyl-2-nitrophenyl triﬂuoromethanesulfonate (39) and

2,5-diethenyl-1-nitrobenzene (30)

Cross coupling of 48 (205 mg, 0.517 mmol) with (ethenyl)trib-

utyltin (213 mg, 0.671 mmol) in the presence of PdCl₂(PPh₃)₂

(7.3 mg, 0.010 mmol) in dioxane (2 mL) was performed as described

under Conditions B. Solvent removal and chromatography on (SiO₂/

K₂CO₃¼ 9:1, hexane/EtOAc, 19:1) gave, in order of elution, 30

(10.0 mg, 0.057 mmol, 8%) and 39(133 mg, 0.449 mmol, 87%) as a

faint yellow oil.

4.6.16. 5-Bromo-2-ethenylacetophenone (54)

Cross coupling of 52 (112 mg, 0.32 mmol) with (ethenyl)tribu-

tyltin (129 mg, 0.41 mmol) in the presence of LiCl (43.5 mg,

1.03 mmol) and Pd(PPh₃)₂Cl₂(4.8 mg, 0.007 mmol) in DMF (1.5 mL)

was performed as described under Conditions C. Extractive work up

and chromatography (hexane/EtOAc, 8:2) gave 54 (42.6 mg,

0.19 mmol, 58%) as a colorless oil. ¹H NMR (400 MHz, CDCl₃)

d 7.73

(d, J ¼ 2.0 Hz, 1H), 7.57 (dd, J ¼ 8.0, 1.6 Hz, 1H), 7.43 (d, J ¼ 8.8 Hz,

1H), 7.09 (dd, J ¼ 17.2, 11.2 Hz, 1H), 5.64 (dd, J ¼ 17.2, 0.8 Hz, 1H),

5.37 (dd, J ¼ 11.2, 1.2 Hz, 1H), 2.56 (s, 3H); ¹³C NMR (100 MHz,

4.6.12. 4-Ethenyl-2-nitrophenyl triﬂuoromethanesulfonate (39), 5-

iodo-2-ethenyl-nitrobenzene (50) and 5-iodo-2-

hydroxynitrobenzene (51)

CDCl₃) d 200.5, 138.9, 136.4, 134.7, 134.4, 131.3, 129.1, 121.1, 117.4,

Cross coupling of 48 (116 mg, 0.29 mmol) with (ethenyl)tribu-

tyltin (120 mg, 0.38 mmol) in the presence of LiCl (39.7 mg,

0.94 mmol) and Pd(PPh₃)₂Cl₂(4.1 mg, 0.006 mmol) in DMF (1.5 mL)

was performed as described under Conditions C. Extractive work up

and chromatography (hexane/EtOAc, 97:3) gave in order of elution,

50 (3.2 mg, 0.01 mmol, 4%) as a brown oil, 51 (8.7 mg, 0.03 mmol,

11%), and a mixture of 39 and 48 (67.1 mg; 43.7 mg, 0.147 mmol,

50% of 39 and 23.3 mg, 0.059 mmol, 20% of 48, calculated from ¹H

NMR spectrum). Analytical data for 50: ¹H NMR (600 MHz, CDCl₃)

29.8; IR (ATR) 3088, 1686, 1472, 1355, 1235, 830 cm^ꢁ1; HRMS (ESI)

calcd for C₁₀H₁₀BrO (M þ H^þ) 224.9915; found 224.9914.

4.6.17. 2-Ethenyl-4-methoxyphenyl triﬂuoromethanesulfonate

(56).⁵⁵

Cross coupling of 2-bromo-4-methoxyphenyl triﬂuoromethane

sulfonate (55)⁵⁶(106 mg, 0.32 mmol) with (ethenyl)tributyltin

(126 mg, 0.40 mmol) in the presence of PPh₃(7.0 mg, 0.03 mmol)

and Pd(dba)₂(3.7 mg, 0.006 mmol) in dioxane (1.5 mL) was per-

formed as described under Conditions A. Extractive work up and

chromatography (hexane/EtOAc, 9:1) gave 56 (29.6 mg, 0.10 mmol,

33%) as a colorless oil. Spectral data for 56 were in accordance with

d

8.25 (d, J ¼ 1.8 Hz, 1H), 7.89 (dd, J ¼ 7.8, 1.8 Hz, 1H), 7.35 (d,

J ¼ 7.8 Hz, 1H), 7.10 (dd, J ¼ 16.8, 10.8 Hz, 1H), 5.77 (d, J ¼ 16.8 Hz,

1H), 5.52 (d, J ¼ 10.8 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃)

d 148.0,

Please cite this article in press as: Ansari NN, et al., Chemoselectivity in the Kosugi-Migita-Stille coupling of bromophenyl triﬂates and bromo-

nitrophenyl triﬂates with (ethenyl)tributyltin, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.02.051

14

N.N. Ansari et al. / Tetrahedron xxx (2018) 1e14

18. Wang B, Sun H-X, Sun Z-H. It has been shown that an increase in temperature

literature values.

from ambient to 70 ^ꢀC resulted in erosion of C-OTf versus C-Br selectivity in

Suzuki couplings. Eur J Org Chem . 2009:3688e3692.

4.6.18. 2-Ethenyl-4-methoxyphenyl triﬂuoromethanesulfonate (56)

and 3-bromo-4-ethenylanisole (57).⁵⁷

19. Echavarren AM, Stille JK. J Am Chem Soc . 1988;110:1557e1565.

20. Related C-OTf speciﬁc carbonylations of 1 and related bromo-triﬂates have

been reported.

a). Dolle RE, Schmidt SJ, Kruse LI. J Chem Soc, Chem Commun . 1987:904e905;

b) Cacchi S, Ciattini PG, Morera E, Ortar G. Tetrahedron Lett . 1986;27:

3931e3934;

c) Holt DA, Levy MA, Ladd DL, et al. J Med Chem . 1990;33:937e942;

d) Brennfuehrer A, Neumann H, Beller M. Synlett . 2007:2537e2540;

e) Hao CY, Wang D, Li YW, et al. RSC Adv . 2016;6:86502e86509.

21. Shen C, Wei Z, Jiao H, Wu X-F. Chem Eur J . 2017;23:13369e13378.

22. High selectivity for C-OTf bond coupling was observed for four additional

substrates (compounds 8, 12, 14, 15) using the same reaction conditions and

reagents however, the isolated yields were <18% in each case.

23. Espino G, Kurbangalieva A, Brown JM. Chem Commun . 2007:1742e1744.

24. Krolski ME, Renaldo AF, Rudisill DE, Stille JK. J Org Chem . 1988;53:1170e1176.

25. Kamikawa T, Hayashi T. Tetrahedron Lett . 1997;38:7087e7090.

26. Singh R, Just G. J Org Chem . 1989;54:4453e4457.

Cross coupling of 55 (103 mg, 0.31 mmol) with (ethenyl)tribu-

tyltin (119 mg, 0.38 mmol) in the presence of LiCl (38.9 mg,

0.92 mmol) and Pd(PPh₃)₂Cl₂(4.5 mg, 0.006 mmol) in DMF (2 mL)

was performed as described under Conditions C. Extractive work up

and chromatography (hexanes/EtOAc, 9:1) gave, in order of elution,

56 (26.3 mg, 0.12 mmol, 39%) as a faint orange oil and 57 (3.3 mg,

0.01 mmol, 4%). Spectral data for 57 were in accordance with

literature values.

Acknowledgements

We gratefully acknowledge the C. Eugene Bennett Department

of Chemistry and funding from the National Institutes of Health (1

R15 GM122002-01) for support. The National Science Foundation-

MRI program is also gratefully acknowledged for the funding of a

400 MHz NMR system (CHE-1228366). HRMS analyses were per-

formed at the West Virginia University BioNano Research Facility.

28. Pd(PPh₃)₄(2-mol%) and CuBr (3-mol%) in triethylamine at reﬂux temperature.

29. a) Chen S, Williams RM. Tetrahedron . 2006;62:11572e11579;

€

b) Scott TL, Soderberg BCG. Tetrahedron . 2003;59:6323e6332;

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2003;59:3635e3641;

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7501e7505.

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32. Rudisill DE, Stille JK. J Org Chem . 1989;54:5856e5866.

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38. This compound has been reported previously without spectral data, see:

Herbert JM, Kohler AD, Le Strat F, Whitehead DJ Labelled Compd Rad . 2007;50:

440e441.

Appendix A. Supplementary data

Supplementary data related to this article can be found at

https://doi.org/10.1016/j.tet.2018.02.051.

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Please cite this article in press as: Ansari NN, et al., Chemoselectivity in the Kosugi-Migita-Stille coupling of bromophenyl triﬂates and bromo-

nitrophenyl triﬂates with (ethenyl)tributyltin, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.02.051

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Chemoselectivity in the Kosugi-Migita-Stille coupling of bromophenyl triflates and bromo-nitrophenyl triflates with (ethenyl)tributyltin

DOI: 10.1016/j.tet.2018.02.051

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