Convenient protocols for Mizoroki-Heck reactions of aromatic bromides and polybromides with fluorous alkenes of the formula H2CCH(CF2)n-1CF3 (n = 8, 10)

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Convenient protocols for Mizoroki–Heck

reactions of aromatic bromides and

Cite this: DOI: 10.1039/c6ob01980c

polybromides with ﬂuorous alkenes of the

formula H₂CvCH(CF₂)_n−1CF₃(n = 8, 10)†

Haw-Lih Su,^aJanos Balogh,^aMohammed Al-Hashimi,^aDave G. Seapy,^a

Hassan S. Bazzi*^aand John A. Gladysz*^b

The ﬂuorous alkenes H₂CvCHR_fn(R_fn= (CF₂)_n−1CF₃; n = 8, 10) undergo the Mizoroki–Heck reaction with

a variety of aromatic monobromides and polybromides such as 1,3- and 1,4-C₆H₄Br₂, 1,3,5-C₆H₃Br₃,

1,3,5-C₆H₃Br₂Cl, 1,4-XC₆H₄Br (X = CF₃, R_f8, COCH₃, CN, 1,4-OC₆H₄Br), 1,2-O₂NC₆H₄Br, 5-bromo-

isoquinoline, 5-bromopyrimidine, 3-bromo-5-methoxypyridine, and 3,5-dibromopyridine (sixteen

examples, 78% average isolated yield). Typically, 1.2–2.4 equiv. of alkene are employed per Ar–Br bond,

together with Pd(OAc)₂catalyst (4–5 mol%/Ar–Br bond), n-Bu₄N⁺Br⁻(0.8–1.0 equiv./Ar–Br bond),

NaOAc (1.2–2.4 equiv./Ar–Br bond), and 3 : 1 w/w DMF/THF as solvent (120 °C). No eﬀort is necessary to

exclude air or moisture, and reactions may be conducted on >10 g scales. Only E isomers of the products

Ar(CHvCHR_fn)_mare detected. Thirteen representative examples are hydrogenated (Pd/C, balloon

pressure H₂), giving Ar(CH₂CH₂R_fn)_m(92% average isolated yield).

Received 8th September 2016,

Accepted 29th September 2016

DOI: 10.1039/c6ob01980c

www.rsc.org/obc

the polarizable π clouds impart marked lipophilic biases, and

multiple phase tags are required for high degrees of immobiliz-

Introduction

The broad utility of fluorous molecules¹is now widely ation. For example, the singly tagged benzenoid compounds

appreciated,^2–4and they see application in a variety of biphasic C₆H₅R_f8and C₆H₅CH₂CH₂CH₂R_f8give perfluoro(methyl-

and monophasic systems. Under many conditions, aqueous, cyclohexane)/toluene partition coeﬃcients of only 77.5 : 22.5

organic, and fluorous liquid phases are mutually orthogonal, and 49.5 : 50.5, respectively.^6,7With the doubly tagged com-

and solutes partition between them largely based upon the pound 1,4-C₆H₄(CH₂CH₂CH₂R_f8)₂, the value rises to 91.1 : 8.9.⁷

familiar “like dissolves like” paradigm.²Examples of fluorous

liquid phases include perfluoroalkanes, aliphatic perfluor- of multiple ponytails of the formula CH₂CH₂CH₂R_fn(n = 6, 8,

oethers, and aliphatic perfluoroamines.

10) into benzenoid⁷and pyridine⁸systems. As depicted in

Some time ago, we developed protocols for the introduction

Solutes can be rendered fluorophilic by introducing appro- Scheme 1, these involved the initial conversion of commercial

priate phase tags or “ponytails”.^1,2Most commonly, these fluorous iodides ICH₂CH₂R_fnto the phosphonium salts

feature perfluoroalkyl groups R_fn((CF₂)_n−1CF₃), although Ph₃PCH₂CH₂R_fnI⁻. The salts were then employed in Wittig

+

additional motifs are evolving.⁵The greater the numbers or reactions with aromatic dialdehydes and trialdehydes to give,

lengths of the perfluoroalkyl segments, the higher the fluoro- after hydrogenations, fluorous arenes with (CH₂)₃spacer seg-

philicities. These are normally quantified by partition coeﬃ- ments, or Ar(CH₂CH₂CH₂R_fn)_m.

cients involving fluorous and organic solvents.²

A variety of fluorous alkenes of the formula H₂CvCHR_fnare

Aliphatic monofunctional substances can usually be commercially available, and there is an extensive literature

rendered highly fluorophilic with a modest complement of involving multifold Mizoroki–Heck reactions of aromatic poly-

phase tags.²However, with aromatic or sp²hybridized systems, halides.⁹Hence, concurrently with the Wittig chemistry in

Scheme 1, we investigated palladium catalyzed couplings of

H₂CvCHR_fnwith various aromatic dibromides and tribro-

^aDepartment of Chemistry, Texas A&M University at Qatar, P.O. Box 23874, Doha,

mides. However, the data were very disappointing and only

compiled in internal reports of negative results.¹⁰

Qatar. E-mail: bazzi@tamu.edu

^bDepartment of Chemistry, Texas A&M University, P.O. Box 30012 College Station,

Nonetheless, several papers subsequently appeared from

Texas, 77842-3012, USA. E-mail: gladysz@mail.chem.tamu.edu

other groups in which a limited range of Mizoroki–Heck coup-

†Electronic supplementary information (ESI) available: Key NMR spectra. See

lings were successfully carried out with aromatic monohalides

DOI: 10.1039/c6ob01980c

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Table 1 Screening of conditions, two-fold Mizoroki–Heck couplings

(R_f8= (CF₂)₇CF₃)

Entry

Solvent

Base

Temp.

Time

Yield^a(%)

1^b

2^b

3^b

4^b

5^b

6^b

7^b

8^e

DMF

K₂CO₃

(NEt₃)

125 °C

120 °C

48 h

21 h

48 h

21 h

48 h

40 h

55^c

60

84

95

12

77

43

2

1 : 1^dDMF/toluene

1 : 1^dDMF/THF

Toluene

Scheme 1 One-, two-, and three-fold Wittig reactions of ﬂuorous

phosphonium salts and aromatic aldehydes.

THF

1,4-Dioxane

Acetonitrile

1 : 1^dDMF/NEt₃

NEt₃

and fluorous alkenes.^11,12Although not directly related, we 9^f

81

45

10^f

should also mention that several fluorous catalysts have been

developed for Mizoroki–Heck reactions of non-fluorous

substrates.^13,14In any event, due to a variety of ongoing

experimental needs¹⁵we decided to reinvestigate multifold

Mizoroki–Heck couplings of aromatic polyhalides, and report

herein the development of a convenient and general protocol.

During the preparation of this manuscript, we became

aware of related couplings of two compounds with dihaloben-

zenoid moieties,¹⁶and these are detailed in the Discussion

section.

^aYield based upon GC-MS analysis (when the system is biphasic after

cooling to room temperature, the less polar upper phase is sampled).

^bConditions: 0.13 mmol of 2, 2.3 equiv. of 1 (1.15 mol 1/Ar–Br bond),

8 mol% of Pd(OAc)₂(4 mol%/Ar–Br bond), 19 mol% or 0.19 equiv. of

n-Bu₄N⁺Br⁻(9.5 mol% or 0.095 mol/Ar–Br bond) 3.5 equiv. of K₂CO₃

(1.75 mol/Ar–Br bond), 0.250 g of solvent. ^c62% isolated yield. ^dw/w.

^eEntry 8 was conducted on a slightly larger scale than 1–7 (0.20 mmol

of 2 in 0.500 g of solvent). ^fEntries 9 and 10 used 0.20 mmol of 2 in

0.400 g and 0.250 g of solvent (= 10 and 12 equiv. of NEt₃),

respectively.

ditions remained monophasic above 120 °C, but the rate and

yield decreased dramatically. When the DMF was replaced by

THF (Table 1, entry 6), the system was monophasic at all temp-

eratures, but the rate and yield remained lower than with

Results

Optimization, Mizoroki–Heck coupling conditions for

fluorous alkenes

A

number of procedures have been developed for the DMF/THF mixtures. Sadly, 1,4-dioxane and acetonitrile (a good

Mizoroki–Heck reaction.¹⁷

A variety of conditions were ligand for palladium) gave progressively worse results (Table 1,

screened with the fluorous alkene H₂CvCHR_f8(1; 1.15 equiv./ entries 7 and 8).

Ar–Br bond) and 1,3-dibromobenzene 2 as outlined in Tables 1

In other experiments, NEt₃was employed as a solvent, thus

and 2. These generally involved “Jeﬀery conditions”,¹⁸which replacing the inorganic base K₂CO₃. In one version, an equal

feature Pd(OAc)₂, tetrabutyl ammonium salts such as n-Bu₄N⁺weight of DMF was present (Table 1, entry 9), and in another

Br⁻, and a carbonate or acetate base. The base neutralizes the the amine was used alone (entry 10); both were monophasic.

HBr that must be eliminated for carbon–carbon bond for- The first gave a reasonable yield of 3 (81%). However, in both

mation. Reactions were conducted at 120–125 °C in sealed cases byproducts were detected by GC-MS. These included a

tubes in a series of solvents. The yields of the two-fold coup- product derived from monocoupling and debromination,

ling product, (E,E)-1,3-C₆H₄(CHvCHR_f8)₂3, were determined PhCHvCHR_f8, and a species originating from the addition of

either by isolation or GC-MS analysis. No evidence was found NEt₃to H₂CvCHR_f8.¹⁹

for Z CvC linkages in any product in this paper.

Table 2 summarizes another series of experiments, carried

GC-MS analysis of entry 1 of Table 1 indicated a 55% yield out at 125 °C, in which the base is further varied, together

of 3, with 62% isolated after workup, but the reaction of 1 and with the amounts of Pd(OAc)₂and n-Bu₄N⁺Br⁻. Higher yields

2 was not complete. Importantly, the polar DMF solvent only were obtained with NaOAc (Table 2, entry 3) as compared to

solubilized a portion of the nonpolar fluorous alkene. Thus, K₂CO₃and KOAc (Table 2, entries 1 and 2). In the reactions

half of the solvent weight was replaced by a solvent of inter- where less than 18 equiv. of n-Bu₄N⁺Br⁻was employed relative

mediate polarity, such as toluene (Table 1, entries 2 and 3) or to the Pd(OAc)₂, the formation of palladium black was

THF (entry 4). Above 120 °C, monophasic conditions were rea- apparent. Therefore, the proportion of n-Bu₄N⁺Br⁻, which is

lized, and the rate of formation and yield of 3 increased. When considered to stabilize soluble, catalytically active palladium

the DMF was replaced by toluene (Table 1, entry 5), the con- species with respect to bulk palladium,²⁰was increased relative

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Table 2 Additional screening of conditions, two-fold Mizoroki–Heck

couplings^a

Scope, Mizoroki–Heck coupling of fluorous alkenes

The applicability of the conditions in entry 11 of Table 2, or

close approximations thereof, to other combinations of fluor-

ous alkenes and aromatic bromides was investigated. First,

multifold couplings were attempted as shown in Scheme 2

without any eﬀort to exclude air or moisture. Good yields were

obtained with all aromatic dibromides and tribromides investi-

gated, even on >10 g scales. The high yield of aryl chloride 7

(89%) reflects the much lower reactivity of the carbon–chlorine

bond. In preliminary experiments, aromatic diiodides gave

mixtures of mono- and two-fold coupling by-products, which

rendered workups diﬃcult.

As shown in Scheme 3, a series of couplings was conducted

with various aromatic monobromides, as well as bis(4-bromo-

phenyl) ether and 3,5-dibromopyridine, to define functional

group tolerance. These substrates also couple with alkenes

when other Mizoroki–Heck catalyst recipes are employed, but

have not been previously evaluated with fluorous alkenes. No

reactions were observed with aromatic tosylates, mesylates,

or triflates. Also, three sterically encumbered or electron

rich aromatic bromides known to be less reactive towards

Mizoroki–Heck couplings – 1-bromomesitylene, 4-bromoanisole,

and 1-bromo-3,5-dimethoxybenzene – were inert under our

conditions.

For many applications in fluorous chemistry, the perfluoro-

alkyl groups are best connected to CH₂CH₂as opposed to

CHvCH linkages. Thus, representative compounds were hydro-

genated using Pd/C as the catalyst and a balloon pressure of H₂

as shown in Scheme 4. Given that fluorous molecules, parti-

cularly those with longer or multiple perfluoroalkyl segments, are

often poorly soluble in organic solvents, some optimization was

required. For example, in an initial screen 3 underwent smooth

reduction in CH₂Cl₂/ethanol. In contrast, 4, 5, and 6 did not,

owing to their low solubilities. However, in acetone/diethyl ether

3–7, 9, and 11 showed good solubilities and were cleanly hydro-

genated. On the other hand, 8 and 10 and gave superior results

in acetone, and the nitrogen heterocycles 15–18 were best

Pd(OAc)₂

(mol%)

n-Bu₄N⁺Br⁻

(mol%)

Yield

(%)

Entry

Solvent

Base

1

2

3

4

5

6

7

8

DMF

5.0

2.7

1.3

2.8

5.0

2.8

8.0

20

156

76

72

24

12

72

78

K₂CO₃

KOAc

48^b

59^b,c

69^b,c

89^b

NaOAc

82^b,c

79^b

42^b,c

13^b,c

67^b

9

10

11

1 : 1^dDMF/THF

3 : 1^dDMF/THF

86^b,c

99^e

170

^aConditions: 0.10 mmol of 2, 2.3 equiv. of 1 (1.15 mol 1/Ar–Br bond),

Pd(OAc)₂(mol% with respect to 2; divide by 2 for mol%/Ar–Br bond),

n-Bu₄N⁺Br⁻(mol% with respect to 2; divide by 2 for mol%/Ar–Br bond

or 200 for equiv./Ar–Br bond), 2.4 equiv. of base (1.2 mol/Ar–Br bond),

0.30 mL total solvent volume, 125 °C, 168 h. Yields are based on

GC-MS analyses unless noted (when the system is biphasic after

cooling to room temperature, the less polar upper phase is sampled).

^bGC-MS showed a significant amount of the byproduct PhCHvCHR_f8.

^cThe reaction was not complete. ^dw/w. ^e88% isolated yield per the pre-

parative reaction in Scheme 2 and the Experimental section (10 mmol

2, 40 g solvent, 84 h, 120 °C).

to Pd(OAc)₂. Indeed, when the amount of n-Bu₄N⁺Br⁻exceeded

18 equiv., no palladium black was visually detected, and good

yields of 3 were obtained after suﬃcient reaction times, even

with modest catalyst loadings (Table 2, entries 4–6). When the

ratios were reduced, the yields dropped and substantial

amounts of the intermediate monocoupling product

1,3-C₆H₄(Br)(CHvCHR_f8) were detected (Table 2, entries 7

and 8).

When DMF was replaced by 1 : 1 w/w DMF/THF (Table 2,

entries 9 and 10), the yields were comparable to those of other

runs with similar Pd(OAc)₂loadings, but within shorter reaction

times. The optimum conditions found to date are illustrated in

entry 11 (Table 2). These entail 3 : 1 w/w DMF/THF, and higher

loadings of both Pd(OAc)₂(8 mol% or 4%/Ar–Br bond) and

n-Bu₄N⁺Br⁻(170 mol% or 1.7 equiv.; 0.85 equiv./Ar–Br bond).

GC-MS analyses indicated a 99% yield of 3, and workup of a

similar preparative reaction gave 3 in 88% isolated yield.

Mizoroki–Heck reactions are often carried out with

Pd(OAc)₂and facilitating phosphine ligands in combination with

a carbonate base (no n-Bu₄N⁺Br⁻).¹⁷When such recipes were

employed (including XPhos and RuPhos) in 1 : 1 v/v DMF/THF

at 125 °C, appreciable amounts of the debrominated mono-

coupling product PhCHvCHR_f8were always obtained. Hence,

this line of inquiry was abandoned.

Scheme 2 Two- and three-fold Mizoroki–Heck coupling reactions of

ﬂuorous alkenes and aromatic dibromides or tribromides (R_fn

=

(CF₂)_n−1CF₃).

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reduced in diethyl ether/ethanol. The Mizoroki–Heck monocou-

pling products of fluorous alkenes reported previously were gen-

erally hydrogenated at elevated pressures (3–80 bar).^11a–gIt

should be noted that the CvO linkage in the aromatic ketone 11

(Scheme 3) is reduced to a methylene group under the hydrogen-

ation conditions, aﬀording the fluorohydrocarbon 26 (Scheme 4).

Discussion

The preceding sections detail the evolution of a procedure for

Mizoroki–Heck couplings of aryl bromides and polybromides

with fluorous alkenes of the formula H₂CvCHR_fnthat has con-

siderable generality. The procedure is furthermore tolerant of

both air and moisture. The only diﬃculties occurred with a few

arenes known to be poorer coupling substrates. However, Jeﬀery

conditions in which n-Bu₄N⁺Br⁻is used in approximately

stoichiometric quantities appear to be essential. The key feature

of this protocol was originally thought to be phase transfer of

the insoluble anionic base into DMF solution via the lipophilic

tetrabutyl ammonium cation.¹⁸However, more recent studies

suggest that the ammonium cations serve to stabilize palladium

nanoparticles, which are the active catalysts.²⁰

As noted in the introduction, other researchers have syn-

thesized fluorous arenes via Mizoroki–Heck coupling reactions

of aromatic monobromides and fluorous alkenes.¹¹These have

generally employed palladacycle catalysts, NaOAc base, and

DMF solvent. Most examples feature the lighter perfluorohexyl

substituted alkene H₂CvCHR_f6, which retains significant

solubility in organic solvents. However, good results with

Scheme 3 Mizoroki–Heck coupling reactions of ﬂuorous alkenes and

other aromatic bromides.

11a,b,d,e,g

11a

H₂CvCHR_f8

and H₂CvCHR_f14

have also been

reported. In no case were Jeﬀery conditions necessary, but

Xiao and Genêt found that they led to much higher yields with

aromatic monoiodides.^11b,dGenêt also found that aromatic

diazonium salts underwent highly eﬃcient Mizoroki–Heck

reactions with H₂CvCHR_fn(n = 6, 8) using Pd(OAc)₂in metha-

nol without the addition of any base.^11d,12a

The earlier results that are most relevant to this study are

depicted in Scheme 5. These represent to our knowledge the

only other Mizoroki–Heck reactions of substrates with di-

haloarene moieties and fluorous alkenes H₂CvCHR_fn.¹⁶In both

examples, Jeﬀery conditions gave fair to good yields of the

target alkenes, which were subsequently hydrogenated. In the

case of the crown ether, the overall yield increased to 38%

when a methylene spacer was added to the fluorous alkene

(H₂CvCHCH₂R_f8).

Another approach to rendering aromatic compounds highly

fluorophilic would involve introducing multiple R_fnsubstitu-

ents without the intervening methylene spacers that are intrin-

sic to the sequences in Schemes 1–5. Indeed, there are many

procedures by which aryl bromides and iodides can be directly

replaced by R_fngroups.^21,22These eﬀorts have been motivated

in part by the intense interest in eﬃcient trifluoromethyl-

ations.²²However, when the methylene spacers are eliminated,

the strong electron withdrawing eﬀects of the (multiple) per-

fluoroalkyl substituents²³are directly transmitted to the aro-

Scheme 4 Hydrogenation reactions.

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Scheme 5 Previously reported multifold Mizoroki–Heck coupling reactions with ﬂuorous alkenes (R_f8= (CF₂)₇CF₃).

matic ring. This compromises many potential applications. common commercial sources. NMR spectra were recorded on

For example, the basicities of proximal heteroatoms would be 400 or 600 MHz spectrometers and referenced as follows

markedly attenuated.

(δ/ppm): ¹H, residual internal CHCl₃(7.24) or acetone-d₅

The hydrogenation products in Scheme 4 can in principle (2.05 ppm); ¹³C, internal CDCl₃(77.00) or acetone-d₆(29.92);

be accessed by other types of coupling reactions of aromatic ¹⁹F, no added standard (delay time parameter = 10 s to opti-

halides or polyhalides. For example, a palladium catalyzed mize the accuracy of integration ratios; data closely agreed

reaction of 3,5-dibromopyridine with the fluorous zinc reagent with those reported for other R_f8and R_f10containing mole-

IZnCH₂CH₂R_f8has previously been used to prepare 31.⁸cules²⁶). Elemental analyses were conducted on a PerkinElmer

However, the yield was only 31%, as compared to 39% overall 2400 Series II CHNS/O analyzer.

for the two step Mizoroki–Heck/hydrogenation sequence.

(E,E)-1,3-C₆H₄(CHvCHR_f8)₂(3)

A variety of applications can be anticipated for the preced-

ing molecules. For example, 31 (Scheme 4) has been employed

as a ligand in a fluorous version of third generation Grubbs’

catalyst.¹⁵The goal was to activate the catalyst by using a fluor-

ous/organic biphase mixture to remove the dissociated ligand

from the reaction phase. Accordingly, 31 was found to have

a perfluoro(methylcyclohexane)/toluene partition coeﬃcient

of 93.9 : 6.1.¹⁵Although the partition coeﬃcient of triply

ponytailed 22 has not yet been measured, it would be

expected to be greater than that of the homolog 1,3,5-

C₆H₃(CH₂CH₂CH₂R_f8)₃available via the Wittig methodology in

Scheme 1 (>99.7 : <0.3),⁷as the latter has three additional

methylene groups. Finally, other products in Scheme 4 have

been elaborated to new fluorous aromatic iodine(^III) dichlor-

ides²⁴with enhanced fluorophilicities.²⁵

In summary, a convenient and scalable procedure has been

developed for the coupling of one to three fluorous alkenes to

aromatic monobromides and polybromides, without recourse

to inert atmosphere conditions, using a modified Jeﬀery

version of the Mizoroki–Heck reaction. Furthermore, this can

likely be extended to a much wider range of substrates, as will

be probed in future studies from these laboratories.

A pressure vessel was charged with a stir bar, 1,3-dibromo-

benzene (2; 2.359 g, 10.00 mmol), H₂CvCHR_f8(10.572 g,

23.698 mmol), Pd(OAc)₂(0.180 g, 0.800 mmol; 4 mol%/Ar–Br

bond), n-Bu₄N⁺Br⁻(5.498 g, 17.05 mmol), NaOAc, (2.313 g,

28.19 mmol), DMF (30 g), and THF (10 g). The mixture was

stirred at 120 °C for 84 h, cooled to room temperature, and

extracted with hexanes (8 × 30 mL). The hexanes were washed

with distilled water (30 mL × 2) and dried (Na₂SO₄). The

volatiles were removed by rotary evaporation. The yellow

brownish solid was dissolved in a minimum of hexanes and

chromatographed (silica gel column, hexanes). The solvent

was removed from the product containing fractions by rotary

evaporation to give 3 as a white crystalline solid (8.52 g,

8.82 mmol, 88%), mp (capillary) 42–44 °C.²⁷Anal. Calcd (%)

for C₂₆H₈F₃₄: C, 32.32; H, 0.83. Found: C, 32.34; H, 0.87.

¹H NMR (400 MHz, CDCl₃) δ 7.53–7.45 (m, 3H), 7.45–7.37

3

4

(m, 1H), 7.16 (dt, J_HH= 16 Hz, J_HF

= 2.2 Hz, 2H,

3

2ArCHvCHR_f8), 6.23 (dt, J_HH= 16 Hz, J_HF= 12 Hz, 2H,

2ArCHvCHR_f8); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 138.8

3

(t, J_CF= 9.5 Hz), 134.4 (s), 129.6 (s), 128.9 (s), 126.9 (s),

2

119–105 (multiple poorly resolved CF₂/CF₃), 115.7 (t, J_CF

=

23 Hz); ¹⁹F NMR (376 MHz, CDCl₃) δ −80.7 (t, J_FF= 9.4 Hz,

6F), −111.3 (m, 4F), −121.3 (m, 4F), −121.9 (m, 8F), −122.7

(m, 4F), −123.1 (m, 4F), −126.1 (m, 4F).

3

Experimental

(E,E)-1,3-C₆H₄(CHvCHR_f10)₂(4)

All reactions were conducted in air unless noted. The starting

materials H₂CvCHR_f8and H₂CvCHR_f10(R_fn= (CF₂)_n−1CF₃) A pressure vessel was charged with a stir bar, 1,3-dibromo-

were obtained from Aldrich or Fluorous Technologies, Inc. benzene (2; 0.234 g, 0.993 mmol), H₂CvCHR_f10(1.329 g,

Other reagents and solvents were used as received from 2.433 mmol), Pd(OAc)₂(0.0183 g, 0.0815 mmol, 4 mol%/Ar–Br

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2

bond), n-Bu₄N⁺Br⁻(0.548 g, 1.70 mmol), NaOAc (0.454 g, resolved CF₂/CF₃), 117.2 (t, J_CF= 23 Hz); ¹⁹F NMR (376 MHz,

3

5.54 mmol), DMF (3.35 g), and THF (1.18 g). The mixture was CDCl₃) δ −80.7 (t, J_FF= 9.4 Hz, 9F), −111.4 (m, 6F), −121.3

stirred at 120 °C for 84 h and cooled to room temperature. The (m, 6F), −121.9 (m, 12F), −122.7 (m, 6F), −123.0 (m, 6F),

THF and excess alkene were removed by rotary evaporation. −126.1 (m, 6F).

Distilled water (25 mL) was added. The mixture was vigorously

stirred until all of the solid became a powder, and filtered

(E,E)-1,3,5-C₆H₃(CHvCHR_f8)₂(Cl) (7)

under reduced pressure. The solid was washed with water 1,3-Dibromo-5-chlorobenzene (0.270 g, 1.000 mmol),

(3 × 10 mL) and dried in vacuo to give a brown crystalline solid, H₂CvCHR_f8(1.061 g, 2.379 mmol), Pd(OAc)₂(0.0177 g,

which was suﬃciently pure for subsequent chemistry. The 0.0788 mmol, 4 mol%/Ar–Br bond), n-Bu₄N⁺Br⁻(0.547 g,

solid was dissolved in 9 : 1 v/v hexane/ether and the sample 1.70 mmol), NaOAc (0.278 g, 3.39 mmol), DMF (2.52 g), and

was filtered through a short silica gel column. The solvent was THF (0.87 g) were combined in a procedure analogous to that

removed in vacuo to give 4 as a white crystalline solid (1.12 g, for 4. An identical workup gave 7 as a white solid (0.8926 g,

0.961 mmol, 97%), mp (capillary) 83–85 °C.²⁷Anal. Calcd (%) 0.8919 mmol, 89%), mp (capillary) 59–60 °C.²⁷Anal. Calcd (%)

for C₃₀H₈F₄₂: C, 30.89; H, 0.69. Found: C, 30.53; H, 0.66.

for C₂₆H₇ClF₃₄: C, 31.21; H, 0.71. Found: C, 30.98; H, 0.60.

¹H NMR (400 MHz, CDCl₃) δ 7.57–7.40 (m, 4H), 7.18

¹H NMR (400 MHz, CDCl₃) δ 7.46 (s, 2H), 7.39 (s, 1H), 7.11

3

(d, J_HH= 16 Hz, 2H, 2ArCHvCHR_f10), 6.24 (dt, J_HH= 16 Hz, (d, J_HH= 16 Hz, 2H, 2ArCHvCHR_f8), 6.24 (dt, J_HH= 16 Hz,

³J_HF= 12 Hz, 2H, 2ArCHvCHR_f8); ¹³C{¹H} NMR (100 MHz, ³J_HF= 12 Hz, 2H, 2ArCHvCHR_f8); ¹³C{¹H} NMR (100 MHz,

3

CDCl₃) δ 138.9 (t, J_CF= 9.5 Hz), 134.4 (s), 130.0 (s), 129.0 (s), CDCl₃) δ 137.1 (t, J_CF= 9.5 Hz), 136.0 (s), 135.9 (s), 128.6 (s),

126.9 (s), 119–105 (multiple poorly resolved CF₂/CF₃), 115.7 125.2 (s), 120–104 (multiple poorly resolved CF₂/CF₃), 117.2

2

3

2

3

(t, J_CF= 23 Hz); ¹⁹F NMR (376 MHz, CDCl₃) δ −81.6 (t, J_FF

=

(t, J_CF= 23 Hz); ¹⁹F NMR (376 MHz, CDCl₃) δ −81.0 (t, J_FF

=

9.4 Hz, 6F), −111.4 (m, 4F), −121.9 (m, 4F), −122.3 (m, 16F), 10.1 Hz, 6F), −111.3 (m, 4F), −121.1 (m, 4F), −121.7 (m, 8F),

−123.2 (m, 4F), −123.7 (m, 4F), −126.7 (m, 4F).

−122.5 (m, 4F), −122.9 (m, 4F), −126.0 (m, 4F).

(E,E)-1,4-C₆H₄(CHvCHR_f8)₂(5)

(E)-1,4-C₆H₄(CHvCHR_f8)(CF₃) (8)

1,4-Dibromobenzene (0.467 g, 1.98 mmol), H₂CvCHR_f81-Bromo-4-(trifluoromethyl)benzene (1.360 g, 6.045 mmol),

(2.131 g, 4.776 mmol), Pd(OAc)₂(0.0352 g, 0.157 mmol, 4 mol H₂CvCHR_f8(4.140 g, 9.280 mmol), Pd(OAc)₂(0.0505 g,

%/Ar–Br bond), n-Bu₄N⁺Br⁻(1.111 g, 3.445 mmol), NaOAc 0.225 mmol, 4 mol%/Ar–Br bond), n-Bu₄N⁺Br⁻(1.995 g,

(0.456 g, 5.56 mmol), DMF (5.01 g), and THF (1.77 g) were 6.188 mmol), NaOAc (0.699 g, 8.520 mmol), DMF (7.671 g),

combined in procedure analogous to that for 4. A similar and THF (2.451 g) were combined in a procedure analogous to

workup (water washing 3 × 20 mL) gave 5 as a white crystalline that for 4 (120 °C, 62 h), A similar workup (40 mL distilled

solid (1.57 g, 1.62 mmol, 82%), mp (capillary) 80–81 °C.²⁷water; water washing 3 × 5 mL) gave 8 as a brownish solid

Anal. Calcd (%) for C₂₆H₈F₃₄: C, 32.32; H, 0.83. Found: (2.7128 g, 4.5964 mmol, 76%), mp (capillary) 36–38 °C.²⁷Anal.

C, 32.17; H, 1.00.

¹H NMR (400 MHz, CDCl₃) δ 7.45 (s, 4H), 7.11 (dt, J_HH

Calcd (%) for C₁₇H₆F₂₀: C, 34.60; H, 1.02. Found: C, 34.29;

H, 0.77.

3

=

4

3

16 Hz, J_HF= 2.4 Hz, 2H, 2ArCHvCHR_f8), 6.23 (dt, J_HH

¹H NMR (400 MHz, CDCl₃) δ 7.65 (d, J_HH= 8.3 Hz, 2H),

3

4

16 Hz, J_HF= 12 Hz, 2H, 2ArCHvCHR_f8); ¹³C{¹H} NMR 7.57 (d, J_HH= 8.3 Hz, 2H), 7.20 (dt, J_HH= 16 Hz, J_HF

=

3

(100 MHz, CDCl₃, 45 °C) δ 138.7 (t, J_CF= 9.0 Hz), 135.3 (s), 2.1 Hz, 1H, ArCHvCHR_f8), 6.28 (dt, ³J_HH= 16 Hz, ³J_HF= 12 Hz,

128.2 (s), 120–105 (multiple poorly resolved CF₂/CF₃), 115.9 1H, ArCHvCHR_f8); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 138.3

2

3

2

(t, J_CF= 23 Hz); ¹⁹F NMR (376 MHz, CDCl₃, 45 °C) δ −80.7 (t, J_CF= 9.6 Hz), 136.9 (s), 132.0 (q, J_CF= 33 Hz, CCF₃),

3

1

(t, J_FF= 9.4 Hz, 6F), −111.2 (m, 4F), −121.3 (m, 4F), −122.0 127.9 (s), 126.0 (q, J_CF= 3.8 Hz, CHCCF₃), 123.8 (q, J_CF

=

(m, 8F), −122.7 (m, 4F), −123.1 (m, 4F), −126.1 (m, 4F).

272 Hz, CF₃), 119–105 (multiple poorly resolved CF₂/CF₃),

2

117.1 (t, J_CF= 23 Hz); ¹⁹F NMR (376 MHz, CDCl₃) δ −63.0

(E,E,E)-1,3,5-C₆H₃(CHvCHR_f8)₃(6)

3

(s, 3F), −80.8 (t, J_FF= 9.9 Hz, 3F), −111.6 (t, J_FF= 13 Hz, 2F),

1,3,5-Tribromobenzene (0.207 g, 0.657 mmol), H₂CvCHR_f8−121.4 (m, 2F), −121.9 (m, 4F), −122.7 (m, 2F), −123.1 (m, 2F),

(1.044 g, 2.341 mmol), Pd(OAc)₂(0.0182 g, 0.0811 mmol, −126.1 (m, 2F).

4 mol%/Ar–Br bond), n-Bu₄N⁺Br⁻(0.520 g, 1.61 mmol),

NaOAc (0.226 g, 2.75 mmol), DMF (2.4 g), and THF (1.0 g) were

(E)-1,4-C₆H₄(CHvCHR_f10)(CF₃) (9)

combined in a procedure analogous to that for 4. A similar 1-Bromo-4-(trifluoromethyl)benzene (0.248 g, 1.10 mmol),

workup (water washing 3 × 20 mL; full silica gel column using H₂CvCHR_f10(1.229 g, 2.250 mmol), Pd(OAc)₂(0.0091 g,

hexanes) gave 5 as a white crystalline solid (0.60 g, 0.43 mmol, 0.041 mmol, 4 mol%/Ar–Br bond), n-Bu₄N⁺Br⁻(0.272 g,

65%), mp (capillary) 81–82 °C.²⁷Anal. Calcd (%) for C₃₀H₉F₅₁: 0.844 mmol), NaOAc (0.113 g, 1.37 mmol), DMF (1.034 g), and

C, 30.66; H, 0.64. Found: C, 30.51; H, 1.11.

THF (0.510 g) were combined in a procedure analogous to that

¹H NMR (400 MHz, CDCl₃) δ 7.52 (s, 3H), 7.15 (d, J = 16.0, for 4 (120 °C, 41 h). A similar workup (10 mL distilled water;

3H, 3ArCHvCHR_f8), 6.25 (dt,

J = 16.0, 11.8 Hz, 3H, water washing 3 × 5 mL) gave 9 as a yellow solid (0.72 g,

3ArCHvCHR_f8); ¹³C{¹H} NMR (100 MHz, CDCl₃, 45 °C) δ 138.1 1.0 mmol, 91%), mp (capillary) 64–66 °C.²⁷Anal. Calcd (%) for

3

(t, J_CF= 9.5 Hz), 135.4 (s), 127.9 (s), 119–105 (multiple poorly C₁₉H₆F₂₄: C, 30.06; H, 0.88. Found: C, 32.83; H, 0.84.

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3

¹H NMR (400 MHz, CDCl₃) δ 7.65 (d, J_HH= 8.3 Hz, 2H), 1H, ArCHvCHR_f8), 2.61 (s, 3H, CH₃); ¹³C{¹H} NMR (100 MHz,

3

4

3

7.57 (d, J_HH= 8.3 Hz, 2H), 7.20 (dt, J_HH= 16 Hz, J_HF

=

CDCl₃) δ 197.2 (s), 138.6 (t, J_CF= 9.7 Hz), 138.1 (s), 137.7 (s),

2.1 Hz, 1H, ArCHvCHR_f8), 6.28 (dt, ³J_HH= 16 Hz, ³J_HF= 12 Hz, 128.9 (s), 127.8 (s), 119–105 (multiple poorly resolved CF₂/CF₃),

1H, ArCHvCHR_f8); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 138.3 117.0 (t, J_CF= 23 Hz), 26.7; ¹⁹F NMR (376 MHz, CDCl₃)

2

3

2

3

(t, J_CF= 9.5 Hz), 136.8 (s), 132.0 (q, J_CF= 33 Hz, CCF₃), δ −80.7 (t, J_FF= 9.9 Hz, 3F), −111.3 (m, 2F), −121.3 (m, 2F),

127.9 (s), 126.0 (q, J_CF= 3.8 Hz, CHCCF₃), 123.7 (q, J_CF

3

1

=

−121.9 (m, 4F), −122.7 (m, 2F), −123.0 (m, 2F), −126.1 (m, 2F).

272 Hz, CF₃), 119–105 (multiple poorly resolved CF₂/CF₃),

2

(E)-1,4-C₆H₄(CHvCHR_f8)(CN) (12)

117.1 (t, J_CF= 23 Hz); ¹⁹F NMR (376 MHz, CDCl₃) δ −63.0

3

(s, 3F), −80.8 (t, J_FF= 9.9 Hz, 3F), −111.6 (t, J_FF= 13 Hz, 2F), 4-Bromobenzonitrile (0.182 g, 1.01 mmol), H₂CvCHR_f8

−121.4 (m, 2F), −121.8 (m, 8F), −122.7 (m, 2F), −123.1 (m, 2F), (0.514 g, 1.15 mmol), Pd(OAc)₂(0.0090 g, 0.040 mmol, 4 mol

−126.1 (m, 2F).

%/Ar–Br bond), n-Bu₄N⁺Br⁻(0.274 g, 0.850 mmol), NaOAc

(0.114 g, 1.40 mmol), DMF (1.213 g), and THF (0.441 g) were

combined in a procedure analogous to that for 4 (120 °C,

(E)-1,4-C₆H₄(CHvCHR_f8)(R_f8) (10)

1-Bromo-4-(perfluorooctyl)benzene (0.575 g, 1.00 mmol), 41 h). A similar workup (10 mL distilled water; water washing

H₂CvCHR_f8(0.551 g, 1.23 mmol), Pd(OAc)₂(0.0092 g, 3 × 5 mL) gave 12 as a brown crystalline solid (0.42 g,

0.041 mmol, 4 mol%/Ar–Br bond), n-Bu₄N⁺Br⁻(0.271 g, 0.77 mmol, 76%), mp (capillary) 74–76 °C.²⁷Anal. Calcd (%)

0.841 mmol), NaOAc (0.112 g, 1.37 mmol), DMF (1.034 g), and for C₁₇H₆F₁₇N: C, 37.31; H, 1.11; N, 2.56. Found: C, 37.00;

THF (0.523 g) were combined in a procedure analogous to that H, 0.93; N, 2.78.

3

for 4 (120 °C, 41 h). A similar workup (10 mL distilled water;

¹H NMR (400 MHz, CDCl₃) δ 7.69 (d, J_HH= 8.3 Hz, 2H),

3

4

water washing 3 × 5 mL) gave 10 as a yellow solid (0.75 g, 7.56 (d, J_HH= 8.3 Hz, 2H), 7.21 (dt, J_HH= 16 Hz, J_HF

0.80 mmol, 80%), mp (capillary) 85–86 °C.²⁷Anal. Calcd (%) 2.1 Hz, 1H, ArCHvCHR_f8), 6.29 (dt, ³J_HH= 16 Hz, ³J_HF= 12 Hz,

for C₂₄H₆F₃₄: C, 30.66; H, 0.64. Found: C, 30.65; H, 0.57.

1H, ArCHvCHR_f8); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 137.9

=

3

¹H NMR (400 MHz, CDCl₃) δ 7.62 (d, J_HH= 8.8 Hz, 2H), (t, ³J_CF= 10 Hz), 137.7, 132.8, 128.1, 118.2, 113.6 (5 s, C₆H₄CN),

3

4

2

7.59 (d, J_HH= 8.8 Hz, 2H), 7.21 (dt, J_HH= 16 Hz, J_HF

=

119–105 (multiple poorly resolved CF₂/CF₃), 118.1 (t, J_CF

=

2.1 Hz, 1H, ArCHvCHR_f8), 6.30 (dt, ³J_HH= 16 Hz, ³J_HF= 12 Hz, 23 Hz); ¹⁹F NMR (376 MHz, CDCl₃) δ −80.7 (t, J_FF= 8.4 Hz,

3

1H, ArCHvCHR_f8); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 138.2 3F), −111.3 (t, ³J_FF= 12 Hz, 2F), −121.3 (m, 2F), −121.9 (m, 4F),

3

2

(t, J_CF= 8.6 Hz), 137.0 (s), 130.4 (t, J_CF= 25 Hz), 127.8 (s), −122.7 (m, 2F), −123.0 (m, 2F), −126.1 (m, 2F).

3

127.6 (t, J_CF= 6.3 Hz), 119–105 (multiple poorly resolved

2

(E)-1,2-C₆H₄(CHvCHR_f8)(NO₂) (13)

CF₂/CF₃), 117.3 (t, J_CF= 23 Hz); ¹⁹F NMR (376 MHz, CDCl₃)

3

δ −80.8 (t, J_FF= 9.8 Hz, 6F), −111.0 (m, 2F), −111.6 (m, 2F), 1-Bromo-2-nitrobenzene (0.207 g, 1.03 mmol), H₂CvCHR_f8

−121.2 (m, 2F), −121.4 (m, 2F), −121.8 (m, 10F), −122.7 (0.637 g, 1.43 mmol), Pd(OAc)₂(0.0094 g, 0.042 mmol,

(m, 4F), −123.1 (m, 2F), −126.1 (m, 4F); ¹H NMR (400 MHz, 4 mol%/Ar–Br bond), n-Bu₄N⁺Br⁻(0.274 g, 0.850 mmol),

acetone-d₆) δ 8.03 (d, ³J_HH= 8.3 Hz, 2H), 7.80 (d, ³J_HH= 8.3 Hz, NaOAc (0.117 g, 1.43 mmol), DMF (1.188 g), and THF (0.452 g)

3

2H), 7.53 (dt, J_HH= 16 Hz, J_HF= 2.3 Hz, 1H, ArCHvCHR_f8), were combined in a procedure analogous to that for 4 (120 °C,

3

6.86 (dt, J_HH= 16 Hz, J_HF= 13 Hz, 1H, ArCHvCHR_f8); 41 h). A similar workup (10 mL distilled water; water washing

¹³C{¹H} NMR (100 MHz, acetone-d₆) δ 139.9 (t, J_CF= 9.4 Hz), 3 × 5 mL) gave 13 as a brown crystalline solid (0.4236 g,

3

2

3

138.7 (s), 130.50 (t, J_CF= 24 Hz), 129.6 (s), 128.5 (t, J_CF

=

0.7468 mmol, 73%), mp (capillary) 40–42 °C.²⁷Anal. Calcd (%)

6.6 Hz), 120–105 (multiple poorly resolved CF₂/CF₃), 118.1 for C₁₆H₆F₁₇NO₂: C, 33.88; H, 1.07; N, 2.47. Found: C, 33.50;

(t, J_CF= 23 Hz); ¹⁹F NMR (376 MHz, acetone-d₆) δ −81.6 H, 0.75; N, 2.68.

(t, J_FF= 10 Hz, 6F), −111.1 (m, 2F), −111.8 (m, 2F), −121.7

(m, 2F), −121.9 (m, 2F), −122.3 (m, 4F), −122.4 (m, 6F), −123.3 1.4 Hz, 1H), 7.72 (dt, J_HH= 16 Hz, J_HF= 2.2 Hz, 1H,

2

3

4

¹H NMR (400 MHz, CDCl₃) δ 8.10 (dd, J_HH= 8.1 Hz, J_HH

=

3

4

3

(m, 4F), −123.7 (m, 2F), −126.7 (m, 4F).

ArCHvCHR_f8), 7.68 (t, J_HH= 7.5 Hz, 1H), 7.59–7.53 (m, 2H),

3

6.12 (dt, J_HH= 16 Hz, J_HF= 12 Hz, 1H, ArCHvCHR_f8);

(E)-1,4-C₆H₄(CHvCHR_f8)(COCH₃) (11)

3

¹³C{¹H} NMR (100 MHz, CDCl₃) δ 147.8 (s), 136.7 (t, J_CF

=

4-Bromoacetophenone (0.198 g, 0.997 mmol), H₂CvCHR_f810 Hz), 133.9 (s), 130.5 (s), 130.1 (s), 129.4 (s), 125.1 (s), 119.3

2

(0.541 g, 1.21 mmol), Pd(OAc)₂(0.0091 g, 0.041 mmol, (t, J_CF= 23 Hz), 119–105 (multiple poorly resolved CF₂/CF₃);

3

4 mol%/Ar–Br bond), n-Bu₄N⁺Br⁻(0.272 g, 0.844 mmol), ¹⁹F NMR (376 MHz, CDCl₃) δ −80.8 (t, J_FF= 9.9 Hz, 3F),

3

NaOAc (0.116 g, 1.41 mmol), DMF (1.21 g), and THF (0.43 g) −111.8 (t, J_FF= 12 Hz, 2F), −121.4 (m, 2F), −121.9 (m, 4F),

were combined in a procedure analogous to that for 4 (120 °C, −122.7 (m, 2F), −123.1 (m, 2F), −126.1 (m, 2F).

41 h). A similar workup (10 mL distilled water; water washing

(E,E)-[1,4-C₆H₄(CHvCHR_f8)]₂O (14)

3 × 5 mL) gave 11 as a yellow solid (0.53 g, 0.94 mmol, 94%),

mp (capillary) 53–54 °C.²⁷Anal. Calcd (%) for C₁₈H₉F₁₇O: Bis(4-bromophenyl) ether (0.329 g, 1.00 mmol), H₂CvCHR_f8

C, 38.32; H, 1.61. Found: C, 38.30; H, 1.44.

(1.368 g, 3.067 mmol), Pd(OAc)₂(0.0181 g, 0.0806 mmol, 4 mol

3

¹H NMR (400 MHz, CDCl₃) δ 7.97 (d, J_HH= 8.3 Hz, 2H), %/Ar–Br bond), n-Bu₄N⁺Br⁻(0.546 g, 1.70 mmol), NaOAc

3

4

7.55 (d, J_HH= 8.3 Hz, 2H), 7.21 (dt, J_HH= 16 Hz, J_HF

=

(0.231 g, 2.81 mmol), DMF (2.50 g), and THF (0.91 g) were

2.2 Hz, 1H, ArCHvCHR_f8), 6.29 (dt, ³J_HH= 16 Hz, ³J_HF= 12 Hz, combined in a procedure analogous to that for 4 (120 °C,

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108 h). A similar workup (20 mL distilled water; water washing 81–83 °C.²⁷Anal. Calcd (%) for C₁₄H₅F₁₇N₂: C, 32.08; H, 0.96; N,

3 × 10 mL) gave 14 as a yellowish solid (0.87 g, 0.82 mmol, 5.34. Found: C, 32.46; H, 0.77; N, 5.73.

82%), mp (capillary) 86–88 °C (dec).²⁷Anal. Calcd (%) for

¹H NMR (400 MHz, CDCl₃) δ 9.21 (s, 1H, pyrimidyl), 8.85

3

4

C₃₂H₁₂F₃₄O: C, 36.31; H, 1.14. Found: C, 36.74; H, 1.31.

(s, 2H, pyrimidyl), 7.14 (dt, J_HH= 16 Hz, J_HF= 2.3 Hz, 1H,

3

¹H NMR (400 MHz, CDCl₃) δ 7.46 (d, J_HH= 8.7 Hz, 4H), CHvCHR_f8), 6.38 (dt, J_HH= 16 Hz, J_HF= 12 Hz, 1H,

3

7.13 (d, J_HH= 16 Hz, 2H, 2ArCHvCHR_f8), 7.02 (d, J_HH

=

CHvCHR_f8); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 159.4 (s),

3

8.7 Hz, 4H), 6.11 (dt, J_HH= 16 Hz, J_HF= 12 Hz, 2H, 155.4 (s), 133.2 (t, J_CF= 9.6 Hz), 127.5 (s), 120–105 (multiple

2ArCHvCHR_f8); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 158.2 (s), poorly resolved CF₂/CF₃), 118.8 (t, J_CF= 24 Hz); ¹⁹F NMR

2

3

138.7 (t, J_CF= 9.6 Hz), 129.4 (s), 129.2 (s), 119.3 (s), 120–104 (376 MHz, CDCl₃) δ −80.7 (t, ³J_FF= 9.9 Hz, 3F), −112.0 (m, 2F),

2

(multiple poorly resolved CF₂/CF₃), 113.6 (t, J_CF= 23 Hz); −121.3 (m, 2F), −121.9 (m, 4F), −122.7 (m, 2F), −122.9 (m, 2F),

¹⁹F NMR (376 MHz, CDCl₃) δ −80.8 (t, J_FF= 10.1 Hz, 6F), −126.1 (m, 2F).

3

−110.9 (m, 4F), −121.4 (m, 4F), −121.9 (m, 8F), −122.7 (m, 4F),

−123.1 (m, 4F), −126.1 (m, 4F).

(E)-3,5-NC₅H₃(CHvCHR_f8)(OMe) (17)

3-Bromo-5-methoxypyridine (0.150 g, 0.798 mmol), Pd(OAc)₂

(0.0090 g, 0.040 mmol, 5 mol%/Ar–Br bond), n-Bu₄N⁺Br⁻

(E)-5-iso-NC₉H₆(CHvCHR_f8) (15)

(0.258 g, 0.800 mmol), NaOAc (0.157 g, 1.91 mmol),

A pressure vessel was charged with a stir bar, 5-bromo-

H₂CvCHR_f8(0.510 mL, 1.92 mmol), DMF (3.0 mL), and THF

isoquinoline (0.166 g, 0.798 mmol), Pd(OAc)₂(0.0090 g,

(3.0 mL) were combined in a procedure analogous to that for

0.040 mmol, 5 mol%/Ar–Br bond), n-Bu₄N⁺Br⁻(0.258 g,

16. Identical monitoring and workup gave 17 as a yellow solid

0.800 mmol), NaOAc (0.197 g, 2.40 mmol), H₂CvCHR_f8

(0.391 g, 0.707 mmol, 89%), mp (capillary) 58–60 °C.²⁷Anal.

(0.266 mL, 1.00 mmol), DMF (3.0 mL), and THF (3.0 mL). The

Calcd (%) for C₁₆H₈F₁₇NO: C, 34.74; H, 1.46; N, 2.53. Found:

mixture was stirred at 120 °C for 48 h (the conversion of the

C, 34.89; H, 1.62; N, 2.89.

bromide was monitored by GC-MS) and cooled to room temp-

4

¹H NMR (400 MHz, CDCl₃) δ 8.32 (d, J_HH= 2.8 Hz, 1H,

erature. The THF and excess alkene were removed by oil pump

4

pyridyl), 8.30 (d, J_HH= 1.5 Hz, 1H, pyridyl), 7.26–7.23 (m, 1H,

vacuum. Distilled water (30 mL) was added, and the mixture

pyridyl), 7.16 (dt, ³J_HH= 16 Hz, ⁴J_HF= 2.3 Hz, 1H, CHvCHR_f8),

6.26 (dt, J_HH= 16 Hz, J_HF= 12 Hz, 1H, CHvCHR_f8), 3.89

(s, 3H, CH₃); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 155.8 (s),

was stirred (5 min) and stored in a refrigerator (overnight). The

3

sample was filtered and the filter cake was washed with water

and dried by oil pump vacuum to give 15 as a yellow solid

(0.235 g, 0.408 mmol, 51%), mp (capillary) 86–87 °C.²⁷Anal.

Calcd (%) for C₁₉H₈F₁₇N₂: C, 39.81; H, 1.41; N, 2.44. Found:

C, 39.72; H, 1.76; N, 2.43.

3

139.2 (s), 136.4 (t, J_CF= 9.6 Hz), 129.8 (s), 117.8 (s), 120–105

2

(multiple poorly resolved CF₂/CF₃), 116.8 (t, J_CF= 23 Hz),

55.7 (s); ¹⁹F NMR (376 MHz, CDCl₃) δ −80.7 (t, J_FF= 9.6 Hz,

3

3F), −111.5 (m, 2F), −121.3 (m, 2F), −121.9 (m, 4F), −122.7

(m, 2F), −123.0 (m, 2F), −126.1 (m, 2F).

¹H NMR (400 MHz, CDCl₃) δ 9.3 (s, 1H, isoquinolyl), 8.62

3

(d, J_HH= 6.1 Hz, 1H, isoquinolyl), 8.05 (d, J_HH= 8.0 Hz, 1H,

isoquinolyl), 7.92–7.83 (m, 3H, isoquinolyl and CHvCHR_f8),

(E,E)-3,5-NC₅H₃(CHvCHR_f8)₂(18)²⁸

3

7.66 (t, J_HH= 7.0 Hz, 1H, isoquinolyl), 6.32 (dt, J_HH= 16 Hz,

³J_HF= 12 Hz, 1H, CHvCHR_f8); ¹³C{¹H} NMR (100 MHz, CDCl₃)

δ 153.1 (s), 143.9 (s), 135.5 (t, J_CF= 9.5 Hz), 133.8, 130.3 (s),

A Schlenk flask was charged with a stir bar, 3,5-dibromopyri-

dine (0.189 g, 0.798 mmol), Pd(OAc)₂(0.018 g, 0.080 mmol,

5 mol%/Ar–Br bond), Bu₄N⁺Br⁻(0.520 g, 1.61 mmol) and

NaOAc (0.167 g, 2.04 mmol), fitted with a septum, and evacu-

ated/filled with argon (3×). Then H₂CvCHR_f8(0.510 mL,

1.92 mmol), DMF (6 mL), and THF (4 mL) were added by

syringe. The mixture was stirred at 120 °C for 72 h (the conver-

sion of the dibromide was monitored by GC-MS) and cooled to

room temperature. The THF and excess alkene were removed

by oil pump vacuum. Distilled water (20 mL) was added. The

3

130.0 (s), 129.0 (s), 128.6 (s), 127.0 (s), 119–105

2

(multiple poorly resolved CF₂/CF₃), 118.6 (t, J_CF= 23 Hz),

116.1; ¹⁹F NMR (376 MHz, CDCl₃) δ −80.7 (t, ³J_FF= 9.9 Hz, 3F),

−111.3 (m, 2F), −121.3 (m, 2F), −121.9 (m, 4F), −122.7 (m, 2F),

−123.0 (m, 2F), −126.1 (m, 2F).

(E)-1,3,5-N₂C₄H₃(CHvCHR_f8) (16)

A pressure vessel was charged with a stir bar, 5-bromopyr- mixture was stirred (5 min) and filtered. The filter cake was

imidine (0.127 g, 0.799 mmol), Pd(OAc)₂(0.0090 g, 0.040 mmol, washed with water (30 mL), dried by oil pump vacuum, and

5 mol%/Ar–Br bond), n-Bu₄N⁺Br⁻(0.258 g, 0.800 mmol), NaOAc chromatographed (silica gel column, 6 : 1 v/v hexanes/ethyl

(0.197 g, 2.40 mmol), H₂CvCHR_f8(0.266 mL, 1.00 mmol), acetate). The solvent was removed from the product containing

DMF (3.0 mL), and THF (3.0 mL). The mixture was stirred at fractions (R_f= 0.47) to give 18 as a white powder (0.325 g,

120 °C for 24 h (the conversion of the bromide was monitored by 0.336 mmol, 42%), mp (capillary) 107–109 °C.²⁷Anal. Calcd

GC-MS) and cooled to room temperature. The THF and excess (%) for C₂₅H₇F₃₄N: C, 31.04; H, 0.73; N, 1.45. Found: C, 30.92;

alkene were removed by oil pump vacuum. The residue was H, 0.74; N, 1.82.

dissolved in ethyl acetate (100 mL). The sample was washed with

distilled water (3 × 30 mL) and brine (25 mL), and dried (Na₂SO₄). (s, 1H, pyridyl), 7.22 (dt, J_HH= 16 Hz, J_HF= 2.3 Hz, 2H,

¹H NMR (400 MHz, CDCl₃) δ 8.74 (br, 2H, pyridyl), 7.89

3

4

3

The volatiles were removed by rotary evaporation to give 16 as a 2CHvCHR_f8), 6.37 (dt, J_HH= 16 Hz, J_HF= 12 Hz, 2H,

yellowish solid (0.285 g, 0.544 mmol, 68%), mp (capillary) 2CHvCHR_f8); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 150.2 (s),

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3

135.6 (t, J_CF= 9.8 Hz), 132.0 (s), 129.6 (s), 120–105 (multiple δ 138.6 (s), 129.7 (s), 120–105 (multiple poorly resolved

2

3

poorly resolved CF₂/CF₃), 118.0 (t, J_CF= 23 Hz); ¹⁹F NMR CF₂/CF₃), 33.2 (t, J_CF= 22 Hz), 26.6 (t, J_CF= 4.1 Hz); ¹⁹F NMR

(376 MHz, CDCl₃) δ −80.7 (t, ³J_FF= 9.4 Hz, 6F), −111.7 (m, 4F), (376 MHz, CDCl₃, 45 °C) δ −80.7 (t, J_FF= 9.4 Hz, 6F), −111.2

3

−121.3 (m, 4F), −121.8 (m, 8F), −122.7 (m, 4F), −122.9 (m, 4F), (m, 4F), −121.3 (m, 4F), −122.0 (m, 8F), −122.7 (m, 4F), −123.1

−126.0 (m, 4F).

(m, 4F), −126.1 (m, 4F).

1,3-C₆H₄(CH₂CH₂R_f8)₂(19)

1,3,5-C₆H₃(CH₂CH₂R_f8)₃(22)

A round bottom flask was charged with a stir bar, 3 (0.390 g,

0.403 mmol), Pd/C (0.030 g, 0.028 mmol), diethyl ether

(3 mL), and acetone (3 mL), partially evacuated, refilled with

hydrogen, and fitted with a hydrogen balloon. The mixture

was stirred overnight. The solvent was removed by rotary

evaporation. Hexane (5 mL) was added. The mixture was

passed through a short Celite column, and the flask and

column were rinsed with hexane (3 × 5 mL). The solvent was

removed from the combined eluates in vacuo to give 19 as a

white solid (0.3829 g, 0.3947 mmol, 98%), mp (capillary)

53–54 °C. Anal. Calcd (%) for C₂₆H₁₂F₃₄: C, 32.18; H, 1.25.

Found: C, 31.95; H, 1.15.

Compound

6 (0.410 g, 0.291 mmol), Pd/C (0.0465 g,

0.0437 mmol), diethyl ether (5 mL), acetone (5 mL), and hydro-

gen were combined in a procedure analogous to that for 19.

A similar reaction (24 h) and workup (10 mL 1 : 1 v/v hexane/

diethyl ether; 5 × 10 mL rinses) gave 22 as a white solid (0.3878 g,

0.2739 mmol, 94%), mp (capillary) 58–60 °C. Anal. Calcd (%) for

C₃₆H₁₅F₅₁: C, 30.53; H, 1.07. Found: C, 30.04; H, 1.08.

¹H NMR (400 MHz, acetone-d₆) δ 7.24 (s, 3H), 2.99–2.93 (m,

6H), 2.64–2.49 (m, 6H); ¹³C{¹H} NMR (100 MHz, acetone-d₆)

δ 141.4 (s), 128.0 (s), 120–105 (multiple poorly resolved

CF₂/CF₃), 33.5 (t, J_CF= 22 Hz), 27.2 (t, J_CF= 4.6 Hz); ¹⁹F NMR

2

3

(376 MHz, CDCl₃, 45 °C) δ −81.7 (t, J_FF= 10 Hz, 9F), −114.4

(m, 6F), −122.0 (m, 6F), −122.2 (m, 12F), −123.0 (m, 6F),

−123.7 (m, 6F), −126.5 (m, 6F).

3

¹H NMR (400 MHz, CDCl₃) δ 7.27 (t, J_HH= 7.6 Hz, 1H),

7.12–7.03 (m, 3H), 3.10–2.80 (m, 4H), 2.50–2.20 (m, 4H);

¹³C{¹H} NMR (100 MHz, CDCl₃) δ 139.9 (s), 129.3 (s), 128.3 (s),

126.7, 120–105 (multiple poorly resolved CF₂/CF₃), 33.1

1,3,5-C₆H₃(CH₂CH₂R_f8)₂(Cl) (23)

2

(t, J_CF= 22 Hz), 26.5 (t, J_CF= 4.1 Hz); ¹⁹F NMR (376 MHz,

3

Compound 7 (0.736 g, 0.736 mmol), Pd/C (0.0741 g,

CDCl₃) δ −80.9 (t, J_FF= 9.9 Hz, 6F), −114.2 (m, 4F), −121.5

0.0696 mmol), diethyl ether (3 mL), acetone (4 g), and hydro-

gen were combined in a procedure analogous to that for 19.

A similar reaction (24 h) and workup (10 mL 1 : 1 v/v hexane/

diethyl ether; 5 × 20 mL rinses) gave 23 as a white solid (0.70 g,

0.70 mmol, 95%), mp (capillary) 66–68 °C. Anal. Calcd (%) for

C₂₆H₁₁ClF₃₄: C, 31.08; H, 1.10. Found: C, 31.74; H, 1.14.

(m, 8F), −121.7 (m, 4F), −122.5 (m, 4F), −123.3 (m, 4F), −125.9

(m, 4F).

1,3-C₆H₄(CH₂CH₂R_f10)₂(20)

Compound

4 (0.368 g, 0.315 mmol), Pd/C (0.0363 g,

0.034 mmol), diethyl ether (10 mL), acetone (7 mL), and hydro-

gen were combined in a procedure analogous to that for 19.

A similar workup (10 mL hexane; 3 × 10 mL rinses) gave 20 as

a white solid (0.3582 g, 0.3061 mmol, 97%), mp (capillary)

93–94 °C. Anal. Calcd (%) for C₃₀H₁₂F₄₂: C, 30.79; H, 1.03.

Found: C, 30.74; H, 0.93.

¹H NMR (400 MHz, CDCl₃) δ 7.08 (s, 2H), 6.93 (s, 1H),

2.90–2.80 (m, 4H), 2.43–2.24 (m, 4H); ¹³C{¹H} NMR (100 MHz,

CDCl₃) δ 141.7 (s), 135.1 (s), 126.9 (s), 126.6 (s), 120–104

2

(multiple poorly resolved CF₂/CF₃), 32.8 (t, J_CF= 22 Hz), 26.3

3

(t, J_CF= 4.3 Hz); ¹⁹F NMR (376 MHz, CDCl₃) δ −80.8 (t, J_FF

=

3

10.0 Hz, 6F), −114.6 (m, 4F), −121.7 (m, 4F), −121.9 (m, 8F),

−122.7 (m, 4F), −123.4 (m, 4F), −126.1 (m, 4F).

¹H NMR (400 MHz, CDCl₃) δ 7.26 (t, J_HH= 7.7 Hz,

1H), 7.10–7.04 (m, 3H), 2.92–2.85 (m, 4H), 2.43–2.28

(m, 4H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 139.9 (s), 129.3 (s),

128.3 (s), 126.7, 120–105 (multiple poorly resolved

1,4-C₆H₄(CH₂CH₂R_f8)(CF₃) (24)²⁹

2

CF₂/CF₃), 33.1 (t, J_CF= 22 Hz), 26.5 (t, J_CF= 4.1 Hz); ¹⁹F NMR Compound

8 (0.621 g, 1.05 mmol), Pd/C (0.0462 g,

3

(376 MHz, CDCl₃) δ −80.8 (t, J_FF= 10 Hz, 6F), −114.5 (m, 4F), 0.043 mmol), acetone (7 mL), and hydrogen were combined in

−121.6 (m, 20F), −122.6 (m, 4F), −123.4 (m, 4F), −126.0 a procedure analogous to that for 19. A similar workup (5 mL

(m, 4F).

5 : 1 v/v hexane/diethyl ether; 3 × 10 mL rinses) gave 24 as a

light yellow solid (0.624 g, 1.05 mmol, >99%), mp (capillary)

40–42 °C. Anal. Calcd (%) for C₁₇H₈F₂₀: C, 34.48; H, 1.36.

1,4-C₆H₄(CH₂CH₂R_f8)₂(21)

Compound

5 (0.559 g, 0.579 mmol), Pd/C (0.0477 g, Found: C, 34.10; H, 1.12.

3

0.0448 mmol), diethyl ether (3 mL), acetone (3 g) and hydro-

gen were combined in a procedure analogous to that for 19. 7.32 (d, J_HH= 8.1 Hz, 2H), 3.00–2.94 (m, 2H), 2.45–2.30

A similar reaction (24 h) and workup (10 mL 1 : 1 v/v hexane/ (m, 2H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 143.1 (s), 129.2

diethyl ether; 5 × 10 mL rinses) gave 21 as a white solid (q, J_CF= 33 Hz, CCF₃), 128.7 (s), 125.8 (q, J_CF= 3.7 Hz,

(0.5462 g, 0.5631 mmol, 97%), mp (capillary) 83–84 °C. Anal. CHCCF₃), 124.1 (q, J_CF= 272 Hz, CHCCF₃), 120–104 (multiple

¹H NMR (400 MHz, CDCl₃) δ 7.57 (d, J_HH= 8.1 Hz, 2H),

3

2

3

1

2

3

Calcd (%) for C₂₆H₁₂F₃₄: C, 32.18; H, 1.25. Found: C, 32.22; poorly resolved CF₂/CF₃), 32.6 (t, J_CF= 22 Hz), 26.4 (t, J_CF

=

H, 1.20.

4.2 Hz); ¹⁹F NMR (376 MHz, CDCl₃) δ −62.6 (s, 3F), −80.8

¹H NMR (400 MHz, acetone-d₆) δ 7.31 (s, 4H), 2.98–2.91 (m, (t, ³J_FF= 10 Hz, 3F), −114.5 (t, ³J_FF= 13 Hz, 2F), −121.7 (m, 2F),

4H), 2.63–2.46 (m, 4H); ¹³C{¹H} NMR (100 MHz, acetone-d₆) −121.9 (m, 4F), −122.7 (m, 2F), −123.4 (m, 2F), −126.1 (m, 2F).

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1,4-C₆H₄(CH₂CH₂R_f8)(R_f8) (25)

5-iso-NC₉H₆(CH₂CH₂R_f8) (28)

Compound

0.019 mmol), acetone (10 mL), diethyl ether (4 mL), and hydro- 0.049 mmol), diethyl ether (8 mL), ethanol (4 mL), and hydro-

gen were combined in procedure analogous to that gen were combined in a procedure analogous to that for 19.

9 (0.382 g, 0.407 mmol), Pd/C (0.0199 g, Compound 15 (0.234 g, 0.408 mmol), Pd/C (0.052 g,

a

for 19. A similar workup (10 mL 2 : 1 v/v hexane/diethyl A similar workup (no solvent removal prior to Celite column;

ether; 3 × 30 mL rinses) gave 25 as a light yellow solid 50 mL diethyl ether rinse) gave 28 as a yellowish crystalline

(0.378 g, 0.401 mmol, 99%), mp (capillary) 64–66 °C. Anal. solid (0.220 g, 0.382 mmol, 94%), mp (capillary) 52–54 °C

Calcd (%) for C₂₄H₈F₃₄: C, 30.59; H, 0.86. Found: C, 30.75; H, (dec). Anal. Calcd (%) for C₁₉H₁₀F₁₇N: C, 39.67; H, 1.75; N,

0.81.

2.43. Found: C, 39.60; H, 1.79; N, 2.63.

3

¹H NMR (400 MHz, CDCl₃) δ 7.53 (d, J_HH= 8.2 Hz,

¹H NMR (400 MHz, CDCl₃) δ 9.27 (s, 1H, isoquinolyl), 8.59

3

2H), 7.34 (d, J_HF

= 8.2 Hz, 2H), 3.10–2.94 (m, 2H), (d, J_HH= 6.0 Hz, 1H, isoquinolyl), 7.89 (d, J_HH= 8.0 Hz, 1H,

2.46–2.31 (m, 2H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 143.4 isoquinolyl), 7.73 (d, J_HH= 6.0 Hz, 1H, isoquinolyl), 7.59–7.52

3

2

(s), 128.6 (s), 127.6 (s), 127.4 (t, J_CF= 22 Hz), 120–104 (m, 2H, isoquinolyl), 3.39–3.31 (m, 2H, CH₂CH₂R_f8), 2.55–2.37

(multiple poorly resolved CF₂/CF₃), 32.5 (t, J_CF= 20 Hz), (m, 2H, CH₂CH₂R_f8); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 153.5

2

26.4 (t, J_CF= 4.4 Hz); ¹⁹F NMR (376 MHz, CDCl₃) δ −80.8 (s), 143.7 (s), 134.4 (s), 134.2 (s), 130.4 (s), 129.1 (s), 127.2 (s),

3

(t, J_FF= 9.7 Hz, 6F), −110.6 (t, J_FF= 14 Hz, 2F), −114.5 127.1 (s), 119–105 (multiple poorly resolved CF₂/CF₃), 115.8 (s),

3

(t, J_FF= 14 Hz, 2F), −121.2 (m, 2F), −121.7 (m, 2F), 32.0 (t, ²J_CF= 22 Hz), 22.9 (t, ³J_CF= 4.5 Hz); ¹⁹F NMR (376 MHz,

3

−121.9 (m, 10F), −122.7 (m, 4F), −123.4 (m, 2F), −126.1 CDCl₃) δ −80.7 (t, J_FF= 9.9 Hz, 3F), −114.7 (m, 2F), −121.6

(m, 4F).

(m, 2F), −121.9 (m, 4F), −122.7 (m, 2F), −123.3 (m, 2F), −126.1

(m, 2F).

1,4-C₆H₄(CH₂CH₂R_f8)(CH₂CH₃) (26)

1,3,5-N₂C₄H₃(CH₂CH₂R_f8) (29)

Compound 10 (0.203 g, 0.360 mmol), Pd/C (0.0515 g,

0.0484 mmol), acetone (5 mL), and hydrogen were combined

in a procedure analogous to that for 19. A similar reaction

(72 h, monitored by H NMR spectra of aliquots) and workup

(4 mL 4 : 1 v/v hexane/diethyl ether; 3 × 10 mL rinses) gave 26

Compound 16 (0.285 g, 0.544 mmol), Pd/C (0.068 g,

0.064 mmol), diethyl ether (8 mL), ethanol (4 mL) and hydro-

gen were combined in a procedure analogous to that for 19.

A similar workup (no solvent removal prior to Celite column;

50 mL diethyl ether rinse) gave 29 as a yellow solid (0.138 g,

0.262 mmol, 48%), mp (capillary) 72–73 °C (dec). Anal. Calcd

(%) for C₁₄H₇F₁₇N₂: C, 31.96; H, 1.34; N, 5.32. Found: C, 31.92;

H, 1.46; N, 5.00.

1

as a colorless liquid (0.192 g, 0.348 mmol, 97%).

3

¹H NMR (400 MHz, CDCl₃) δ 7.15 (d, J_HH= 8.2 Hz, 2H),

3

7.12 (d, J_HH= 8.2 Hz, 2H), 2.90–2.84 (m, 2H), 2.62 (q, J_HH

=

3

7.6 Hz, 2H), 2.42–2.26 (m, 2H), 1.22 (t, J_HH= 7.6 Hz, 3H);

¹³C{¹H} NMR (100 MHz, CDCl₃) δ 142.7 (s), 136.3 (s), 128.3 (s),

128.2 (s), 120–104 (multiple poorly resolved CF₂/CF₃), 33.1

(t, ²J_CF= 22 Hz), 28.4 (s), 26.0 (t, ³J_CF= 4.2 Hz), 15.6 (s); ¹⁹F{¹H}

NMR (376 MHz, CDCl₃) δ −80.8 (t, J_FF= 10 Hz, 3F), −114.7

(t, J_FF= 12 Hz, 2F), −121.7 (m, 2F), −121.9 (m, 4F), −122.7

¹H NMR (400 MHz, CDCl₃) δ 9.12 (s, 1H, pyrimidyl), 8.64

(s, 2H, pyrimidyl), 2.98–2.90 (m, 2H, CH₂CH₂R_f8), 2.49–2.32

(m, 2H, CH₂CH₂R_f8); ¹³C{¹H} NMR (100 MHz, CDCl₃)

δ 157.5 (s), 156.7 (s), 132.3 (s), 120–105 (multiple poorly

3

2

3

resolved CF₂/CF₃), 31.9 (t, J_CF= 22 Hz), 21.5 (t, J_CF= 4.5 Hz);

3

¹⁹F NMR (376 MHz, CDCl₃) δ −80.7 (t, J_FF= 9.9 Hz, 3F),

3

(m, 2F), −123.5 (m, 2F), −126.1 (m, 2F).

−114.5 (m, 2F), −121.6 (m, 2F), −121.9 (m, 4F), −122.7 (m, 2F),

−123.4 (m, 2F), −126.1 (m, 2F).

1,4-C₆H₄(CH₂CH₂R_f8)(CN) (27)

3,5-NC₅H₃(CH₂CHR_f8)(OMe) (30)

Compound 11 (0.274 g, 0.500 mmol), Pd/C (0.0230 g,

0.022 mmol), acetone (1.7 g), diethyl ether (1.7 mL), and Compound 17 (0.391 g, 0.707 mmol), Pd/C (0.089 g,

hydrogen were combined in a procedure analogous to that 0.084 mmol), diethyl ether (10 mL), ethanol (5 mL), and hydro-

for 19. A similar workup (5 mL 2 : 1 v/v hexane/diethyl ether; gen were combined in a procedure analogous to that for 19.

3 × 10 mL rinses) gave 27 as a white solid (0.269 g, A similar workup (no solvent removal prior to Celite column;

0.490 mmol, 98%), mp (capillary) 70–72 °C. Anal. Calcd (%) 50 mL diethyl ether rinse) gave 30 as a white solid (0.329 g,

for C₁₇H₈F₁₇N: C, 37.18; H, 1.47; N, 2.55. Found: C, 36.98; 0.593 mmol, 84%), mp (capillary) 69–70 °C. Anal. Calcd (%)

H, 1.26; N, 2.53.

for C₁₆H₁₀F₁₇NO: C, 34.61; H, 1.82; N, 2.52. Found: C, 35.01;

3

¹H NMR (400 MHz, CDCl₃) δ 7.60 (d, J_HH= 8.3 Hz, 2H), H, 2.07; N, 2.70.

3

7.32 (d, J_HH= 8.3 Hz, 2H), 3.00–2.92 (m, 2H), 2.46–2.28

¹H NMR (400 MHz, CDCl₃) δ 8.20 (d, ⁴J_HH= 2.8 Hz, 1H, pyri-

(m, 2H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 144.5, 132.6, 129.1, dine), 8.10 (d, J_HH= 1.7 Hz, 1H, pyridine), 7.06–7.03 (m, 1H,

4

118.6, 110.9 (5 s, C₆̲ H₄C̲N), 120–104 (multiple poorly resolved pyridine), 3.86 (s, 3H, CH₃), 2.93–2.87 (m, 2H, CH₂CH₂R_f8),

2

3

CF₂/CF₃), 32.3 (t, J_CF= 22 Hz), 26.6 (t, J_CF= 4.3 Hz); ¹⁹F NMR 2.45–2.28 (m, 2H, CH₂CH₂R_f8); ¹³C{¹H} NMR (100 MHz, CDCl₃)

(376 MHz, CDCl₃) δ −80.9 (t, ³J_FF= 8.8 Hz, 3F), −114.6 (m, 2F), δ 155.7 (s), 141.9 (s), 135.8 (s), 135.1 (s), 120.6 (s), 120–105

−121.8 (m, 2F), −122.0 (m, 4F), −122.8 (m, 2F), −123.5 (m, 2F), (multiple poorly resolved CF₂/CF₃), 32.5 (t, J_CF= 22 Hz), 23.7

2

3

−126.2 (m, 2F).

(t, J_CF= 4.5 Hz); ¹⁹F NMR (376 MHz, CDCl₃) δ −80.7 (t, J_FF

=

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9.6 Hz, 3F), −114.6 (m, 2F), −121.7 (m, 2F), −121.9 (m, 4F),

−122.7 (m, 2F), −123.4 (m, 2F), −126.1 (m, 2F).

A. M. Stuart, W. Chen, Y. Hu and J. Xiao, Tetrahedron Lett.,

2001, 42, 8551–8553; (d) S. Darses, M. Pucheault and

J.-P. Genêt, Eur. J. Org. Chem., 2001, 1121–1128;

(e) D. V. Filippov, D. J. van Zoelen, S. P. Oldfield, G. A. van

der Marel, H. S. Overkleeft, J. W. Drijfhout and J. H. van

Boom, Tetrahedron Lett., 2002, 43, 7809–7812; (f) E. G. Hope,

A. M. Stuart and A. J. West, Green Chem., 2004, 6, 345–350;

(g) B. Gourdet, K. Singh, A. M. Stuart and J. A. Vidal,

J. Fluorine Chem., 2010, 131, 1133–1143; (h) J. Feng and

C. Cai, J. Fluorine Chem., 2013, 146, 6–10.

3,5-NC₅H₃(CH₂CH₂R_f8)₂(31)^9,15

Compound 18 (1.470 g, 1.520 mmol), Pd/C (0.1976 g,

0.1857 mmol), diethyl ether (20 mL), ethanol (10 mL), and

hydrogen were combined in a procedure analogous to that for

19. A similar workup (no solvent removal prior to Celite

column; 100 mL diethyl ether rinse) gave 31 as a white fluﬀy

white solid (1.357 g, 1.397 mmol, 92%), mp (capillary)

123–124 °C. Anal. Calcd (%) for C₂₅H₁₁F₃₄N: C, 30.91; H, 1.14; 12 (a) For examples where the aromatic substrate is fluorous

N, 1.44. Found: C, 30.60; H, 0.91; N, 1.38.

as opposed to the alkene, see: J. Salabert, R. M. Sebastián,

A. Vallribera, A. Roglans and C. Nájera, Tetrahedron, 2011,

67, 8659–8664; (b) For an example where two R_f8groups are

three sp³carbon atoms removed from the H₂CvCH

linkage, see: M. Wende, F. Seidel and J. A. Gladysz,

J. Fluorine Chem., 2003, 124, 45–54.

4

¹H NMR (400 MHz, CDCl₃) δ 8.41 (d, J_HH= 2 Hz, 2H), 7.41

(t, ⁴J_HH= 2 Hz, 1H), 2.97–2.92 (m, 4H), 2.46–2.33 (m, 4H); ¹³C{¹H}

NMR (100 MHz, CDCl₃) δ 147.5 (s), 136.5 (s), 135.0 (s), 120–105

2

(multiple poorly resolved CF₂/CF₃), 32.4 (t, J_CF= 22 Hz), 23.8

3

(t, J_CF= 4.5 Hz); ¹⁹F NMR (376 MHz, CDCl₃) δ −80.8 (t, J_FF

=

3

9.4 Hz, 6F), −111.5 (t, J_FF= 14 Hz, 4F), −121.8 (m, 4F), −122.0 13 (a) J. Moineau, G. Pozzi, S. Quici and D. Sinou, Tetrahedron

(m, 8F), −122.8 (m, 8F), −123.6 (m, 8F), −126.2 (m, 8F).

Lett., 1999, 40, 7683–7686; (b) L. Xu, W. Chen, J. F. Bickley,

A. Steiner and J. Xiao, J. Organomet. Chem., 2000, 598, 409–

416; (c) Y. Nakamura, S. Takeuchi, S. Zhang, K. Okumura

and Y. Ohgo, Tetrahedron Lett., 2002, 43, 3053–3056;

(d) M. Moreno-Mañas, R. Pleixats and S. Villarroya,

Organometallics, 2001, 20, 4524–4528; (e) K. S. A. Vallin,

Q. Zhang, M. Larhed, D. P. Curran and A. Hallberg,

J. Org. Chem., 2003, 68, 6639–6645; (f) D. P. Curran,

K. Fischer and G. Moura-Letts, Synlett, 2004, 1379–1382;

(g) T. Fukuyama, M. Arai, H. Matsubara and I. Ryu, J. Org.

Chem., 2004, 69, 8105–8107; (h) N. Lu, Y.-C. Lin, J.-Y. Chen,

C.-W. Fan and L.-K. Liu, Tetrahedron, 2007, 63, 2019–2023;

(i) S. Niembro, A. Shafir, A. Vallribera and R. Alibés, Org.

Lett., 2008, 10, 3215–3218; and earlier work by this group

cited therein.

Acknowledgements

We thank the Qatar National Research Fund for support

(project number 5-848-1-142), and Mr. Che Wu for assistance

in preparing the manuscript.

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Org. Biomol. Chem.

Article Doi

Convenient protocols for Mizoroki-Heck reactions of aromatic bromides and polybromides with fluorous alkenes of the formula H2CCH(CF2)n-1CF3 (n = 8, 10)

DOI: 10.1039/c6ob01980c

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Full text of DOI:10.1039/c6ob01980c

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