Preparation of Functionalized Diorganomagnesium Reagents in Toluene via Bromine or Iodine/Magnesium-Exchange Reactions

SYNTHESIS

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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart

2021, 53, A–P

paper

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en

A. Desaintjean et al.

Paper

Synthesis

Preparation of Functionalized Diorganomagnesium Reagents in

Toluene via Bromine or Iodine/Magnesium-Exchange Reactions

Alexandre Desaintjean^◊

Fanny Danton^◊

NO₂

Mes₂Mg (0.6 equiv)

DMPU (4.0 equiv)

Me

I

Mg

2

[Cu⁺] cat.

Me

toluene

–70 °C, 60 min

Paul Knochel*

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3

2

EtO₂C

Br

60%

Ludwig-Maximilians-Universität, Department Chemie,

Butenandstraße 5-13, 81377 München, Germany

paul.knochel@cup.uni-muenchen.de

^◊These authors contributed equally

PLeuMaudalwiCKliopgnr-aorMucehlsa.kpexnloimoncdihliineagln@sA-cuUutpnh.iouvrneri-smitäute, nDcehpeanr.tdmeent Chemie, Butenandstraße 5-13, 81377 München, Germany

Received: 01.07.2021

Accepted after revision: 15.07.2021

Published online: 15.07.2021

M solution in toluene (Scheme 1, c).⁹This method was suc-

cessfully extended to alkenyl iodides to provide dialkenyl-

magnesium species in toluene that reacted well with vari-

ous electrophiles.

DOI: 10.1055/a-1551-4093; Art ID: ss-2021-t0382-op

Abstract A wide range of polyfunctionalized di(hetero)aryl- and di-

alkenyl-magnesium reagents are prepared in toluene within 10 to 120

minutes between –78 °C and 25 °C via an I/Mg- or Br/Mg-exchange re-

action using reagents of the general formula R₂Mg (R = sBu, Mes). High-

ly sensitive functional groups, such as triazene or nitro, are tolerated in

these exchange reactions, enabling the synthesis of various functional-

ized (hetero)arene and alkene derivatives after quenching with several

electrophiles including allyl bromides, acyl chlorides, aldehydes, ke-

tones, and aryl iodides.

a) Previous work: Br/Mg exchange in THF⁴

iPrMgCl·LiCl

MgY

Br

or sBu₂Mg·LiCl

(Het)

THF

Y = Br, (Het)Ar

b) Recent work: Br/Mg and Cl/Mg exchange in apolar solvents⁵

sBuMgOR·LiOR

or sBu₂Mg·2LiOR

+ TMEDA or PMDTA

X

MgY

Key words alkenes, apolar solvents, arenes, Grignard reaction, halo-

gen/magnesium-exchange, heterocycles, magnesium

(Het)

toluene or hexanes

R = 2-ethylhexyl

X = Br, Cl

Y = OR·LiOR,

(Het)Ar·2LiOR

Polyfunctionalized organometallic reagents are essen-

tial intermediates in modern organic chemistry.^1,2Further-

more, organomagnesium reagents are ideal for industrial

applications as they combine excellent functional group

tolerance with high reactivity while being available at mod-

erate cost and having moderate toxicity.³One of the best

methods for preparing Grignard reagents in ethereal sol-

vents is the halogen/magnesium exchange, which has been

well-established since the development of iPrMgCl·LiCl

(turbo-Grignard) (Scheme 1, a).⁴Recently, we reported a

halogen/magnesium exchange in apolar solvents using new

reagents of the type sBuMgOR·LiOR (1a, R = 2-ethylhexyl)

and sBu₂Mg·2LiOR (1b) (Scheme 1, b).^5,6The use of toluene

or related hydrocarbon solvents was attractive for industrial

applications and deserved further investigation.⁷

c) This work: I/Mg and Br/Mg exchange of (hetero)aryl halides in apolar solvents

sBuLi

(1.00 equiv)

1) solvent

switch

sBu₂Mg + LiCl

sBuMgCl

sBu₂Mg

0–25 °C, 1 h

2) filtration

in Et₂O

1c: 0.43–0.48 M in

toluene or hexanes

X

Mg

2

R₂Mg (+ DMPU)

(Het)

toluene or hexanes

X = I (2), Br (5)

R = sBu (1c), Mes (1d)

3, 6

– No LiOR or magnesiates; increased functional group tolerance

– No LiCl; compatible with the industrial-friendly solvent toluene

Scheme 1 Current halogen/magnesium-exchange reagents and the

preparation and use of sBu₂Mg (1c)⁸in apolar solvents

First, we investigated the I/Mg exchange on 2-iodoben-

zonitrile (2a) in toluene using various exchange reagents

(Table 1). We treated 2a with sBuMgOR·LiOR (1a, R = 2-eth-

ylhexyl)⁵in toluene at –78 °C for 10 minutes, which led to

the organomagnesium species 3a (Y = OR·LiOR) in 42% yield

(Table 1, entry 1). In an attempt to improve the yield of this

exchange reaction, 1a was replaced with sBu₂Mg·2LiOR

(1b).⁵Thus, treatment of 2a with 1b at –78 °C led after 10

Herein, we now report new I/Mg- and Br/Mg-exchange

reactions on various (hetero)aryl halides in apolar solvents

using sBu₂Mg (1c),⁸which was readily prepared by reaction

of sBuMgCl in diethyl ether with sBuLi (1.0 equiv) in cyclo-

hexane at 25 °C (2 h). After a solvent switch to toluene and

filtration, sBu₂Mg was obtained in 96% yield as a 0.43–0.48

Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B

A. Desaintjean et al.

Paper

Synthesis

minutes to the magnesium reagent 3a (Y = aryl·2LiOR) in

61% yield (Table 1, entry 2). However, on using sBu₂Mg (1c)

(0.6 equiv), the magnesiation of 2a was complete after 10

minutes at –78 °C, affording 3a (Y = aryl) in 98% yield (Table

1, entry 3).

53% yield (entry 21). In addition, aryl polyiodides 2o–q led

to the corresponding mono-magnesiated aryl iodides 3o–q

when the exchange was performed in the presence of

DMPU (N,N′-dimethylpropyleneurea) (1.0 equiv),¹³which

furnished after allylation, addition to benzaldehyde deriva-

tives or to ethyl cyanoformate, the products 4oa,ob, 4pa,pb,

and 4q in 45–73% yield (entries 22–26). An extension of

this method was possible by switching from sBu₂Mg (1c) to

Mes₂Mg (1d) (Mes = mesityl) in the case of particularly sen-

sitive aryl iodides.¹⁴This exchange reagent was prepared

analogously to sBu₂Mg (1c). Thus, mixing the aryl iodide

bearing a triazine moiety (2r) with 1d in the presence of

DMPU (1.0–4.0 equiv)¹³afforded, after allylation with allyl

bromide, the arene 4r in 79% yield (entry 27). Under similar

conditions, the diarylmagnesium species generated from 2-

iodonitrobenzene derivatives 2s,t were allylated, providing

the nitro-substituted compounds 4s,t in yields of 71% and

60%, respectively (entries 28 and 29).

Table 1 Optimization of the I/Mg Exchange on 2-Iodobenzonitrile (2a)

Leading to Magnesium Reagents of Type 3

I

MgY

CN

Exchange reagent

toluene, –78 °C,

10 min

CN

2a

3a: Y = OR·LiOR,

aryl·2LiOR, aryl

Entry

Exchange reagent (equiv)^a

Yield (%)^b

1

2

3

sBuMgOR·LiOR (1a) (1.2 equiv)

sBu₂Mg·2LiOR (1b) (0.6 equiv)

sBu₂Mg (1c) (0.6 equiv)

42

61

98

^aR = 2-ethylhexyl. These reactions were carried out at a concentration of

0.50 M. All reagents are displayed according to their stoichiometry and not

their actual structure.

Table 2 Reactions of Various Aryl Iodides with R₂Mg (1c, R = sBu; 1d,

R = Mes) Followed by Electrophilic Functionalization¹⁵

^bCalibrated yields determined by GC analysis of reaction aliquots after Cu-

catalyzed allylation.

sBu₂Mg

(1c) (0.6–0.7 equiv)

Mg

2

I

E

E⁺

(Het)

Subsequently, after Cu(I)-catalyzed allylation¹⁰of 3a

with 3-bromocyclohexene and ethyl 2-(bromomethyl)acry-

late, transmetalation with ZnCl₂¹¹followed by Pd-catalyzed

Negishi cross-coupling with 4-iodoanisole,¹²or addition to

a ketone, the functionalized benzonitriles 4aa–ad were iso-

lated in 55–98% yield (Table 2, entries 1–4). Similarly, the

iodobenzonitrile derivatives 2b–d underwent complete

I/Mg exchange upon treatment with 1c (–78 °C, 10 min).

The corresponding diarylmagnesium reagents 3b–d under-

went Pd-catalyzed cross-couplings with ethyl 4-iodobenzo-

ate, or a Cu-mediated acylation with 4-chlorobenzoyl chlo-

ride, producing the biaryl compounds 4b–d in 70–76% yield

(entries 5–7). Analogously, ethyl 2-iodobenzoate (2e) was

converted into the corresponding organomagnesium com-

pound 3e, which after allylation with methallyl bromide

gave the ester 4e in 92% yield (entry 8). Also, the reaction of

sBu₂Mg (1c) (0.6 equiv) with the halogenated iodopyridines

2f,g generated within 15 minutes the corresponding het-

eroaryl organomagnesium compounds 3f,g. After acylation

or addition to 2-adamantanone, the polyfunctionalized het-

erocycles 4fa,fb and 4g were obtained in 73–75% yield (en-

tries 9–11). The diiodoanisole derivatives 2h,i reacted

smoothly with 1c to provide, after allylation and addition to

benzaldehyde, the products 4h,i in 51% and 53% yields, re-

spectively (entries 12 and 13). Electron-rich substrates such

as the anisole derivatives 2j–l and the silyl ether 2m were

quantitatively converted into the corresponding diorgano-

magnesium reagents 3j–m. These were then reacted with a

range of electrophiles to afford products 4ja,jb, 4ka–kc and

4l,m in 60–94% yield (entries 14–20). Interestingly, 2-bro-

mo-4-iodotoluene (2n) underwent selective I/Mg exchange

to provide, after reaction with a ketone, the alcohol 4n in

R

(Het)

R

(0.8–1.2 equiv)

toluene, –78 to 25 °C

10–60 min

2

3

4

Entry Magnesium reagent Electrophile^a

Product, yield

(%)^b

(°C, min)

(0.8–1.2 equiv)

Mg

2

Br

1

2

CN

3a (–78, 10)

4aa: 98

CO₂Et

Br

CN

4ab: 88

OMe

3

3a (–78, 10)

I

CN

4ac: 73

O

OH

Ph

4

5

Ph

CN

4ad: 55

CO₂Et

NC

Mg

CO₂Et

NC

2

I

3b (–78, 10)

4b: 72

C

A. Desaintjean et al.

Paper

Synthesis

Entry Magnesium reagent Electrophile^a

Product, yield

(%)^b

Entry Magnesium reagent Electrophile^a

Product, yield

(%)^b

(°C, min)

(0.8–1.2 equiv)

(°C, min)

(0.8–1.2 equiv)

CO₂Et

O

F

O

F

Mg

2

MeO

CO₂Et

17^c

18^c

3k (25, 30)

Cl

6

7

NC

I

NC

3c (–78, 10)

4kb: 60

4c: 70

O

CN

O

OH

MeO

O

Cl

Mg

2

3k (25, 30)

F

Cl

4kc: 94

Cl

Br

3d (–78, 10)

4d: 76

OMe OH Cl

O

Cl

Mg

2

Mg

2

Me

19^c

H

Me

Br

OMe

8

9

Cl

CO₂Et

Cl

3l (25, 30)

4l: 75

3e (–78, 15)

4e: 92

OMe

O

F

O

Cl

Mg

2

Mg

2

OMe

20^c

TBSO

N

F

I

N

Cl

TBSO

Cl

3m (25, 30)

3f (–78, 15)

4fa: 73

4m: 65

HO

O

Br

Mg

2

OH

10^c

3f (–78, 15)

Br

adamantanone

benzoyl chloride

21^c

N

F

Me

F

4fb: 74

F

3n (25, 30)

4n: 53

O

Cl

Mg

I

Mg

I

Cl

N

2

Ph

2

22^d

23^d

N

Br

11

Cl

3o (–20, 60)

4oa: 65

Cl

3g (–78, 15)

4g: 75

OH

O

I

OMe

3o (–20, 60)

H

I

Mg

I

F

Me

Br

2

F

12

13

Me

4ob: 73

CN

4h: 51

Mg

2

CO₂Et

3h (–78, 15)

24^d

25^d

NCCO₂Et

I

OMe

OMe OH

Ph

4pa: 45

3p (–20, 60)

I

Mg

2

I

PhCHO

Br

CO₂Et

3p (–20, 60)

3i (–78, 15)

4i: 53

I

4pb: 64

Mg

2

Br

I

Mg

I

14^c

15^c

16^c

2

MeO

Me

MeO

26^d

3j (25, 30)

Br

4ja: 78

I

3q (–20, 60)

4q: 66

O

OH

Mg

2

3j (25, 30)

N

27^e

N

MeO

Cl

4jb: 63

4r: 79

3r (–20, 60)

CN

MeO

Mg

2

CN

MeO

I

3k (25, 30)

4ka: 88

D

A. Desaintjean et al.

Paper

Synthesis

Table 3 Reactions of Various Aryl and Heteroaryl Bromides with

sBu₂Mg (1c) Followed by Trapping with Electrophiles Leading to Prod-

ucts of Type 7¹⁵

Entry Magnesium reagent Electrophile^a

Product, yield

(%)^b

(°C, min)

(0.8–1.2 equiv)

Mg

2

Br

sBu₂Mg

(1c) (0.6 equiv)

28^e

Mg

2

Br

E

E⁺

NO₂

(Het)

R

NO₂

3s (–50, 60)

(0.8–1.2 equiv)

toluene

–40 to 25 °C

45–120 min

4s: 71

5

6

7

Mg

Me

Br

2

29^e

Entry

1^c

Magnesium

reagent (°C, min)

Electrophile^a

(0.8–1.2 equiv)

Product, yield

(%)^b

EtO₂C

NO₂

EtO₂C

NO₂

3t (–70, 60)

4t: 60

^aSee the Supporting Information for detailed electrophilic trappings.

^bIsolated yield of analytically pure product.

^cTHF (1.2 equiv) was used.

F

Mg

2

F

Me

Br

Me

NC

^dDMPU (1.0 equiv) was used.

F

^eMes₂Mg (0.6 equiv) in the presence of DMPU (1.0–4.0 equiv) was used.

6a (–20, 120)

7a: 98

OH

Ph

F

Mg

2

We next turned our attention to (hetero)aryl bromides

(Table 3). Thus, the bromobenzonitrile derivatives 5a–e un-

derwent smooth Br/Mg-exchange reactions with sBu₂Mg in

the presence of DMPU (1.0 equiv)¹³within 2 hours at –20 °C

to generate the diarylmagnesium reagents 6a–e. After al-

lylation, addition to benzaldehyde or transmetalation with

ZnCl₂followed by Pd-catalyzed Negishi cross-coupling with

4-iodoanisole, the corresponding products 7a–e were ob-

tained in 55–98% yield (entries 1–5). Under similar condi-

tions, the dibromofuran 5f led within 90 minutes at –20 °C

to the di(bromofuryl)magnesium species 6f, which fur-

nished, after allylation with methallyl bromide, the alkylat-

ed furan 7f in 51% yield (entry 6). More electron-poor thio-

phenes 5g–i reacted quantitatively with 1c solely, providing

the magnesiated thiophenes 6g–i. After acylation or cross-

coupling with 4-iodoanisole, the functionalized thiophenes

7g–i were isolated in 63–91% yield (entries 7–9). Analo-

gously, the bromoquinolines 5j,k and bromoisoquinoline 5l

underwent complete Br/Mg exchange upon treatment with

1c (25 °C, 60 min). The corresponding diheteroarylmagne-

sium compounds 6j–l were smoothly engaged in a Pd-cata-

lyzed cross-coupling with (E)-1-iodooct-1-ene or in Cu-cat-

alyzed allylations with 3-bromocyclohexene, producing the

functionalized (iso)quinolines 7ja,jb and 7k,l in 70–79%

yield (entries 10–13).

F

2^c

PhCHO

NC

6b (–20, 120)

7b: 62

Mg

2

Br

3^c

CN

6c (–20, 120)

7c: 79

OMe

Mg

2

OMe

4^c

NC

I

NC

6d (–20, 120)

7d: 55

CN

Mg

2

Me

Br

5^c

6^c

7

Br

6e (–20, 120)

7e: 85

Me

Br

Mg

Br

Me

Br

2

CO₂Et

O

CO₂Et

O

6f (–20, 90)

7f: 51

O

Mg

O

Cl

2

Cl

CN

S

CN

S

Cl

We further studied the reactivity of the exchange re-

agents with alkenyl iodides in toluene (Table 4). First, we

treated (E)-1-iodooct-1-ene (8a) with the previously de-

6g (–20, 45)

7g: 91

O

Br

Mg

Br

O

scribed sBuMgOR·LiOR (1a,

R

=

2-ethylhexyl) and

2

8

sBu₂Mg·2LiOR (1b)⁵in toluene at 0 °C for 60 minutes, which

both led to total decomposition of 8a (entries 1 and 2). In an

attempt to achieve a full exchange reaction, we mixed 8a

with 1c under various conditions. Thus, treatment of 8a

with 1c at 0 °C led after 60 minutes to 9a (Y = alkenyl) in 6%

yield (entry 3). However, using sBu₂Mg (1c) (0.6 equiv) in

the presence of DMPU (1.0 equiv)¹³led to complete magne-

siation of 8a after 60 minutes at 0 °C, affording 9a (Y = alke-

nyl) in 99% yield (entry 4).

Cl

S

6h (–20, 45)

7h: 63

OMe

R

Mg

R

S

2

9

OMe

6i (R = CO₂Et; –40,

45)

I

7i: R = CO₂Et, 72

E

A. Desaintjean et al.

Paper

Synthesis

0 °C, providing the (Z)-dialkenyl magnesium species 9c (Z/E =

99:1). On the one hand, when 9c reacted with DMF, the un-

saturated aldehyde was fully isomerized into its (E)-isomer,

providing product 10ca in 53% yield. On the other hand, al-

lylation with allyl bromide generated the Z-alkene 10cb in

73% yield. Finally, the (Z)-alkene 8d and (E)-alkene 8e fur-

nished after thioalkylation the corresponding alkenes 10d

and 10e in yields of 82% and 70%, respectively, with reten-

tion of configuration.

Entry

10

Magnesium

reagent (°C, min)

Electrophile^a

(0.8–1.2 equiv)

Product, yield

(%)^b

I

Hex

N

Mg

2

N

Hex

7ja: 78

6j (25, 60)

Br

N

11

6j (25, 60)

7jb: 70

sBu₂Mg

(1c) (0.6 equiv)

DMPU (1.0 equiv)

Br

E⁺

Br

R¹

I

Mg

E

2

12^d

toluene, 0 °C

60 min

R²

8a–e

R²

9a–e

R²

10a–e

(0.8 equiv)

N

Mg

2

6k (25, 60)

8a: R¹= Hex, R²= H, Z/E = 1:99

8c: R¹= H, R²= CH(OTBDMS)Hex,

Z/E = 99:1

8b: R¹= H, R²= Pent, Z/E = 99:1

8d: R¹= H, R²= 4-CF₃-C₆H₄, Z/E = 99:1

^l8e: R¹= 2-Br-C₆H₄, R²= H, Z/E = 1:99

7k: 71

Br

N

OTBDMS

CO₂Et

Br

N

Hex

Pent

Hex

CHO

13

2

Mg

10a: Z/E = 1:99, 82%^a

10b: Z/E = 99:1, 66%^a

SBu

10ca: Z/E = 1:99, 53%

6l (25, 60)

7l: 79

Br

TBDMSO

^aSee the Supporting Information for detailed electrophilic trappings.

^bIsolated yield of analytically pure product.

^cDMPU (1.0 equiv) was used.

Hex

SMe

CF₃

10d: Z/E = 99:1, 82%

^aCuCN·2LiCl (10 mol%) was used.

10cb: Z/E = 99:1, 73%^a

^dA 97:3 ratio of the regioisomers was obtained.

10e: Z/E = 1:99, 70%

Scheme 2 Reactions of various alkenyl iodides with sBu₂Mg (1c) in the

The newly formed dialkenylmagnesium reagent 9a

smoothly reacted in toluene with ethyl 2-(bromomethyl)-

acrylate in the presence of copper to provide the allylated

(E)-alkene 10a in 82% yield (Scheme 2).

presence of DMPU followed by electrophilic functionalization¹⁵

In summary, various polyfunctionalized iodo- and bro-

mo(hetero)arenes underwent efficient halogen/magnesium

exchange upon addition of R₂Mg (R = sBu, Mes) in toluene

under mild reaction conditions. The resulting di(hete-

ro)arylmagnesium reagents 3 and 6, which tolerated func-

tional groups like nitro and triazene, underwent smooth

electrophilic functionalizations such as cross-couplings, al-

lylations, acylations, and addition to aldehydes or ketones.

The method was successfully extended to a retentive I/Mg

exchange on alkenyl iodides to provide reactive alkenyl-

magnesium species in toluene.

Table 4 Screening of the I/Mg Exchange on (E)-1-Iodooct-1-ene (8a)

I

MgY

Exchange reagent

Hex

toluene, 0 °C

60 min

9a: Y = OR·LiOR,

8a

alkenyl·2LiOR, alkenyl

Entry

Exchange reagent (equiv)^a

Yield (%)^b

1

2

3

4

sBuMgOR·LiOR (1a) (1.2 equiv)

sBu₂Mg·2LiOR (1b) (0.6 equiv)

sBu₂Mg (1c) (0.6 equiv)

0

6

Unless stated otherwise, all reactions were carried out with magnetic

stirring in flame-dried glassware under argon. Syringes used to trans-

fer anhydrous solvents or reagents were purged with argon prior to

use. Reactions were monitored by gas chromatography or by thin-lay-

er chromatography. TLC was performed using aluminum plates coat-

ed with SiO₂(Merck 60, F-254) and samples were visualized under UV

radiation. Purification by column chromatography was performed us-

ing silica gel 60 (40–63 mm, 230–400 mesh, ASTM from Merck).

Commercially available starting materials were used without further

purification unless stated otherwise. THF was continuously refluxed

and freshly distilled from sodium benzophenone. Non-commercially

available halo(hetero)arenes and alkenyl iodides were prepared as re-

quired (see the Supporting Information). Yields refer to those of iso-

sBu₂Mg (1c) (0.6 equiv) + DMPU (1.0 equiv)

99

^aR = 2-Ethylhexyl. These reactions were carried out at a concentration of

0.50 M. Reagents are displayed according to their stoichiometry and not

their actual structure.

^bCalibrated yields determined by GC analysis of reaction aliquots quenched

with water. A 0% yield indicates that complete decomposition was ob-

served.

The exchange using (Z)-1-iodohept-1-ene (8b) followed

by allylation proceeded with retention of the configuration,

affording the (Z)-alkene 10b in 66% yield and a Z/E ratio of

99:1. In addition, the protected allylic alcohol 8c under-

went retentive I/Mg exchange with 1c within 60 min at

F

A. Desaintjean et al.

Paper

Synthesis

lated compounds estimated to be >95% pure as determined by ¹H

NMR spectroscopy (25 °C) and capillary GC analysis. Melting points

were measured with a Büchi B-540 apparatus and are uncorrected. IR

spectra were recorded on a Perkin Elmer spectrum BX-59343 instru-

ment. For detection, a Smiths Detection DuraSamplIR II Diamond ATR

sensor was used. NMR spectra of samples in CDCl₃were recorded on a

Bruker Avance III HD 400 spectrometer. Mass spectra and high-reso-

lution mass spectra were recorded on Finnigan MAT 90 or Finnigan

MAT 95 instruments using electron ionization (EI).

overnight. After work-up, the crude product was purified via column

chromatography (isohexane/ethyl acetate = 60:40, R_f= 0.29) to give

the product 4aa (90 mg, 491 mol, 98% yield) as an orange oil.

IR (ATR): 2931, 1633, 1570, 1445, 1046.

¹H NMR (400 MHz, CDCl₃):  = 7.61 (dd, J = 7.7, 1.4 Hz, 1 H), 7.52 (td,

J = 7.7, 1.5 Hz, 1 H), 7.36 (dd, J = 8.0, 1.2 Hz, 1 H), 7.28 (td, J = 7.6, 1.2

Hz, 1 H), 6.04–5.94 (m, 1 H), 5.63 (dd, J = 10.1, 2.5 Hz, 1 H), 3.86 (ddt,

J = 8.3, 5.6, 2.8 Hz, 1 H), 2.19–2.05 (m, 3 H), 1.75–1.61 (m, 2 H), 1.57–

1.47 (m, 1 H).

¹³C NMR (101 MHz, CDCl₃):  = 150.4, 133.0, 132.9, 130.1, 128.4,

128.1, 126.7, 118.2, 112.1, 40.2, 31.7, 24.9, 21.0.

sBu₂Mg (1c)

A dry and argon-flushed Schlenk flask equipped with a stirring bar

and a septum was charged with sBuMgCl (10.2 mL, 20 mmol, 1.95 M

in Et₂O, 1.0 equiv). Next, sBuLi (12.8 mL, 20 mmol, 1.56 M in cyclo-

hexane, 1.0 equiv) was added at room temperature under vigorous

stirring. The resulting suspension was stirred for 2 h at room tem-

perature. The solvents were removed under vacuum followed by ad-

dition of dry toluene (40 mL). The resulting suspension was vigorous-

ly stirred and allowed to settle overnight. The solution was carefully

separated from the residue by cannula using a syringe filter to afford

sBu₂Mg (0.43–0.48 M, 96% yield) in toluene.

MS (EI, 70 eV): m/z (%) = 183 (18), 182 (100), 168 (24), 167 (27), 166

(15), 165 (45), 154 (31), 140 (15), 115 (23).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₃H₁₃N: 183.1048; found:

183.1040.

Ethyl 2-(2-Cyanobenzyl)acrylate (4ab)

Ethyl 2-(2-cyanobenzyl)acrylate (4ab) was prepared via GP1 using 2-

iodobenzonitrile (2a) (115 mg, 0.50 mmol) and dry toluene (5.0 mL).

sBu₂Mg (1c) (0.63 mL, 0.30 mmol) was then added at –78 °C. After

stirring at –78 °C for 10 min, CuCN·2LiCl (1.00 M in THF, 50 L, 50

mol) and ethyl 2-(bromomethyl)acrylate (83 L, 0.60 mmol) were

added and the reaction solution was allowed to warm to room tem-

perature overnight. After work-up, the crude product was purified via

column chromatography (isohexane/ethyl acetate = 80:20, R_f= 0.35)

to give the product 4ab (88 mg, 409 mol, 88% yield) as a yellow oil.

Mes₂Mg (1d)

A dry and argon-flushed Schlenk flask equipped with a stirring bar

and a septum was charged with MesMgCl (23.5 mL, 20 mmol, 0.85 M

in Et₂O, 1.0 equiv). Next, MesLi (13.3 mL, 20 mmol, 1.50 M in Et₂O, 1.0

equiv) was added at –60 °C under vigorous stirring. The resulting sus-

pension was stirred overnight at –20 °C. The solvents were removed

under vacuum followed by addition of dry toluene (30 mL). The re-

sulting suspension was vigorously stirred and allowed to settle over-

night. The solution was carefully separated from the residue by can-

nula using a syringe filter to afford Mes₂Mg (0.55–0.65 M, 80% yield)

in toluene.

IR (ATR): 2981, 2224, 1712, 1137, 761 cm^–1

.

¹H NMR (400 MHz, CDCl₃):  = 7.63 (dd, J = 7.8, 1.4 Hz, 1 H), 7.51 (td,

J = 7.7, 1.5 Hz, 1 H), 7.40–7.35 (m, 1 H), 7.31 (td, J = 7.6, 1.2 Hz, 1 H),

6.32 (d, J = 1.0 Hz, 1 H), 5.57 (d, J = 1.3 Hz, 1 H), 4.18 (q, J = 7.1 Hz, 2 H),

3.86 (s, 2 H), 1.25 (t, J = 7.1 Hz, 3 H).

¹³C NMR (101 MHz, CDCl₃):  = 166.3, 142.7, 138.2, 133.0, 132.8,

130.3, 127.7, 127.1, 118.0, 113.1, 61.1, 36.6, 14.2.

Preparation of Diorganomagnesium Species by Halide/Magnesium

Exchange Followed by Electrophilic Functionalization; General

Procedure 1 (GP1)

MS (EI, 70 eV): m/z (%) = 187 (20), 170 (9), 169 (14), 143 (10), 142

(28), 141 (100), 140 (32), 115 (30), 114 (19).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₃H₁₃NO₂: 215.0946; found:

215.0941.

A dry and argon-flushed Schlenk flask equipped with a magnetic stir-

ring bar and a septum was charged with the corresponding (hete-

ro)aryl or alkenyl halide (1.0 equiv) and dry toluene at the indicated

concentration. When necessary, DMPU was added (detailed for each

compound thereafter). Next, the exchange reagent R₂Mg (1c, R = sBu;

1d, R = Mes) (0.6–0.7 equiv) was added dropwise at the indicated

temperature and the resulting mixture was stirred for the indicated

amount of time. Subsequent reactions with electrophiles were car-

ried out under the indicated conditions. The mixture was then

quenched with sat. aq NH₄Cl solution (10 mL), diluted with water (10

mL) and extracted with ethyl acetate (3 × 30 mL). The combined or-

ganic extracts were dried over Na₂SO₄, filtered and concentrated in

vacuo. The crude residue was purified by flash chromatography on

silica gel using the appropriate eluent.

4′-Methoxy-[1,1′-biphenyl]-2-carbonitrile (4ac)

Biaryl 4ac was prepared via GP1 using 2-iodobenzonitrile (2a) (115

mg, 0.50 mmol) and dry toluene (5.0 mL). sBu₂Mg (1c) (0.63 mL, 0.30

mmol) was then added at –78 °C. After stirring at –78 °C for 10 min,

ZnCl₂(1.00 M in THF, 0.65 mL, 0.65 mmol), Pd(OAc)₂(5 mg, 4 mol%),

SPhos (17 mg, 8 mol%) and 4-iodoanisole (93 mg, 0.40 mmol) were

added and the reaction mixture was stirred at room temperature

overnight. After work-up, the crude product was purified via column

chromatography (isohexane/ethyl acetate = 90:10, R_f= 0.30) to give

the product 4ac (61 mg, 291 mol, 73% yield) as a white solid.

Mp 84–86 °C.

1′,2′,3′,4′-Tetrahydro-[1,1′-biphenyl]-2-carbonitrile (4aa)

IR (ATR): 2922, 2222, 1608, 1478, 1246, 763 cm^–1

.

¹H NMR (400 MHz, CDCl₃):  = 7.74 (dd, J = 7.7, 1.4 Hz, 1 H), 7.62 (td,

J = 7.7, 1.4 Hz, 1 H), 7.55–7.47 (m, 3 H), 7.40 (td, J = 7.6, 1.2 Hz, 1 H),

7.04–6.99 (m, 2 H), 3.87 (s, 3 H).

¹³C NMR (101 MHz, CDCl₃):  = 160.2, 145.3, 133.9, 132.9, 130.6,

130.1, 130.0, 127.2, 119.2, 114.3, 111.2, 55.5.

The benzonitrile derivative 4aa was prepared via GP1 using 2-iodo-

benzonitrile (2a) (115 mg, 0.50 mmol) and dry toluene (5.0 mL).

sBu₂Mg (1c) (0.63 mL, 0.30 mmol) was then added at –78 °C. After

stirring at –78 °C for 10 min, CuCN·2LiCl (1.00 M in THF, 50 L, 50

mol) and 3-bromocyclohexene (47 L, 0.40 mmol) were added and

the reaction solution was allowed to warm to room temperature

MS (EI, 70 eV): m/z (%) = 210 (15), 209 (100), 194 (12), 167 (7), 166

(47), 140 (27), 139 (13), 113 (7), 63 (8), 42 (6).

G

A. Desaintjean et al.

Paper

Synthesis

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₄H₁₁NO: 209.0841; found:

Mp 118–120 °C.

209.0831.

IR (ATR): 2987, 2223, 1707, 1098, 771 cm^–1

.

¹H NMR (400 MHz, CDCl₃):  = 8.18–8.12 (m, 2 H), 7.78–7.70 (m, 4 H),

7.67–7.63 (m, 2 H), 4.41 (q, J = 7.1 Hz, 2 H), 1.42 (t, J = 7.1 Hz, 3 H).

¹³C NMR (101 MHz, CDCl₃):  = 166.3, 144.6, 143.4, 132.9, 130.7,

2-[Cyclobutyl(hydroxy)(phenyl)methyl]benzonitrile (4ad)

Tertiary alcohol 4ad was prepared via GP1 using 2-iodobenzonitrile

(2a) (115 mg, 0.50 mmol) and dry toluene (5.0 mL). sBu₂Mg (1c) (0.63

mL, 0.30 mmol) was then added at –78 °C. After stirring at –78 °C for

10 min, cyclobutyl(phenyl)methanone (91 L, 0.60 mmol) was added

and the reaction solution was stirred at room temperature overnight.

After work-up, the crude product was purified via column chroma-

tography (isohexane/ethyl acetate = 80:20, R_f= 0.34) to give the prod-

uct 4ad (72 mg, 273 mol, 55% yield) as a colorless oil.

130.5, 128.1, 127.3, 118.8, 111.9, 61.4, 14.5.

MS (EI, 70 eV): m/z (%) = 251 (88), 223 (83), 207 (42), 206 (100), 178

(58), 177 (71), 152 (16), 151 (64), 150 (18).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₆H₁₃NO₂: 251.0946; found:

251.0944.

IR (ATR): 2938, 2168, 1724, 906, 730 cm^–1

.

4-Bromo-2-(4-chlorobenzoyl)benzonitrile (4d)

¹H NMR (400 MHz, CDCl₃):  = 7.60–7.52 (m, 2 H), 7.51–7.43 (m, 2 H),

7.38–7.20 (m, 5 H), 3.39 (dt, J = 16.6, 8.5 Hz, 1 H), 2.26 (s, 1 H), 2.08–

1.96 (m, 3 H), 1.94–1.84 (m, 1 H), 1.83–1.73 (m, 1 H), 1.72–1.64 (m, 1

H).

¹³C NMR (101 MHz, CDCl₃):  = 151.4, 145.2, 132.0, 128.6, 128.5,

127.7, 127.1, 126.5, 126.3, 119.1, 110.6, 78.5, 43.8, 23.3, 22.3, 17.2.

Diaryl ketone 4d was prepared via GP1 using 4-bromo-2-iodobenzo-

nitrile (2d) (154 mg, 0.50 mmol) and dry toluene (1.0 mL). sBu₂Mg

(1c) (0.63 mL, 0.30 mmol) was then added at –78 °C. After stirring

at –78 °C for 10 min, CuCN·2LiCl (1.00 M in THF, 50 L, 50 mol) and

4-chlorobenzoyl chloride (77 L, 0.60 mmol) were added and the re-

action solution was allowed to warm to –20 °C and stirred at this

temperature overnight. After work-up, the crude product was puri-

fied via column chromatography (isohexane/ethyl acetate = 90:10,

R_f= 0.23) to give the product 4d (121 mg, 380 mol, 76% yield) as a

white solid.

MS (EI, 70 eV): m/z (%) = 209 (15), 208 (100), 190 (2), 130 (80), 105

(5), 102 (2), 77 (3).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₈H₁₇NO: 263.1310; found:

263.1308.

Mp 171–173 °C.

IR (ATR): 2922, 1665, 1580, 1286, 941 cm^–1

¹H NMR (400 MHz, CDCl₃):  = 7.82 (dd, J = 8.2, 2.0 Hz, 1 H), 7.78–7.73

(m, 3 H), 7.70 (d, J = 8.3 Hz, 1 H), 7.54–7.49 (m, 2 H).

¹³C NMR (101 MHz, CDCl₃):  = 191.2, 142.7, 141.2, 135.3, 134.9,

133.8, 133.0, 131.8, 129.5, 127.7, 116.4, 110.7.

.

Ethyl 3′-Cyano-[1,1′-biphenyl]-4-carboxylate (4b)

Biaryl 4b was prepared via GP1 using 3-iodobenzonitrile (2b) (115

mg, 0.50 mmol) and dry toluene (2.0 mL). sBu₂Mg (1c) (0.63 mL, 0.30

mmol) was then added at –78 °C. After stirring at –78 °C for 10 min,

ZnCl₂(1.00 M in THF, 0.65 mL, 0.65 mmol), Pd(OAc)₂(5 mg, 4 mol%),

SPhos (17 mg, 8 mol%) and ethyl 4-iodobenzoate (67 L, 0.40 mmol)

were added and the reaction mixture was stirred at room tempera-

ture overnight. After work-up, the crude product was purified via col-

umn chromatography (isohexane/ethyl acetate = 90:10, R_f= 0.30) to

give the product 4b (72 mg, 286 mol, 72% yield) as a white solid.

MS (EI, 70 eV): m/z (%) = 287 (7), 286 (47), 285 (8), 284 (49), 242 (7),

240 (22), 141 (33), 140 (7), 139 (100), 111 (14), 100 (7), 75 (11).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₄H₇BrClNO: 318.9400; found:

318.9393.

Mp 89–91 °C.

IR (ATR): 2981, 1710, 1273, 1103, 767 cm^–1

Ethyl 2-(2-Methylallyl)benzoate (4e)

.

Ester 4e was prepared via GP1 using ethyl 2-iodobenzoate (2e) (138

mg, 0.50 mmol) and dry toluene (0.8 mL). sBu₂Mg (1c) (0.63 mL, 0.30

mmol) was then added at –78 °C. After stirring at –78 °C for 15 min,

CuCN·2LiCl (1.00 M in THF, 50 L, 50 mol) and methallyl bromide

(60 L, 0.60 mmol) were added and the reaction solution was allowed

to warm to room temperature overnight. After work-up, the crude

product was purified via column chromatography (isohexane/ethyl

acetate = 99:1, R_f= 0.15) to give the product 4e (94 mg, 459 mol, 92%

yield) as a pale yellow oil.

¹H NMR (400 MHz, CDCl₃):  = 8.19–8.11 (m, 2 H), 7.90 (t, J = 1.7 Hz, 1

H), 7.84 (dt, J = 7.7, 1.4 Hz, 1 H), 7.68 (dt, J = 7.8, 1.4 Hz, 1 H), 7.65–

7.61 (m, 2 H), 7.58 (t, J = 7.8 Hz, 1 H), 4.41 (q, J = 7.1 Hz, 2 H), 1.42 (t,

J = 7.1 Hz, 3 H).

¹³C NMR (101 MHz, CDCl₃):  = 166.3, 143.1, 141.5, 131.7, 131.6,

131.0, 130.5, 129.9, 127.2, 118.7, 113.3, 61.3, 14.5.

MS (EI, 70 eV): m/z (%) = 252 (5), 251 (28), 224 (5), 223 (30), 207 (15),

206 (100), 179 (5), 178 (23), 177 (28), 176 (5), 152 (9), 151 (26), 150

(9), 75 (6), 51 (5).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₆H₁₃NO₂: 251.0946; found:

IR (ATR): 2925, 1717, 1253, 1076, 740 cm^–1

.

¹H NMR (400 MHz, CDCl₃):  = 7.86 (dd, J = 7.8, 1.5 Hz, 1 H), 7.43 (td,

J = 7.5, 1.5 Hz, 1 H), 7.35–7.18 (m, 2 H), 4.78 (dq, J = 2.4, 1.3 Hz, 1 H),

4.45 (tt, J = 1.6, 0.8 Hz, 1 H), 4.33 (q, J = 7.1 Hz, 2 H), 3.71 (s, 2 H), 1.74

(dd, J = 1.4, 0.8 Hz, 3 H), 1.37 (t, J = 7.1 Hz, 3 H).

251.0934.

Ethyl 4′-Cyano-[1,1′-biphenyl]-4-carboxylate (4c)

¹³C NMR (101 MHz, CDCl₃):  = 168.0, 145.5, 140.9, 131.7, 131.5,

Biaryl 4c was prepared via GP1 using 4-iodobenzonitrile (2c) (115

mg, 0.50 mmol) and dry toluene (2.0 mL). sBu₂Mg (1c) (0.63 mL, 0.30

mmol) was then added at –78 °C. After stirring at –78 °C for 10 min,

ZnCl₂(1.00 M in THF, 0.65 mL, 0.65 mmol), Pd(OAc)₂(5 mg, 4 mol%),

SPhos (17 mg, 8 mol%) and ethyl 4-iodobenzoate (67 L, 0.40 mmol)

were added and the reaction mixture was stirred at room tempera-

ture overnight. After work-up, the crude product was purified via col-

umn chromatography (isohexane/ethyl acetate = 90:10, R_f= 0.23) to

give the product 4c (70 mg, 278 mol, 70% yield) as a white solid.

130.9, 130.5, 126.3, 111.6, 61.0, 41.9, 23.0, 14.4.

MS (EI, 70 eV): m/z (%) = 189 (100), 161 (85), 159 (56), 158 (57), 157

(25), 143 (20), 131 (51), 130 (25), 129 (74), 128 (26), 115 (51), 91 (29).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₃H₁₆O₂: 204.1150; found:

204.1144.

H

A. Desaintjean et al.

Paper

Synthesis

(4-Chlorophenyl)(2-fluoropyridin-3-yl)methanone (4fa)

the crude product was purified via column chromatography (isohex-

ane/ethyl acetate = 90:10, R_f= 0.46) to give the product 4g (95 mg,

377 mol, 75% yield) as a white solid.

Ketone 4fa was prepared via GP1 using 2-fluoro-3-iodopyridine (2f)

(112 mg, 0.50 mmol) and dry toluene (1.0 mL). sBu₂Mg (1c) (0.63 mL,

0.30 mmol) was then added at –78 °C. After stirring at –78 °C for 15

min, CuCN·2LiCl (1.00 M in THF, 0.30 mL, 0.30 mmol) and 4-chloro-

benzoyl chloride (77 L, 0.60 mmol) were added and the reaction

solution was allowed to warm to room temperature overnight. After

work-up, the crude product was purified via column chromatography

(isohexane/ethyl acetate = 90:10, R_f= 0.15) to give the product 4fa (86

mg, 365 mol, 73% yield) as a white solid.

Mp 85–87 °C.

IR (ATR): 3079, 1657, 1280, 1165, 661 cm^–1

.

¹H NMR (400 MHz, CDCl₃):  = 7.85–7.77 (m, 2 H), 7.73–7.66 (m, 1 H),

7.59–7.49 (m, 4 H).

¹³C NMR (101 MHz, CDCl₃):  = 192.3, 151.4, 149.9, 135.1, 134.4,

130.2, 129.1, 122.5.

Mp 93–95 °C.

MS (EI, 70 eV): m/z (%) = 251 (12), 216 (3), 146 (3), 110 (4), 106 (8),

105 (100), 77 (25).

IR (ATR): 2921, 1656, 1090, 848, 772 cm^–1

.

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₂H₇Cl₂NO: 250.9905; found:

250.9894.

¹H NMR (400 MHz, CDCl₃):  = 8.44 (d, J = 4.3 Hz, 1 H), 8.05 (ddd, J =

9.2, 7.4, 2.0 Hz, 1 H), 7.82–7.72 (m, 2 H), 7.54–7.44 (m, 2 H), 7.38 (ddd,

J = 7.0, 4.8, 1.9 Hz, 1 H).

3-Iodo-4-methoxy-5-(2-methylallyl)benzonitrile (4h)

¹³C NMR (101 MHz, CDCl₃):  = 190.7 (d, J = 4.8 Hz), 161.3, 158.9,

150.9 (d, J = 14.9 Hz), 142.0 (d, J = 3.3 Hz), 135.0, 131.1 (d, J = 1.3 Hz),

129.2, 122.0 (d, J = 4.7 Hz), 121.3 (d, J = 30.1 Hz).

Iodoanisole 4h was prepared via GP1 using 3,5-diiodo-4-methoxy-

benzonitrile (2h) (192 mg, 0.50 mmol) and dry toluene (1.0 mL).

sBu₂Mg (1c) (0.63 mL, 0.30 mmol) was then added at –78 °C. After

stirring at –78 °C for 15 min, CuCN·2LiCl (1.00 M in THF, 50 L, 50

mol) and methallyl bromide (60 L, 0.60 mmol) were added and the

reaction solution was allowed to warm to –20 °C and stirred at this

temperature overnight. After work-up, the crude product was puri-

fied via column chromatography (isohexane/ethyl acetate = 90:10,

R_f= 0.54) to give the product 4h (80 mg, 255 mol, 51% yield) as a col-

orless oil.

¹⁹F NMR (377 MHz, CDCl₃):  = –62.4.

MS (EI, 70 eV): m/z (%) = 237 (5), 235 (16), 141 (33), 140 (8), 139

(100), 124 (7), 111 (9), 96 (5), 75 (6).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₂H₇ClFNO: 235.0200; found:

235.0194.

(1R,3R,5R,7R)-2-(2-Fluoropyridin-3-yl)adamantan-2-ol (4fb)

IR (ATR): 2940, 2359, 1464, 1265, 994 cm^–1

.

Tertiary alcohol 4fb was prepared via GP1 using 2-fluoro-3-iodopyri-

dine (2f) (112 mg, 0.50 mmol), dry THF (48 L, 0.60 mmol) and dry

toluene (1.0 mL). sBu₂Mg (1c) (0.63 mL, 0.30 mmol) was then added

at –78 °C. After stirring at –78 °C for 15 min, adamantone (150 mg,

1.00 mmol) previously dissolved in toluene (0.2 mL) was added and

the reaction solution was allowed to warm to room temperature

overnight. After work-up, the crude product was purified via column

chromatography (isohexane/ethyl acetate = 60:40, R_f= 0.32) to give

the product 4fb (91 mg, 368 mol, 74% yield) as a white solid.

¹H NMR (400 MHz, CDCl₃):  = 7.95 (d, J = 2.0 Hz, 1 H), 7.56–7.37 (m, 1

H), 4.93 (tt, J = 1.7, 0.9 Hz, 1 H), 4.66 (tq, J = 1.4, 0.7 Hz, 1 H), 3.81 (s, 3

H), 3.40 (s, 2 H), 1.72 (t, J = 1.0 Hz, 3 H).

¹³C NMR (101 MHz, CDCl₃):  = 162.2, 143.2, 141.3, 135.5, 135.0,

117.3, 113.9, 110.0, 92.5, 61.5, 38.4, 22.6.

MS (EI, 70 eV): m/z (%) = 313 (86), 284 (35), 186 (45), 171 (100), 170

(64), 157 (65), 156 (93), 144 (26), 143 (35), 140 (26), 115 (60).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₂H₁₂INO: 312.9964; found:

312.9964.

Mp 110–113 °C.

IR (ATR): 2915, 1596, 1242, 1103, 968, 808 cm^–1

.

¹H NMR (400 MHz, CDCl₃):  = 8.17–8.05 (m, 1 H), 7.89 (ddd, J = 10.4,

7.6, 1.9 Hz, 1 H), 7.19 (ddd, J = 7.7, 4.8, 2.1 Hz, 1 H), 2.65 (s, 2 H), 2.42

(d, J = 12.5 Hz, 2 H), 2.13 (d, J = 2.8 Hz, 1 H), 1.93–1.78 (m, 4 H), 1.76–

1.63 (m, 6 H).

¹³C NMR (101 MHz, CDCl₃):  = 161.8 (d, J = 241.3 Hz), 146.2 (d, J =

16.1 Hz), 139.4 (d, J = 5.5 Hz), 127.8 (d, J = 24.2 Hz), 121.4 (d, J = 4.2

Hz), 75.8 (d, J = 5.1 Hz), 37.6, 35.6, 35.5, 35.1, 32.9, 27.2, 26.7.

Ethyl 3-[Hydroxy(phenyl)methyl]-5-iodo-4-methoxybenzoate (4i)

Alcohol 4i was prepared via GP1 using ethyl 3,5-diiodo-4-methoxy-

benzoate (2i) (215 mg, 0.50 mmol) and dry toluene (1.0 mL). sBu₂Mg

(1c) (0.63 mL, 0.30 mmol) was then added at –78 °C. After stirring at

–78 °C for 15 min, benzaldehyde (0.69 L, 0.60 mmol) was added and

the reaction solution was allowed to warm to room temperature

overnight. After work-up, the crude product was purified via column

chromatography (isohexane/ethyl acetate = 80:20, R_f= 0.12) to give

the product 4i (109 mg, 265 mol, 53% yield) as a colorless oil.

¹⁹F NMR (377 MHz, CDCl₃):  = –62.0.

MS (EI, 70 eV): m/z (%) = 230 (16), 229 (100), 204 (11), 187 (40), 186

(11), 175 (12), 152 (15), 151 (19), 150 (16), 140 (20), 136 (20), 127

(11), 124 (25), 93 (15), 91 (14), 81 (12), 79 (18).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₅H₁₈FNO: 247.1372; found:

IR (ATR): 3439, 1715, 1275, 1144, 700 cm^–1

.

¹H NMR (400 MHz, CDCl₃):  = 8.41 (d, J = 2.1 Hz, 1 H), 8.18 (d, J = 2.1

Hz, 1 H), 7.39–7.32 (m, 4 H), 7.30–7.27 (m, 1 H), 6.09 (d, J = 4.8 Hz, 1

H), 4.36 (qd, J = 7.1, 1.2 Hz, 2 H), 3.62 (s, 3 H), 2.57 (d, J = 5.1 Hz, 1 H),

1.38 (t, J = 7.1 Hz, 3 H).

247.1369.

(2,6-Dichloropyridin-4-yl)(phenyl)methanone (4g)

¹³C NMR (101 MHz, CDCl₃):  = 164.9, 160.9, 143.0, 140.7, 138.5,

129.9, 128.8, 128.5, 128.1, 126.8, 91.4, 72.1, 61.6, 61.5, 14.5.

Ketone 4g was prepared via GP1 using 2,6-dichloro-4-iodopyridine

(2g) (137 mg, 0.50 mmol) and dry toluene (1.0 mL). sBu₂Mg (1c) (0.63

mL, 0.30 mmol) was then added at –78 °C. After stirring at –78 °C for

15 min, CuCN·2LiCl (1.00 M in THF, 0.30 mL, 0.30 mmol) and benzoyl

chloride (70 L, 0.60 mmol) were added and the reaction solution

was allowed to warm to room temperature overnight. After work-up,

MS (EI, 70 eV): m/z (%) = 412 (31), 398 (17), 397 (100), 394 (11), 367

(12), 349 (14), 347 (27), 333 (11), 319 (35), 291 (15), 194 (20), 165

(12), 152 (13).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₇H₁₇IO₄: 412.0172; found:

412.0167.

I

A. Desaintjean et al.

Paper

Synthesis

4′-Methoxy-1,2,3,4-tetrahydro-1,1′-biphenyl (4ja)

¹H NMR (400 MHz, CDCl₃):  = 7.83–7.61 (m, 4 H), 7.40 (t, J = 7.9 Hz, 1

H), 7.17 (ddd, J = 7.6, 1.8, 0.9 Hz, 1 H), 7.10 (t, J = 2.1 Hz, 1 H), 6.97

(ddd, J = 8.2, 2.6, 0.9 Hz, 1 H), 3.87 (s, 3 H).

¹³C NMR (101 MHz, CDCl₃):  = 160.2, 145.6, 140.7, 132.7, 130.3,

127.9, 119.8, 119.1, 114.0, 113.2, 111.1, 55.5.

Allylated anisole 4ja was prepared via GP1 using 4-iodoanisole (2j)

(94 mg, 0.40 mmol), dry THF (39 L, 0.48 mmol) and dry toluene (0.8

mL). sBu₂Mg (1c) (0.58 mL, 0.28 mmol) was then added at 25 °C. After

stirring at 25 °C for 30 min, CuCN·2LiCl (1.00 M in THF, 40 L, 40

mol) and 3-bromocyclohexene (55 L, 0.48 mmol) were added at 0

°C and the reaction solution was allowed to warm to room tempera-

ture overnight. After work-up, the crude product was purified via col-

umn chromatography (isohexane, R_f= 0.29) to give the product 4ja

(59 mg, 312 mol, 78% yield) as a yellow oil.

MS (EI, 70 eV): m/z (%) = 210 (15), 209 (100), 180 (38), 179 (82), 178

(28), 166 (25), 151 (10), 140 (36), 139 (14).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₄H₁₁NO: 209.0841; found:

209.0832.

IR (ATR): 2931, 1510, 1245, 1035, 827 cm^–1

.

(2-Fluorophenyl)(3-methoxyphenyl)methanone (4kb)

¹H NMR (400 MHz, CDCl₃):  = 7.16–7.12 (m, 2 H), 7.00–6.64 (m, 2 H),

5.87 (dtd, J = 9.9, 3.6, 2.3 Hz, 1 H), 5.69 (dq, J = 10.2, 2.5 Hz, 1 H), 3.79

(s, 3 H), 3.36 (ddt, J = 8.2, 5.6, 2.8 Hz, 1 H), 2.11–2.04 (m, 2 H), 2.02–

1.94 (m, 1 H), 1.72 (dddd, J = 11.7, 6.6, 4.8, 2.2 Hz, 1 H), 1.61 (dddd, J =

12.2, 6.9, 3.6, 1.5 Hz, 1 H), 1.52 (dddd, J = 13.1, 10.6, 8.0, 2.6 Hz, 1 H).

¹³C NMR (101 MHz, CDCl₃):  = 158.0, 138.9, 130.6, 128.8, 128.3,

113.8, 55.4, 41.1, 32.9, 25.2, 21.3.

Ketone 4kb was prepared via GP1 using 3-iodoanisole (2k) (94 mg,

0.40 mmol), dry THF (39 L, 0.48 mmol) and dry toluene (0.8 mL).

sBu₂Mg (1c) (0.58 mL, 0.28 mmol) was then added at 25 °C. After stir-

ring at 25 °C for 30 min, CuCN·2LiCl (1.00 M in THF, 0.24 mL, 0.24

mmol) and 2-fluorobenzoyl chloride (76 mg, 0.48 mmol) were added

at 0 °C and the reaction solution was allowed to warm to room tem-

perature overnight. After work-up, the crude product was purified via

column chromatography (isohexane/ethyl acetate = 98:2, R_f= 0.24) to

give the product 4kb (55 mg, 239 mol, 60% yield) as a colorless oil.

MS (EI, 70 eV): m/z (%) = 188 (52), 160 (25), 111 (33), 109 (25), 97

(72), 95 (34), 85 (36), 83 (54), 81 (32), 71 (54), 69 (52), 57 (100), 56

(30), 55 (52), 43 (63), 41 (34).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₃H₁₆O: 188.1201; found:

IR (ATR): 1664, 1482, 1450, 1295, 753 cm^–1

.

¹H NMR (400 MHz, CDCl₃):  = 7.56–7.47 (m, 2 H), 7.44–7.42 (m, 1 H),

7.39–7.32 (m, 2 H), 7.26 (td, J = 7.6, 1.1 Hz, 1 H), 7.19–7.11 (m, 2 H),

3.86 (s, 3 H).

188.1199.

(4-Chlorophenyl)(cyclopropyl)(4-methoxyphenyl)methanol (4jb)

¹³C NMR (101 MHz, CDCl₃):  = 193.4, 160.2 (d, J = 252.4 Hz), 159.8,

138.8, 133.2 (d, J = 8.4 Hz), 130.8 (d, J = 2.9 Hz), 129.6, 127.2 (d, J =

14.8 Hz), 124.3 (d, J = 3.6 Hz), 123.1 (d, J = 1.5 Hz), 120.2, 116.4 (d, J =

21.7 Hz), 113.7, 55.6.

Alcohol 4jb was prepared via GP1 using 4-iodoanisole (2j) (94 mg,

0.40 mmol), dry THF (39 L, 0.48 mmol) and dry toluene (0.8 mL).

sBu₂Mg (1c) (0.58 mL, 0.28 mmol) was then added at 25 °C. After stir-

ring at 25 °C for 30 min, (4-chlorophenyl)(cyclopropyl)methanone

(87 mg, 0.48 mmol) was added and the reaction solution was stirred

at room temperature overnight. After work-up, the crude product was

purified via column chromatography (isohexane/ethyl acetate = 9:1,

R_f= 0.29) to give the product 4jb (73 mg, 253 mol, 63% yield) as a

colorless oil.

¹⁹F NMR (377 MHz, CDCl₃):  = –111.4.

MS (EI, 70 eV): m/z (%) = 230 (59), 210 (14), 199 (19), 135 (100), 123

(67), 107 (32), 95 (11), 77 (22).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₄H₁₁FO₂: 230.0743; found:

230.0736.

IR (ATR): 3490, 3004, 1509, 1248, 825 cm^–1

.

Cyclopropyl(4-fluorophenyl)(3-methoxyphenyl)methanol (4kc)

¹H NMR (400 MHz, CDCl₃):  = 7.38–7.29 (m, 4 H), 7.29–7.21 (m, 2 H),

6.88–6.79 (m, 2 H), 3.78 (s, 3 H), 1.81 (s, 1 H), 1.54 (tt, J = 8.2, 5.4 Hz, 1

H), 0.73–0.56 (m, 1 H), 0.56–0.47 (m, 1 H), 0.43 (dddd, J = 9.1, 6.6, 5.2,

3.7 Hz, 2 H).

¹³C NMR (101 MHz, CDCl₃):  = 158.9, 146.1, 139.1, 132.8, 128.3 (2 C),

128.1, 113.5, 55.4, 21.8, 2.3, 1.5.

Alcohol 4kc was prepared via GP1 using 3-iodoanisole (2k) (94 mg,

0.40 mmol), dry THF (39 L, 0.48 mmol) and dry toluene (0.8 mL).

sBu₂Mg (1c) (0.58 mL, 0.28 mmol) was then added at 25 °C. After stir-

ring at 25 °C for 30 min, (4-fluorophenyl)(cyclopropyl)methanone (79

mg, 0.48 mmol) was added and the reaction solution was stirred at

room temperature overnight. After work-up, the crude product was

purified via column chromatography (isohexane/ethyl acetate = 95:5,

R_f= 0.18) to give the product 4kc (102 mg, 375 mol, 94% yield) as a

yellowish oil.

MS (EI, 70 eV): m/z (%) = 262 (20), 260 (60), 247 (15), 141 (25), 139

(76), 135 (38), 121 (100), 77 (12).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₇H₁₇ClO₂: 288.0917; found:

IR (ATR): 3490, 3004, 1506, 1221, 777 cm^–1

.

288.0911.

¹H NMR (400 MHz, DMSO-d₆):  = 7.57–7.33 (m, 2 H), 7.20 (t, J = 7.9

Hz, 1 H), 7.13–7.06 (m, 2 H), 6.99–6.90 (m, 2 H), 6.77 (ddd, J = 8.2, 2.6,

0.9 Hz, 1 H), 5.26 (s, 1 H), 3.71 (s, 3 H), 1.96–1.45 (m, 1 H), 0.43 (dddd,

J = 15.2, 6.8, 3.8, 1.8 Hz, 4 H).

¹³C NMR (101 MHz, DMSO-d₆):  = 160.8 (d, J = 242.3 Hz), 158.7,

150.2, 144.8 (d, J = 3.0 Hz), 128.7, 128.4 (d, J = 8.0 Hz), 119.0, 114.2 (d,

J = 21.0 Hz), 112.7, 111.2, 74.7, 54.9, 21.3, 1.4 (2 C).

3′-Methoxy-[1,1′-biphenyl]-4-carbonitrile (4ka)

Biaryl 4ka was prepared via GP1 using 3-iodoanisole (2k) (94 mg,

0.40 mmol), dry THF (39 L, 0.48 mmol) and dry toluene (0.8 mL).

sBu₂Mg (1c) (0.58 mL, 0.28 mmol) was then added at 25 °C. After stir-

ring at 25 °C for 30 min, ZnCl₂(1.00 M in THF, 0.52 mL, 0.52 mmol),

Pd(OAc)₂(4 mg, 4 mol%), SPhos (13 mg, 8 mol%) and 4-iodobenzo-

nitrile (73 mg, 0.32 mmol) were added and the reaction solution was

stirred at room temperature overnight. After work-up, the crude

product was purified via column chromatography (isohexane/ethyl

acetate = 98:2, R_f= 0.21) to give the product 4ka (59 mg, 282 mol,

88% yield) as a yellow oil.

¹⁹F NMR (377 MHz, DMSO-d₆):  = –117.0.

MS (EI, 70 eV): m/z (%) = 245 (11), 244 (64), 183 (10), 136 (36), 135

(14), 123 (100), 108 (11), 95 (10).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₇H₁₇FO₂: 272.1213; found:

272.1209.

IR (ATR): 2226, 1603, 1480, 1296, 1215, 836 cm^–1

.

J

A. Desaintjean et al.

Paper

Synthesis

(2,4-Dichlorophenyl)(2-methoxyphenyl)methanol (4l)

¹H NMR (400 MHz, CDCl₃):  = 7.63 (d, J = 1.8 Hz, 1 H), 7.47–7.34 (m, 2

H), 7.24–7.11 (m, 2 H), 7.05–6.93 (m, 2 H), 2.37 (s, 3 H), 1.83 (s, 1 H),

1.56 (tt, J = 8.3, 5.4 Hz, 1 H), 0.72–0.55 (m, 2 H), 0.45 (dd, J = 5.4, 1.8

Hz, 2 H).

¹³C NMR (101 MHz, CDCl₃):  = 162.1 (d, J = 246.1 Hz), 146.8, 142.7 (d,

J = 3.3 Hz), 136.8, 130.7, 130.5, 128.7 (d, J = 8.0 Hz), 125.9, 124.8, 115.0

(d, J = 21.2 Hz), 76.4, 22.7, 21.8, 2.1, 1.9.

Secondary alcohol 4l was prepared via GP1 using 2-iodoanisole (2l)

(234 mg, 1.00 mmol), dry THF (100 L, 1.20 mmol) and dry toluene

(2.0 mL). sBu₂Mg (1c) (1.46 mL, 0.70 mmol) was then added at 25 °C.

After stirring at 25 °C for 30 min, 2,4-dichlorobenzaldehyde (263 mg,

1.50 mmol) was added and the reaction solution was stirred at room

temperature overnight. After work-up, the crude product was puri-

fied via column chromatography (isohexane/ethyl acetate = 90:10,

R_f= 0.28) to give the product 4l (211 mg, 745 mol, 75% yield) as a

white solid.

¹⁹F NMR (377 MHz, CDCl₃):  = –115.6.

MS (EI, 70 eV): m/z (%) = 308 (49), 306 (50), 295 (11), 293 (11), 199

(37), 197 (20), 184 (10), 183 (17), 136 (26), 123 (100).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₇H₁₆BrFO: 334.0369; found:

334.0363.

Mp 92–94 °C.

IR (ATR): 3368, 1463, 1241, 1022, 749 cm^–1

.

¹H NMR (400 MHz, CDCl₃):  = 7.53 (d, J = 8.4 Hz, 1 H), 7.38 (d, J = 2.1

Hz, 1 H), 7.32–7.27 (m, 2 H), 7.09–6.77 (m, 3 H), 6.38 (s, 1 H), 3.88 (s, 3

H), 3.03 (s, 1 H).

1-Allyl-3-iodobenzene (4oa)

Iodobenzene 4oa was prepared via GP1 using 1,3-diiodobenzene (2o)

(165 mg, 0.50 mmol), DMPU (60 L, 0.50 mmol) and dry toluene (0.50

mL). sBu₂Mg (1c) (0.63 mL, 0.30 mmol) was then added at –20 °C. Af-

ter stirring at –20 °C for 60 min, CuCN·2LiCl (1.00 M in THF, 50 L, 50

mol) and allyl bromide (52 L, 0.60 mmol) were added and the reac-

tion solution was allowed to warm to room temperature overnight.

After work-up, the crude product was purified via column chroma-

tography (isohexane, R_f= 0.60) to give the product 4oa (79 mg, 324

mol, 65% yield) as a colorless oil.

¹³C NMR (101 MHz, CDCl₃):  = 157.1, 138.7, 133.7, 133.6, 130.0,

129.6, 129.4, 129.2, 127.7, 127.3, 120.9, 110.7, 68.4, 55.6.

MS (EI, 70 eV): m/z (%) = 284 (28), 282 (51), 229 (31), 173 (34), 137

(37), 135 (52), 109 (100), 107 (29), 77 (36).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₄H₁₂Cl₂O₂: 282.0214; found:

282.0206.

tert-Butyl[(4′-methoxy-[1,1′-biphenyl]-4-yl)oxy]dimethylsilane

(4m)

IR (ATR): 2923, 1710, 1456, 1259, 1024 cm^–1

.

¹H NMR (400 MHz, CDCl₃):  = 7.84–7.50 (m, 2 H), 7.27–7.15 (m, 1 H),

7.11–6.87 (m, 1 H), 5.92 (ddt, J = 15.8, 11.0, 6.7 Hz, 1 H), 5.11 (t, J = 1.5

Hz, 1 H), 5.08 (dq, J = 7.6, 1.6 Hz, 1 H), 3.33 (dt, J = 6.7, 1.5 Hz, 2 H).

¹³C NMR (101 MHz, CDCl₃):  = 142.6, 137.7, 136.7, 135.3, 130.3,

128.0, 116.7, 94.7, 39.8.

Diaryl 4m was prepared via GP1 using tert-butyl(4-iodophenoxy)di-

methylsilane (2m) (134 mg, 0.40 mmol), dry THF (39 L, 0.48 mmol)

and dry toluene (0.8 mL). sBu₂Mg (1c) (0.58 mL, 0.28 mmol) was then

added at 25 °C. After stirring at 25 °C for 30 min, ZnCl₂(1.00 M in THF,

0.52 mL, 0.52 mmol), Pd(OAc)₂(4 mg, 4 mol%), SPhos (13 mg, 8 mol%)

and 4-iodoanisole (75 mg, 0.32 mmol) were added and the reaction

solution was stirred at room temperature overnight. After work-up,

the crude product was purified via column chromatography (isohex-

ane/toluene = 70:30, R_f= 0.49) to give the product 4m (65 mg, 207

mol, 65% yield) as a white solid.

MS (EI, 70 eV): m/z (%) = 244 (33), 118 (10), 117 (100), 115 (82), 91

(14).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₉H₉I: 243.9749; found:

243.9744.

Mp 84–86 °C.

IR (ATR): 2926, 2364, 1502, 1251, 822 cm^–1

(4-Fluorophenyl)(3-iodophenyl)methanol (4ob)

.

Secondary alcohol 4ob was prepared via GP1 using 1,3-diiodoben-

zene (2o) (165 mg, 0.50 mmol), DMPU (60 L, 0.50 mmol) and dry

toluene (0.50 mL). sBu₂Mg (1c) (0.63 mL, 0.30 mmol) was then added

at –20 °C. After stirring at –20 °C for 60 min, 4-fluorobenzaldehyde

(0.69 L, 0.60 mmol) was added and the reaction solution was al-

lowed to warm to room temperature overnight. After work-up, the

crude product was purified via column chromatography (isohex-

ane/ethyl acetate = 90:10, R_f= 0.17) to give the product 4ob (120 mg,

366 mol, 73% yield) as a colorless oil.

¹H NMR (400 MHz, CDCl₃):  = 7.68–7.35 (m, 4 H), 7.02–6.76 (m, 4 H),

3.84 (s, 3 H), 1.00 (s, 9 H), 0.22 (s, 6 H).

¹³C NMR (101 MHz, CDCl₃):  = 158.8, 154.9, 134.1, 133.7, 127.9,

127.8, 120.4, 114.2, 55.5, 25.9, 18.4, –4.2.

MS (EI, 70 eV): m/z (%) = 314 (66), 258 (34), 257 (100), 71 (19), 57

(29), 43 (35).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₉H₂₆SiO₂: 314.1702; found:

314.1701.

IR (ATR): 3341, 1506, 1221, 905, 727 cm^–1

.

¹H NMR (400 MHz, CDCl₃):  = 7.74 (t, J = 1.8 Hz, 1 H), 7.61 (dt, J = 7.8,

1.4 Hz, 1 H), 7.36–7.27 (m, 3 H), 7.10–6.99 (m, 3 H), 5.76 (d, J = 3.0 Hz,

1 H), 2.23 (d, J = 3.4 Hz, 1 H).

¹³C NMR (101 MHz, CDCl₃):  = 162.4 (d, J = 246.4 Hz), 146.0, 139.1 (d,

J = 3.2 Hz), 136.9, 135.4, 130.4, 128.4 (d, J = 8.2 Hz), 125.8, 115.7 (d, J =

21.6 Hz), 94.7, 75.0.

(3-Bromo-4-methylphenyl)(cyclopropyl)(4-fluorophenyl)metha-

nol (4n)

Alcohol 4n was prepared via GP1 using 2-bromo-4-iodo-1-methyl-

benzene (2n) (119 mg, 0.40 mmol), dry THF (39 L, 0.48 mmol) and

dry toluene (0.8 mL). sBu₂Mg (1c) (0.58 mL, 0.28 mmol) was then

added at 25 °C. After stirring at 25 °C for 30 min, (4-fluorophenyl)-

(cyclopropyl)methanone (79 mg, 0.48 mmol) was added and the reac-

tion solution was stirred at room temperature overnight. After work-

up, the crude product was purified via column chromatography (iso-

hexane/ethyl acetate = 9:1, R_f= 0.46) to give the product 4n (71 mg,

212 mol, 53% yield) as a colorless oil.

¹⁹F NMR (377 MHz, CDCl₃):  = –114.3.

MS (EI, 70 eV): m/z (%) = 328 (15), 231 (92), 204 (19), 203 (11), 201

(11), 183 (22), 125 (14), 123 (100), 97 (19), 78 (11), 77 (15), 76 (11).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₃H₁₀FIO: 327.9760; found:

327.9755.

IR (ATR): 3467, 1506, 1225, 1159, 836 cm^–1

.

K

A. Desaintjean et al.

Paper

Synthesis

Ethyl 2-Iodobenzoate (4pa)

¹³C NMR (101 MHz, CDCl₃):  = 144.1, 143.6, 143.0, 137.3, 113.4, 94.9,

43.8, 22.1.

Ester 4pa was prepared via GP1 using 1,2-diiodobenzene (2p) (165

mg, 0.50 mmol), DMPU (60 L, 0.50 mmol) and dry toluene (0.50 mL).

sBu₂Mg (1c) (0.63 mL, 0.30 mmol) was then added at –20 °C. After

stirring at –20 °C for 60 min, ethyl cyanoformate (59 L, 0.60 mmol)

was added and the reaction solution was allowed to warm to room

temperature overnight. After work-up, the crude product was puri-

fied via column chromatography (isohexane/ethyl acetate = 99:1, R_f=

0.31) to give the product 4pa (62 mg, 225 mol, 45% yield) as a color-

less oil.

MS (EI, 70 eV): m/z (%) = 384 (12), 257 (18), 226 (19), 196 (14), 194

(18), 165 (12), 130 (26), 129 (15), 115 (21), 57 (26), 55 (10), 45 (100),

44 (40), 43 (17), 41 (15).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₀H₁₀I₂: 383.8872; found:

383.8875.

1-[(4-Allylphenyl)diazenyl]pyrrolidine (4r)

Triazene 4r was prepared via GP1 using 1-[(4-iodophenyl)diaze-

nyl]pyrrolidine (2r) (90 mg, 0.30 mmol), DMPU (36 L, 0.30 mmol)

and dry toluene (0.60 mL). Mes₂Mg (1d) (0.28 mL, 0.18 mmol) was

then added at –20 °C. After stirring at –20 °C for 1 h, CuCN·2LiCl (1.00

M in THF, 30 L, 30 mol) and allyl bromide (31 L, 0.36 mmol) were

added and the reaction solution was allowed to warm to room tem-

perature overnight. After work-up, the crude product was purified via

column chromatography (isohexane/ethyl acetate = 97:3, R_f= 0.25) to

give the product 4r (51 mg, 237 mol, 79% yield) as a yellowish solid.

IR (ATR): 2979, 1725, 1288, 1250, 741 cm^–1

.

¹H NMR (400 MHz, CDCl₃):  = 7.97 (dd, J = 8.0, 1.2 Hz, 1 H), 7.78 (dd,

J = 7.8, 1.7 Hz, 1 H), 7.39 (td, J = 7.6, 1.2 Hz, 1 H), 7.13 (td, J = 7.7, 1.7

Hz, 1 H), 4.39 (q, J = 7.1 Hz, 2 H), 1.40 (t, J = 7.1 Hz, 3 H).

¹³C NMR (101 MHz, CDCl₃):  = 166.7, 141.3, 135.5, 132.6, 130.9,

128.0, 94.1, 61.8, 14.3.

MS (EI, 70 eV): m/z (%) = 276 (24), 248 (33), 231 (100), 203 (30), 127

(11), 76 (37), 50 (14).

Mp 50–52 °C.

IR (ATR): 2973, 2870, 1430, 1404, 1319 cm^–1

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₉H₉O₂I: 275.9647; found:

275.9645.

.

¹H NMR (400 MHz, CDCl₃):  = 7.56–7.31 (m, 2 H), 7.20–6.98 (m, 2 H),

5.98 (ddt, J = 16.8, 10.1, 6.6 Hz, 1 H), 5.21–4.89 (m, 2 H), 3.78 (s, 4 H),

3.37 (dd, J = 6.7, 1.6 Hz, 2 H), 2.39–1.49 (m, 4 H).

¹³C NMR (101 MHz, CDCl₃):  = 149.9, 137.9, 137.0, 129.2, 120.5,

115.6, 39.9, 24.0 (2 C).

2′-Iodo-1,2,3,4-tetrahydro-1,1′-biphenyl (4pb)

Iodobenzene 4pb was prepared via GP1 using 1,2-diiodobenzene (2p)

(165 mg, 0.50 mmol), DMPU (60 L, 0.50 mmol) and dry toluene (0.50

mL). sBu₂Mg (1c) (0.63 mL, 0.30 mmol) was then added at –20 °C. Af-

ter stirring at –20 °C for 60 min, CuCN·2LiCl (1.00 M in THF, 50 L, 50

mol) and 3-bromocyclohexene (69 L, 0.60 mmol) were added and

the reaction solution was allowed to warm to room temperature

overnight. After work-up, the crude product was purified via column

chromatography (isohexane, R_f= 0.79) to give the product 4pb (91

mg, 320 mol, 64% yield) as a red oil.

MS (EI, 70 eV): m/z (%) = 207 (20), 145 (74), 117 (16), 115 (100), 91

(33).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₃H₁₇N₃: 215.1422; found:

215.1417.

2′-Nitro-1,2,3,4-tetrahydro-1,1′-biphenyl (4s)

IR (ATR): 2928, 1460, 1432, 1009, 750 cm^–1

.

Nitrobenzene 4s was prepared via GP1 using 1-iodo-2-nitrobenzene

(2s) (125 mg, 0.50 mmol), DMPU (0.25 mL, 2.00 mmol) and dry tolu-

ene (0.50 mL). Mes₂Mg (1d) (0.46 mL, 0.30 mmol) was then added at

–50 °C. After stirring at –50 °C for 1 h, CuCN·2LiCl (1.00 M in THF, 50

L, 50 mol) and 3-bromocyclohexene (46 L, 0.40 mmol) were add-

ed and the reaction solution was allowed to warm to –20 °C and

stirred at this temperature overnight. After work-up, the crude prod-

uct was purified via column chromatography (isohexane/ethyl acetate

= 97:3, R_f= 0.25) to give the product 4s (58 mg, 284 mol, 71% yield)

as a yellowish oil.

¹H NMR (400 MHz, CDCl₃):  = 7.83 (dd, J = 7.9, 1.3 Hz, 1 H), 7.36–7.13

(m, 2 H), 6.89 (td, J = 7.5, 1.9 Hz, 1 H), 5.96 (dtd, J = 9.9, 3.7, 2.3 Hz, 1

H), 5.65 (dq, J = 10.2, 2.5 Hz, 1 H), 3.69 (ddp, J = 8.3, 5.5, 2.8 Hz, 1 H),

2.08 (tqd, J = 8.7, 6.1, 3.4 Hz, 3 H), 1.79–1.60 (m, 2 H), 1.41 (dddd, J =

13.1, 9.9, 7.8, 3.4 Hz, 1 H).

¹³C NMR (101 MHz, CDCl₃):  = 148.3, 139.6, 129.7, 129.2, 128.7,

128.4, 128.0, 101.3, 45.9, 30.6, 25.2, 20.9.

MS (EI, 70 eV): m/z (%) = 284 (100), 230 (27), 142 (20), 141 (23), 129

(92), 128 (70), 116 (23), 115 (37).

IR (ATR): 2928, 1672, 1564, 1233, 758 cm^–1

.

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₂H₁₃I: 284.0062; found:

¹H NMR (400 MHz, CDCl₃):  = 7.78 (dd, J = 8.1, 1.4 Hz, 1 H), 7.53 (td,

J = 7.6, 1.4 Hz, 1 H), 7.45 (dd, J = 7.9, 1.6 Hz, 1 H), 7.33 (ddd, J = 8.7, 7.2,

1.6 Hz, 1 H), 6.04–5.92 (m, 1 H), 5.65–5.53 (m, 1 H), 3.95 (ddt, J = 8.4,

5.6, 2.8 Hz, 1 H), 2.26–2.16 (m, 1 H), 2.11 (ddq, J = 6.9, 3.8, 2.0, 1.4 Hz,

2 H), 1.81–1.60 (m, 2 H), 1.58–1.47 (m, 1 H).

¹³C NMR (101 MHz, CDCl₃):  = 149.9, 140.7, 132.6, 130.4, 129.8,

129.0, 127.0, 124.2, 36.9, 31.8, 25.0, 21.3.

284.0057.

1,3-Diiodo-5-(2-methylallyl)benzene (4q)

Diiodobenzene 4q was prepared via GP1 using 1,3,5-triiodobenzene

(2q) (228 mg, 0.50 mmol), DMPU (60 L, 0.50 mmol) and dry toluene

(0.50 mL). sBu₂Mg (1c) (0.63 mL, 0.30 mmol) was then added at –20

°C. After stirring at –20 °C for 60 min, CuCN·2LiCl (1.00 M in THF, 50

L, 50 mol) and methallyl bromide (60 L, 0.60 mmol) were added

and the reaction solution was allowed to warm to room temperature

overnight. After work-up, the crude product was purified via column

chromatography (isohexane, R_f= 0.75) to give the product 4q (126

mg, 328 mol, 66% yield) as a colorless oil.

MS (EI, 70 eV): m/z (%) = 186 (60), 169 (12), 168 (93), 167 (58), 158

(66), 156 (21), 153 (17), 152 (16), 147 (13), 146 (63), 143 (39), 141

(20), 132 (18), 130 (100), 129 (14), 128 (54), 117 (20), 115 (55), 105

(13), 91 (17), 77 (20).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₂H₁₃NO₂: 203.0946; found:

203.0894.

IR (ATR): 2907, 1572, 1539, 1416, 895, 707 cm^–1

.

¹H NMR (400 MHz, CDCl₃):  = 8.07–7.81 (m, 1 H), 7.50 (d, J = 1.5 Hz, 2

H), 4.86 (t, J = 1.7 Hz, 1 H), 4.74 (dd, J = 2.1, 1.1 Hz, 1 H), 3.19 (s, 2 H),

1.66 (t, J = 1.1 Hz, 3 H).

L

A. Desaintjean et al.

Paper

Synthesis

Ethyl 4-(2-Methylallyl)-3-nitrobenzoate (4t)

IR (ATR): 3438, 2237, 1620, 1427, 906, 726 cm^–1

.

¹H NMR (400 MHz, CDCl₃):  = 7.56 (dd, J = 8.1, 6.5 Hz, 1 H), 7.40–7.30

(m, 6 H), 7.28–7.24 (m, 1 H), 5.84 (d, J = 2.8 Hz, 1 H), 2.44 (d, J = 3.0 Hz,

1 H).

¹³C NMR (101 MHz, CDCl₃):  = 163.40 (d, J = 259.3 Hz), 152.3 (d, J =

7.2 Hz), 142.4, 133.5, 129.2, 128.8, 126.9, 122.7 (d, J = 3.3 Hz), 114.4,

114.2 (d, J = 5.2 Hz), 100.1 (d, J = 15.7 Hz), 75.4 (d, J = 1.7 Hz).

Nitrobenzene 4t was prepared via GP1 using ethyl 4-iodo-3-nitroben-

zoate (2t) (160 mg, 0.50 mmol), DMPU (0.25 mL, 2.00 mmol) and dry

toluene (1.0 mL). Mes₂Mg (1d) (0.46 mL, 0.30 mmol) was then added

at –70 °C. After stirring at –70 °C for 1 h, CuI (13 mg, 10 mol%) and

methallyl bromide (40 L, 0.40 mmol) were added and the reaction

solution was allowed to warm to –20 °C and stirred at this tempera-

ture overnight. After work-up, the crude product was purified via col-

umn chromatography (isohexane/ethyl acetate = 90:10, R_f= 0.46) to

give the product 4t (60 mg, 240 mol, 60% yield) as a red oil.

¹⁹F NMR (377 MHz, CDCl₃):  = –105.9.

MS (EI, 70 eV): m/z (%) = 227 (13), 226 (8), 208 (18), 207 (8), 190 (8),

148 (77), 122 (42), 121 (18), 107 (12), 106 (8), 105 (100), 100 (12), 79

(66), 78 (17), 77 (46).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₄H₁₀FNO: 227.0746; found:

IR (ATR): 2980, 1720, 1532, 1261, 727 cm^–1

.

¹H NMR (400 MHz, CDCl₃):  = 8.54 (d, J = 1.8 Hz, 1 H), 8.18 (dd, J = 8.0,

1.8 Hz, 1 H), 7.45 (d, J = 8.0 Hz, 1 H), 4.89–4.85 (s, 1 H), 4.54–4.49 (s, 1

H), 4.42 (q, J = 7.1 Hz, 2 H), 3.69 (s, 2 H),1.75 (s, 3 H), 1.42 (t, J = 7.1 Hz,

3 H).

227.0741.

1′,2′,3′,4′-Tetrahydro-[1,1′-biphenyl]-2-carbonitrile (7c)

¹³C NMR (101 MHz, CDCl₃):  = 164.6, 142.6, 139.2, 133.4, 132.7,

Benzonitrile 7c was prepared via GP1 using 2-bromobenzonitrile (5c)

(91 mg, 0.50 mmol), DMPU (60 L, 0.50 mmol) and dry toluene (0.50

mL). sBu₂Mg (1c) (0.63 mL, 0.30 mmol) was then added at –20 °C. Af-

ter stirring at –20 °C for 2 h, CuCN·2LiCl (1.00 M in THF, 50 L, 50

mol) and 3-bromocyclohexene (47 L, 0.40 mmol) were added and

the reaction solution was allowed to warm to room temperature

overnight. After work-up, the crude product was purified via column

chromatography (isohexane/ethyl acetate = 98:2, R_f= 0.36) to give the

product 7c (58 mg, 317 mol, 79% yield) as a pale yellow oil.

130.3, 125.9, 113.4, 100.1, 61.9, 40.7, 23.0, 14.4.

MS (EI, 70 eV): m/z (%) = 219 (54), 204 (31), 203 (60), 191 (35), 188

(16), 176 (16), 175 (29), 174 (53), 172 (17), 163 (21), 162 (17), 158

(100), 146 (23), 144 (28), 130 (52), 128 (16), 118 (40), 117 (18), 115

(18).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₃H₁₅NO₄: 249.1001; found:

249.0998.

2,6-Difluoro-4-(2-methylallyl)benzonitrile (7a)

IR (ATR): 2931, 1633, 1570, 1445, 1046 cm^–1

.

Benzonitrile 7a was prepared via GP1 using 4-bromo-2,6-difluoro-

benzonitrile (5a) (108 mg, 0.50 mmol), DMPU (60 L, 0.50 mmol) and

dry toluene (1.0 mL). sBu₂Mg (1c) (0.63 mL, 0.30 mmol) was then

added at –20 °C. After stirring at –20 °C for 2 h, CuCN·2LiCl (1.00 M in

THF, 50 L, 50 mol) and methallyl bromide (60 L, 0.60 mmol) were

added and the reaction solution was allowed to warm to room tem-

perature overnight. After work-up, the crude product was purified via

column chromatography (isohexane/ethyl acetate = 90:10, R_f= 0.54)

to give the product 7a (95 mg, 492 mol, 98% yield) as a pale yellow

oil.

¹H NMR (400 MHz, CDCl₃):  = 7.61 (dd, J = 7.7, 1.4 Hz, 1 H), 7.52 (td,

J = 7.7, 1.5 Hz, 1 H), 7.36 (dd, J = 8.0, 1.2 Hz, 1 H), 7.28 (td, J = 7.6, 1.2

Hz, 1 H), 6.04–5.94 (m, 1 H), 5.63 (dd, J = 10.1, 2.5 Hz, 1 H), 3.86 (ddt, J

= 8.3, 5.6, 2.8 Hz, 1 H), 2.19–2.05 (m, 3 H), 1.75–1.61 (m, 2 H), 1.57–

1.47 (m, 1 H).

¹³C NMR (101 MHz, CDCl₃):  = 150.4, 133.0, 132.9, 130.1, 128.4,

128.1, 126.7, 118.2, 112.1, 40.2, 31.7, 24.9, 21.0.

MS (EI, 70 eV): m/z (%) = 183 (40), 182 (100), 168 (22), 167 (26), 166

(19), 165 (43), 154 (27), 140 (13), 128 (12), 115 (19).

IR (ATR): 2924, 1632, 1442, 1044, 904 cm^–1

.

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₃H₁₃N: 183.1048; found:

183.1040.

¹H NMR (400 MHz, CDCl₃):  = 6.91 (s, 1 H), 6.89 (s, 1 H), 4.96–4.92 (s,

1 H), 4.80–4.76 (s, 1 H), 3.36 (s, 2 H), 1.67 (s, 3 H).

4′-Methoxy-[1,1′-biphenyl]-4-carbonitrile (7d)

¹³C NMR (101 MHz, CDCl₃):  = 164.5 (d, J = 4.9 Hz), 161.9 (d, J = 4.9

Hz), 150.2 (t, J = 9.2 Hz), 142.1, 114.7, 112.7 (d, J = 3.4 Hz), 112.5 (d, J =

3.3 Hz), 109.5, 90.2 (t, J = 19.4 Hz), 44.8 (t, J = 1.8 Hz), 22.1.

Diaryl 7d was prepared via GP1 using 4-bromobenzonitrile (5d) (91

mg, 0.50 mmol), DMPU (60 L, 0.50 mmol) and dry toluene (1.0 mL).

sBu₂Mg (1c) (0.63 mL, 0.30 mmol) was then added at –20 °C. After

stirring at –20 °C for 2 h, ZnCl₂(1.00 M in THF, 0.65 mL, 0.65 mmol),

Pd(OAc)₂(5 mg, 4 mol%), SPhos (17 mg, 8 mol%) and 4-iodoanisole (94

mg, 0.40 mmol) were added and the reaction mixture was stirred at

room temperature overnight. After work-up, the crude product was

purified via column chromatography (isohexane/ethyl acetate = 96:4,

R_f= 0.25) to give the product 7d (47 mg, 220 mol, 55% yield) as a

white solid.

¹⁹F NMR (377 MHz, CDCl₃):  = –104.5.

MS (EI, 70 eV): m/z (%) = 194 (13), 193 (85), 192 (17), 179 (12), 178

(100), 176 (13), 165 (13), 153 (14), 152 (41), 125 (10).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₁H₉F₂N: 193.0703; found:

193.0690.

2-Fluoro-4-[hydroxy(phenyl)methyl]benzonitrile (7b)

Mp 107–109 °C.

IR (ATR): 2224, 1605, 1494, 1036, 822, 753 cm^–1

¹H NMR (400 MHz, CDCl₃):  = 7.79–7.59 (m, 4 H), 7.57–7.43 (m, 2 H),

7.09–6.84 (m, 2 H), 3.87 (s, 3 H).

¹³C NMR (101 MHz, CDCl₃):  = 160.3, 145.4, 132.7, 131.6, 128.5,

127.2, 119.2, 114.7, 110.2, 55.5.

Benzonitrile 7b was prepared via GP1 using 4-bromo-2-fluorobenzo-

nitrile (5b) (99 mg, 0.50 mmol), DMPU (60 L, 0.50 mmol) and dry

toluene (0.50 mL). sBu₂Mg (1c) (0.63 mL, 0.30 mmol) was then added

at –20 °C. After stirring at –20 °C for 2 h, benzaldehyde (0.61 L, 0.60

mmol) was added and the reaction solution was allowed to warm to

room temperature overnight. After work-up, the crude product was

purified via column chromatography (isohexane/ethyl acetate =

60:40, R_f= 0.46) to give the product 7b (70 mg, 308 mol, 62% yield)

as a pale yellow solid.

.

MS (EI, 70 eV): m/z (%) = 210 (15), 209 (100), 194 (59), 166 (62), 140

(31), 139 (12).

Mp 54–56 °C.

M

A. Desaintjean et al.

Paper

Synthesis

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₄H₁₁ON: 209.0841; found:

Mp 71–73 °C.

209.0835.

IR (ATR): 2220, 1656, 1264, 1089, 863, 725 cm^–1

.

¹H NMR (400 MHz, CDCl₃):  = 7.83–7.77 (m, 2 H), 7.67 (d, J = 5.1 Hz, 1

H), 7.54–7.48 (m, 2 H), 7.39 (d, J = 5.1 Hz, 1 H).

¹³C NMR (101 MHz, CDCl₃):  = 187.5, 147.9, 141.0, 135.3, 132.4,

3-Bromo-2-(2-methylallyl)benzonitrile (7e)

Benzonitrile 7e was prepared via GP1 using 2,3-dibromobenzonitrile

(5e) (131 mg, 0.50 mmol), DMPU (60 L, 0.50 mmol) and dry toluene

(1.0 mL). sBu₂Mg (1c) (0.63 mL, 0.30 mmol) was then added at –20 °C.

After stirring at –20 °C for 2 h, CuCN·2LiCl (1.00 M in THF, 50 L, 50

mol) and methallyl bromide (60 L, 0.60 mmol) were added and the

reaction solution was allowed to warm to –20 °C and was stirred at

this temperature overnight. After work-up, the crude product was pu-

rified via column chromatography (isohexane/ethyl acetate = 90:10,

R_f= 0.52) to give the product 7e (100 mg, 425 mol, 85% yield) as a

colorless oil.

131.6, 129.8, 129.6, 114.0, 113.0.

MS (EI, 70 eV): m/z (%) = 247 (9), 219 (7), 213 (12), 212 (100), 184 (6),

141 (23), 139 (77), 136 (33), 110 (11), 75 (9).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₂H₆ClNOS: 246.9859; found:

246.9853.

(4-Bromothiophen-3-yl)(cyclopropyl)methanone (7h)

Ketone 7h was prepared via GP1 using 3,4-dibromothiophene (5h)

(121 mg, 0.50 mmol) and dry toluene (1.0 mL). sBu₂Mg (1c) (0.63 mL,

0.30 mmol) was then added at –20 °C. After stirring at –20 °C for 45

min, CuCN·2LiCl (1.00 M in THF, 50 L, 50 mol) and cyclopropane-

carbonyl chloride (92 L, 1.00 mmol) were added and the reaction

solution was stirred at this temperature overnight. After work-up, the

crude product was purified via column chromatography (isohex-

ane/ethyl acetate = 60:40, R_f= 0.74) to give the product 7h (72 mg,

313 mol, 63% yield) as a yellow oil.

IR (ATR): 2225, 1439, 1116, 891, 784, 723 cm^–1

.

¹H NMR (400 MHz, CDCl₃):  = 7.80 (dd, J = 8.1, 1.3 Hz, 1 H), 7.62 (dd,

J = 7.7, 1.3 Hz, 1 H), 7.20 (t, J = 7.9 Hz, 1 H), 4.87 (s, 1 H), 4.34 (s, 1 H),

3.70 (s, 2 H), 1.86 (s, 3 H).

¹³C NMR (101 MHz, CDCl₃):  = 143.1, 141.4, 137.6, 132.2, 128.3,

126.4, 117.5, 115.4, 112.5, 42.5, 23.3.

MS (EI, 70 eV): m/z (%) = 237 (31), 236 (28), 235 (31), 234 (29), 156

(100), 155 (17), 154 (18), 129 (88), 128 (46), 116 (25), 115 (19).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₁H₁₀BrN: 234.9997; found:

234.9992.

IR (ATR): 3105, 1664, 1416, 1052, 931, 727 cm^–1

.

¹H NMR (400 MHz, CDCl₃):  = 8.04 (d, J = 3.5 Hz, 1 H), 7.33 (d, J = 3.5

Hz, 1 H), 2.62–2.53 (m, 1 H), 1.25 (dt, J = 6.9, 3.4 Hz, 2 H), 1.07–1.01

(m, 2 H).

Ethyl 4-Bromo-3-(2-methylallyl)furan-2-carboxylate (7f)

¹³C NMR (101 MHz, CDCl₃):  = 195.1, 140.3, 132.6, 125.6, 109.7, 19.8,

Furan 7f was prepared via GP1 using ethyl 3,4-dibromofuran-2-car-

boxylate (5f) (148 mg, 0.50 mmol), DMPU (60 L, 0.50 mmol) and dry

toluene (0.50 mL). sBu₂Mg (1c) (0.63 mL, 0.30 mmol) was then added

at –20 °C. After stirring at –20 °C for 90 min, CuCN·2LiCl (1.00 M in

THF, 50 L, 50 mol) and methallyl bromide (40 L, 0.40 mmol) were

added and the reaction solution was allowed to warm to –20 °C and

was stirred at this temperature overnight. After work-up, the crude

product was purified via column chromatography (isohexane/ethyl

acetate = 90:10, R_f= 0.51) to give the product 7f (55 mg, 202 mol,

51% yield) as a colorless oil.

12.2.

MS (EI, 70 eV): m/z (%) = 232 (4), 230 (4), 193 (4), 192 (5), 191 (100),

190 (5), 189 (98), 150 (6), 82 (13).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₈H₇BrOS: 229.9401; found:

229.9396.

Ethyl 5-(4-Methoxyphenyl)thiophene-2-carboxylate (7i)

Thiophene 7i was prepared via GP1 using ethyl 5-bromothiophene-2-

carboxylate (5i) (118 mg, 0.50 mmol) and dry toluene (1.0 mL).

sBu₂Mg (1c) (0.63 mL, 0.30 mmol) was then added at –40 °C. After

stirring at –40 °C for 45 min, ZnCl₂(1.00 M in THF, 0.65 mL, 0.65

mmol), Pd(OAc)₂(5 mg, 4 mol%), SPhos (17 mg, 8 mol%) and 4-iodo-

anisole (93 mg, 0.40 mmol) were added and the reaction mixture was

stirred at room temperature overnight. After work-up, the crude

product was purified via column chromatography (isohexane/ethyl

acetate = 90:10, R_f= 0.32) to give the product 7i (75 mg, 282 mol,

72% yield) as a white solid.

IR (ATR): 1720, 1303, 1181, 906, 729 cm^–1

.

¹H NMR (400 MHz, CDCl₃):  = 7.13 (s, 1 H), 4.86 (s, 1 H), 4.74 (s, 1 H),

4.34 (q, J = 7.1 Hz, 2 H), 3.42 (s, 2 H), 1.75 (t, J = 1.1 Hz, 3 H), 1.36 (t, J =

7.1 Hz, 3 H).

¹³C NMR (101 MHz, CDCl₃):  = 158.2, 155.3, 143.5, 140.1, 121.1,

113.4, 99.3, 61.3, 35.0, 22.4, 14.5.

MS (EI, 70 eV): m/z (%) = 275 (100), 272 (99), 259 (25), 257 (26), 246

(18), 244 (18), 229 (33), 227 (34), 205 (39), 203 (40), 201 (46), 199

(43), 173 (29), 171 (20), 150 (19), 120 (77), 119 (31), 92 (28), 91 (61).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₁H₁₃BrO₃: 272.0048; found:

Mp 71–73 °C.

IR (ATR): 2930, 1697, 1446, 1252, 1091, 749 cm^–1

¹H NMR (400 MHz, CDCl₃):  = 7.73 (d, J = 3.9 Hz, 1 H), 7.61–7.53 (m, 2

H), 7.18 (d, J = 3.9 Hz, 1 H), 6.97–6.90 (m, 2 H), 4.36 (q, J = 7.1 Hz, 2 H),

3.84 (s, 3 H), 1.39 (t, J = 7.1 Hz, 3 H).

.

272.0041.

3-(4-Chlorobenzoyl)thiophene-2-carbonitrile (7g)

¹³C NMR (101 MHz, CDCl₃):  = 162.5, 160.3, 151.3, 134.4, 131.6,

127.6, 126.4, 122.7, 114.6, 61.2, 55.5, 14.5.

Thiophene 7g was prepared via GP1 using 3-bromothiophene-2-car-

bonitrile (5g) (94 mg, 0.50 mmol) and dry toluene (1.0 mL). sBu₂Mg

(1c) (0.63 mL, 0.30 mmol) was then added at –20 °C. After stirring at

–20 °C for 45 min, CuCN·2LiCl (1.00 M in THF, 0.30 mL, 0.30 mmol)

and 4-chlorobenzoyl chloride (77 L, 0.60 mmol) were added and the

reaction solution was allowed to warm to room temperature over-

night. After work-up, the crude product was purified via column

chromatography (isohexane/ethyl acetate = 60:40, R_f= 0.49) to give

the product 7g (113 mg, 456 mol, 91% yield) as a light yellow solid.

MS (EI, 70 eV): m/z (%) = 263 (15), 262 (100), 235 (12), 234 (94), 220

(10), 219 (84), 217 (50), 191 (42), 190 (36), 189 (13), 175 (16), 163

(11), 145 (57), 102 (14).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₄H₁₄O₃S: 262.0664; found:

262.0659.

N

A. Desaintjean et al.

Paper

Synthesis

(E)-2-(Oct-1-en-1-yl)quinoline (7ja)

IR (ATR): 2930, 1663, 1575, 1491, 762 cm^–1

.

¹H NMR (400 MHz, CDCl₃):  = 8.14 (dd, J = 8.4, 1.4 Hz, 1 H), 8.05 (d, J =

8.5 Hz, 1 H), 7.73 (ddd, J = 8.4, 6.9, 1.5 Hz, 1 H), 7.65 (s, 1 H), 7.58 (ddd,

J = 8.2, 6.9, 1.2 Hz, 1 H), 6.05–5.98 (m, 1 H), 5.89–5.83 (m, 1 H), 3.82–

3.72 (m, 1 H), 2.22–2.13 (m, 3 H), 1.88–1.80 (m, 1 H), 1.80–1.69 (m, 2

H).

¹³C NMR (101 MHz, CDCl₃):  = 166.0, 148.6, 134.5, 130.4, 130.0,

129.5, 128.0, 127.2, 126.7, 126.6, 124.2, 45.0, 30.8, 25.1, 21.5.

Quinoline 7ja was prepared via GP1 using 2-bromoquinoline (5j) (105

mg, 0.50 mmol) and dry toluene (1.0 mL). sBu₂Mg (1c) (0.63 mL, 0.30

mmol) was then added at 25 °C. After stirring at 25 °C for 60 min,

ZnCl₂(1.00 M in THF, 0.65 mL, 0.65 mmol), Pd(OAc)₂(5 mg, 4 mol%),

SPhos (17 mg, 8 mol%) and trans-1-iodo-1-octene (95 mg, 0.40 mmol)

were added and the reaction mixture was stirred at room tempera-

ture overnight. After work-up, the crude product was purified via col-

umn chromatography (isohexane/ethyl acetate = 90:10, R_f= 0.51) to

give the product 7ja (75 mg, 313 mol, 78% yield) as an orange oil.

MS (EI, 70 eV): m/z (%) = 289 (44), 288 (55), 287 (45), 286 (79), 274

(40), 272 (41), 260 (97), 258 (100), 223 (41), 221 (42), 208 (43), 204

(35), 179 (30), 178 (32), 167 (31).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₅H₁₄BrN: 287.0310; found:

IR (ATR): 2923, 1596, 1502, 966, 749 cm^–1

.

¹H NMR (400 MHz, CDCl₃):  = 8.07 (d, J = 8.6 Hz, 1 H), 8.02 (d, J = 8.5

Hz, 1 H), 7.75 (d, J = 8.3 Hz, 1 H), 7.67 (ddd, J = 8.4, 6.8, 1.5 Hz, 1 H),

7.53 (d, J = 8.6 Hz, 1 H), 7.51–7.40 (m, 1 H), 6.83 (dt, J = 16.0, 6.7 Hz, 1

H), 6.71 (d, J = 15.9 Hz, 1 H), 2.39–2.28 (m, 2 H), 1.60–1.51 (m, 2 H),

1.41–1.29 (m, 6 H), 0.90 (t, J = 6.7 Hz, 3 H).

287.0307.

4-Bromo-1-(cyclohex-2-en-1-yl)isoquinoline (7l)

Isoquinoline 7l was prepared via GP1 using 1,4-dibromoisoquinoline

(5l) (143 mg, 0.50 mmol) and dry toluene (1.0 mL). sBu₂Mg (1c) (0.63

mL, 0.30 mmol) was then added at 25 °C. After stirring at 25 °C for 60

min, CuCN·2LiCl (1.00 M in THF, 50 L, 50 mol) and 3-bromocyclo-

hexene (69 L, 0.50 mmol) were added at 0 °C and the reaction solu-

tion was cooled to –20 °C and was stirred at this temperature over-

night. After work-up, the crude product was purified via column

chromatography (isohexane/ethyl acetate = 80:20, R_f= 0.70) to give

the product 7l (114 mg, 397 mol, 79% yield) as a colorless oil.

¹³C NMR (101 MHz, CDCl₃):  = 156.7, 148.2, 138.2, 136.3, 131.1,

129.6, 129.2, 127.6, 127.3, 125.9, 118.8, 33.2, 31.9, 29.1, 29.0, 22.8,

14.3.

MS (EI, 70 eV): m/z (%) = 238 (15), 210 (43), 196 (20), 183 (12), 182

(84), 180 (18), 168 (77), 167 (100), 166 (12), 156 (26), 143 (20).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₇H₂₁N: 239.1674; found:

239.1670.

2-(Cyclohex-2-en-1-yl)quinoline (7jb)

IR (ATR): 2928, 1671, 1233, 903, 760, 722 cm^–1

.

¹H NMR (400 MHz, CDCl₃):  = 8.68 (s, 1 H), 8.23 (d, J = 8.5 Hz, 1 H),

8.19 (d, J = 8.4 Hz, 1 H), 7.77 (ddd, J = 8.3, 6.8, 1.2 Hz, 1 H), 7.65 (ddd,

J = 8.3, 6.9, 1.3 Hz, 1 H), 6.05–5.99 (m, 1 H), 5.93–5.87 (m, 1 H), 4.44–

4.37 (m, 1 H), 2.27–2.10 (m, 3 H), 1.94–1.74 (m, 3 H).

¹³C NMR (101 MHz, CDCl₃):  = 164.4, 143.9, 135.2, 131.1, 128.8,

128.7, 128.0, 127.9, 127.0, 125.4, 118.1, 40.2, 30.4, 25.0, 22.1.

Quinoline 7jb was prepared via GP1 using 2-bromoquinoline (5j)

(105 mg, 0.50 mmol) and dry toluene (1.0 mL). sBu₂Mg (1c) (0.63 mL,

0.30 mmol) was then added at 25 °C. After stirring at 25 °C for 60 min,

CuCN·2LiCl (1.00 M in THF, 50 L, 50 mol) and 3-bromocyclohexene

(47 L, 0.40 mmol) were added at 0 °C and the reaction solution was

cooled to –20 °C and was stirred at this temperature overnight. After

work-up, the crude product was purified via column chromatography

(isohexane/ethyl acetate = 80:20, R_f= 0.62) to give the product 7jb (59

mg, 280 mol, 70% yield) as a brown oil.

MS (EI, 70 eV): m/z (%) = 288 (17), 286 (18), 261 (11), 260 (98), 258

(100), 223 (18), 221 (18), 179 (18), 166 (15).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₅H₁₄BrN: 287.0310; found:

287.0308.

IR (ATR): 2931, 1661, 1595, 1502, 819, 754 cm^–1

.

¹H NMR (400 MHz, CDCl₃):  = 8.09 (d, J = 8.7 Hz, 1 H), 8.06 (d, J = 8.3

Hz, 1 H), 7.78 (dd, J = 8.1, 1.4 Hz, 1 H), 7.68 (ddd, J = 8.4, 6.8, 1.5 Hz, 1

H), 7.49 (ddd, J = 8.1, 6.8, 1.2 Hz, 1 H), 7.37 (d, J = 8.5 Hz, 1 H), 6.03–

5.94 (m, 1 H), 5.92–5.84 (m, 1 H), 3.84–3.75 (m, 1 H), 2.22–2.13 (m, 3

H), 1.88–1.81 (m, 1 H), 1.78–1.69 (m, 2 H).

¹³C NMR (101 MHz, CDCl₃):  = 166.0, 147.9, 136.6, 129.5, 129.3,

129.1, 128.7, 127.6, 127.1, 125.9, 120.3, 45.4, 30.9, 25.2, 21.6.

Ethyl (E)-2-Methyleneundec-4-enoate (10a)

Alkene 10a was prepared via GP1 using (E)-1-iodooct-1-ene (8a) (95

mg, 0.40 mmol), DMPU (48 L, 0.40 mmol) and dry toluene (0.40 mL).

sBu₂Mg (1c) (0.50 mL, 0.24 mmol) was then added at 0 °C. After stir-

ring at 0 °C for 1 h, CuCN·2LiCl (1.00 M in THF, 40 L, 40 mol) and

ethyl 2-(bromomethyl)acrylate (44 L, 0.32 mmol) were added and

the reaction solution was allowed to warm to room temperature

overnight. After work-up, the crude product was purified via column

chromatography (isohexane/ethyl acetate = 99:1, R_f= 0.16) to give the

product 10a (59 mg, 263 mol, 82% yield) as a colorless oil.

MS (EI, 70 eV): m/z (%) = 210 (11), 209 (82), 208 (100), 206 (11), 194

(61), 193 (16), 192 (10), 180 (52), 167 (24), 143 (14), 128 (11).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₅H₁₅N: 209.1204; found:

209.1200.

IR (ATR): 2926, 1720, 1465, 1190, 1025 cm^–1

.

4-Bromo-2-(cyclohex-2-en-1-yl)quinoline (7k)

¹H NMR (400 MHz, CDCl₃):  = 6.15 (q, J = 1.1 Hz, 1 H), 5.53 (d, J = 1.6

Hz, 1 H), 5.50–5.38 (m, 2 H), 4.20 (q, J = 7.1 Hz, 2 H), 3.12–2.72 (m, 2

H), 2.01 (q, J = 6.7 Hz, 2 H), 1.48–1.15 (m, 11 H), 1.01–0.72 (m, 3 H).

¹³C NMR (101 MHz, CDCl₃):  = 167.3, 140.3, 133.5, 126.4, 124.8, 60.8,

34.9, 32.7, 31.9, 29.5, 29.0, 22.8, 14.4, 14.3.

Bromoquinoline 7k was prepared via GP1 using 2,4-dibromoquino-

line (5k) (143 mg, 0.50 mmol) and dry toluene (1.0 mL). sBu₂Mg (1c)

(0.63 mL, 0.30 mmol) was then added at 25 °C. After stirring at 25 °C

for 60 min, CuCN·2LiCl (1.00 M in THF, 50 L, 50 mol) and 3-bromo-

cyclohexene (69 L, 0.50 mmol) were added at 0 °C and the reaction

solution was cooled to –20 °C and was stirred at this temperature

overnight. After work-up, the crude product was purified via column

chromatography (isohexane/ethyl acetate = 80:20, R_f= 0.68) to give

the product 7k [97:3 (regioisomeric ratio), 102 mg, 355 mol, 71%

yield] as a colorless oil.

MS (EI, 70 eV): m/z (%) = 149 (20), 139 (57), 121 (19), 111 (100), 107

(18), 95 (34), 94 (18), 93 (50), 91 (19), 81 (43), 79 (60), 77 (19), 67

(48).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₄H₂₄O₂: 224.1776; found:

224.1767.

O

A. Desaintjean et al.

Paper

Synthesis

(Z)-3-(Hept-1-en-1-yl)cyclohex-1-ene (10b)

¹H NMR (400 MHz, CDCl₃):  = 5.80 (ddt, J = 16.6, 10.1, 6.2 Hz, 1 H),

5.42 (ddt, J = 11.3, 8.4, 1.5 Hz, 1 H), 5.34 (dtd, J = 11.0, 7.3, 1.0 Hz, 1 H),

5.05 (dq, J = 17.1, 1.7 Hz, 1 H), 5.00 (dq, J = 10.1, 1.6 Hz, 1 H), 4.47–

4.33 (m, 1 H), 2.86–2.75 (m, 2 H), 1.52 (ddd, J = 12.8, 6.0, 3.3 Hz, 1 H),

1.40–1.32 (m, 2 H), 1.28 (dq, J = 13.9, 5.3, 4.5 Hz, 7 H), 0.91–0.86 (m,

12 H), 0.04 (s, 3 H), 0.03 (s, 3 H).

Alkene 10b was prepared via GP1 using (Z)-1-iodohept-1-ene (8b)

(90 mg, 0.40 mmol), DMPU (48 L, 0.40 mmol) and dry toluene (0.40

mL). sBu₂Mg (1c) (0.50 mL, 0.24 mmol) was then added at 0 °C. After

stirring at 0 °C for 1 h, CuCN·2LiCl (1.00 M in THF, 40 L, 40 mol) and

3-bromocyclohexene (37 L, 0.32 mmol) were added and the reaction

solution was allowed to warm to room temperature overnight. After

work-up, the crude product was purified via column chromatography

(isohexane, R_f= 0.72) to give the product 10b (38 mg, 213 mol, 66%

yield) as a colorless oil.

¹³C NMR (101 MHz, CDCl₃):  = 136.7, 135.5, 125.8, 115.2, 68.8, 38.6,

32.3, 32.1, 29.4, 26.0, 25.5, 22.8, 18.4, 14.3, –4.1, –4.6.

MS (EI, 70 eV): m/z (%) = 240 (3), 239 (23), 221 (3), 211 (25), 75 (100).

HRMS (EI, 70 eV): m/z [M – Me]⁺calcd for C₁₇H₃₃OSi: 281.2301;

found: 281.2291.

IR (ATR): 3017, 3010, 3003, 1684, 1456, 668 cm^–1

.

¹H NMR (400 MHz, CDCl₃):  = 5.70 (dtd, J = 9.9, 3.7, 2.3 Hz, 1 H), 5.45

(dq, J = 10.0, 2.4 Hz, 1 H), 5.39–5.30 (m, 1 H), 5.23 (ddt, J = 10.9, 9.5,

1.6 Hz, 1 H), 3.06 (ddq, J = 11.1, 5.4, 2.6 Hz, 1 H), 2.06 (qd, J = 7.2, 1.5

Hz, 2 H), 1.98 (dtt, J = 9.5, 5.0, 2.7 Hz, 2 H), 1.74 (dtd, J = 9.7, 5.7, 5.1,

2.1 Hz, 2 H), 1.56 (tdd, J = 12.5, 7.3, 3.6 Hz, 2 H), 1.40–1.19 (m, 6 H),

0.91–0.86 (m, 3 H).

(Z)-Butyl[4-(trifluoromethyl)styryl]sulfane (10d)

Alkene 10d was prepared via GP1 using (Z)-1-(2-iodovinyl)-4-(triflu-

oromethyl)benzene (8d) (119 mg, 0.40 mmol), DMPU (48 L, 0.40

mmol) and dry toluene (0.40 mL). sBu₂Mg (1c) (0.50 mL, 0.24 mmol)

was then added at 0 °C. After stirring at 0 °C for 1 h, S-butyl benzene-

sulfonothioate (74 mg, 0.32 mmol) was added and the reaction solu-

tion was allowed to warm to room temperature overnight. After

work-up, the crude product was purified via column chromatography

(isohexane, R_f= 0.41) to give the product 10d (68 mg, 261 mol, 82%

yield) as a colorless oil.

¹³C NMR (101 MHz, CDCl₃):  = 134.1, 130.9, 129.5, 127.3, 34.0, 31.7,

29.8, 29.7, 27.5, 25.0, 22.7, 21.3, 14.2.

MS (EI, 70 eV): m/z (%) = 135 (21), 107 (20), 94 (26), 93 (21), 91 (20),

81 (25), 80 (23), 79 (100), 77 (13).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₃H₂₂: 178.1722; found:

178.1714.

IR (ATR): 2959, 1319, 1112, 1066, 838 cm^–1

.

¹H NMR (400 MHz, CDCl₃):  = 7.68–7.50 (m, 4 H), 6.43 (dd, J = 11.0,

2.6 Hz, 2 H), 2.82 (t, J = 7.4 Hz, 2 H), 1.82–1.61 (m, 2 H), 1.46 (dq, J =

14.6, 7.4 Hz, 2 H), 0.95 (t, J = 7.4 Hz, 3 H).

¹³C NMR (101 MHz, CDCl₃):  = 140.6 (q, J = 1.3 Hz), 131.1, 128.7,

128.2 (q, J = 32.4 Hz), 125.3 (q, J = 3.9 Hz), 124.4 (q, J = 271.8 Hz),

123.8, 35.9, 32.4, 21.8, 13.8.

(E)-4-[(tert-Butyldimethylsilyl)oxy]dec-2-enal (10ca)

Michael acceptor 10ca was prepared via GP1 using (Z)-tert-butyl[(1-

iodonon-1-en-3-yl)oxy]dimethylsilane (8c) (147 mg, 0.40 mmol),

DMPU (48 L, 0.40 mmol) and dry toluene (0.40 mL). sBu₂Mg (1c)

(0.50 mL, 0.24 mmol) was then added at 0 °C. After stirring at 0 °C for

1 h, DMF (25 L, 0.32 mmol) was added and the reaction solution was

allowed to warm to room temperature overnight. After work-up, the

crude product was purified via column chromatography (isohex-

ane/ethyl acetate = 99:1, R_f= 0.35) to give the product 10ca (48 mg,

169 mol, 53% yield) as a colorless oil.

¹⁹F NMR (377 MHz, CDCl₃):  = –62.5.

MS (EI, 70 eV): m/z (%) = 260 (74), 204 (47), 183 (36), 135 (100), 134

(18).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₃H₁₅F₃S: 260.0847; found:

260.0841.

IR (ATR): 2929, 2857, 1699, 1095, 836 cm^–1

.

¹H NMR (400 MHz, CDCl₃):  = 9.57 (d, J = 8.0 Hz, 1 H), 6.80 (dd, J =

15.5, 4.6 Hz, 1 H), 6.26 (ddd, J = 15.5, 8.0, 1.6 Hz, 1 H), 4.40 (tdd, J = 6.1,

4.5, 1.6 Hz, 1 H), 1.71–1.46 (m, 2 H), 1.40–1.17 (m, 8 H), 0.91 (s, 9 H),

0.89–0.86 (m, 3 H), 0.06 (s, 3 H), 0.03 (s, 3 H).

¹³C NMR (101 MHz, CDCl₃):  = 193.9, 160.5, 130.8, 71.8, 37.3, 31.9,

29.4, 25.9, 24.9, 22.7, 18.3, 14.2, –4.5, –4.8.

(E)-(2-Bromostyryl)(methyl)sulfane (10e)

Alkene 10e was prepared via GP1 using (E)-1-bromo-2-(2-iodo-

vinyl)benzene (8e) (124 mg, 0.40 mmol), DMPU (48 L, 0.40 mmol)

and dry toluene (0.40 mL). sBu₂Mg (1c) (0.50 mL, 0.24 mmol) was

then added at 0 °C. After stirring at 0 °C for 1 h, S-methyl methanethio-

sulfonate (33 L, 0.32 mmol) was added and the reaction solution was

allowed to warm to room temperature overnight. After work-up, the

crude product was purified via column chromatography (isohexane,

R_f= 0.45) to give the product 10e (51 mg, 223 mol, 70% yield) as a

pale yellow oil.

MS (EI, 70 eV): m/z (%) = 227 (54), 199 (26), 143 (37), 131 (13), 129

(100), 75 (100), 73 (35).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₁₆H₃₂O₂Si: 284.2172; found:

284.2534.

IR (ATR): 2916, 1588, 1432, 1020, 927, 740 cm^–1

.

(Z)-tert-Butyl(dodeca-1,4-dien-6-yloxy)dimethylsilane (10cb)

¹H NMR (400 MHz, CDCl₃):  = 7.53 (dd, J = 8.1, 1.3 Hz, 1 H), 7.43 (dd,

J = 7.8, 1.6 Hz, 1 H), 7.23 (dd, J = 7.7, 1.3 Hz, 1 H), 7.04 (td, J = 7.7, 1.7

Hz, 1 H), 6.80 (d, J = 15.3 Hz, 1 H), 6.61 (d, J = 15.4 Hz, 1 H), 2.43 (s, 3

H).

¹³C NMR (101 MHz, CDCl₃):  = 136.9, 133.1, 129.2, 128.0, 127.7,

126.2, 123.0, 122.7, 14.8.

Alkene 10cb was prepared via GP1 using (Z)-tert-butyl((1-iodonon-1-

en-3-yl)oxy)dimethylsilane (8c) (147 mg, 0.40 mmol), DMPU (48 L,

0.40 mmol) and dry toluene (0.40 mL). sBu₂Mg (1c) (0.50 mL, 0.24

mmol) was then added at 0 °C. After stirring at 0 °C for 1 h, CuCN·2LiCl

(1.00 M in THF, 40 L, 40 mol) and allyl bromide (28 L, 0.32 mmol)

were added at 0 °C and the reaction solution was allowed to warm to

room temperature overnight. After work-up, the crude product was

purified via column chromatography (isohexane, R_f= 0.48) to give the

product 10cb (69 mg, 233 mol, 73% yield) as a colorless oil.

MS (EI, 70 eV): m/z (%) = 149 (92), 134 (100).

HRMS (EI, 70 eV): m/z [M]⁺calcd for C₉H₉BrS: 227.9608; found:

227.9601.

IR (ATR): 2927, 1251, 1071, 833, 773 cm^–1

.

P

A. Desaintjean et al.

Paper

Synthesis

Conflict of Interest

Chem. 2005, 118, 165. (c) Schnegelsberg, C.; Bachmann, S.;

Kolter, M.; Auth, T.; John, M.; Stalke, D.; Koszinowski, K. Chem.

Eur. J. 2016, 22, 7752.

The authors declare no conflict of interest.

(5) (a) Ziegler, D. S.; Karaghiosoff, K.; Knochel, P. Angew. Chem. Int.

Ed. 2018, 57, 6701; Angew. Chem. 2018, 130, 6811. (b) Ziegler, D.

S.; Wei, B.; Knochel, P. Chem. Eur. J. 2019, 25, 2695.

(c) Desaintjean, A.; Haupt, T.; Bole, L. J.; Judge, N. R.; Hevia, E.;

Knochel, P. Angew. Chem. Int. Ed. 2021, 60, 1513; Angew. Chem.

2021, 133, 1536. (d) Bole, L. J.; Judge, N. R.; Hevia, E. Angew.

Chem. Int. Ed. 2021, 60, 7626; Angew. Chem. 2021, 133, 7704.

(6) Balkenhohl, M.; Ziegler, D. S.; Desaintjean, A.; Bole, L. J.;

Kennedy, A. R.; Hevia, E.; Knochel, P. Angew. Chem. Int. Ed. 2019,

58, 12898; Angew. Chem. 2019, 131, 13030 features a related

halogen/zinc exchange.

Funding Information

We thank the Deutsche Forschungsgemeinschaft (DFG) and Ludwig-

Maximilians-Universität München for financial support.

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Acknowledgment

We thank Albemarle (Hoechst, Germany) and BASF (Ludwigshafen,

Germany) for the generous gift of chemicals.

(7) (a) Solvent Recovery Handbook; Smallwood, I. M., Ed.; Blackwell

Science: Oxford, 2002. (b) Delhaye, L.; Ceccato, A.; Jacobs, P.;

Köttgen, C.; Merschaert, A. Org. Process Res. Dev. 2007, 11, 160.

(8) This reagent still contained 0.5 equivalents of Et₂O, having the

formula sBu₂Mg·0.5Et₂O (determined by ¹H NMR analysis) that

we have abbreviated as sBu₂Mg for the sake of clarity: Hess, A.;

Prohaska, J. P.; Doerrich, S. B.; Trauner, F.; Lutter, F. H.; Lemaire,

S.; Wagschal, S.; Karaghiosoff, K.; Knochel, P. Chem. Sci. 2021,

12, 8424.

(9) The same reactivity was observed after 5 days of storage of the

sBu₂Mg toluene solution at –20 °C.

(10) Knochel, P.; Yeh, M. C. P.; Berk, S. C.; Talbert, J. J. Org. Chem.

1988, 53, 2390.

Supporting Information

Supporting information for this article is available online at

https://doi.org/10.1055/a-1551-4093.

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(15) The syntheses of all starting materials and the corresponding

literature references are given in the Supporting Information.

Article Doi

Preparation of Functionalized Diorganomagnesium Reagents in Toluene via Bromine or Iodine/Magnesium-Exchange Reactions

DOI: 10.1055/a-1551-4093

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Article abstract of DOI:10.1055/a-1551-4093

Full text of DOI:10.1055/a-1551-4093

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