The preparation of HCF2CdX and HCF2ZnX via direct insertion into the carbon halogen bond of CF2HY (Y = Br, I)

Journal of Fluorine Chemistry 128 (2007) 1198–1215

www.elsevier.com/locate/ﬂuor

The preparation of HCF₂CdX and HCF₂ZnX via direct insertion

into the carbon halogen bond of CF₂HY (Y = Br, I)

*

Donald J. Burton , Greg A. Hartgraves

Department of Chemistry, University of Iowa, Iowa City, IA 52242, United States

Received 13 March 2007; received in revised form 18 May 2007; accepted 18 May 2007

Available online 25 May 2007

Dedicated to Professor Kenji Uneyama.

Abstract

The diﬂuoromethylcadmium and zinc reagents have been prepared in DMF via direct insertion of Cd⁰into the carbon halogen bond of CF₂HY

(Y = Br, I). These reagents are stable at 65–75 8C and exhibit prolonged stability and activity at room temperature. Metathesis of the diﬂuor-

omethylcadmium reagents with Cu(I)X (X = Br, Cl) at ꢀ55 8C rapidly produces diﬂuoromethylcopper. The copper reagent is signiﬁcantly less stable

than the cadmium or zinc reagent and rapidly decomposes at room temperature. The diﬂuoromethylcadmium and copper reagents exhibit good reacti-

vity with allylic halides, propargylic derivatives and 1-iodoalkynes to provide good yields of the corresponding diﬂuoromethylalkenes, diﬂuor-

omethylallenesand diﬂuoromethyl-2-alkynes. Alkylation issuccessful onlywithreactive alkylhalides. Generally, the diﬂuoromethylcopperreagentis

morereactivethanthediﬂuoromethylcadmiumreagentandgenerallyexhibitshigherregioselectivityinreactionsthatcanoccurbyeithera-org-attack.

Keywords: Diﬂuoromethylcadmium reagent; Diﬂuoromethylzinc reagent; Diﬂuoromethylcopper reagent; Allenes; Alkynes; Diﬂuoromethyl allylic derivatives;

Organometallics

1. Introduction

aliphatic aldehydes, which contain a-hydrogens, are signiﬁ-

cantly lower due to complicating side reactions, which include

the formation of 1,2-diﬂuoroalkanes and bis-(1-ﬂuoroalkyl)

ethers [5] (Eq. (2)). The formation of these products and their

ratio

The methods for the incorporation of the diﬂuoromethyl

group into organic compounds fall into two main categories.

One is the ﬂuorination of aldehydes with ﬂuorinating agents,

such as SF₄, DAST and related analogues, or metal ﬂuorides

(MoF₆, CoF₃, etc.). For example, SF₄reacts with aldehydes to

afford the corresponding diﬂuoromethyl substituted com-

pounds. A number of reviews have dealt with the properties

and reactions of SF₄with carbonyl compounds [1–3]. A typical

example is illustrated in Eq. (1) [4]. In general, aldehydes which

do not possess a-hydrogens give good yields of the

diﬂuoromethylated product. The yields of

ꢁ

RCH₂CHO þ SF₄^ꢀ20ꢀ^to!^{þ40 C}RCFHCFH₂þ ðRCFHÞ O

2

þ RCH₂CF₂H

(2)

is strongly dependent on the degree of alkyl substitution of the

aldehydes and on the reaction conditions. Most straight chain

aldehydes produce the corresponding 1,1-diﬂuoroalkanes as the

predominant or sole product; however, substituted aldehydes,

such as isobutyraldehyde, a-ethylbutyraldehyde and a-methyl-

butyraldehydes, afford comparable amounts of 1,1-diﬂuoroalk-

anes and rearranged 1,2-diﬂuoroalkanes [5]. Heterocyclic

aldehydes have also been demonstrated to successfully provide

the diﬂuoromethylated product with SF₄[6]. Interest in che-

motherapeutic agents similarly led to the preparation of the

(1)

diﬂuoromethyl

(Eq. (3)) [7]. Fluorination of a,b-unsaturated aldehydes with

heteroaromatic,

5-diﬂuoromethyluracil

* Corresponding author.

E-mail address: donald-burton@uiowa.edu (D.J. Burton).

SF₄, DAST and Et₂NCF₂CFHCl afforded the corresponding

doi:10.1016/j.jﬂuchem.2007.05.015

D.J. Burton, G.A. Hartgraves / Journal of Fluorine Chemistry 128 (2007) 1198–1215

1199

diﬂuoromethyl substituted oleﬁns [8]. Middleton reported the

ﬂuorination of substituted aldehydes with DAST and indi-

cated that the amount of side-products could be controlled

using DAST in the appropriate solvent [9]. The yields

reported by Middleton are comparable to those reported with

SF₄and aldehydes without a-hydrogen. The primary use of

DAST has been for the introduction of the ﬂuorinated sub-

stituent into natural products [10–14]. DAST avoids several of

the disadvantages of SF₄: (1) ﬂuorinations are more selective;

(2) fewer rearrangements or eliminations result; (3) less

elaborate apparatus is required, and (4) DAST or related

analogues are commercially available and easier to handle

than SF₄.

then utilized to prepare a ﬂuorinated analog of methotrexate

[21].

(6)

The preparation of F-alkyl and F-vinyl cadmium reagents

has recently received considerable attention [22–26]. The F-

cadmium, zinc, and copper reagents display excellent thermal

stability and have been utilized in a variety of F-alkyl and F-

vinyl transfer reactions. However, partially ﬂuorinated F-

organometallic reagents have received little attention and

hydro-ﬂuoro organometallic reagents have received no atten-

tion. Thus, our attention was drawn to the preparation of a

diﬂuoromethyl organometallic reagent and its ability to transfer

the diﬂuoromethyl group to produce new diﬂuoromethyl

building blocks.

(3)

The second major method utilized for the introduction of the

diﬂuoromethyl group into organic compounds is chlorodi-

ﬂuoromethane. This methodology relies on the fact that a

stabilized a-carbanion can be formed with an appropriate base

and was ﬁrst introduced by Sarett and co-workers [15]. Bey

et al. prepared a number of diﬂuoromethyl amino acids using

chlorodiﬂuoromethane as the diﬂuoromethyl precursor

(Eq. (4)) [16–19]. Although these reactions with CHF₂Cl

can be rationalized

The ease of reaction of F-alkyl iodides and bromides, F-

vinylhalides, and bromopentaﬂuorobenzene with cadmium

metal prompted us to explore this approach as a route to a

partially ﬂuorinated cadmium reagent [27–30]. Our initial

interest focused on: (1) the ease of formation of a partially

ﬂuorinated cadmium reagent versus the F-alkyl analog; (2) the

stability of this reagent versus the F-analog; and (3) the

reactivity of this reagent versus the F-analog. A preliminary

report documents our preliminary work to prepare an

HCF₂CdX reagent [31]. Subsequent to our preliminary report,

German workers reported an alternative preparation of this

reagent via the reaction of R₂Cd (R = Me, Et) with CF₂HI [32].

This work focused on the preparation of the reagent, its

spectroscopic properties and the formation of adducts with

(4)

as an S_N2 process, more likely they involve diﬂuorocarbene as a

reaction intermediate (Eq. (5)). Diﬂuoromethylation via chlor-

odiﬂuoromethane has been

(5)

extended to aminomalonates by Tsushima and Kawada for the

preparation of b-ﬂuorinated alanines [20] (Eq. (6)). Amino

malonates provide methodology for the preparation of amino

acids which are only substituted at the a-carbon by the

diﬂuoromethyl group. Tsushimi et al. utilized this methodol-

ogy to prepare an a-diﬂuoromethyl glutamic acid, which was

donors, such as diglyme or TMEDA. Little or no chemistry with

organic substrates was reported. In this manuscript, we detail

the preparation and thermal stability of HCF₂CdX, its

metathesis to prepare HCF₂Cu, and the reaction of the reagent

with allyl halides, propargyl halides, haloacetylenes, and

alkylating reagents.

1200

D.J. Burton, G.A. Hartgraves / Journal of Fluorine Chemistry 128 (2007) 1198–1215

2. Results and discussion

a 96% isolated yield of HCF₂I (Eq. (9)). By the same procedure,

2.1. Preparation of the diﬂuoromethylcadmium reagent

Diﬂuoromethylcadmium can be readily prepared from

iododiﬂuoromethane or bromodiﬂuoromethane and acid-

washed cadmium metal in DMF. The CHF₂I rapidly inserts

cadmium at RT to give a 91% ¹⁹F NMR yield of a mixture of

mono- and bis-diﬂuoromethylcadmium. In contrast, bromodi-

ﬂuoromethane requires 5 days at 55 8C (in DMF) to give a 65–

75% ¹⁹F NMR yield of the mono- and bis-diﬂuoromethylcad-

mium reagent (Eq. (7)) with a mono/bis ratio of ꢂ3/1.

(9)

DCF₂Br was converted to the corresponding deuterated cad-

mium reagent. This reagent can be utilized to incorporate the –

CF₂D group into organic compounds (Eq. (10)). The thermal

stability of the diﬂuoromethylcadmium reagent was evaluated

(7)

(10)

as follows: a 0.5 ml aliquot of the diﬂuoromethylcadmium

reagent (in DMF) was charged into a 5 mm NMR tube and

10 ml of C₆H₅CF₃was added as a reference. The NMR tube was

placed in the probe of a 90 MHz JEOL FX90Q NMR spectro-

meter. The ¹⁹F NMR spectrum was recorded at 25 8C and then

recorded every 10–20 min as the temperature was slowly raised

(in 10 8C intervals) to 115 8C. The diﬂuoromethylcadmium

reagent exhibits excellent stability at RT—with a loss of only

31% activity of the original reagent after 2 months. Thus, a large

solution of the reagent can be prepared, and aliquots utilized

over a period of days to weeks. On heating (in DMF) little

decomposition occurs until 65–75 8C. At temperatures >75 8C

the rate of decomposition slowly increases, and at temperatures

above 105 8C decomposition is rapid. The main decomposition

product detected is CF₂H₂[33].

The mono/bis reagents were identiﬁed via their characteristic ¹⁹

F

NMR spectrum, which exhibited the expected doublet at

ꢀ117.7 ppm and ꢀ119.2 ppm, respectively, for the diﬂuoro-

methyl group with the distinctive ¹¹¹Cd/¹¹³Cd satellites (cf.

Ref. [31] for a detailed picture of this spectrum). The mono

and bis reagents were unequivocally identiﬁed from the ¹¹³Cd

NMR spectrum of the mixture, which shows a triplet of doublets

at 253.3 ppm for the mono reagent and a pentet of triplets for the

bis reagent (see Ref. [31] for a detailed picture of this spectrum).

Additional evidence for the assignments of the mono- and bis-

diﬂuoromethylcadmium reagents was obtained by addition of

CdI₂to the diﬂuoromethylcadmium reagent. The mono/bis ratio

was shifted in favor of the mono-reagent, with a corresponding

increase in the signal at ꢀ117.7 ppm in agreement with the

Schlenk equilibrium shown in the following equation:

2.2. Preparation of the diﬂuoromethylzinc reagent

Similar to the preparation of the diﬂuoromethylcadmium

reagent, the analogous diﬂuoromethylzinc reagent can be

prepared via the reaction of HCF₂Br at 60 8C/5 days to give 73–

85% ¹⁹F NMR yield of the zinc reagent, with a mono/bis ratio

of 88:12 (Eq. (11)). The mono/bis assignment is based on the

decrease in the intensity

ðHCF₂Þ₂Cd þ CdI₂@ HCF₂CdI

(8)

Further identiﬁcation was obtained chemically by hydrolysis of

the reaction mixture with D₂O to give a 65% isolated yield of

HCF₂D. Likewise, treatment of the reaction mixture with I₂gave

(11)

D.J. Burton, G.A. Hartgraves / Journal of Fluorine Chemistry 128 (2007) 1198–1215

1201

Table 1

Reaction of diﬂuoromethylcadmium reagent with allylic halides

Entry

Allylic halides

Isolated yield (%)

a (attack)

g (attack)

1

2

3

4

5

6

7

8

9

H₂C CHCH₂Br

85

68

55

62

45

68

63

87

62

–

H₂C C(CH₃)CH₂Cl

H₂C CHCD₂Cl

26

37

7

74

63

93

3^a

78^b

48

44

(E)-CH₃CH CHCH₂Cl

H₂C CHCH(Cl)CH₃

(CH₃)₂C CHCH₂Cl

H₂C CHC(CH₃)₂Cl

(E)-PhCH CHCH₂Br

(E)-PhCH CHCH₂Cl

89

15

52

56

a

8% H₂C C(CH₃)CH CH₂.

b

5% H₂C C(CH₃)CH CH₂.

of the signal at ꢀ126.0 ppm (bis reagent) with a corresponding

increase in the intensity of the signal at ꢀ125.9 ppm upon the

addition of ZnCl₂to the reaction mixture.

gave both 1,1-dideutero-4,4-diﬂuoro-1-butene and 3,3-dideu-

tero-4,4-diﬂuoro-1-butene (Eq. (13)). This result indicates that

there is a preference for

(13)

attack at the g-carbon in a 3/1 ratio when the a- and g-carbons

do not possess alkyl substituents.

2.3. Allylation of the HCF₂CdX reagent

The effect of steric hindrance on the regioselectivity of the

HCF₂CdX reagent with allylic halides was examined by the

reaction of HCF₂CdX with allylic halides substituted at the a-

and g-carbons. (These results are summarized in Table 1.) The

regiospeciﬁcity of the reaction of HCF₂CdX is that expected.

As the steric hindrance at the a-center increases, the amount of

the g-attack product increases, and as the steric hindrance at the

g-center increases, the yield of the a-product increases.

The HCF₂ZnX reagent was also found to react with allylic

halides; however, the reactivity of this reagent is signiﬁcantly

lower than the HCF₂CdX reagent. For example, after heating

HCF₂ZnX (in DMF) with cinnamyl bromide for 19 h at 45 8C,

Typically, organocadmium reagents have been used to

prepare ketones from acyl halides. A less common reaction of

organocadmium reagents is their coupling with allylic halides

[34]. Jones and Costanzo have demonstrated that diphenyl-

cadmium reacts with allyl bromide and 3-bromo-1-cyclohexene

in reﬂuxing ether to give 39% and 81% GLPC yields of the

allylated products [35]. However, di-n-octylcadmium failed to

react with allyl bromide [36]. Similarly, CF₃CdX gave less than

5% of CF₃CH₂CH CH₂when reacted for 7 days with allyl

bromide in DMF. The reactivity of a partially ﬂuorinated

organocadmium reagent had not previously been reported.

Thus, for HCF₂CdX to provide a convenient method for the

introduction of the diﬂuoromethyl moiety into organic

substrates via allylation, it must exhibit a unique reactivity

with these substrates relative to n-octyl and triﬂuoromethyl-

cadmium reagents.

followed by 28 h at 55 8C, 18% of HCF₂ZnX still remained. ¹⁹

F

NMRanalysis of the reaction mixtureindicated a 74% (¹⁹F NMR

yield) of a mixture containing (E)-4,4-diﬂuoro-1-phenyl-1-but-

ene and 4,4-diﬂuoro-3-phenyl-1-butene in a 42:58 ratio. Altho-

ughtheyield wasslightlylower duetounreactedzinc reagentand

longer reaction times were required, it is noteworthy that the

HCF₂ZnXreagentdoesreactwithallylhalides(albeitslower)and

provides a less toxic alternative to the cadmium analog.

Fortunately, when HCF₂CdX was reacted with allyl

bromide, the reaction occurred readily to give an 85% isolated

yield of 4,4-diﬂuoro-1-butene (Eq. (12)) [37].

The mechanism for attack at the a-carbon most likely

involves a simple S_N2 displacement of the halide to give the

corresponding diﬂuoromethyl-substituted oleﬁn (Scheme 1).

The preference for g-substitution in the reaction of HCF₂CdX

with H₂C CHCD₂Cl discounts the possibility of a free ionic

intermediate, since an ionic intermediate would give ꢂ1/1 ratio

of both isomers. An alternative explanation is that a six-

(12)

Since both a- and g-attack would yield the same product, we

investigated the same reaction with the corresponding 3-chloro-

3,3-dideutero-1-propene. Reaction of the deuterated analog

1202

D.J. Burton, G.A. Hartgraves / Journal of Fluorine Chemistry 128 (2007) 1198–1215

Scheme 1. Mechanism of nucleophilic attack at the a- and g-carbons.

membered cyclic intermediate is involved (Scheme 1) in which

the cadmium reagent is co-ordinated to the halide and the

diﬂuoromethyl group is co-ordinated to the g-carbon. The

ability of the HCF₂CdX to act as both the alkylating agent and

halogen abstraction agent in the six-membered intermediate is

the driving force behind its formation. A similar intermediate

can explain the elimination product observed in reaction with 1-

chloro-3-methyl-2-butene and 3-chloro-3-methyl-1-butene

(Scheme 2). In this case the diﬂuoromethyl group accepts an

a-hydrogen to give CF₂H₂, a product observed in the reaction.

metathesis reaction occurs to form diﬂuoromethylcopper in

>90% ¹⁹F NMR yield. This HCF₂Cu^areagent exhibits a

doublet at ꢀ114.6 ppm (¹⁹F NMR). When the temperature of

the solution was increased, a second HCF₂Cu^breagent

appeared (¹⁹F NMR, ꢀ116.4 (d)). At T > ꢀ30 8C the copper

reagent began to decompose rapidly to HCF₂CF₂H and cis-

CFH CFH (Eq. (14)) [43,44].

(14)

2.4. Formation of the HCF₂Cu reagent

In previous work with triﬂuoromethylcadmium [38],

ﬂuorinated vinyl cadmium reagents [39], perﬂuoroallyl

cadmium reagents and ﬂuorinated arylcadmium reagents

[40,41,42] we have shown that ﬂuorinated cadmium reagents

readily exchange with Cu(I) halides to form (in situ) the

analogous ﬂuorinated copper reagent. A number of qualities

make organocopper reagents attractive; these include (1) easy

preparation, (2) good reactivity, (3) low toxicity, and (4)

generally good regiospeciﬁcity when alternative sites of attack

exist. Thus, we were prompted to attempt to prepare HCF₂Cu,

study its stability, and to investigate its reactivity and

regiospeciﬁcity with allylic halides compared to HCF₂CdX.

When the diﬂuoromethylcadmium reagent (in DMF) is

reacted with CuBr or CuCl at ꢀ50 to ꢀ60 8C, a rapid

2.5. Allylation of the HCF₂Cu reagent

Although HCF₂Cu is relatively unstable, reactions with allyl

halides are rapid and the reagent is a useful diﬂuoromethyl

transfer reagent. Generally, the HCF₂CdX (in DMF) reagent is

cooled to ꢀ50 to ꢀ60 8C, and an equivalent amount of CuBr or

CuCl is added, maintaining the ꢀ50 to ꢀ60 8C temperature;

then the allyl halide is added and the solution slowly warmed to

RT (Eq. (15)). Since the HCF₂Cu easily decomposes, a slight

excess of HCF₂Cu is utilized in these allylation reactions.

These results are summarized in Table 2. Comparison of the

results summarized in

(15)

D.J. Burton, G.A. Hartgraves / Journal of Fluorine Chemistry 128 (2007) 1198–1215

1203

Scheme 2. Mechanism for the elimination reaction of dimethyl-substituted allylic halides.

Table 2 shows that the HCF₂Cu is generally a more

regiospeciﬁc reagent for the introduction of the –CF₂H into

allylic halides. The reactions are faster (even at the ꢀ50 8C

temperature) and the diene (elimination) products noted in

Table 1 are not observed with the HCF₂Cu reagent. Also, 3-

chlorocyclohexene cleanly gives 3-(diﬂuoromethyl)-1-cyclo-

hexene with HCF₂Cu, whereas HCF₂CdX with 3-chlorocyclo-

hexene gives signiﬁcant amounts of 1,3-cyclohexadiene and

diﬂuoromethane.

least hindered site. The HCF₂Cu reagent is presumably

aggregated in solution and hence more sterically bulkier than

the HCF₂CdX reagent; hence the increased selectivity for

preferred attack at the less hindered site.

2.6. Reaction of the HCF₂CdX reagent with propargyl

derivatives

The increased nucleophilicity of HCF₂CdX compared to n-

octylcadmium and triﬂuoromethylcadmium prompted us to

study the reaction of HCF₂H with propargyl halides and

tosylates. We had previously demonstrated that perﬂuoroalk-

ylcopper reagents readily reacted with this class of substrates to

afford the corresponding allenes in good yields (Eq. (16)) [45].

Since H₂C CHCD₂Cl does not give approximately equal

amounts of product from a- or g-attack, a free ionic

intermediate has been ruled out for the HCF₂Cu reactions

with allylic halides. Thus, a concerted S_N2 or S_N2¹mechanism

is proposed for this reaction with preference for attack at the

Table 2

Reaction of diﬂuoromethylcopper reagent with allylic halides

Entry

Allylic halides

Isolated yield (%)

a (attack)

g (attack)

1

2

3

4

5

6

7

8

H₂C CHCD₂Cl

63

68

74

80

76

86

74

62

10

54

–

90

46

100

–

(E)-CH₃CH CHCH₂Cl

H₂C CHCH(Cl)CH₃

(CH₃)₂C CHCH₂Cl

H₂C CHC(CH₃)₂Cl

(E)-PhCH CHCH₂Cl

H₂C CHCF₂Br

100

–

100

–

100

–

100

–

1204

D.J. Burton, G.A. Hartgraves / Journal of Fluorine Chemistry 128 (2007) 1198–1215

Table 3

Yields and isomeric ratio for the reaction of HCF₂CdX with propargylic halides and tosylates

Propargylic halide/OTs

Yield (%)^a

a (attack)

g (attack)

HCBB CCH₂Cl

41

5

0

95

100

78

HCBB CCH(CH₃)OTs

HCBB CCH(CH₃)Cl

HCBB CC(CH₃)₂Br

CH₃CBB CCH₂Br

(87)

(84)

64

0

69

(56)^b

22

0

100

ClCH₂CBB CCH₂Cl

(52)

0

100

a

Yields in parentheses are ¹⁹F NMR yields; all other yields are isolated yields.

30% of 1-ethynyl-1-cyclohexene.

b

Thus, we were interested to determine if

2.7. Reaction of the HCF₂Cu reagent with propargyl

derivatives

(16)

In contrast to the sluggish reaction of HCF₂CdX with

propargyl derivatives, the HCF₂Cu reagent reacted readily

with most of these derivatives. When HCF₂Cu reacted with

propargyl chloride only a 7% (¹⁹F NMR) yield of 4,4-diﬂuoro-

1,2-butadiene was detected. Similar reaction with the more

reactive tosylate derivative was employed; only a 33% (¹⁹F

NMR) yield was detected; and 3-chloro-1-butyne gave only a

25% (¹⁹F NMR) yield of the expected allene. With the more

reactive 1-tosyl-2-butyne, a 53% isolated yield was obtained.

The low reactivity of HCF₂Cu with simple propargyl

derivatives could be explained by complexation of the

HCF₂Cu reagent with the triple bond of the alkyne. We had

observed similar complexation of ﬂuorinated aryl copper

reagents with alkynes in other work in our laboratory [42,46].

Fortunately, with derivatives other than simple propargyl

compounds, reasonable isolated yields of the products was

obtained. These results are summarized in Table 4. The results

HCF₂CdX was sufﬁciently nucleophilic to accomplish a

similar transformation. When HCF₂CdX reacts with propar-

gyl chloride at RT, a slow reaction (3 days at RT and 7 days at

50 8C) produced a mixture (isolated) of 4,4-diﬂuoro-1,2-

butadiene and 4,4-diﬂuoro-1-butyne; some propargyl chloride

remained unreacted. A similar reaction with 3-tosyl-1-butyne

(7 h at RT) gave an 87% (¹⁹F NMR) yield of 1,1-diﬂuoro-2,3-

pentadiene. Several other propargyl derivatives were inves-

tigated and these results are summarized in Table 3. Only

HCBB CC(CH₃)₂Cl gave a clean, rapid, regiospeciﬁc reaction

to form the allene. Several other derivatives gave good

regioselectivity, but the reactions were sluggish or gave

by-products that made isolation of the allene difﬁcult (cf.

Section 3).

Table 4

Isolated yields for the reaction of the HCF₂Cu reagent with propargylic halides or tosylates

Entry

Propargyl halide/OTs

Yield^a

a

g (%)

1

2

3

4

5

6

7

HCBB CCH₂Cl

(7)

0

100

87

HCBB CCH₂OTs

(33)

0

HCBB CCH(Cl)CH₃

HCBB CCH(OTs)CH₃

HCBB CC(CH₃)₂Cl

CH₃CBB CCH₂Br

(25)

53 (61)

78 (77)

59 (74)

71 (72)

0

13

0

100

8

ClCH₂CBB CCH₂Cl

46 (55)

0

100

a

Yields in parentheses are ¹⁹F NMR yields.

D.J. Burton, G.A. Hartgraves / Journal of Fluorine Chemistry 128 (2007) 1198–1215

1205

Scheme 3. Mechanism of the formation of diﬂuoromethyl allenes from propargyl substrates and diﬂuoromethyl copper reagent.

in Table 4 (compared to Table 3) again demonstrate the

enhanced reactivity of the HCF₂Cu reagent and the enhanced

regioselectivity of the copper reagent. For entries (4–7,

Table 4) good isolated yields of the allenes were obtained. In

entry 7 only the allene was obtained, no 1-ethynyl-1-

cyclohexene was formed (cf. Table 3). With 1,4-dichloro-2-

butyne, the bis-2,3-(diﬂuoromethyl)-1,3-butadiene was

formed by two successive g-attacks of HCF₂Cu. Thus, for

the preparation of diﬂuoromethylallenes from a propargyl

precursor, HCF₂CdX may be the reagent of choice for simple

analogs, such as propargyl halides or tosylates; whereas

HCF₂Cu would be the reagent of choice for more reactive

analogs.

g-carbon by a diﬂuoromethyl group occurs by oxidative

addition at the g-carbon to form a copper(III) intermediate;

reductive elimination of copper halide affords the diﬂuor-

omethylated allene.

2.8. Preparation of diﬂuoromethylated substituted alkynes

Perﬂuoroalkylcopper reagents, prepared from the corre-

sponding iodide and copper metal in DMSO, have been coupled

with iodoalkynes at temperatures below 5 8C to produce the

perﬂuoroalkyl substituted alkynes in a single step [47]. At

higher temperatures self-coupling of the iodoalkynes to form

the symmetrical diynes was a signiﬁcant side reaction

(Eq. (17)). With 1-iodoperﬂuoroalkynes and R_FCu, an

The mechanism for the reaction of HCF₂Cu with propargylic

halides or tosylates is proposed to occur via initial complexa-

tion of the copper reagent with the triple bond of the alkyne

(Scheme 3). A stronger complex would be expected for

HCF₂Cu, since the electron-withdrawing effect of the

ﬂuoroalkyl group results in a greater electron deﬁciency for

the copper atom. Oxidative addition occurs to afford a

copper(III) intermediate which subsequently undergoes a

reductive elimination to afford the diﬂuoromethyl substituted

allene. The oxidative addition–reduction elimination mechan-

ism has been previously proposed by Posner for coupling

reactions of ﬂuoroalkyl copper reagents [46]. The regiospeci-

ﬁcity observed in the formation of the allenes is due to the

complexation of the copper reagent and the proximity of the

copper atom to the g-carbon as a result of the complexation. In

addition, the g-carbon is always the least hindered site when the

propargylic halide is a terminal alkyne. Substitution at the

(17)

exchange reaction occurs between the iodoperﬂuoroalkyne and

the R_FCu reagent to produce R_FI and the perﬂuoroalkynyl

copper reagent, which then couples with a second equivalent

of the iodoperﬂuoroalkyne to give a perﬂuoroalkyldiyne [48].

Thus, it was not obvious that HCF₂Cu would couple with both

classes of iodoalkynes.

1206

D.J. Burton, G.A. Hartgraves / Journal of Fluorine Chemistry 128 (2007) 1198–1215

Table 5

Typically CDCl₃was used as the NMR lock solvent and

chemical shifts are reported in ppm relative to internal TMS.

The ¹³C NMR spectra were recorded on a Bruker WM 360X

Spectrometer operated at 90.56 MHz. The spectra were run

unlocked with neat samples and an internal TMS capillary or as

10–20% (v/v) solutions in CDCl₃with TMS as an internal

standard. The ²D NMR spectra were recorded on a JEOL

FX90Q Spectrometer operated at 13.63 MHz. Solvent and

internal references are reported with the NMR data for any

deuterium-containing compound. The ¹¹³Cd NMR spectra were

recorded on a Bruker WM 360X Spectrometer operated at

19.84 MHz. The samples were reaction mixtures in DMF and

chemical shifts are reported relative to external CdSO₄. Mass

spectra of liquid samples were recorded on a Hewlett-Packard

5985 GC–MS system operated at 30 eV in the electron impact

mode. The GC contained an 8 ft ꢃ 1/8 in. glass column packed

with 5% ov101 on Chromosorb P. Solid samples were recorded

by direct inlet into the probe in the electron impact mode. High

resolution MS were recorded on a VG Analytical ZAB-HF

operated at 70 eV in the electron impact mode. Infrared spectra

Isolated yields from the reaction of HCF₂Cu with 1-iodo-1-alkynes HCF₂Cu þ

DMF

RCBB CIꢀ!_ꢀ_{55 C to RT}RCBB CCF₂H

ꢁ

R

Isolated yield of RCBB CCF₂H (%)

C₄H₉

C₅H₁₁

C₆H₅

C₄F₉

75

74

44

52

55

66

C₆F₁₃

C₈F₁₇

To our delight, HCF₂Cu readily coupled with RCBBCI to

give moderate to good yields of the resultant diﬂuoromethyl

alkyne. With 1-iodoperﬂuoroalkyl alkynes, two different

situations were observed. With 1-iodo-triﬂuoropropyne only

traces of the desired diﬂuoromethyl substituted F-alkyne was

observed. However, with longer chain R_Fderivatives, good

isolated yields of the diﬂuoromethyl substituted alkyne was

obtained (cf. Table 5) (Eq. (18)), Thus, HCF₂Cu exhibits a

unique reactivity with 1-iodoperﬂuoroalkynes.

(18)

were recorded on a Mattson Cygnus 25 FTIR Spectrometer as

solutions in CCl₄. Spectra of gaseous samples were recorded in

a 10 cm evacuated gas cell containing ꢂ10 mm of gas sample.

Analytical GLPC were performed on a Hewlett-Packard model

5890 equipped with a TCD. Capillary GLPC was performed

using a FID. All bp were determined during fractional

2.9. Alkylation with HCF₂Cu

The HCF₂Cu reagent reacts with strong alkylating agents,

such as chloromethyl ethyl ether or benzyl bromide to give the

corresponding diﬂuoromethylated product (Eq. (19)). The by-

products of the reaction were

(19)

CF₂HCF₂H and cis-CFH CFH from the decomposition of

HCF₂Cu. With less reactive alkylating reagents the diﬂuor-

omethylalkylated product is either not obtained or only in trace

amounts.

distillation and are incorrected. Melting points were determined

in a Thomas-Hoover Unimelt apparatus and are incorrected.

Bromodiﬂuoromethane was used as received from the Dow

Chemical Company. Bromodeuterodiﬂuoromethane was pre-

pared by hydrolysis of bromodiﬂuoromethyltriphenylpho-

sphornium bromide with D₂O and puriﬁed by bulb-to-bulb

3. Experimental

2

distillation. D NMR (DMF, d₆-acetone ref.): 6.2 ppm (t); ¹⁹F

3.1. General experimental procedures

NMR (DMF): ꢀ69.3 ppm (t, J_FD= 9.8 Hz). Allylic halides,

benzyl bromide and ethylchloroethyl ether were purchased

commercially and used directly. The 3-chloro-3,3-dideutero-1-

propene was prepared by reported procedures [49,50].

Propargyl chloride and 1,4-dichloro-2-butyne were purchased

commercially and distilled prior to use. The propargyl tosylates

and halo-substituted alkynes were prepared by the procedure

reported by Brandsma and Verkuijsse [51] from the corre-

sponding alcohols. The aliphatic alkynyl iodides were prepared

by Brandsma’s procedure [51]. The perﬂuoroalkynyl iodides

were prepared by the procedure developed by Spawn [52].

The ¹⁹F NMR spectra were recorded on a JEOL FX90Q

Spectrometer operated at 83.81 MHz. Chemical shifts have

been reported relative to CFCl₃and were generally determined

in CDCl₃solvent (unless otherwise noted). Quantitative

measurements were carried out by integration relative to

internal benzotriﬂuoride. Routine ¹H NMR spectra were

recorded on a JEOL FX90Q Spectrometer operated at

1

89.09 MHz. High ﬁeld H NMR spectra were recorded on a

Bruker WM 360X Spectrometer operated at 360.14 MHz.

D.J. Burton, G.A. Hartgraves / Journal of Fluorine Chemistry 128 (2007) 1198–1215

1207

3.2. Preparation of the diﬂuoromethylcadmium reagent

3.4. Hydrolysis of diﬂuoromethylcadmium with D₂O

3.2.1. From bromodiﬂuoromethane

A 56 ml aliquot of a 0.88 M HCF₂CdX reagent (49 mmol) in

50 ml DMF was syringed into a three-neck ﬂask equipped with

septum, stir bar and a dry ice/isopropyl alcohol condenser (with

nitrogen inlet). Then, 1.5 g (75 mmol) of D₂O was added

dropwise to the cadmium reagent solution, and the reaction

mixture was stirred for 2 h at RTand then heated at 50 8C for an

additional 2 h. The dry ice/isopropyl alcohol condenser was

replaced by a ﬂash distillation head equipped with a 100 ml

receiving ﬂask (cooled in liquid N₂) and the product distilled

under full vacuum at 50 8C. Trap-to-trap distillation gave 1.73 g

(65%) of CF₂HD. ¹⁹F NMR (CCl₄) (ppm): d ꢀ143 (dt,

²J_FD= 7.8 Hz, ²J_FH= 50.8 Hz); ¹H NMR (CCl₄) (ppm) 5.6 (t);

²D NMR (CCl₄. d₆-acetone ref.): 3.6 ppm (t); MW (expt.):

53.1 g/mol, calculated. 53.02 g/mol; GC–MS, m/z (relative

intensity): 53 (12.1), 52 (100.0), 51 (43.1), 50 (5.4). IR (6 mm

Hg): 2988 (w), 2232 (w), 1367 (w), 1113 (s).

A three-neck 500 ml ﬂask ﬁtted with a septum, stir bar, and a

400 cm isopropyl alcohol condenser with a nitrogen inlet was

charged which 250 ml of dry DMFand 84.3 g (0.75 mol) of acid-

washed cadmium metal. A low temperature probe of a Neslab

Cryocool 100 was employed to cool the isopropyl alcohol to

ꢀ78 8C. Bromodiﬂuoromethane (50 g, 0.38 mol)wascondensed

into the reaction mixture, and the solution was heated for 5–7

days at 50–55 8C. Completion of the reaction was determined via

¹⁹F NMR analysis of the reaction mixture. Typically 65–75% ¹⁹

F

NMR yields were obtained in 5 days with a mono:bis ratio of

75:25. HCF₂CdBr; ¹⁹F NMR: ꢀ117.7 ppm, J(¹¹³CdF) =

2

341.9 Hz, J(¹¹¹CdF) = 327.0 Hz, J_HF= 43.0 Hz; ¹¹³Cd NMR:

253.3 ppm, J(¹¹³CdH) = 115.6 Hz. (HCF₂)₂Cd; ¹⁹F NMR:

ꢀ119.2 ppm, J(¹¹³CdF) = 292.4 Hz, J(¹¹¹CdF) = 277.8 Hz,

²J_HF= 43.2 Hz; ¹¹³Cd NMR: 228.6 ppm, J(¹¹³CdH) = 75.9 Hz

(see Ref. [31] for a detailed picture).

3.5. Iodination of diﬂuoromethylcadmium

3.2.2. From iododiﬂuoromethane

A 25 ml ﬂask equipped with a septum, stir bar and dry ice/

isopropyl alcohol condenser (with nitrogen inlet) was charged

with 10 ml of dry DMF and 1.7 g (15 mmol) of acid-washed

cadmium metal. Iododiﬂuoromethane (1.6 g, 9.2 mmol) was

condensed into the reaction mixture. After an induction period

(ꢂ10 min) a slight exotherm was observed. After the reaction

mixture was stirred at room temperature for 1 h, ¹⁹F NMR

analysis indicated a 91% yield of the diﬂuoromethylcadmium

reagent. The ¹⁹F NMR data was consistent with that obtained

with the diﬂuoromethylcadmium reagent prepared from

HCF₂Br.

A 62 ml aliquot of a 0.81 M HCF₂CdX reagent (50 mmol) in

DMF was syringed into a three-neck ﬂask equipped with a

septum, stir bar and dry/ice isopropyl condenser (with nitrogen

inlet). The solution was cooled in an ice bath and 25.4 g

(100 mmol) of I₂was added in small portions from a solids

addition tube. Then the reaction mixture was warmed and

stirred at RT for 2 h. The condenser was replaced by a ﬂash

distillation head, and the product distilled under full vacuum at

50 8C, trap-to-trap distillation gave 8.5 g (96%) of HCF₂I. ¹⁹

F

2

NMR (d₆-acetone) (ppm): d ꢀ67.5 (d, J_FH= 56.2 Hz); ¹H

NMR (d₆-acetone) (ppm): d 8.16 (t); MW (expt.): 176.4 g/mol,

calculated 177.9 g/mol; GC–MS, m/z (relative intensity): 178

(60.6), 159 (21.9), 140 (3.0), 127 (100.0), 51 (33.7). IR (6 mm

Hg): 3015 (w), 1251 (m), 1090 (s), 503 (m).

3.2.3. From bromodeuterodiﬂuoromethane

Following the procedure outlined in Section 3.2.1, DCF₂Br

(6.6 g, 50 mol), 5.7 (100 mmol) of acid-catalyzed cadmium

metal and 50 ml dry DMF gave a 96% (¹⁹F NMR) yield of the

deuterateddiﬂuoromethylcadmium reagent after 4 days at 60 8C;

mono:bis ratio ꢂ3/1. DCF₂CdBr; ¹⁹F NMR: ꢀ120.0 ppm,

3.6. General procedure for the allylation of

diﬂuoromethylcadmium

2

J(¹¹³CdF) = 341.9 Hz; J(¹¹¹CdF) = 328.9 Hz, J_DF= 6.8 Hz;

A 67 ml aliquot of a 0.75 M diﬂuoromethylcadmium reagent

(50 mmol) in DMF was syringed into a dry three-neck 100 ml

ﬂask equipped with a septum, stir bar and a dry ice/isopropyl

alcohol condenser (with a nitrogen inlet). The reaction ﬂask

was cooled in an ice water bath and then 6.1 g (50 mmol) of

allyl bromide was added dropwise via a syringe. The reaction

mixture was warmed and stirred for 4 h at RT. The condenser

was replaced by a ﬂash distillation head equipped with a 100 ml

receiving ﬂask (cooled in liquid N₂). The product was ﬂash

distilled under full vacuum, then trap-to-trap distilled to give

3.9 g (85%) of 4,4-diﬂuoro-1-butene, GLPC = 100%. ¹⁹F NMR

(CDCl₃) (ppm): d ꢀ115.3 (dt, ²J_FH= 56.5 Hz, ³J_FH= 18.3 Hz);

¹H NMR (360 MHz) (CDCl₃) (ppm): d (CF₂H) = 6.09 (tt,

¹¹³Cd NMR: 262.0 ppm. (DCF₂)₂Cd: ¹⁹F NMR: ꢀ121.6 ppm,

2

J(¹¹³CdF) = 293.4 Hz, J(¹¹¹CdF) = 280.3 Hz, J_DF= 6.8 Hz;

¹¹³Cd NMR: 234.7 ppm, J(¹¹³CdD) = 11.4 Hz.

3.3. Preparation of the diﬂuoromethylzinc reagent

A 50 ml ﬂask ﬁtted with a septum, stir bar and a 400 cm

isopropyl alcohol condenser (with a nitrogen inlet) was charged

with 25 ml of dry DMF and 1.6 g (25 mmol) of acid-washed

zinc metal. With cooling of the isopropyl alcohol to ꢀ78 8C

with a Neslab Cryocool 100 3.3 g (25 mmol) of HCF₂Br was

condensed into the reaction mixture. The suspension was

heated for 5 days at 60 8C to give 73–85% of the

diﬂuoromethylzinc reagent, as determined by ¹⁹F NMR

analysis; mono:bis ratio of 88:12. HCF₂ZnBr: ¹⁹F

3

²J_FH= 56.5 Hz, J_HH= 4.3 Hz) d (CH₂) 2.61 (tdddd, J_FH

=

3

4

18.3 Hz, J_HH= 4.3 Hz, J_HH= 6.9 Hz, J_HH= 1 Hz, J_HH

1 Hz), d (vinyl H) = 5.76 (ddt, ³J_HH= 17.3 Hz, ³J_HH= 10.3 Hz,

2

3

NMR:ꢀ125.9 ppm (d, J_HF= 43.9 Hz); (HCF₂)₂Zn: ¹⁹F

³J_HH= 6.9 Hz), d (vinyl H) 5.22 = (ddd, J_HH= 10.3 Hz,

2

4

NMR: ꢀ126.0 ppm (d, J_HF) = 43.9 Hz.

²J_HH= 1.2 Hz, J_HH= 1 Hz),

d

(vinyl H) = 5.25 (ddd,

1208

D.J. Burton, G.A. Hartgraves / Journal of Fluorine Chemistry 128 (2007) 1198–1215

2

4

³J_HH= 17.3 Hz, J_HH= 1.2 Hz, J_HH= 1 Hz); ¹³C NMR

3.6.3. Reaction of diﬂuoromethylcadmium with 3-chloro-1-

butene

1

(CDCl₃) (ppm): 116.5 (t, J_CF= 238.0 Hz), 38.0 (t,

²J_CF= 21.2 Hz), 128.9 (t, J_CF= 6.6 Hz) 120.2 (s). GC–MS,

3

A 86 ml aliquot of a 0.58 M diﬂuoromethylcadmium reagent

(50 mmol)inDMFwasreactedwith3.6 g(40 mmol)of3-chloro-

1-butene. The reaction mixture was stirred at RT for 48 h, then

ﬂash distilled, an equal volume of ice water added to the ﬂash

distillate, the organiclayerseparated andwashed with2ꢃ 100 ml

m/z (relative intensity): 92 (50.3), 77 (28.2), 73 (50.4), 72

(19.7), 64 (14.9), 57 (13.1), 53 (28.0), 51 (100.0), 50 (22.7), 46

(28.2), 45 (13.3), 41 (19.7). IR (6 mm Hg): 3097 (w), 2977 (m),

1654 (w), 1648 (w), 1435 (w), 1400 (w), 1394 (m), 1389 (w),

1123 (s), 1077 (s), 1004 (m), 929 (m), 875 (w).

˚

of water and dried over 4 A molecular sieves. The crude product

was distilled (bp 45–47 8C) to give 1.9 g (45%) of a mixture that

contained 92.4% (E)-5,5-diﬂuoro-2-pentene (E/Z = 87:13) and

6.9% 4,4-diﬂuoro-3-methyl-1-butene (as determined by GLPC

analysis). NMR (E-CH₃CH CHCH₂CF₂H): ¹⁹F NMR (neat)

(ppm): d ꢀ116.3 (dt, ²J_FH= 56.9 Hz, ³J_FH= 17.4 Hz), ¹H NMR

(360 MHz) (CDCl₃) (ppm): d (CF₂H) = 5.78 (tt, ²J_HH= 56.9 Hz,

3.6.1. Reaction of diﬂuoromethylcadmium with 3-chloro-

3,3-dideutero-1-propene

Similarly, a 56 ml aliquot of a 0.88 M diﬂuoromethylcad-

mium reagent (49 mmol) in DMF was reacted with 2.6 g

(33.3 mmol) of 3-chloro-3,3-dideutero-1-propene. After trap-

to-trap distillation, 1.7 g (55%) of a 74:26 mixture of 1,1-

³J_HH= 4.6 Hz),

d

(CH₂) 2.51 (tddd, ³J_FH= 17.4 Hz,

3

4

dideutero-4,4-diﬂuoro-1-butene

diﬂuoro-1-butene was obtained. The isomeric ratio was

and

3,3-dideutero-4,4-

³J_HH= 7.4 Hz, J_HH= 4.6 Hz, J_HH= 1.2 Hz), d 5.38 ( CH,

3

4

dtq, J_HH= 15.9 Hz, J_HH= 7.4 Hz, J_HH= 1.7 Hz), d 5.64

2

3

4

determined by integration of the D NMR spectrum of the

( CH, dt, J_HH= 15.9 Hz, J_HH= 1.2 Hz), d 1.70 (CH₃, dd,

³J_HH= 6.4 Hz, ⁴J_HH= 1.7 Hz); ¹³C NMR (neat) (ppm): 117.5 (t,

isolated mixture. NMR: D₂C CHCH₂CF₂H: ¹⁹F NMR

(CDCl₃) (ppm): d ꢀ116.1 (dt, ²J_FH= 56.7 Hz, ³J_FH= 17.8 Hz);

¹H NMR (360 MHz) (CDCl₃) (ppm): d (CF₂H) = 5.97 (tt,

¹J_CF= 239.1 Hz), 38.5 (t, J_CF= 21.8 Hz), 121.9 (t, J_CF

=

F

2

3

6.6 Hz), 131.7 (s), 18.1 (s). NMR(H₂C CHCH(CF₂H)CH₃): ¹⁹

²J_FH= 56.7 Hz, ³J_HH= 4.4 Hz),

d

(CH₂) = 2.62 (tdd,

(vinyl

H) = 5.79 (dm, J_HH= 7.0 Hz); D NMR (CDCl₃) (ppm): d

NMR (CDCl₃) (ppm): d^a= ꢀ123.9 (ddd), d ꢀ122.2 (ddd (AB),

3

2

3

³J_FH= 17.8 Hz, J_HH= 4.4 Hz, J_HH= 7.0 Hz),

d

²J_FF= 276.6 Hz, J_FH= 56.8 Hz, J_FH= 14.6 Hz), ¹H NMR

3

2

(360 MHz) (CDCl₃) (ppm): d 5.62 (CF₂H, dt, J_FH= 56.8 Hz,

3

ꢀ2.10 (s), d ꢀ1.94 (d, J_HD= 0.5 Hz). GC–MS, m/z (relative

³J_HH= 14.6 Hz), d 2.56 (–CH(CH₃)CF₂H, m), d 1.12 (CH₃, d,

3

intensity): 94 (100.0), 79 (10.0), 78 (20.1), 77 (36.6), 75 (19.2),

55 (14.5), 51 (30.5), 46 (10.4), 43 (92.9), 41 (26.9), 40 (37.4).

NMR: H₂C CHCD₂CF₂H: ¹⁹F NMR (CDCl₃) (ppm): d ꢀ116.3

³J_HH= 7.0 Hz), d 5.78 ( CH, ddd, J_HH= 15.5 Hz, J_HH

=

3

10.2 Hz, J_HH= 7.3 Hz), d 5.18 ( CH, dd, J_HH= 10.2 Hz,

3

²J_HH= 1.1 Hz), d 5.20 ( CH, dd, J_HH= 15.5 Hz, J_HH

=

3

2

(dp, J_FH= 56.6 Hz, J_FD= 2.6 Hz), ¹H NMR (360 MHz)

1.1 Hz), ¹³C NMR (neat) (ppm): 119.0 (t, J_CF= 242.6 Hz),

2

3

1

2

3

(CDCl₃) (ppm): d (CF₂H) = 5.97 (tm, ²J_FH= 56.6 Hz), d (vinyl

42.8 (t, J_CF= 20.2 Hz), 12.5 (t, J_CF= 4.5 Hz), 136.0 (t,

³J_CF= 5.5 Hz), d 118.0 (s).

3

H) = 5.79 (m), d ( CH₂) = 5.21 (dm, J_HH= 10.4 Hz), d

3

2

( CH₂) = 5.25 (dd, J_HH= 17.4 Hz, J_HH= 1.8 Hz); D NMR

3

(CDCl₃) (ppm): (d ꢀ4.71 CD₂, tdd, J_FD= 2.6 Hz),

3.6.4. Reaction of diﬂuoromethylcadmium with (E)-1-

chloro-2-butene

3

³J_HH= 1 Hz, J_HH= 1). ¹³C NMR (mixture) (CDCl₃) (ppm):

1

d (CF₂H) = 117.4 (t, J_CF= 238.3 Hz), d (CH₂) = 39.1 (t,

A 74 ml aliquot of a 0.68 M diﬂuoromethylcadmium reagent

(50 mmol) in DMF was reacted with 4.4 g (49 mmol) of (E)-1-

chloro-2-butene. The reaction mixture was stirred at RT for

24 h and worked-up as described previously. After trap-to-trap

distillation 3.2 g (62%) of a 63:37 mixture (determined by

GLPC) of 4,4-diﬂuoro-3-methyl-1-butene and (E)-5,5-diﬂuoro-

2-pentene was obtained, GLPC purity = 92%. Spectroscopic

data was identical to the data described in Section 3.6.3 for 3-

chloro-1-butene.

²J_CF= 19.2 Hz), d (vinyl C) = 129.5 (t, J_CF= 6.9 Hz), d

3

( CD₂) = 120.5 (p). GC–MS, m/z (relative intensity): 94

(4.1), 80 (18.5), 78 (55.3), 45 (11.2), 43 (100.0), 41 (38.1), 40

(49.9).

3.6.2. Reaction of diﬂuoromethylcadmium with 3-chloro-2-

methyl-1-propene

A 64 ml aliquot of a 0.78 M diﬂuoromethylcadmium reagent

(50 mmol) in DMF was reacted with 4.3 g (48 mmol) of 3-

chloro-2-methyl-1-butene. After trap-to-trap distillation, 2.9 g

(68%) of 4,4-diﬂuoro-2-methyl-1-butene was obtained, GLPC

purity = 95%. ¹⁹F NMR (CDCl₃) (ppm): d ꢀ113.9 (dt,

²J_FH= 56.6 Hz, ³J_FH= 17.2 Hz); ¹H NMR (360 MHz) (CDCl₃)

3.6.5. Reaction of diﬂuoromethylcadmium with 1-chloro-3-

methyl-2-butene

An 82 ml aliquot of a 0.61 M diﬂuoromethylcadmium

reagent (50 mmol) in DMF was reacted with 3.7 g (35 mmol) of

1-chloro-3-methyl-2-butene at 0 8C. The reaction mixture was

stirred overnight at RT, then ﬂash distilled at 80 8C. The

distillate was washed (in a separatory funnel) with an equal

volume of ice water; the organic layer separated and washed

2

3

(ppm): d (CF₂H) = 5.86 (tt, J_FH= 56.6 Hz, J_HH= 4.7 Hz), d

(CH₂) = 2.54 (td, ³J_FH= 17.2 Hz, ³J_HH= 4.7 Hz),

(CH₃) = 1.80 (s), d ( CH₂), 5.88 (s), 5.95 (s). ¹³C NMR (neat)

d

1

2

(ppm): 117.4 (t, J_CF= 239.8 Hz), 43.1 (t, J_CF= 21.4 Hz),

3

138.4 (t, J_CF= 5.7 Hz), 23.1 (s), 115.6 (s). GC–MS, m/z

˚

with water (2ꢃ 100 ml), dried over 4 A molecular sieves, and

(relative intensity): 106 (9.3), 91 (4.0), 85 (4.1), 66 (3.5), 64

(11.9), 51 (100.0), 46 (14.4). IR (6 mm Hg): 3094 (w), 2980

(m), 2935 (w), 1659 (w), 1450 (w), 1392 (m), 1214 (w), 1123

(s), 1079 (s), 1047 (w), 903 (m).

distilled (by 88–90 8C/atm. press.) to give 2.9 g (68%) of a

mixture which contained 8.3% H₂C C(CH₃)CH CH₂, 3.1%

4,4-diﬂuoro-3-3-dimethyl-1-butene and 88.6% 5,5-diﬂuoro-2-

methyl-2-pentene (as determined by GLPC analysis). NMR

D.J. Burton, G.A. Hartgraves / Journal of Fluorine Chemistry 128 (2007) 1198–1215

1209

(CF₂HCH₂CH C(CH₃)₂: ¹⁹F NMR (CDCl₃) (ppm): d ꢀ115.9

d^b= ꢀ119.3

(ddd,

²J_FF= 277.8 Hz,

²J_FH= 56.3 Hz,

2

3

(dt, J_FH= 57.0 Hz, J_FH= 17.6 Hz); ¹H NMR (360 MHz)

³J_FH= 15.5 Hz). (AB), ¹H NMR (360 MHz) (CDCl₃) (ppm): d

2

(CDCl₃) (ppm): d (CF₂H) = 5.72 (tt, J_FH= 57.0 Hz, J_HH

3

=

4.6 Hz), d (CH₂) = 2.53 (tdd, J_FH= 17.8 Hz, J_HH= 7.4 Hz,

(CF₂H) 5.92 (td, ²J_FH= 56.3 Hz, J_HH= 15.5 Hz), d (CH) 3.72

3

(m), d (aromatic H)7.29 (m), d ( CH) 6.08 (ddd, ³J_HH= 17.3 Hz,

³J_HH= 4.6 Hz),

d

( CH) = 5.12 (tqq, ³J_HH= 7.4 Hz,

³J_HH= 10.4 Hz, ³J_HH= 7.5 Hz),

d

( CH) 5.30 (d,

4

3

⁴J_HH= 1 Hz, J_HH= 1 Hz), d (–CH₃) = 1.74 (d, J_HH= 1 Hz),

³J_HH= 10.4 Hz), d ( CH) 5.20 (d, J_HH= 17.2 Hz); ¹³C NMR

(neat) (ppm):117.4(t, ¹J_CF= 244.4 Hz), 54.2(t, ²J_CF= 20.5 Hz),

133.4 (t, ³J_CF= 5.0 Hz), 119.5 (s), 136.6 (s), 129.0 (s), 129.2 (s),

127.9 (s). GC–MS, m/z (relative intensity): 168 (10.8), 117

(100.0), 116 (11.9), 115 (60.6), 91 (24.1). IR (CCl₄): 3089 (m),

3066 (m), 3034 (m), 2972 (m), 1642 (m), 1603 (m), 1495 (m),

1455 (m), 1377 (m), 1126 (s), 1077 (s), 1058 (s), 991 (m), 930

(m).

d (–CH₃) = 1.65 (d, J_HH= 1 Hz); ¹³C NMR (neat) (ppm):

4

1

2

116.8 (t, J_CF= 239.9 Hz), 33.6 (t, J_CF= 21.8 Hz), 113.9 (t,

³J_CF= 6.4 Hz), 137.4 (s), 35.8 (s) 18.0 (s). GC–MS

[(CH₃)₂C CHCH₂CF₂H] m/z (relative intensity): 120 (27.1),

69 (100.0), 59 (14.7), 53 (17.6), 51 (31.3), 41 (93.7). GC–MS,

m/z (CF₂HC(CH₃)₂CH CH₂) (relative intensity): 120 (8.9), 84

(11.7), 77 (19.4), 69 (100.0), 67 (13.5), 65 (14.3), 59 (12.5), 53

(23.2), 51 (31.4), 49 (22.4), 41 (69.1). GC–MS

(H₂C C(CH₃)CH CH₂): m/z (relative intensity): 68 (65.4),

67 (100.0).

3.6.8. Reaction of diﬂuoromethylcadmium with (E)-3-

chloro-1-phenyl-1-propene

A 75 ml aliquot of a 0.80 M diﬂuoromethylcadmium

reagent (60 mmol) in DMF was reacted with 7.6 g (50 mmol)

of (E)-3-chloro-1-phenyl-1-propene. The reaction mixture

was stirred for 53 h at RT, steam distilled and worked up as

described for (E)-3-bromo-1-phenyl-1-propene to give

5.2 g (62%) of a 56:44 mixture of 4,4-diﬂuoro-3-phenyl-1-

butene and (E)-4,4-diﬂuoro-1-phenyl-1-butene (as deter-

mined by GLPC analysis). Spectroscopic data was identical

to the isomers prepared from (E)-3-bromo-1-phenyl-1-

propene.

3.6.6. Reaction of diﬂuoromethylcadmium with 3-chloro-3-

methyl-1-butene

A 80 ml aliquot of a 0.57 M diﬂuoromethylcadmium reagent

(46 mmol) in DMF was reacted with 4.7 (45 mmol) of 3-

chloro-3-methyl-1-butene. The reaction mixture was stirred for

several hours at RT, ﬂash distilled, washed with water as

described in Section 3.6.3 and the crude product distilled (bp

88–90 8C/atm. press.) to give 3.4 g (63%) of a mixture that

contained 4.8% (CH₂C(CH₃)CH CH₂), 14.7% 4,4-diﬂuoro-

3,3-dimethyl-1-butene and 77.9% 5,5-diﬂuoro-2-methyl-2-

pentene. Spectroscopic data were identical to the compounds

described in Section 3.6.5.

3.6.9. Reaction of diﬂuoromethylcadmium with propargyl

chloride

Via the general procedure utilized for allyl halides, a 66 ml

3.6.7. Reaction of diﬂuoromethylcadmium with (E)-3-

bromo-1-phenyl-1-propene

aliquot of

a

0.76 M diﬂuoromethylcadmium reagent

(50 mmol) in DMF was reacted with 3.7 g (49 mmol) of

propargyl chloride. The reaction mixturewas stirred at RT for 3

days and heated at 50 8C for an additional 7 days. After ﬂash

distillation and trap-to-trap distillation, 1.8 g (41%) of a

mixture, which contained 80% 4,4-diﬂuoro-1,2-butadiene,

4.3% 4,4-diﬂuoro-1-butyne, 11% unreacted propargyl chlor-

A 72 ml aliquot of a 0.54 diﬂuoromethylcadmium reagent

(39 mmol) in DMF was reacted with 7.7 g (38.8 mmol) of (E)-3-

bromo-1-phenyl-1-propene. The reaction mixture was stirred

overnightatRT, steamdistilled, the organiclayerseparated,dried

˚

over 4 A molecular sieves to give 5.7 g (87%) of a 47.6:52.3

mixture of 4,4-diﬂuoro-3-phenyl-1-butene and (E)-4,4-diﬂuoro-

1-phenyl-1-butene (as determined by GLPC). The regioisomers

were separated by spinning band distillation (1 ft column) to give

two major fractions with GLPC purity 98%: bp 81–82 8C/

0.5 mm (4,4-diﬂuoro-3-phenyl-1-butene) and bp 101–103 8C/

0.5 mm [(E)-4,4-diﬂuoro-1-phenyl-1-butene]. NMR: (E)-4,4-

diﬂuoro-1-phenyl-1-butene): ¹⁹F (CDCl₃) (ppm): d ꢀ116.1 (dt,

²J_FH= 56.6 Hz, ³J_FH= 17.2 Hz); ¹H NMR (360 MHz) (CDCl₃)

ide and 5% of two other impurities was obtained. NMR

ꢄ

(CF₂HCH

CH₂): ¹⁹F NMR (CDCl₃) (ppm): d ꢀ107.9 (ddt,

3

5

²J_FH= 56.2 Hz, J_DH= 7.3 Hz, J_FH= 7.6 Hz); ¹H NMR

2

(360 MHz) (CDCl₃) (ppm): d (CF₂H) = 6.14 (tdt, J_FH

=

56.2 Hz, J_HH= 6.2 Hz, J_HH= 1 Hz), d (CF₂HCH ) = 5.41

3

5

3

(ttd, J_FH= 7.3 Hz, J_HH= 6.2 Hz, J_HH= 6.8 Hz), d ( CH₂)

4

5.11 (tdd, J_FH= 7.6 Hz, J_HH= 6.8 Hz, J_HH= 1 Hz); ¹³C

5

4

3

1

NMR (neat) (ppm): 115.3 (t, J_CF= 236.1 Hz), 88.4 (t,

2

3

(ppm): d (CF₂H) = 5.84 (tt, J_FH= 56.6 Hz, J_HH= 4.5 Hz), d

²J_CF= 29.0 Hz), 211.1 (t, J_CF= 12.3 Hz), 79.7 (s). GC–MS,

m/z (relative intensity): 90 (44.4), 71 (25.9), 70 (15.5), 51

(100.0), 50 (26.9).

3

(CH₂) = 2.73 (tddd, J_FH= 17.2 Hz, J_HH= 7.3 Hz, J_HH

3

=

4.5 Hz, J_HH= 1.4 Hz), d 6.13 ( CH, dt, J_HH= 15.9 Hz,

4

3

³J_HH= 7.3 Hz), d 6.54 ( CH, d, J_HH= 15.9 Hz), d 7.29 (m).

1

¹³C NMR (neat) (ppm): 116.8 (t, J_CF= 240.0 Hz), 38.1 (t,

3.6.10. Reaction of diﬂuoromethylcadmium with 3-tosyl-1-

butyne

3

²J_CF= 21.9 Hz), 119.8 (t, J_CF= 6.7 Hz), 135.5 (s), 137.2 (s),

126.7 (s), 128.9 (s), 128.0 (s). GC–MS, m/z (relative intensity):

168 (39.3), 117 (100.0), 116 (11.2), 115 (54.5), 91 (17.8). IR

(CCl₄): 3085 (w), 3061 (w), 3029 (w), 2917 (m), 1495 (m), 1450

(m), 1427 (m), 1397 (m), 1382 (m), 1215 (m), 1117 (s), 1055 (s),

1025 (s), 968 (s), 926 (w), 887 (m). NMR: (4,4-diﬂuoro-3-

phenyl-1-butene): ¹⁹F NMR (CDCl₃) (ppm): d^aꢀ121.5 (ddd),

A 0.5 ml aliquot of a 0.84 M diﬂuoromethylcadmium

reagent (0.42 mmol) was added to a 5 mm NMR tube, followed

by addition of 0.094 g (0.42 mmol) of 3-tosyl-1-butyne and

10 ml of C₆H₅CF₃. After 7 h at RT, an 87% yield of 1,1-

diﬂuoro-2,3-pentadiene was determined by ¹⁹F NMR analysis

of the reaction mixture. See Section 3.7.9 for NMR data.

1210

D.J. Burton, G.A. Hartgraves / Journal of Fluorine Chemistry 128 (2007) 1198–1215

3

3.6.11. Reaction of diﬂuoromethylcadmium with 3-chloro-

1-butyne

³J_HH= 4.5 Hz), d (CH₂) 2.69 (tdq, J_FH= 15.6 Hz, J_HH

=

4.5 Hz, J_HH= 2.6 Hz), d (CH₃) 1.80 (t, J_HH= 2.6 Hz); ¹³C

3

5

1

NMR (neat) (ppm): 115.1 (t, J_CF= 241.0 Hz), 25.6 (t,

A 0.5 ml aliquot of a 0.76 M diﬂuoromethylcadmium

reagent (0.38 mmol) in DMF was reacted with 0.034 g

(0.38 mmol) of 3-chloro-1-butyne in an NMR tube (as

described above) for 2 days to give an 84% ¹⁹F NMR yield

of 1,1-diﬂuoro-2,3-pentadiene. See Section 3.7.9 for NMR

data.

²J_CF= 26.5 Hz), 69.9 (t, J_CF= 9.7 Hz), 79.3 (s), 14.9 (s).

3

GC–MS, m/z (relative intensity): 104 (88.8), 103 (10.6), 84

(14.2), 83 (18.3), 77 (15.7), 65 (11.7), 59 (10.4), 57 (14.3), 53

(100.0), 52 (18.7), 51 (54.3), 50 (23.5), 49 (16.1).

3.6.14. Reaction of diﬂuoromethylcadmium with 1-chloro-

1-ethynylcyclohexane

3.6.12. Reaction of diﬂuoromethylcadmium with 3-bromo-

3-methyl-1-butyne

A 70 ml aliquot of a 0.71 M diﬂuoromethylcadmium reagent

(50 mmol) in DMF was reacted with 5.7 g (40 mmol) of 1-

chloro-1-ethynylcyclohexane as described above for 3-bromo-3-

methyl-1-butyne. Distillation (bp 61–73 8C/20 mm) gave three

fractions (combined wt. of 3.4 g) which contained 52%, 71% and

94%of4,4-diﬂuoro-1-pentamethylene-1,2-propadieneand48%,

29% and 6% of 1-ethynyl-1-cyclohexene, respectively. GC–MS,

m/z (relative intensity) for (CH₂)₅C C CHCF₂H: 158(100.0)).

GC–MS, m/z (relative intensity) for c-C₆H₉CBBCH: 106 (62.9),

105 (29.5), 91 (100). See Section 3.7.12 for NMR data of 4,4-

diﬂuoro-1-pentamethylene-1,2-propadiene.

An 86 ml aliquot of a 0.70 M diﬂuoromethylcadmium

reagent (60 mmol) in DMF was reacted with 10.0 g (60 mmol)

of 3-bromo-3-methyl-1-butyne at 0 8C in a three-neck ﬂask

ﬁtted with a septum, stir bar and a nitrogen tee. The reaction

mixture was stirred overnight at RT. After ﬂash distillation the

distillate was washed with an equal volume of ice water, the

organic layer separated and washed with 2ꢃ 100 ml of water

˚

and dried over 4 A molecular sieves. Distillation gave 3.80 g

(64%), bp 77–79 8C, of 1,1-diﬂuoro-4-methyl-2,3-pentadiene,

GLPC purity = 100%. ¹⁹F NMR (CDCl₃) (ppm): d ꢀ107.4 (dd,

3

²J_FH= 56.6 Hz, J_FH= 6.4 Hz); ¹H NMR (360 Hz) (CDCl₃)

(ppm): d (CF₂H) 6.02 (td, ²J_FH= 56.6 Hz, ³J_HH= 6.3 Hz), d (–

3.6.15. Reaction of diﬂuoromethylcadmium with 1,4-

dichloro-2-butyne

3

CH ) 5.21 (tdsept, J_FH= 6.4 Hz, J_HH= 6.3 Hz, J_HH

3

=

5

3.0 Hz), d ( C(CH₃)₂) 1.75 (d, J_HH= 3.0 Hz); ¹³C NMR

A 0.5 ml aliquot of a 0.67 M diﬂuoromethylcadmium

reagent (0.34 mmol) in DMF was reacted with 0.021 g

(0.17 mmol) of 1,4-dichloro-2-butyne in a 5 mm NMR tube.

After 70 h at RT, a 52% yield of bis-(2,3-diﬂuoromethyl)-1,3-

butadiene was determined by ¹⁹F NMR of the reaction mixture.

See Section 3.7.13 for NMR data.

1

(neat) (ppm): 115.2 (t, J_CF= 236.2 Hz), 86.6 (t, J_CF

2

=

3

28.9 Hz), 204.4 (t, J_CF= 12.4 Hz), 101.2 (s), 19.3 (s). GC–

MS, m/z (relative intensity): 118 (51.0), 103 (17.8), 97 (12.1),

83 (18.9), 79 (11.8), 77 (32.4), 67 (100.0), 65 (27.3), 57 (12.0),

51 (47.0), 50 (14.2), 41 (55.9). IR (CCl₄): 2989 (m), 2948 (m),

2916 (m), 2859 (w), 1978 (m), 1449 (m), 1421 (m), 1367 (m),

1329 (m), 1121 (s), 1055 (s), 1021 (s).

3.7. In situ preparation of the diﬂuoromethylcopper

reagent

3.6.13. Reaction of diﬂuoromethylcadmium with 1-bromo-

2-butyne

A 50 ml aliquot of the 1.13 M diﬂuoromethylcadmium

reagent (56.5 mmol) in DMF was added to a 100 ml three-neck

ﬂask equipped with septum, stir bar and dry ice/isopropyl

alcohol condenser (with nitrogen inlet). The solution was

cooled to ꢀ60 8C and then 5.6 g (56.6 mmol) of CuCl was

added in one portion. The solution was slowly warmed to RT

over 4 h. 1,1,2,2-Tetraﬂuoroethane and cis-diﬂuoroethene were

obtained in a 77:23 ratio, as determined by ¹⁹F NMR analysis of

the reaction mixture. Flash distillation followed by trap-to-trap

distillation gave 2.85 g of a mixture which contained

CF₂HCF₂H and cis-CFH CFH. GC–MS, m/z (relative inten-

sity) of the mixture: 102 (1.5), 101 (4.4), 83 (66.1), 82 (7.4), 64

(36.9), 63 (11.9), 51 (100.0), 45 (39.9), 44 (29.6). The chemical

shift and coupling constants reported by Stone for cis-

CFH CFH are consistent with those observed in our spectrum

[53], and the ¹⁹F NMR spectrum reported by Ellerman et al.

match our observed spectral data for CF₂HCF₂H [54].

A 94 ml aliquot of a 0.64 M diﬂuoromethylcadmium reagent

(60 mmol) in DMF was reacted with 6.7 g (50 mmol) of 1-

bromo-2-butyne as described above for 3-bromo-3-methyl-1-

butyne. After stirring overnight at RT, the reaction mixture was

worked-up as described in the previous experiment to give 3.6 g

(69%, bp 53–56 8C, of an isomeric mixture (77.6:22.4) of 4,4-

diﬂuoro-3-methyl-1,2-butadiene and 5,5-diﬂuoro-2-pentyne (as

determined by GLPC analysis). NMR: (CF₂HC(CH₃) C CH₂):

2

¹⁹F NMR (CDCl₃) (ppm): d = ꢀ114.3 (dt, J_FH= 56.5 Hz,

⁵J_FH= 6.8 Hz); ¹H NMR (360 MHz) (CDCl₃) (ppm): d (CF₂H)

2

5

6.09 (t, J_FH= 56.5 Hz), d (–CH₃) 1.77 (td, J_HH= 3.2 Hz,

⁴J_HH< 1 Hz), d ( CH₂) 4.97 (qt, ³J_HH= 3.2 Hz, ⁵J_FH= 6.8 Hz);

¹³C NMR (neat) (ppm): 116.1 (t, J_CF= 239.3 Hz), 95.9 (t,

1

²J_CF= 26.2 Hz), 9.9 (t, ³J_CF= 9.8 Hz), 208.4 (s), 77.7 (s). GC–

MS, m/z(relativeintensity):104(100.0), 103(16.8), 83(14.7), 77

(11.6), 57 (13.7), 53 (57.9), 51 (48.4), 50 (21.0). IR (CCl₄)

(mixture of isomers): 2986 (w), 2935 (w), 2865 (w), 1989 (w),

1962 (w), 1685 (w), 1463 (w), 1441 (w), 1385 (m), 1367 (w),

1228 (w), 1079 (s), 1063 (m), 1040 (m), 1026 (vs), 993 (w), 861

(m). NMR: (CF₂HCH₂CBBCCH₃): ¹⁹F NMR (CDCl₃) (ppm): d

In a separate NMR tube experiment, the diﬂuoromethyl-

cadmium reagent in DMF was reacted with CuBr or CuCl at

ꢀ55 8C to afford HCF₂Cu^ain >90% yield, d ꢀ114.6 ppm (d,

²J_FH= 44.0 Hz). When the temperature of the NMR tube was

increased, a second HCF₂Cu^breagent appeared in the ¹⁹F NMR

2

3

ꢀ115.7 (dt, J_FH= 56.4 Hz, J_FH= 15.6 Hz); ¹H NMR

2

(360 MHz) (CDCl₃) (ppm): d (CF₂H) 5.83 (tt, J_FH= 56.4 Hz,

2

spectrum at d ꢀ116.4 (d, J_HF= 51.3 Hz). At temperatures

D.J. Burton, G.A. Hartgraves / Journal of Fluorine Chemistry 128 (2007) 1198–1215

1211

>ꢀ30 8C the copper reagents began to decompose rapidly to

CF₂HCF₂H and cis-CFH CFH. After 5 h at RT, no CF₂HCu^a

remained and <13% of CF₂HCu^bremained.

(50 mmol) of 3-chloro-3-methyl-1-butene were reacted

at ꢀ50 8C (as described previously). The reaction mixture

was slowly warmed to RT over 5 h. Isolation and distillation

(as described above) gave 4.9 g (76%) (bp 88–90 8C)

3.7.1. Reaction of diﬂuoromethylcopper with 3-chloro-3,3-

dideutero-1-propene

of

5,5-diﬂuoro-2-methyl-2-pentene,

GLPC

purity =

100%. ¹⁹F, ¹H and ¹³C NMR data were identical to the

product formed from the reaction of HCF₂CdX with

(CH₃)₂C(Cl)CH CH₂.

A 42 ml aliquot of a 0.92 M diﬂuoromethylcadmium reagent

(39 mmol) in DMF was added into a three-neck 100 ml ﬂask

equipped with a septum stir bar and nitrogen tee. The solution

was cooled to ꢀ50 8C and then 5.6 g (39 mmol) of CuBr added.

After 15 min, 2.9 g (33 mmol) of 3-chloro-3,3-dideutero-1-

propene was added dropwise from a syringe. The reaction

mixture was slowly warmed to RTover 4 h. Flash distillation of

the reaction mixture followed by trap-to-trap distillation of the

crude distillate gave 1.8 g (63%) of a 90:10 mixture of

CD₂CHCH₂CF₂H and CH₂CHCD₂CF₂H, respectively, as

3.7.5. Reaction of diﬂuoromethylcopper with 1-chloro-3-

methyl-2-butene

A 77 ml aliquot of a 0.88 M diﬂuoromethylcadmium reagent

(68 mmol) in DMF, 9.9 g (68 mmol) CuBr, and 6.3 g

(60 mmol) of 1-chloro-3-methyl-2-butene were reacted at

ꢀ50 8C (as described previously). The reaction mixture was

slowly warmed to RT over 5 h. Isolation and distillation (as

described previously) gave 5.7 g (80%) (bp 88–90 8C) of 5,5-

diﬂuoro-2-methyl-2-pentene, GLPC purity = 100%. ¹⁹F, ¹H,

¹³C NMR data were identical to the product from the reaction of

HCF₂CdX with 1-chloro-3-methyl-2-butene.

1

2

determined by ¹⁹F NMR analysis. The ¹⁹F, H, D and ¹³C

NMR data were identical to the data reported for the reaction of

HCF₂CdX with CH₂CHCD₂Cl.

3.7.2. Reaction of diﬂuoromethylcopper with 3-chloro-1-

butene

3.7.6. Reaction of diﬂuoromethylcopper with (E)-3-chloro-

1-phenyl-1-propene

Similar to the reaction with CH₂CHCD₂Cl, a 62 ml aliquot

of a 0.89 M diﬂuoromethylcadmium reagent (55 mmol) in

DMF, 7.9 g (55 mmol) of CuBr, and 4.5 g (50 mmol) of 3-

chloro-1-butene were reacted at ꢀ50 8C. The reaction mixture

was slowly warmed to RT over 5 h. Flash distillation, followed

by addition of an equivalent volume of ice water, separation of

the organic layer, washing with 2ꢃ 100 ml of water and drying

A 58 ml aliquot of a 0.89 M diﬂuoromethyl cadmium

reagent (52 mmol) in DMF, 7.6 g (52 mmol) CuBr, and 7.6 g

(50 mmol) of (E)-3-chloro-1-phenyl-1-propene were reacted at

ꢀ50 8C (as described previously). The reaction mixture was

slowly warmed to RTover 5 h, then steam distilled. The organic

˚

layer of the steam distillate was separated, dried over 4 A

˚

over a 4 A molecular sieves, and fractional distillation (bp 68–

molecular sieves and distilled to give 7.2 g (86%) (bp 100–

103 8C/0.5 mm) of (E)-4,4-diﬂuoro-1-phenyl-1-butene, GLPC

purity = 100%. The ¹⁹F, ¹H, ¹³C NMR data were identical to the

product from the reaction of HCF₂CdX with (E)-3-bromo-1-

phenyl-1-propene.

70 8C) gave 3.9 g (74%) of (E)-5,5-diﬂuoro-2-pentene, GLPC

purity = 100%. The ¹⁹F, ¹H and ¹³C NMR data were identical to

the data obtained from the reaction of HCF₂CdX with

CH₃CH(Cl)CH CH₂. GC–MS, m/z (relative intensity): 106

(100.0), 85 (8.6), 77 (8.6), 59 (9.5), 55 (39.5), 51 (11.2). IR

(CCl₄): 3031 (w), 2972 (m), 2945 (m), 2920 (w), 2887 (w),

2858 (w), 1451 (w), 1437 (w), 1428 (w), 1391 (w), 1364 (w),

1218 (w), 1119 (vs), 1057 (vs), 1031 (m), 1012 (m), 969 (m),

913 (w), 875 (w), 855 (w).

3.7.7. Reaction of diﬂuoromethylcopper with 3-chloro-1-

cyclohexene

A 53 ml aliquot of a 0.84 M diﬂuoromethyl cadmium

reagent (45 mmol) in DMF, 6.5 g (45 mmol) CuBr, and 2.8 g

(24 mmol) of 3-chloro-1-cyclohexene were reacted at ꢀ50 8C.

The reaction mixture was slowly warmed to RT over 5 h. Flash

distillation, washing of the ﬂash distillate with water (as

3.7.3. Reaction of diﬂuoromethylcopper with (E)-1-chloro-

2-butene

˚

described previously), drying over 4 A molecular sieves and

A 58 ml aliquot of a 0.89 M diﬂuoromethylcadmium reagent

(52 mmol) in DMF, 7.6 g (50 mmol) CuBr, and 4.5 g (50 mol)

of (E)-1-chloro-2-butene were reacted at ꢀ50 8C. The reaction

mixture was warmed to RT over 5 h. Isolation and distillation

(as described above) gave 3.5 g (68%) (bp 68–70 8C) of a 46:54

isomeric mixture of 4,4-diﬂuoro-3-methyl-1-butene and (E)-

5,5-diﬂuoro-2-pentene (as determined by GLPC analysis). The

distillation gave 2.0 g (62%) (bp 51–53 8C/53 mm) of 3-

(diﬂuoromethyl-1-cyclohexene), GLPC purity = 95%. ¹⁹F

2

NMR (CDCl₃) (ppm): d ꢀ121.4 (ddd, J_FF= 277.5 Hz,

3

1

²J_FH= 57.0 Hz, J_FH= 13.9 Hz), d ꢀ122.9 (AB system); H

NMR (360 M) (CDCl₃) (ppm)

d

(CF₂H) 5.55 (td,

3

²J_FH= 57.0 Hz, J_HH= 13.9 Hz), 2.55 (m), 5.59 (m), 5.82

¹⁹F, H, and ¹³C NMR data were identical to the compounds

(m), 2.03 (m), 1.81 (m), 1.53 (m); ¹³C NMR (neat) (ppm): 118.6

1

2

formed from the reaction of HCF₂CdX with 3-chloro-1-butene

(as described above).

(t, J_CF= 242.8 Hz), 40.1 (t, J_CF= 19.6 Hz), 122.4 (t,

³J_CF= 6.0 Hz), 131.4 (s), 24.9 (s), 20.5 (s), 22.3 (t,

³J_CF= 4.5 Hz). GC–MS, m/z (relative intensity): 132 (16.7),

81 (100.0), 79 (42.7), 77 (14.4), 51 (11.6). IR (CCl₄): 3035 (w),

2953 (m), 2944 (m), 2938 (m), 1687 (vs), 1451 (w), 1435 (w),

1388 (w), 1130 (m), 1086 (m) 1076 (s), 1050 (s), 1029 (w), 987

(w), 887 (w).

3.7.4. Reaction of diﬂuoromethylcopper with 3-chloro-3-

methyl-1-butene

A 72 ml aliquot of a 0.83 M diﬂuoromethylcadmium

reagent (60 mmol) in DMF, 8.6 g (60 mmol) CuBr and 5.2 g

1212

D.J. Burton, G.A. Hartgraves / Journal of Fluorine Chemistry 128 (2007) 1198–1215

3.7.8. Reaction of diﬂuoromethylcopper with 3-bromo-3,3-

diﬂuoro-1-propene

1,1-diﬂuoro-4-methyl-2,3-pentadiene (bp 77–80 8C) was

1

obtained, GLPC purity = 100%. ¹⁹F, H and ¹³C NMR data

A 76 ml aliquot of a 0.79 diﬂuoromethylcadmium reagent

(60 mmol) in DMF, 8.6 g (60 mmol) CuBr and 8.6 (55 mmol)

of 3-bromo-3,3-diﬂuoro-1-propene were reacted at ꢀ50 8C (as

described previously). The reaction mixture was slowly

warmed to RT over 5 h. Flash distillation followed by trap-

to-trap distillation gave 6.09 g (87%), GLPC purity = 100%, of

1,1,4,4-tetraﬂuoro-1-butene. Distillation gave 5.2 g (74%) (bp

38–39 8C). ¹⁹F NMR (CDCl₃) (ppm): d = ꢀ117.3 (dtdd,

were identical to the data reported previously from the

reaction of diﬂuoromethylcadmium with 3-bromo-3-methyl-

1-butyne. HRMS: C₆H₈F₂calculated, 118.0594; found,

118.0587.

3.7.11. Reaction of diﬂuoromethylcopper with 1-bromo-2-

butyne

Similarly, a 30 ml aliquot of a 0.84 M diﬂuoromethylcad-

mium reagent (25 mmol) in DMF, 3.6 g (25 mmol) CuBr and

2.6 g (19.2 mmol) of 1-bromo-2-butyne were reacted at

ꢀ50 8C. After distillation, 1.2 g (59%) (bp 53–56 8C) of a

87:13 isomeric mixture of 4,4-diﬂuoro-3-methyl-1,2-butadiene

and 5,5-diﬂuoro-2-pentyne was obtained (as determined by

3

5

²J_FH=56.4 Hz, J_FH= 17.0 Hz, J_FF= 1.8 Hz, J_FF= 1.8 Hz),

3

5

d ꢀ85.2 (dm, J_FH= 38.5 Hz), d ꢀ88.5 (ddtt, J_FF= 1.8 Hz,

⁴J_FH= 1.8 Hz, J_FH= 24.2 Hz, J_FH= 38.5 Hz), ¹H NMR

3

2

3

(CDCl₃) (ppm): d (CF₂H) 5.79 (tt, J_FH= 56.4 Hz, J_HH

=

4.2 Hz), d (–CH₂) 2.53 (tm, J_FH= 17.0 Hz), d (–CH ) 4.23

3

(ddt, J_FH= 38.5 Hz, J_FH= 24.2 Hz, J_HH= 8.1 Hz). ¹³C

GLPC). ¹⁹F, H and ¹³C NMR data were identical to the data

3

1

NMR (neat) (ppm): 115.0 (t, J_CF= 239.1 Hz), 27.2 (td,

reported previously for the reaction of diﬂuoromethylcadmium

with 1-bromo-2-butyne.

²J_CF= 23.7 Hz, J_CF= 4.6 Hz), 69.1 (ddt, J_CF= 28.5 Hz,

3

2

²J_CF= 20.1 Hz, J_CF= 7.2 Hz), 157.7 (t, J_CF= 286.8 Hz).

GC–MS, m/z (relative intensity): 128 (38.5), 89 (13.8), 77

(100.0). 51 (25.5). IR (CCl₄): 2979 (w), 1755 (w), 1398 (w)

1341 (w), 1311 (w), 1291 (m), 1254 (m), 1201 (m), 1128 (m),

1123 (m), 1069 (m), 1049 (m), 1033 (w), 917 (w).

3

2

3.7.12. Reaction of diﬂuoromethylcopper with 1-chloro-1-

ethynylcyclohexane

Similarly, a 72 ml aliquot of a 0.83 M diﬂuoromethylcad-

mium reagent (60 mmol) in DMF, 8.6 g (60 mmol) CuBr and

7.1 g (50 mmol) of 1-chloro-1-ethynylcyclohexane were

reacted at ꢀ50 8C. After distillation, 5.6 g (71%) (bp 68–

72 8C) of 4,4-diﬂuoro-1-pentamethylene-1,2-butadiene was

obtained, GLPC purity, 100%. ¹⁹F NMR (CDCl₃) (ppm): d

3.7.9. Reaction of diﬂuoromethylcopper with 3-tosyl-1-

butyne

A 65 ml aliquot of a 0.85 M diﬂuoromethylcadmium reagent

(55 mmol) in DMF was added to a three-neck 100 ml ﬂask

equipped with a septum, stir bar and nitrogen tee. The solution

was cooled to ꢀ50 8C, then 7.9 g (55 mmol) of CuBr was

added. After 15 min, 11.2 g (50 mmol) of 3-tosyl-1-butyne was

added in one portion. The reaction mixture was slowly warmed

to RT over 5 h. Flash distillation, followed by washing of the

ﬂash distillate with an equal volume of ice water, separation of

the organic layer, followed by washing with 2ꢃ 100 ml of

2

3

ꢀ106.8 (dd, J_FH= 56.7 Hz, J_FH= 6.3 Hz), ¹H NMR

(360 MHz) (CDCl₃) (ppm): d (CF₂H) 6.02 (td, ²J_FH= 56.7 Hz,

³J_HH= 6.2 Hz), d (CF₂HCH ) 5.21 (bs), 2.16 (bs), 1.61 (bs),

1

1.54 (bs), ¹³C NMR (neat) (ppm): 115.5 (t, J_CF= 236.8 Hz),

86.7 (²J_CF= 28.8 Hz), 201.4 (t, ³J_CF= 12.4 Hz), 108.2 (s), 31.2

(s), 27.6 (s), 26.3 (s). GC–MS, m/z (relative intensity): 158

(100.0), 143 (26.0), 130 (17.7), 129 (24.8), 125 (15.5), 123

(26.0), 116(13.2), 115(38.7), 111 (13.8), 109 (27.7), 107 (26.3),

105 (15.7), 103 (16.0), 101 (13.7), 97 (34.7), 93 (15.9), 91

(48.4), 79 (60.8), 77 (33.4), 51 (12.5). IR (CCl₄): 2936 (s), 2895

(m), 2857 (m), 1973 (m), 1685 (w), 1448 (s), 1438 (s), 1369

(w), 1355 (m), 1336 (w), 1120 (vs), 1078 (s), 1055 (vs), 1024

(vs), 973 (w), 932 (w), 896 (w), 853 (w).

˚

water, drying over 4 A molecular sieves, and distillation gave

2.8 g (53%) of 1,1-diﬂuoro-2,3-pentadiene. ¹⁹F NMR (CDCl₃)

2

3

5

(ppm): d ꢀ107.6 (ddd, J_FH= 56.5 Hz, J_FH= 6.4 Hz, J_FH

=

1

7.2 Hz); H NMR (360 MHz) (CDCl₃) (ppm): d (CF₂H) 6.07

(tdd, ²J_FH= 56.5 Hz, ³J_HH= 6.2 Hz, ⁵J_HH= < 1 Hz), d (–CH )

3

5.32 (tddq, J_FH= 6.4 Hz, J_HH= 6.2 Hz, J_HH= 6.8 Hz,

3

4

⁵J_HH= 3.2 Hz), d ( CHCH₃) (qtdd, J_HH= 7.3 Hz, J_FH

=

7.2 Hz, J_HH= 6.8 Hz, J_HH= < 1), d (–CH₃) 1.74 (dd,

3.7.13. Reaction of diﬂuoromethylcopper with 1,4-

dichloro-2-butyne

3

5

4

5

³J_HH= 7.3 Hz, J_HH= 3.2 Hz); ¹³C NMR (neat) (ppm): 115.0

Similarly, a 46 ml aliquot of a 1.2 M diﬂuoromethyl

cadmium reagent (55 mmol) in DMF, 5.4 g (55 mmol) CuCl,

and 3.1 g (50 mol) of 1,4-dichloro-2-butyne were reacted at

ꢀ60 8C. After distillation 1.8 g (46%) (bp 53–55 8C/94 mm) of

bis-2,3-(diﬂuoromethyl)-1,3-butadiene was obtained, GLPC

purity 100%). ¹⁹F NMR (CDCl₃) (ppm): d ꢀ115.4 (d,

²J_CFH= 56.2 Hz), ¹H NMR (360 MHz) (CDCl₃) (ppm): d

3

1

2

(t, J_CF= 236.3 Hz), 87.9 (t, J_CF= 29.0 Hz), 207.2 (t,

³J_CF= 12.2 Hz), 90.9 (s), 12.9 (s). HRMS: C₅F₂H₆calculated,

104.0438; found, 104.0433. IR (CCl₄): 2984 (w), 2958 (w),

2930 (w), 2929 (w), 2864 (w), 1973 (w), 1428 (s), 1374 (w),

1344 (m), 1155 (w), 1136 (m), 1108 (vs), 1097 (s), 1072 (s),

1057 (vs), 1029 (vs), 888 (w), 866 (w).

2

(CF₂H) 6.21 (t, J_FH= 56.2 Hz), d ( CH) 5.72 (m), d ( CH)

5.71 (s); ¹³C NMR (CDCl₃) (ppm): 114.9 (t, ¹J_CF= 240.1 Hz),

3.7.10. Reaction of diﬂuoromethylcopper with 3-chloro-3-

methyl-1-butyne

3

135.9 (²J_CF= 20.3 Hz), 121.3 (t, J_CF= 10.0 Hz). HRMS:

Similarly, a 35 ml aliquot of a 0.90 M diﬂuoromethyl-

cadmium reagent (31.5 mmol) in DMF, 4.6 g (32 mmol) of

CuBr and 2.4 g (23.4 mmol) of 3-chloro-3-methyl-1-butyne

were reacted at ꢀ50 8C. After distillation, 2.15 g (78%) of

C₆H₆F₄calculated, 154.0406; found, 154.0373. IR (CCl₄):

3745 (w), 2972 (w), 1607 (w), 1405 (m), 1389 (m), 1350 (m),

1261 (w), 1218 (m), 1196 (m), 1185 (m), 1110 (s), 1093 (s),

1058 (s), 1045 (vs), 947 (m), 833 (w).

D.J. Burton, G.A. Hartgraves / Journal of Fluorine Chemistry 128 (2007) 1198–1215

1213

2

3.7.14. Reaction of diﬂuoromethylcopper reagent with 1-

iodo-1-hexyne

(CDCl₃) (ppm): d ꢀ105.7 (d, J_FH= 55.2 Hz); ¹H NMR

2

(CDCl₃) (ppm): d (CF₂H) 6.40 (t, J_FH= 55.2 Hz), 7.4

(aromatics) (m); ¹³C NMR (neat) (ppm): 104.5 (t, J_CF

1

A 66 ml aliquot of a 0.78 M diﬂuoromethylcadmium reagent

(52 mmol) in DMF, 7.5 g (52 mmol) CuBr, and 10.0 g

(48 mmol) of 1-iodo-1-hexyne were reacted at ꢀ50 8C. After

distillation 4.8 g (75%) (bp 74–76 8C/127 mm) of 1,1-diﬂuoro-

2-heptyne was obtained, GLPC purity 100%. ¹⁹F NMR

=

2

3

231.2 Hz), 79.7 (t, J_CF= 33.7 Hz), 88.3 (t, J_CF= 7.4 Hz),

119.6 (s), 128.4 (s), 131.9 (s), 130.0 (s). GC–MS, m/z (relative

intensity): 152 (80.5), 151 (100.0), 133 (48.9), 102 (57.9), 99

(10.7), 76 (10.0), 75 (13.2), 74 (12.1). IR (CCl₄): 3062 (w),

2971 (w), 2956 (w), 2286 (m), 2222 (w), 1687 (m), 1491 (m),

1445 (w), 1372 (vs), 1258 (w), 1049 (s), 973 (m), 918 (w).

2

5

(CDCl₃) (ppm): d ꢀ104.4 (dt, J_FH= 55.7 Hz, J_FH= 5.9 Hz);

¹H NMR (360 MHz) (CDCl₃) (ppm): d (CF₂H) 6.16 (tt,

5

²J_FH= 55.7 Hz, J_HH= 1.5 Hz), d (–CH₂–) 2.29 (m), d (–

3

CH₂CH₂CH₂) 1.50 (m), d (–CH₃) 0.92 (t, J_HH= 7.0 Hz). ¹³C

3.7.17. Reaction of diﬂuoromethylcopper with 1-iodo-1-

perﬂuorohexyne

1

NMR (neat) (ppm): 104.3 (t, J_CF= 229.8 Hz), 72.4 (t,

3

²J_CF= 33.5 Hz), 90.5 (t, J_CF= 7.1 Hz), 30.0 (s), 22.0 (s),

A 50 ml aliquot of a 0.87 M diﬂuoromethylcadmium reagent

(44 mmol) in DMF, 6.5 g (45 mmol) of CuBr and 13.2 g

(35.8 mmol) of 1-iodo-1-perﬂuorohexyne were reacted at

ꢀ50 8C. After ﬂash distillation washing with water and drying

the organic layer, distillation gave 5.52 g (52%) (bp 68–73 8C)

of 1-hydro-2-perﬂuoroheptyne, was obtained, GLPC purity

100%. ¹⁹F NMR (CDCl₃) (ppm): d (CF₂H) ꢀ111.8 (dt,

17.9 (s), 13.1 (s). GC–MS, m/z (relative intensity): 117 (44.0),

104 (26.0) 103 (15.7), 101 (19.0), 99 (56.8), 97 (68.7), 91

(20.8), 86 (33.5), 85 (24.9), 83 (34.6), 81 (100.0), 79 (26.9), 77

(56.2), 70 (35.8), 67 (17.5), 51 (24.9), 43 (37.5), 41 (17.9). IR

(CCl₄): 2961 (m), 2938 (m), 2876 (w), 2337 (s), 2257 (m), 1687

(s), 1467 (w), 1429 (w), 1374 (vs), 1341 (w), 1168 (vs), 1087

(w), 1046 (vs).

²J_FH= 52.7 Hz, J_FF= 5.5 Hz), ꢀ101.4 (m), ꢀ121.8 (m),

5

ꢀ123.3 (m), ꢀ123.1 (m), ꢀ126.6 (m), ꢀ81.3 (t, ⁴J_FF= 9.8 Hz);

¹H NMR (360 MHz) (CDCl₃) (ppm): 6.31 (tt, ²J_FH= 52.7 Hz,

⁵J_FH= 2.4 Hz); ¹³C NMR (CDCl₃) (ppm): 102.0 (CF₂H) (t,

¹J_CF= 236.3 Hz), 72.8 (CF₂H–CBBC–CF₂–) (tt, ²J_CF= 37.8 Hz,

3.7.15. Reaction of diﬂuoromethylcopper with 1-iodo-1-

heptyne

A 52 ml aliquot of a 1.16 M diﬂuoromethylcadmium reagent

(60 mmol) in DMF, 5.9 g (60 mmol) of CuCl and 12.3 g

(55.3 mmol) of 1-iodo-1-heptyne was reacted at ꢀ50 8C. After

distillation 6.0 g (74%) (bp 71–73 8C/76 mm) of 1,1-diﬂuoro-

2-octyne was obtained, GLPC purity 100%. ¹⁹F NMR (CDCl₃)

(ppm): d ꢀ104.4 (dt, ²J_FH= 55.7 Hz, ⁵J_FH= 5.8 Hz); ¹H NMR

(360 MHz) (CDCl₃) (ppm): d (CF₂H) 6.16 (tt, ²J_FH= 55.7 Hz,

⁵J_HH= 1.4 Hz), d (–CH₂) 2.28 (m), d (–CH₂CH₂CH₂CH₂–)

³J_CF= 6.9 Hz), 80.9 (CF₂HCBBCCF₂–) (tt, J_CF= 5.9 Hz,

3

²J_CF= 36.4 Hz), 105–113 (m, 3CF₂), 112.4 (CF₃) (qt,

¹J_CF= 286.4 Hz, J_CF= 33.1 Hz). GC–MS, m/z (relative

2

intensity): 293 (M ꢀ 1, 0.1), 187 (10.8), 137 (14.5), 125

(100.0), 119 (13.1), 106 (18.3), 100 (13.1), 75 (25.2), 69 (20.7).

IR (CCl₄): 1372 (w), 1354 (w), 1263 (w), 1240 (vs), 1217 (m),

1212 (m), 1141 (s), 1081 (m), 980 (w), 873 (w).

3

1.40 (m), d (–CH₃) 0.91 (t, J_HH= 7.1 Hz). ¹³C NMR (neat)

(ppm): 103.6 (t, ¹J_CF= 230.3 Hz), 71.9 (t, ²J_CF= 33.7 Hz), 89.9

(t, ³J_CF= 7.1 Hz), 30.6 (s), 27.2 (s), 21.8 (s), 17.7 (s), 13.01 (s).

GC–MS, m/z (relative intensity): 145 (M ꢀ 1, 1.4), 117 (18.4),

97 (29.1), 95 (74.2), 81 (24.9), 78 (21.5), 77 (32.4), 70 (31.8),

67 (23.8), 63 (38.6), 57 (75.2), 56 (46.3), 55 (85.5), 51 (57.0),

41 (100.0). IR (CCl₄): 2960 (m), 2934 (m), 2875 (w), 2884 (w),

2337 (w), 2257 (m), 1468 (w), 1461 (w), 1457 (w), 1374 (vs),

1053 (vs), 1049 (vs).

3.7.18. Reaction of diﬂuoromethylcopper with 1-iodo-1-

perﬂuorooctyne

A 45 ml aliquot of a 0.97 M diﬂuoromethylcadmium reagent

(43.7 mmol) in DMF, 6.3 g (44 mmol) of CuBr and 15.9 g

(33.7 mmol) of 1-iodo-1-perﬂuorooctyne were reacted at

ꢀ50 8C and the reaction mixture was worked-up as described

in the previous reaction. After distillation 7.3 g (55%) (bp 115–

117 8C) of 1-hydro-2-perﬂuorononye was obtained, GLPC

purity 95%. ¹⁹F NMR (CDCl₃) (ppm): d (CF₂H) ꢀ111.8 (dt,

5

3.7.16. Reaction of diﬂuoromethylcopper with 1-iodo-2-

phenylethyne

²J_FH= 52.7 Hz, J_FF= 5.5 Hz), ꢀ101.4 (m), ꢀ121.8 (m),

ꢀ123.3 (m), ꢀ123.1 (m), ꢀ126.6 (m), ꢀ81.3 (t, ⁴J_FF= 9.8 Hz);

A 45 ml aliquot of a 0.96 M diﬂuoromethylcadmium reagent

(43 mmol) in DMF, 6.4 g (43 mmol) of CuBr and 8.5 g

(37 mmol) of 1-iodo-2-phenylethyne was reacted at ꢀ50 8C.

After ﬂash distillation, the ﬂash distillate was washed with an

equal volume of ice water. The organic layer was washed with

¹H NMR (360 MHz) (CDCl₃) (ppm): d (CF₂H) 6.31 (tt,

5

²J_FH= 52.7 Hz, J_FH= 2.4 Hz); ¹³C NMR (CDCl₃) (ppm):

1

102.4 (CF₂H) (t, J_CF= 236.9 Hz), 73.7 (CF₂H–CBBC) (t,

3

²J_CF= 37.5 Hz), 81.7 (t, J_CF= 36.3 Hz), 105–118 (m,

(CF₂)₅CF₃). GC–MS, m/z (relative intensity): 393 (M ꢀ 1,

0.1), 125 (100.0), 75 (18.4), 69 (17.4): IR (CCl₄): 1686 (w),

1552 (w), 1372 (m), 1242 (vs), 1208 (s), 1150 (s), 1128 (m),

1080 (m).

˚

2ꢃ 25 ml of water, and dried over 4 A molecular sieves. Then,

15 ml of tetraglyme were added to the reaction pot and the

mixture ﬂash distilled, washed with an equal volume of ice

water, the organic layer separated, washed with 2ꢃ 25 ml and

˚

dried over 4 A molecular sieves. Repetition of the addition of

3.7.19. Reaction of diﬂuoromethylcopper with 1-iodo-1-

perﬂuorodecyne

tetraglyme an additional time, followed by combination of the

organic layers gave 2.7 g of crude 3,3-diﬂuoro-1-phenylpro-

pyne. Distillation gave 2.5 g (44%) (bp 50–52 8C/4 mm) of 3,3-

diﬂuoro-1-phenylpropyne, GLPC purity 100%. ¹⁹F NMR

An 8 ml aliquot of 1.45 M diﬂuoromethylcadmium reagent

(11.6 mmol) in DMF, 1.7 g (11.6 mmol) CuBr and 5.4 g

(9.5 mmol) of 1-iodo-1-perﬂuorodecyne were reacted at

1214

D.J. Burton, G.A. Hartgraves / Journal of Fluorine Chemistry 128 (2007) 1198–1215

ꢀ50 8C, and the reaction mixture worked-up as described

previously. The dry organic layer obtained was 3.1 g (66%) of

1-hydro-2-perﬂuorodecyne, GLPC; purity 100%. ¹⁹F NMR

1495 (m), 1457 (m), 1434 (m), 1393 (s), 1363 (m), 1336 (w),

1208 (m), 1118 (vs), 1083 (s), 1060 (vs), 1032 (s), 1018 (m),

867 (m).

2

(CDCl₃) (ppm). d (CF₂H) ꢀ111.9 (dt, J_FH= 52.7 Hz,

⁵J_FF= 5.5 Hz), ꢀ101.5 (bs), ꢀ121.7 (bs), ꢀ122.6 (4 CF₂)

4. Conclusions

4

1

(m), ꢀ126.7 (bs), ꢀ81.4 (CF₃) (t, J_FF= 9.2 Hz); H NMR

2

(360 MHz) (CDCl₃) (ppm): 6.29 (tt, J_FH= 52.7 Hz,

Diﬂuoromethylcadmium is readily prepared by oxidative

addition of cadmium with iododiﬂuoromethane and bromodi-

ﬂuoromethane. The diﬂuoromethylcadmium reagent is ther-

mally stable to 65–70 8C; rapid decomposition occurs at

temperatures >105 8C. At room temperature the reagent is

stable for weeks and only loses 31% of its activity after 2

months at RT. The diﬂuoromethylcadmium reagent reacts

readily with allylic halides at RT to give products of both a- and

g-attack in good yields. Metathesis of the diﬂuoromethylcad-

mium reagent with Cu(I)X (X = Cl, Br) in DMF at ꢀ55 8C

readily gives the diﬂuoromethylcopper reagent. The copper

reagent is stable only at low temperatures (ꢀ30 to ꢀ55 8C) and

rapidly decomposes to HCF₂CF₂H and cis-CFH CFH above

these temperatures. However, HCF₂Cu is more nucleophilic

than HCF₂CdX, and the copper reagent readily reacts with

allylic halides at ꢀ55 8C, The regiospeciﬁcity of HCF₂Cu is

vastly superior to HCF₂CdX and most of the reactions of

HCF₂Cu with allylic halides occur regiospeciﬁcally. When

HCF₂CdX is reacted with propargylic halides or tosylates, the

predominant product is the corresponding allene. The HCF₂Cu

reagent again is more reactive, completely regiospeciﬁc, and in

most cases gives good isolated yields of the allenes. The

HCF₂Cu reagent also readily couples with 1-iodoalkynes and 1-

iodoperﬂuoroalkynes to give good yields of the corresponding

diﬂuoromethylalkynes. The HCF₂Cu reagent only undergoes

alkylation with reactive alkylating agents, such as chloromethyl

ethyl ether and benzyl bromide.

⁵J_FH= 2.3 Hz); ¹³C NMR (CDCl₃) (ppm): 101.8 (CF₂H) (t,

2

¹J_CF= 236.3 Hz), 72.7 (CF₂HCBB C–CF₂–) (tt, J_CF= 37.7 Hz,

2

³J_CF= 6.8 Hz), 80.9 (tt, –CBBCCF₂CF₂–, J_CF= 36.4 Hz,

³J_CF= 5.9 Hz), ꢀ103 to 122 (7 CF₂) (m), 117.0 (CF₃) (qt,

2

¹J_CF= 286.9 Hz, J_CF= 33.0 Hz). GC–MS, m/z (relative

intensity): 493 (M ꢀ 1, 0.1), 131 (14.4), 125 (100.0), 119

(1.4), 75 (24.4), 69 (45.8). IR (CCl₄): 1685 (w), 1372 (m), 1243

(vs), 1218 (vs), 1156 (s), 1137 (m), 1123 (m), 1081 (m), 1005

(w).

3.7.20. Reaction of diﬂuoromethylcopper with

ethylchloromethyl ether

A 65 ml aliquot of 0.85 M diﬂuoromethylcadmium reagent

(55 mmol) in DMF, 7.9 g (55 mmol) CuBr and 4.9 g (52 mmol)

of ethylchloromethyl ether were reacted at ꢀ50 8C, The

reaction mixture was slowly warmed to RT over 5 h. Flash

distillation was followed by simple distillation of the volatile

material to give 4.1 g (72%) (bp 65–67 8C) of 2,2-diﬂuoroethyl

ethyl ether, GLPC; purity 100%. ¹⁹F NMR (CDCl₃) (ppm). d

(CF₂H) ꢀ125.5 (dt, ²J_FH= 56.2 Hz, ³J_FH= 14.2 Hz); ¹H NMR

2

3

(360 MHz) (CDCl₃) (ppm): 5.86 (tt, J_FH= 56.2 Hz, J_HH

=

4.2 Hz), 3.62 (q, J_HH= 7.1 Hz), 1.22 (t, J_HH= 7.1 Hz); ¹³C

3

1

NMR (neat) (ppm): 115.0 (t, J_CF= 239.7 Hz), 69.8 (t,

²J_CF= 27.2 Hz), 67.3 (s), 14.3 (s). GC–MS, m/z (relative

intensity): 110 (38.8), 95 (46.4), 85 (95.0), 63 (33.6), 59

(100.0), 51 (37.3), 46 (12.1), 45 (38.3), 43 (35.9). IR (CCl₄):

2983 (s), 2952 (m), 2945 (m), 2875 (w), 1437 (w), 1394 (w),

1317 (w), 1269 (w), 1244 (w), 1179 (w), 1149 (s), 1123 (vs),

1073 (vs), 1034 (w), 914 (w).

Acknowledgement

We gratefully appreciate the ﬁnancial support from the Air

Force Ofﬁce of Scientiﬁc Research and the National Science

Foundation.

3.7.21. Reaction of diﬂuoromethylcopper with benzyl

bromide

A 61 ml aliquot of 0.90 M diﬂuoromethylcadmium reagent

(55 mmol) in DMF, 8.0 g (56 mmol) CuBr and 8.6 g (50 mmol)

of benzyl bromide were reacted at ꢀ50 8C. The reaction was

slowly warmed to RTover 5 h. Flash distillation; washing of the

ﬂash distillate with an equal volume of water, separation of the

organic layer, washing of the organic layer with 2ꢃ 50 ml water

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˚

and drying of the organic layer with 4 A molecular sieves gave

the crude product, which on distillation gave 2.5 g (35%) of 1,1-

diﬂuoro-2-phenylethane. ¹⁹F NMR (CDCl₃) (ppm). d ꢀ115.3

(dt, ²J_FH= 56.6 Hz, ³J_FH= 17.3 Hz); ¹H NMR (CDCl₃) (ppm):

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2

3

d

(CF₂HCH₂–) (td, J_FH= 17.3 Hz, J_HH= 4.6 Hz), d 7.2–7.3

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3

[7] M.P. Merkes, S.E. Saheb, J. Med. Chem. 6 (1963) 619.

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(m, aromatic H’s); ¹³C NMR (neat) (ppm): 116.7 (t,

2

3

¹J_CF= 240.0 Hz), 40.2 (t, J_CF= 21.8 Hz), 132.4 (t, J_CF

=

5.6 Hz), 129.6 (s), 128.3 (s), 127.1 (s). GC–MS, m/z (relative

intensity): 142 (17.0), 91 (100.0), 89 (5.6), 65 (9.4), 51 (6.2). IR

(CCl₄): 3092 (m), 3069 (m), 3035 (m), 2975 (m), 2934 (w),

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(HCF₂)₂Cd with diglyme, Me₃P and DMF are stable; upon heating in

vacuo at 70 8C, CF₂H₂is eliminated.

[34] P.R. Jones, P.J. Desio, Chem. Rev. 78 (1978) 491.

[14] cf. also to the chapter by S. Bohm, Houben-Weyl, vol. E 10b/Part 1,

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Article Doi

The preparation of HCF2CdX and HCF2ZnX via direct insertion into the carbon halogen bond of CF2HY (Y = Br, I)

DOI: 10.1016/j.jfluchem.2007.05.015

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