Fenton-Inspired C-H Functionalization: Peroxide-Directed C-H Thioetherification

Article

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Cite This: J. Org. Chem. XXXX, XXX, XXX −XXX

Fenton-Inspired C−H Functionalization: Peroxide-Directed C−H

Thioetheriﬁcation

Brian J. Groendyke, Atanu Modak, and Silas P. Cook*

Department of Chemistry, Indiana University, 800 East Kirkwood Avenue, Bloomington, Indiana 47405-7102, United States

S

* Supporting Information

ABSTRACT: Substoichiometric iron mediates the thioether-

iﬁcation of unactivated aliphatic C−H bonds directed by

resident silylperoxides. Upon exposure to a catalytic amount of

iron(II) triﬂate, TIPS-protected peroxides bearing primary,

secondary, and tertiary C−H sites undergo chemoselective

thioetheriﬁcation of remote C−H bonds with diaryl disulﬁdes.

The reaction demonstrates a broad substrate scope and

functional group tolerance without the use of any noble metal

additives. Mechanistic experiments suggest that the reaction proceeds through 1,5-H atom abstraction by a hydroxyl radical

generated with iron.

promote the selective thiophenylation of unactivated C−H

bonds under photolytic conditions.¹⁸With this limited

precedent, a robust, catalytic method for the selective

thioetheriﬁcation of C(sp³)−H bonds remains desirable.

While directed C−H functionalization has developed quickly

over the past 20 years,¹⁹strict steric and electronic require-

ments imposed by the transition metal-mediated C−H

activation step have limited extension of this strategy to

C(sp³)−H bonds. Here, we oﬀer a directed, radical C−H

thioetheriﬁcation reaction that can overcome such limitations

and enable facile C−H oxidations.

The Fenton reaction (Figure 2a) represents the most widely

implemented C−H oxidation in history.²⁰⁻²³Inspired by this

precedent, we sought to investigate an intramolecular variant

of Fenton’s initial discovery. We hypothesized that by

harnessing the facile 1,5-H-atom abstraction observed in

other heteroatom-based radical systems, we could employ

easily obtained peroxides in the presence of iron to generate

the requisite H-atom abstractor.

INTRODUCTION

■

Thioethers are versatile synthetic intermediates, as they are

readily oxidized to either the sulfoxide or the sulfone.¹

Sulfoxides are well-known for enabling syn eliminations,²

Mislow−Evans rearrangements,^3,4Pummerer reactions,^5,6and

sulfoxide−metal exchanges^7,8while also acting as a useful

ligand class for transition metal catalysis.⁹The higher-oxidation

state sulfones also provide ample opportunities in organic

synthesis, most notably as alkene precursors in the Julia−

Lythgoe oleﬁnation,^1,10Kocienski-modiﬁed Julia oleﬁna-

tion,^11,12and Ramberg−Backlund rearrangement.^13,14A recent

̈

report has also highlighted the utility of sulfones as radical

cross-coupling partners.¹⁵The preparation of alkyl thioethers

generally proceeds through nucleophilic displacement of a

(pseudo)halide with a thiol or the trapping of an alkyl radical

or organometallic nucleophile with a disulﬁde.¹⁶In addition to

the synthetic versatility of thioethers, thioethers themselves are

found in a variety of bioactive molecules such as Zofenopril, an

FDA-approved angiotensin converting enzyme (ACE) inhib-

itor with antihypertensive and cardioprotective properties

RESULTS AND DISCUSSION

■

(Figure 1).¹⁷Cekovic has reported that phenylsulfenyl ethers

̌

́

To test the hypothesis, a series of peroxides were prepared

from the oxidation of the primary alcohol (see the Supporting

Information for full details). We have previously demonstrated

that Fe(OTf)₂is an eﬀective catalyst for the generation of N-

centered radicals (Figure 2b).²⁴Interestingly, exposure of

symmetrical peroxide 1 to Fe(OTf)₂in the presence of excess

disulﬁde trap provided the desired product in 50% NMR yield

(Scheme 1). Encouraged by this preliminary result, we sought

to improve the reaction with the goal of developing a general

method for selective C−H thioetheriﬁcation.

Special Issue: C-H Bond Functionalization

Received: July 26, 2019

Figure 1. Bioactive molecules bearing a 1,4-oxy-thio motif.

A

DOI: 10.1021/acs.joc.9b01979

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

could be decreased to 1.1 equiv with no loss of yield (entry 5,

Table 1). As with the iron-catalyzed peroxide reductions that

Bao has reported,^25,26all other precatalysts that wee evaluated

were inferior to Fe(OTf)₂(see the Supporting Information).

At this stage, we noticed that a number of reactions with

Fe(OTf)₂provided yields between 40% and 45% with a nearly

1:1 4a:1-dodecanol ratio. Both of these outcomes suggested

that all steps of the putative catalytic cycle (O−O cleavage,

HAT, radical quench, and catalyst turnover) were proceeding

eﬃciently, but the O−O cleavage simply lacked selectivity.

Therefore, we reasoned that replacing the methyl with a variety

of substituents would be the most likely way to improve the

reaction beyond its current state.

A series of sacriﬁcial substituents with varying electronic and

steric properties were evaluated in the C−H thioetheriﬁcation

reaction (Table 2). The hydroperoxide provided a very similar

Table 2. Investigation of Nonsymmetrical Peroxides

Figure 2. Directed radical chemistry as a route to C(sp³)−H

thioetheriﬁcation.

Scheme 1. Thioetheriﬁcation of an Unactivated C−H Bond

a

entry

R group

Me

H

C(O)CF₃

Si(OEt)₃

SiMe₃

yield (%)

RSM (%) 1-dodecanol (%)

1

2

3

4

5

6

7

8

9

3a

3b

3c

3d

3e

3f

3g

3h

3i

41

39

6

0

43

37

28

nd

36

37

30

27

11

20

21

0

4

0

43

34

37

50

44

23

71

SiEt₃

The use of an unsymmetric peroxide improves the atom

economy of the transformation but also introduces a challenge

of selectivity for the desired alkoxy radical during O−O bond

cleavage. We selected dodecyl-methyl peroxide 3a as a model

substrate for optimization of the reaction parameters (Table

1). Although the room-temperature reaction did not proceed

Si(C₂H₃)Me₂

SiMePh₂

SiMe₂tBu

SiiPr₃

0

55

0

10

11

3j

b

SiiPr₃

a

b

NMR yield using BHT as an internal standard. At 80 °C and 0.1 M.

Table 1. Optimization of Pertinent Reaction Parameters

39% yield (entry 2, Table 2), perhaps due to the similar pK_a

values of a primary alcohol and water.²⁷Surprisingly, acyl

peroxides performed poorly in the reaction (entry 3, Table

2).²⁸Considering the mechanism of the Fenton reaction, the

acyl peroxide should exhibit high selectivity for the alkoxy

radical and carboxylate with negligible formation of the

opposite pair. The 6% yield from triﬂuoroacetyl peroxide 3c,

however, was the highest of all acyl peroxides examined (see

the Supporting Information). Although most silyl groups were

comparable to the methyl- and hydroperoxides (entries 4−9,

Table 2), triisopropylsilyl (TIPS)-protected peroxide 3j stood

out because of its incomplete conversion and 2:1 4a:1-

dodecanol ratio (entry 10, Table 2), the ﬁrst sign of selective

O−O bond cleavage. Further experiments revealed that the

reaction proceeded most eﬃciently at higher temperatures and

lower concentrations, with an optimal 71% yield and 3.5:1

selectivity at 80 °C and 0.1 M (entry 11, Table 2). Further

experiments revealed that the reaction proceeded to full

conversion within 5 h. Slight modiﬁcations to the reaction

conditions, such as addition of Fe(OTf)₂as a solution in

methanol (3 is insoluble in methanol), an increased disulﬁde

loading, or an increased catalyst loading, had a minimal impact

on the reaction. The TIPS group remained superior after an

extensive screening of other silyl groups (see the Supporting

Information for additional details).

Ph₂S₂

temp

product

a

1-dodecanol

(%)

entry

(equiv)

(°C)

% Fe

(%)

b

1

1.5

1.1

1.5

4.0

rt

40

80

rt

5

20

5

0

41

23

41

45

35

43

10

43

52

45

43

35

42

2

3

4

5

6

7

8

20

5

a

NMR yield using BHT as the internal standard. Full conversion

unless otherwise noted. Reaction run at a 0.05 M concentration and

24% conversion.

b

at a low concentration, we found that at 0.5 M, the reaction

with 5 mol % Fe(OTf)₂and 1.5 equiv of disulﬁde provided 4a

in 41% yield (entries 1 and 2, Table 1). Although higher

reaction temperatures, catalyst loadings, or disulﬁde loadings

did not substantially improve the reaction (entries 3, 4, and 6−

8, Table 1), we were pleased to ﬁnd that the disulﬁde loading

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With optimized conditions for the directed C(sp³)−H

thioetheriﬁcation, we evaluated the performance of the

reaction across a number of substrates. Pleasingly, the reaction

is eﬀective for the functionalization of primary, secondary, and

tertiary C−H sites (Table 3), with the highest yields obtained

Table 4. Disulﬁde Scope for Thioetheriﬁcation

a

Table 3. Substrate Scope for Thioetheriﬁcation

a

Isolated yield. Full conversion in all cases.

observed with 2-carboxyphenyl disulﬁde 32. Attempts to

extend the methodology to dialkyl disulﬁdes proved diﬃcult as

alkyl disulﬁdes trap alkyl radicals more slowly than aryl

disulﬁdes.^29,30For example, dimethyl disulﬁde 33 and dioctyl

disulﬁde fail to produce any product.

To examine the electronic preference during C−S bond

formation, we tested the reaction with electronically diﬀer-

entiated disulﬁdes (Table 5). Little diﬀerence was observed in

Table 5. Thioetheriﬁcation with an Unsymmetrical

Disulﬁde

a

b

c

Isolated yield. Reaction run for 10 h. Isolated as a mixture with

d

e

another regioisomer with a 1:0.08 ratio. Reaction run for 8 h. Total

thioarylation yield, as deacylation occurred in the reaction. TIPS

deportection of alcohol observed during the reaction. TBDS

f

g

deprotection of alcohol observed during the reaction, reaction run

for 12 h.

for secondary systems (Table 3, 4a, 8, 9, and 11−23).

Interestingly, the 2-hexyl peroxide provided a 5:1 mixture of

[1,5] and [1,6] products, but 8 was isolated as a single isomer.

The improved yield of primary thioether 6 in comparison to 5

is likely the result of a Thorpe−Ingold eﬀect imposed by the

methyl group. As expected, a secondary C−H undergoes

preferential (1:0.8) thioarylation over primary C−H bonds

(Table 3, 11). Moreover, alcohols bearing chloro, ester, amide,

and sulfonic ester functional groups (14−20) function well

under the reaction conditions. Usefully, silyl-protected alcohols

undergo desilylation during the reaction to produce thioary-

lated diols (22 and 23).

Next, we examined the scope of various disulﬁde traps

(Table 4). Although naphthyl disulﬁde 4b proved to be less

eﬀective (perhaps due to its poor solubility in methanol), we

found that both electron-poor and electron-rich aryl disulﬁdes

24−31 performed similarly to Ph₂S₂. In contrast, 4-nitro-

disulﬁde 31 provided very low yields, and no product was

a competition between phenyl and naphthyl (product ratio of

1.03). Upon comparison of electron-poor (4-nitrophenyl) or

electron-rich (4-methoxyphenyl) to phenyl disulﬁdes, however,

the reaction clearly favored the product that incorporated the

more electron-rich sulfur system.

The presumption of a Fenton mechanism guided the

conceptual development of this thioetheriﬁcation reaction.

To test this mechanistic hypothesis, experiments were

conducted to uncover evidence of the presence of radical

C

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intermediates. Providing support for an oxy-radical intermedi-

ate, 1-pentenyl peroxide 34 undergoes 5-exo-trig cyclization

and subsequent trapping to form the substituted tetrahy-

drofuran 35. Additionally, cyclopentyl peroxide 36 provides α-

cleavage product 37 in 40% isolated yield as the dimethyl

acetal (Scheme 2a). Interestingly, substrate 38 could undergo

iron-catalyzed variants produced, at best, trace quantities of 1-

dodecanal.

Intrigued by this result, we examined the thermal proﬁle of

the background reaction in greater detail. When run to 18 h,

thermal decomposition of the O−O bond begins between 50

and 60 °C. At temperatures above 80 °C, the maximum yield is

59%. Importantly, we found that at 80 °C, thermal

decomposition only begins to set in at the 5 h mark, and the

half-life of the peroxide is approximately 10 h (see the

Supporting Information for full details), thereby providing

strong evidence of an iron-mediated mechanism.

Scheme 2. Radical-Clock Experiments

In conclusion, we developed a mild silylperoxide-directed

C−H thioetheriﬁcation reaction catalyzed by a simple iron salt,

Fe(OTf)₂. The reaction proceeds in good yield with broad

functional group tolerance under simple reaction conditions.

Importantly, the use of a TIPS protecting group biases the

scission of the O−O bond and enables a selective alkoxy-

radical formation. The reaction proceeds through short-lived

radical intermediates that provide high selectivity for 1,5-HAT.

EXPERIMENTAL PROCEDURES AND

CHARACTERIZATIONS

■

General Methods. Analytical grade solvents and commercially

available reagents were purchased from commercial sources and used

directly without further puriﬁcation unless otherwise stated. THF and

DME were puriﬁed according to the Grubbs procedure.³²Thin layer

chromatography (TLC) was carried out on Merck 60 F₂₅₄precoated,

glass silica plates that were visualized with ultraviolet light or stained

1

with KMnO₄. H NMR and ¹³C{¹H} NMR spectra were recorded at

5-exo-dig cyclization to form tetrasubstituted enol 39 in a

remarkable 41% yield. Furthermore, cyclopropylmethyl sub-

strate 40 undergoes complete ring opening to aﬀord primary

sulﬁde 41 in 51% isolated yield (Scheme 2b). The sum of these

results suggests that the reaction occurs via a radical

intermediate with a lifetime of approximately 10⁻³−10⁻⁴s.³¹

If the iron catalyst acted as an initiator and the reaction

proceeded thereafter through a radical chain propagation, then

PhS^•should be capable of initiating the reaction. When PhSH

and AIBN were used to generate PhS^•, the peroxide underwent

full conversion with no sign of thioetheriﬁcation (entry 1,

Table 6). In contrast, with Ph₂S₂(2.1 or 1.1 equiv) and AIBN,

room temperature using a Varian I400 or VXR400 (¹H NMR at 400

MHz and ¹³C{¹H} NMR at 100 MHz), Varian I500 (¹H NMR at 500

MHz and ¹³C{¹H} NMR at 125 MHz), and Varian I600 (¹H NMR at

600 MHz and ¹³C{¹H} NMR at 150 MHz) instruments. ¹⁹F NMR

spectra were recorded at room temperature using a Varian I400 or

VXR400 instrument (¹⁹F NMR at 376 MHz). Chemical shifts are

reported in parts per million with reference to solvent signals [¹H

NMR, CDCl₃(7.26 ppm) and acetone-d₆(2.05 ppm); ¹³C NMR,

CDCl₃(77.2 ppm)]. ¹⁹F NMR was externally referenced to a

triﬂuoroacetic acid standard (−77.55 ppm). Signal patterns are

indicated as follows: s, singlet; d, doublet; t, triplet; q, quartet; m,

multiplet. Infrared spectra (IR) were recorded on a Bruker Tensor II

FTIR spectrometer analyzed as a thin ﬁlm and recorded in

wavenumbers (cm⁻¹). High-resolution mass spectrometry (HRMS)

analysis was performed using either an Agilent 7890B/7250 GC-

QTOF system for electron-impact ionization (EI) and reported as m/

z (relative intensity) for the molecular ion [M]/suitable fragment ion

or a Waters/Micromass LCT Classic system (ESI-TOF) for

electrospray ionization (ESI) or atmospheric-pressure chemical

ionization (APCI) and reported molecular ion [M + H] or [M +

Na] or a suitable fragment ion.

Table 6. Disulﬁde Scope for Thioetheriﬁcation

yield

a

RSM

(%)

1-dodecanol

(%)

1-dodecanal

(%)

General Procedure A. Synthesis of Alkyl Mesylates. To a round-

bottom ﬂask with a stir bar were added alcohol (1 equiv), DCM (0.4

M), and methanesulfonyl chloride (1.1 equiv). At room temperature,

triethylamine (1.2 equiv) was added dropwise. The reaction mixture

was stirred at room temperature for 3−15 h, the reaction quenched

with 1 M aqueous HCl, and the mixture diluted with water and DCM

and transferred to a separatory funnel. The organic layer was

removed, and the aqueous layer was then extracted three times with

DCM. The combined organic layers were washed with saturated

aqueous NaHCO₃and then brine. The organic layer was dried

(MgSO₄), ﬁltered, and concentrated by rotary evaporation. In general,

the crude alkyl mesylate was pure as determined by ¹H NMR and did

not require further puriﬁcation. The spectra of 1-butyl, 1-pentyl, 1-

hexyl, 2-hexyl, 1-dodecyl, 4-pentenyl, and cyclopentyl mesylates

matched the reported spectra.

entry precursor

(%)

1

2

3

4

PhSH

Ph₂S₂

0

9

26

54

0

69

36

0

75

7

17

8

7

12

15

b

c

21

a

b

NMR yield using BHT as the internal standard. With 2.1 equiv of

c

Ph₂S₂. No AIBN.

we observed low yields of the product (entries 2 and 3, Table

6). Additional experimentation revealed that the reaction did

not require an exogenous initiator as the reaction with 1.1

equiv of Ph₂S₂and no AIBN provided a 54% yield (entry 4,

Table 6). Interestingly, the thermal, iron-free reactions

produced 7−15% 1-dodecanal as a side product while the

General Procedure B. Synthesis of Dialkyl Peroxides.³³To a

round-bottom ﬂask with a stir bar were added alkyl mesylate (2

D

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Article

equiv), methanol (1.0 M), and 35% aqueous H₂O₂(1 equiv). The

stirred solution was cooled in an ice bath, and 50% (w/w) aqueous

KOH (2 equiv) was added dropwise. The reaction mixture was

allowed to warm to room temperature and stirred for 14−24 h. After

this time, the reaction mixture was diluted with water and hexanes.

The organic layer was removed, and the aqueous layer was extracted

three times with hexanes. The combined organic layers were washed

once with 1 M aqueous NaOH to remove residual hydrogen peroxide,

washed three times with water until the washings were neutral,

followed by brine, and then dried (MgSO₄), ﬁltered, and concentrated

by rotary evaporation (keeping the water bath below 40 °C) to aﬀord

a clear, colorless oil. The peroxides were puriﬁed by silica ﬂash

chromatography to clear, colorless oils. Typical R_fvalues are 0.65−

0.75 in 25% EtOAc/hexanes.

General Procedure C. Synthesis of Hydroperoxides from Alkyl

Mesylate.³⁴To a round-bottom ﬂask with a stir bar were added alkyl

mesylate (1 equiv), methanol/water (9:1, 0.8 M), and 35% aqueous

H₂O₂(6 equiv). The stirred solution was cooled in an ice bath, and

50% (w/w) aqueous KOH (1.5 equiv) was added dropwise. The

reaction mixture was allowed to warm to room temperature and

stirred for 14−24 h. Then, the reaction mixture was diluted with water

and diethyl ether. The organic layer was removed, and the aqueous

layer was extracted three times with ether. The combined organic

layers were washed three times with water and twice with brine, dried

(MgSO₄), ﬁltered, and concentrated by rotary evaporation (keeping

the water bath below 40 °C) to aﬀord a clear, colorless oil. The

hydroperoxides were puriﬁed by silica ﬂash chromatography to clear,

colorless oils. Hydroperoxides stain brightly with KMnO₄, and typical

R_fvalues are 0.3−0.4 in 15% EtOAc/hexanes.

General Procedure D. Synthesis of Hydroperoxides from Alkyl

Iodide.³⁵The hydroperoxides were prepared by adding silver

triﬂuoroacetates (1.2 equiv) in small portions to an ice-cooled

solution in the ether of the appropriate alkyl halide and hydrogen

peroxide in a ≤1-fold excess. The reactions were run for 1−3 h. The

silver halide was ﬁltered oﬀ, and the triﬂuoroacetic acid formed; the

excess of hydrogen peroxide was removed by treatment with aqueous

sodium bicarbonate, and the solvent was removed to leave the crude

hydroperoxide. The hydroperoxides were puriﬁed by silica ﬂash

chromatography to clear, colorless oils. Hydroperoxides stain brightly

with KMnO₄, and typical R_fvalues are 0.3−0.4 in 15% EtOAc/

hexanes.

EtOAc, and concentrated. Screening eﬀorts were usually run on a

0.05−0.2 mmol scale. Products were isolated by ﬂash chromatography

or analyzed by crude NMR using BHT as the internal standard.

Preparation and Characterization of the Starting Material.

1-Hydroperoxydodecane (3b). 1-Dodecyl mesylate (2.652 g, 10.0

mmol) was subjected to general procedure C, using diethyl ether

(1.25 M) and 12:1 MeOH/H₂O (0.3 M) as the solvents, for 42 h.

Silica ﬂash chromatography provided 3b (1.522 g, 75% yield) as a

clear, colorless oil that matched the reported spectra:³⁷¹H NMR (400

MHz, CDCl₃) δ 7.80 (s, 1H), 4.02 (t, J = 6.6 Hz, 2H), 1.62 (p, J = 7.1

Hz, 2H), 1.42−1.18 (m, 18H), 0.88 (t, J = 6.7 Hz, 3H); TLC R_f=

0.40 (20% EtOAc/hexanes).

(Dodecylperoxy)triisopropylsilane (3j). 1-Dodecyl hydroperoxide

3b (1.089 g, 5.0 mmol, 1 equiv) was subjected to general procedure E

using triisopropylsilyl triﬂate (1.40 mL, 5.0 mmol, 1 equiv) for 23 h.

The reaction mixture was diluted with 10 mL of hexanes, ﬁltered

through a silica plug, washing with an additional 5 mL of hexanes, and

concentrated to provide 3j (1.375 g, 76% yield) as a clear, colorless

oil: ¹H NMR (400 MHz, CDCl₃) δ 3.99 (t, J = 6.6 Hz, 2H), 1.58 (p, J

= 6.7 Hz, 2H), 1.39−1.14 (m, 21H), 1.10 (d, J = 6.8 Hz, 18H), 0.88

(t, J = 6.8 Hz, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 76.9, 32.1,

29.8, 29.8, 29.8, 29.7, 29.6, 29.5, 27.9, 26.3, 22.9, 18.1, 14.3, 11.7;

LRMS (GCMS) mass fragmentation 315.3 (100), 273.1 (8), 131.2

(13), 103.1 (13), 77.1 (13), 43.2 (6); IR (neat) 2922, 2865, 1737,

1463, 1377, 997, 882, 677 cm⁻¹; TLC R_f= 0.74 (15% EtOAc/

hexanes).

(Butylperoxy)triisopropylsilane. TIPSOOH (295 mg, 1.5 mmol, 1

equiv) was subjected to general procedure F for 15 h using

iodobutane (0.51 mL, 4.5 mmol, 3 equiv). Silica ﬂash chromatog-

raphy provided (butylperoxy)triisopropylsilane (197.1 mg, 53% yield)

as a clear, colorless oil: ¹H NMR (600 MHz, CDCl₃) δ 4.00 (t, J = 6.6

Hz, 2H), 1.58 (p, J = 6.9 Hz, 2H), 1.38 (sext, J = 7.3 Hz, 2H), 1.20

(sext, J = 7.3 Hz, 2H), 1.10 (d, J = 7.4 Hz, 18H), 0.92 (t, J = 7.4 Hz,

3H); ¹³C{¹H} NMR (125 MHz, CDCl₃) δ 76.7, 30.1, 19.6, 18.1, 14.1,

11.7; HRMS (APCI) calcd for C₁₃H₃₁O₂Si [M + H]⁺247.2093, found

247.2086; IR (neat) 2943, 2866, 1463, 1382, 1064, 881, 676 cm⁻¹;

TLC R_f= 0.63 (5% EtOAc/hexanes).

Triisopropyl(pentan-2-ylperoxy)silane. TIPSOOH (380 mg, 2.0

mmol, 1 equiv) was subjected to general procedure F for 16 h using 2-

iodopentane (0.60 mL, 4.6 mmol, 2.3 equiv). Silica ﬂash

chromatography provided triisopropyl(pentan-2-ylperoxy)silane

General Procedure E. Silylation of Hydroperoxides.³⁶To a ﬂame-

dried round-bottom ﬂask with a stir bar were added hydroperoxide

(1.0 equiv) and pentane (0.5 M). The ﬂask was cooled in an ice bath,

and the silyl chloride or triﬂate (1.0 equiv) was added dropwise,

followed by the dropwise addition of distilled 2,6-lutidine (1.0 equiv).

The reaction mixture was slowly warmed to room temperature and

stirred for 3−24 h. After the speciﬁed time, the reaction mixture was

diluted with diethyl ether and washed with water, followed by brine.

The organic layer was dried (MgSO₄), ﬁltered, and concentrated to

provide a clear, colorless oil. If necessary, the alkyl silyl peroxide was

puriﬁed by silica ﬂash chromatography.

General Procedure F. Silyl Hydroperoxide Alkylation. To a

reaction vial with a stir bar were added triisopropyl hydroperoxide (1

equiv) and pentane (0.5 M). The solution was cooled in an ice bath.

Ag₂O (3 equiv) was added, followed by the dropwise addition of alkyl

iodide (3 equiv). The reaction vessel was covered with foil and left in

the ice bath to warm to room temperature slowly. After 14 h, the

reaction mixture was diluted with diethyl ether, ﬁltered, and

concentrated by rotary evaporation. The alkyl silyl peroxide product

was puriﬁed by silica ﬂash chromatography. The alkyl iodide closely

elutes in many cases but can often be removed under high vacuum.

General Procedure G. C−H Thioetheriﬁcation Reaction. To a

ﬂame-dried 40 mL reaction vial with a septum-lined cap and a stir bar

were added TIPS peroxide (1.0 equiv), disulﬁde (1.1 equiv), and

Fe(OTf)₂(0.05 equiv). The ﬂask was evacuated and backﬁlled three

times with N₂. Degassed MeOH (0.1 M) was added via syringe, and

then the reaction mixture was heated to 80 °C on a preheated oil

bath. After 5 h, the reaction mixture was cooled, diluted with ethyl

acetate (5 mL), ﬁltered through a silica plug, washing with ∼10 mL of

1

(247 mg, 47% yield) as a clear, colorless oil: H NMR (500 MHz,

CDCl₃) δ 4.04 (sextet, J = 6.0 Hz, 1H), 1.67−1.53 (m, 1H), 1.45−

1.28 (m, 3H), 1.25−1.14 (m, 6H), 1.09 (d, J = 7.3 Hz, 18H), 0.94−

0.88 (m, 3H); ¹³C{¹H} NMR (125 MHz, CDCl₃) δ 81.1, 36.8, 18.9,

18.7, 18.2, 14.4, 11.8; LRMS (GCMS) mass fragmentation 201.3 (3),

173.3 (6), 147.2 (20), 105.2 (43), 103.1 (30), 77.2 (100), 76.1 (35),

61.1 (17), 43.3 (14); IR (neat) 2960, 2866, 1738, 1463, 1370, 997,

881, 676 cm⁻¹; TLC R_f= 0.71 (10% EtOAc/hexanes).

(Isopentylperoxy)triisopropylsilane. 1-Iodo-3-methylbutane (1.98

g, 10 mmol) was subjected to general procedure D for 2 h. Silica ﬂash

chromatography provided 1-hydroperoxy-3-methylbutane (392 mg,

1

38% yield) as a clear, colorless oil: H NMR (400 MHz, CDCl₃) δ

7.46 (s, 1H), 4.06 (t, J = 6.8 Hz, 2H), 1.69 (dp, J = 13.3, 6.7 Hz, 1H),

1.52 (q, J = 6.9 Hz, 2H), 0.92 (d, J = 6.6 Hz, 6H); ¹³C{¹H} NMR

(100 MHz, CDCl₃) δ 75.95, 36.46, 25.39, 22.84; TLC R_f= 0.5 (20%

EtOAc/hexanes). 1-Hydroperoxy-3-methylbutane (330 mg, 3.17

mmol) was subjected to general procedure E for 3 h. Silica ﬂash

chromatography provided (isopentylperoxy)triisopropylsilane (640

mg, 78% yield) as a clear, colorless oil: ¹H NMR (400 MHz, CDCl₃)

δ 4.02 (t, J = 6.8 Hz, 2H), 1.69 (dq, J = 13.4, 6.7 Hz, 1H), 1.55−1.40

(m, 2H), 1.29−1.13 (m, 3H), 1.15−0.99 (m, 18H), 0.90 (d, J = 6.6

Hz, 6H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ 75.5, 36.7, 25.5, 22.8,

18.1, 11.7; LRMS (GCMS) mass fragmentation 201.3 (1), 175.2 (1),

168.2 (1), 147.2 (1), 129.2 (8), 119.2 (27), 77.2 (100), 76.1 (35),

69.2 (35), 61.1 (20), 43.3 (10); IR (neat) 2945, 2867, 1464, 1367,

1014, 997, 881, 819, 743 cm⁻¹; TLC R_f= 0.5 (5% EtOAc/hexanes).

1-Hydroperoxyhexane. 1-Hexyl mesylate (1.465 g, 8.0 mmol) was

subjected to general procedure C for 20 h. Silica ﬂash chromatog-

raphy provided 1-hydroperoxyhexane (623 mg, 66% yield) as a clear,

E

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The Journal of Organic Chemistry

Article

colorless oil that matched the reported spectra:³⁸¹H NMR (600

MHz, CDCl₃) δ 7.91−7.84 (br s, 1H), 4.02 (t, J = 6.7 Hz, 2H), 1.61

(p, J = 7.0 Hz, 2H), 1.45−1.20 (m, 6H), 0.89 (t, J = 6.8 Hz, 3H);

TLC R_f= 0.31 (15% EtOAc/hexanes).

29.1, 24.0, 23.1, 14.2, 11.1; IR (neat) 3423 (b), 2559, 2928,

1540,1462, 1379, 1172, 941, 816, 412 cm⁻¹; TLC R_f= 0.43 (30%

EtOAc/hexanes). Next, 3-(hydroperoxymethyl)heptane (426 mg,

2.91 mmol) was subjected to general procedure E for 3 h. Silica

ﬂash chromatography provided [(2-ethylhexyl)peroxy]-

(Hexylperoxy)triisopropylsilane. 1-Hydroperoxyhexane (258 mg,

2.2 mmol, 1 equiv) was subjected to general procedure E using

triisopropylsilyl triﬂate (0.59 mL, 2.2 mmol, 1 equiv) for 14 h. The

reaction mixture was diluted with 3 mL of pentane, ﬁltered through a

silica plug, washing with an additional 5 mL of pentane, and

concentrated to provide (hexylperoxy)triisopropylsilane (366 mg,

60% yield) as a clear, colorless oil that did not require further

puriﬁcation: ¹H NMR (400 MHz, CDCl₃) δ 3.99 (t, J = 6.6 Hz, 2H),

1.59 (p, J = 6.9 Hz, 2H), 1.41−1.25 (m, 6H), 1.21 (hept, J = 7.9, 7.1

Hz, 3H), 1.10 (d, J = 7.4 Hz, 18H), 0.89 (t, J = 6.8 Hz, 3H); ¹³C{¹H}

NMR (100 MHz, CDCl₃) δ 76.9, 31.8, 27.9, 26.0, 22.7, 18.1, 14.1,

11.7; HRMS (EI) calcd for C₁₂H₂₇O₂Si [M − C₃H₇]⁺231.1775,

found 231.1769; IR (neat) 2942, 2866, 1741, 1463, 1381, 882, 676

cm⁻¹.

1

triisopropylsilane (588 mg, 67% yield) as a clear, colorless oil: H

NMR (400 MHz, CDCl₃) δ δ 3.91 (d, J = 5.9 Hz, 2H), 1.57 (td, J =

11.7, 5.7 Hz, 1H), 1.43−1.24 (m, 8H), 1.24−1.14 (m, 3H), 1.14−

1.03 (m, 18H), 0.88 (t, J = 7.3 Hz, 6H); ¹³C{¹H} NMR (126 MHz,

CDCl₃) δ 79.8, 38.7, 30.9, 29.2, 24.3, 23.1, 18.2, 14.2, 11.7, 11.3;

HRMS (EI) calcd for C₁₇H₃₈O₂Si [M]⁺302.2636, found 302.2632;

IR (neat) 2927, 2866, 1463, 1381, 1250, 997, 881, 677 cm⁻¹; TLC R_f

= 0.64 (5% EtOAc/hexanes).

(Cyclooctylperoxy)triisopropylsilane. TIPSOOH (380 mg, 2.0

mmol, 1 equiv) was subjected to general procedure F using

iodocyclooctane (1.42 g, 6 mmol, 3 equiv). Silica ﬂash chromatog-

raphy provided (cyclooctylperoxy)triisopropylsilane (288 mg, 48%

1

yield) as a clear, colorless oil: H NMR (400 MHz, chloroform-d) δ

2-Hydroperoxyhexane. 2-Hexyl mesylate (3.62 g, 20 mmol, 1

equiv) was subjected to general procedure C at a concentration of 0.3

M (12:1 MeOH/H₂O) for 19 h. Silica ﬂash chromatography provided

2-hydroperoxyhexane (879 mg, 37% yield) as a clear, colorless oil:³⁹

¹H NMR (600 MHz, CDCl₃) δ 7.69−7.54 (m, 1H), 4.06 (h, J = 6.1

Hz, 1H), 1.71−1.55 (m, 1H), 1.49−1.26 (m, 5H), 1.22 (d, J = 6.2 Hz,

3H), 0.90 (t, J = 7.0 Hz, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ

81.9, 33.8, 27.7, 22.9, 18.3, 14.1; IR (neat) 3374, 2933, 2862, 1737,

1461, 1375, 1114 cm⁻¹; TLC R_f= 0.31 (15% EtOAc/hexanes).

(Hexan-2-ylperoxy)triisopropylsilane. 2-Hexyl hydroperoxide

(473 mg, 4.0 mmol, 1 equiv) was subjected to general procedure E

using triisopropylsilyl triﬂate (1.07 mL, 4.0 mmol, 1 equiv) and

anhydrous ammonia as the base (sparge for 10 min and then a balloon

atmosphere) for 16 h. Silica ﬂash chromatography provided (hexan-2-

ylperoxy)triisopropylsilane (796 mg, 72% yield) as a clear, colorless

oil: ¹H NMR (400 MHz, CDCl₃) δ 4.03 (sext, J = 6.0 Hz, 1H), 1.70−

1.56 (m, 1H), 1.47−1.25 (m, 5H), 1.24−1.15 (m, 6H), 1.09 (d, J =

7.3 Hz, 18H), 0.89 (t, J = 6.9 Hz, 3H); ¹³C{¹H} NMR (100 MHz,

CDCl₃) δ 81.3, 34.3, 27.8, 23.0, 18.6, 18.2, 14.2, 11.8; HRMS (EI)

calcd for C₁₂H₂₇O₂Si [M − C₃H₇]⁺231.1775, found 231.1769; IR

(neat) 2942, 2866, 1738, 1463, 1371, 881, 791 cm⁻¹; TLC R_f= 0.75

(10% EtOAc/hexanes).

4.06 (tt, J = 8.4, 3.5 Hz, 1H), 1.92 (ddt, J = 14.0, 8.1, 2.8 Hz, 2H),

1.70 (dtd, J = 12.6, 8.0, 3.5 Hz, 2H), 1.62−1.30 (m, 10H), 1.30−1.12

(m, 3H), 1.09 (d, J = 6.7 Hz, 18H); ¹³C{¹H} NMR (101 MHz,

chloroform-d) δ 85.8, 30.1, 27.4, 25.9, 23.7, 18.3, 11.8; LRMS

(GCMS) mass fragmentation 257.3 (3), 173.2 (3), 147.2 (33), 105.2

(66), 77.2 (100), 69.2 (20), 61.2 (20), 41.3 (13); IR (neat) 2922,

2865, 1463, 1447, 1382, 1366, 1250, 1052, 1014, 997, 881, 776, 676

cm⁻¹; TLC R_f= 0.7 (5% EtOAc/hexanes).

3-Phenylbutyl Methanesulfonate. 3-Phenylbutan-1-ol (1.5 g, 10

mmol) was subjected to general procedure A for 14 h. After the

workup procedure, the crude material was isolated with high purity.

We moved to the next step without any further puriﬁcation (2.3 g,

98% yield): ¹H NMR (400 MHz, CDCl₃) δ 7.34 (dd, J = 8.2, 6.9 Hz,

2H), 7.27−7.19 (m, 3H), 4.34−3.89 (m, 2H), 3.01−2.80 (m, 4H),

2.17−1.94 (m, 2H), 1.33 (d, J = 7.0 Hz, 3H); ¹³C{¹H} NMR (100

MHz, CDCl₃) δ 145.4, 128.8, 127.1, 126.7, 68.6, 37.3, 37.3, 36.3, 27.2,

22.4; HRMS (ESI) calcd for C₁₁H₁₆O₃SNa [M + Na]⁺251.0712,

found 251.0714; IR (neat) 2962, 2935, 1494, 1348, 1170, 935, 700,

525 cm⁻¹; TLC R_f= 0.7 (30% EtOAc/hexanes).

(4-Hydroperoxybutan-2-yl)benzene. 3-Phenylbutyl methanesulfo-

nate (1.2 g, 5.26 mmol) was subjected to general procedure C, using

diethyl ether (1.25 M) and 12:1 MeOH/H₂O (0.3 M) as the solvents,

for 48 h. Silica ﬂash chromatography provided (4-hydroperoxybutan-

Triisopropyl[(4-methylpentyl)peroxy]silane. TIPSOOH (344 mg,

1.8 mmol, 1 equiv) was subjected to general procedure F using 1-

iodo-4-methylpentane (0.80 mL, 5.4 mmol, 3 equiv). Silica ﬂash

chromatography provided triisopropyl[(4-methylpentyl)peroxy]silane

1

2-yl)benzene (340 mg, 39% yield) as a clear, colorless oil: H NMR

(400 MHz, CDCl₃) δ 7.96−7.76 (m, 1H), 7.31 (t, J = 7.7 Hz, 2H),

7.24−7.16 (m, 3H), 3.97−3.86 (m, 2H), 3.14−2.74 (m, 1H), 2.01−

1.86 (m, 2H), 1.29 (d, J = 6.9 Hz, 3H); ¹³C{¹H} NMR (100 MHz,

CDCl₃) δ 146.6, 128.6, 127.1, 126.3, 75.5, 36.7, 35.9, 22.6; HRMS

(ESI) calcd for C₁₀H₁₄O₄Na [M + Na + O₂]⁺221.0784, found

221.0784; IR (neat) 3372 (b), 2959, 1493, 1451, 1374, 1051, 761,

698, 546 cm⁻¹; TLC R_f= 0.38 (20% EtOAc/hexanes).

1

(205.5 mg, 41% yield) as a clear, colorless oil: H NMR (400 MHz,

CDCl₃) δ 3.97 (t, J = 6.7 Hz, 2H), 1.68−1.46 (m, 3H), 1.29−1.14

(m, 5H), 1.10 (d, J = 7.0 Hz, 18H), 0.88 (d, J = 6.6 Hz, 6H); ¹³C{¹H}

NMR (100 MHz, CDCl₃) δ 77.2, 35.3, 28.0, 25.8, 22.6, 18.1, 11.7;

HRMS (EI) calcd for C₁₂H₂₇O₂Si [M − C₃H₇]⁺231.1775, found

231.1769; IR (neat) 2945, 2867, 1463, 1367, 1250, 1015, 882, 676

cm⁻¹; TLC R_f= 0.60 (5% EtOAc/hexanes).

2-Ethylhexyl Methanesulfonate. 2-Ethylhexan-1-ol (4.69 mL, 30.0

mmol) was subjected to general procedure A for 14 h. After the

workup procedure, the crude material was isolated with high purity.

We moved to the next step without any further puriﬁcation (5.933 g,

95% yield): ¹H NMR (400 MHz, CDCl₃) δ 4.27−4.01 (m, 2H), 3.00

(s, 3H), 1.65 (p, J = 6.0 Hz, 1H), 1.48−1.20 (m, 8H), 1.02−0.82 (m,

6H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 72.2, 39.2, 37.1, 29.9, 28.8,

23.3, 22.9, 14.0, 10.8; HRMS (ESI) calcd for C₉H₂₀O₃NaS [M + Na]⁺

231.1025, found 231.1026; IR (neat) 2959, 2931, 2861, 1463, 1350,

1172, 939, 845, 816, 748, 527 cm⁻¹; TLC R_f= 0.69 (30% EtOAc/

hexanes).

Triisopropyl[(3-phenylbutyl)peroxy]silane. (4-Hydroperoxybutan-

2-yl)benzene (238 mg, 2.64 mmol) was subjected to general

procedure E for 3 h. Silica ﬂash chromatography provided

triisopropyl[(3-phenylbutyl)peroxy]silane (611 mg, 72% yield) as a

1

clear, colorless oil: H NMR (400 MHz, CDCl₃) δ 7.29 (dd, J = 8.1,

6.9 Hz, 2H), 7.22−7.14 (m, 3H), 3.91 (t, J = 6.7 Hz, 2H), 2.84 (h, J =

7.1 Hz, 1H), 1.98−1.81 (m, 2H), 1.27 (d, J = 7.0 Hz, 3H), 1.24−1.12

(m, 3H), 1.12−1.01 (m, 18H); ¹³C{¹H} NMR (126 MHz, CDCl₃) δ

146.9, 128.5, 127.1, 126.2, 75.1, 36.8, 36.2, 22.6, 18.1, 11.7; HRMS

(EI) calcd for C₁₆H₂₇O₂Si [M − C₃H₇]⁺279.1775, found 279.1776;

IR (neat) 2943, 2866, 1493, 1367, 1016, 881, 759, 698, 676 cm⁻¹;

TLC R_f= 0.64 (5% EtOAc/hexanes).

6-Chlorohexyl Methanesulfonate. 6-Chlorohexan-1-ol (2.732 g,

20.0 mmol) was subjected to general procedure A for 14 h. After the

workup procedure, the crude material was isolated with high purity.

We moved to the next step without any further puriﬁcation (4.1 g,

96% yield)L ¹H NMR (400 MHz, CDCl₃) δ 4.23 (t, J = 6.5 Hz, 2H),

3.54 (t, J = 6.6 Hz, 2H), 3.01 (s, 3H), 1.90−1.70 (m, 4H), 1.47 (dtt, J

= 14.9, 9.1, 5.8 Hz, 4H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 69.8,

44.8, 37.4, 32.3, 29.0, 26.2, 24.8; HRMS (ESI) calcd for

C₇H₁₅O₃ClNaS [M + Na]⁺237.0323, found 237.0324; IR (neat)

[(2-Ethylhexyl)peroxy]triisopropylsilane. 2-Ethylhexyl methanesul-

fonate (5.208 g, 25.0 mmol) was subjected to general procedure C,

using diethyl ether (1.25 M) and 12:1 MeOH/H₂O (0.3 M) as the

solvents, for 40 h. Silica ﬂash chromatography provided 3-

(hydroperoxymethyl)heptane (1.501 g, 42% yield) as a clear, colorless

1

oil: H NMR (400 MHz, CDCl₃) δ 8.07−7.87 (m, 1H), 3.91 (d, J =

6.1 Hz, 2H), 1.61 (q, J = 5.9 Hz, 1H), 1.45−1.12 (m, 8H), 0.87 (t, J =

7.4 Hz, 6H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 80.4, 38.1, 30.6,

F

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Article

2939, 2863, 1348, 1170, 943, 915, 817, 717, 526 cm⁻¹; TLC R_f= 0.36

(30% EtOAc/hexanes).

2865, 1741, 1463, 1365, 1250, 1198, 1168, 1104, 997, 919, 882, 854,

779, 677, 663, 503 cm⁻¹; TLC R_f= 0.3 (5% EtOAc/hexanes).

Methyl 6-Bromohexanoate. A mixture of 6-bromohexanoic acid

(1.95 g, 10 mmol) and concentrated H₂SO₄(0.3 mL) in methanol

(20 mL) was reﬂuxed for 5 h, Then, the volatile was evaporated. The

mixture was poured into H₂O (30 mL) and extracted with EtOAc (3

× 30 mL). The combined organic layer was washed with a saturated

NaHCO₃solution (30 mL) and a brine solution (30 mL) and dried

over anhydrous MgSO₄. After the solvent had evaporated, methyl 6-

bromohexanoate was isolated (1.585 g, 76%) with high purity as

colorless oil that matched the reported spectra:⁴²¹H NMR (400

MHz, CDCl₃) δ 3.67 (s, 3H), 3.41 (t, J = 6.8 Hz, 2H), 2.33 (t, J = 7.4

Hz, 2H), 1.97−1.83 (m, 2H), 1.73−1.60 (m, 2H), 1.53−1.41 (m,

2H); TLC R_f= 0.4 (10% EtOAc/hexanes).

Methyl 6-Iodomohexanoate. A mixture of methyl 6-bromohex-

anoate (1.59 g, 7.6 mmol) was added to a solution of NaI (1.245 g,

8.3 mmol) in acetone (10 mL), and the mixture was stirred for 2 h at

65 °C. After 2 h, the reaction mixture was cooled to room

temperature, the precipitate ﬁltered, and the ﬁltrate evaporated.

Then, Et₂O (50 mL) was added to the residue, and the mixture was

washed with saturated aqueous Na₂S₂O₃(1 × 50 mL), H₂O (1 × 50

mL), and brine (1 × 50 mL). The organic solution was dried over

anhydrous MgSO₄. After the solvent had been evaporated, methyl 6-

iodohexanoate was isolated (1.710 g, 88%) with high purity as

colorless oil that matched the reported spectra:⁴²¹H NMR (400

MHz, CDCl₃) δ 3.67 (s, 3H), 3.18 (t, J = 7.0 Hz, 2H), 2.32 (t, J = 7.5

Hz, 2H), 2.04−1.77 (m, 2H), 1.73−1.60 (m, 2H), 1.53−1.34 (m,

2H); TLC R_f= 0.42 (10% EtOAc/hexanes).

Methyl 6-[(Triisopropylsilyl)peroxy]hexanoate. Methyl 6-iodohex-

anoate (1.586 g, 6.19 mmol) was subjected to general procedure F for

14 h. Silica ﬂash chromatography provided methyl 6-

[(triisopropylsilyl)peroxy]hexanoate (270 mg, 14% yield) as a clear,

colorless oil: ¹H NMR (400 MHz, CDCl₃) δ 3.96 (t, J = 6.5 Hz, 2H),

3.64 (s, 3H), 2.29 (t, J = 7.5 Hz, 2H), 1.61 (dq, J = 11.2, 7.1 Hz, 4H),

1.37 (q, J = 8.4 Hz, 2H), 1.26−1.11 (m, 3H), 1.07 (d, J = 7.1 Hz,

18H); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 174.1, 76.5, 51.5, 34.1,

27.6, 25.8, 24.9, 18.1, 11.7; HRMS (EI) calcd for C₁₃H₂₇O₄Si [M −

C₃H₇]⁺275.1673, found 275.1676; IR (neat) 2944, 2866, 1741, 1463,

1435, 1366, 1197, 1015, 882, 854, 677 cm⁻¹; TLC R_f= 0.33 (5%

EtOAc/hexanes).

N,N-Diethyl-6-iodohexanamide. To a round-bottom ﬂask with a

stir bar were added 6-bromohexanoic acid (3.9 g, 20 mmol) and

DCM (60 mL). DMF (0.05 equiv, 73 μL) was added at rt. Oxalyl

chloride (30 mmol, 2.5 mL) was added dropwise. The reaction

mixture was stirred at room temperature until bubbling stopped (1 h).

Without being transferred from the reaction ﬂask, volatile

components were removed by rotary evaporation and high vacuum.

The crude reaction product was dissolved in DCM (60 mL) and

stirred. N,N-Diethylamine (20 mmol, 3.1 mL), followed by triethyl-

amine (30 mmol, 4.2 mL), was added at room temperature, and the

reaction mixture was stirred overnight. The reaction was quenched

with 1 M aqueous HCl, and the mixture transferred to a separatory

funnel. The crude mixture was diluted with DCM (0.1 M) and water

(0.1 M). The organic layer was removed, and the aqueous layer was

then extracted with DCM (3 × 0.1 M). The combined organic layers

were washed with saturated aqueous NaHCO₃and then brine. The

organic layer was dried with MgSO₄, ﬁltered, and concentrated by

rotary evaporation. Without any further puriﬁcation, we isolated 6-

bromo-N,N-diethylhexanamide as an oily liquid (4.5 g, 90%) that

matched previously reported spectra:⁴³¹H NMR (400 MHz, CDCl₃)

δ 3.47−3.33 (m, 4H), 3.29 (q, J = 7.1 Hz, 2H), 2.30 (t, J = 7.5 Hz,

2H), 1.88 (p, J = 7.0 Hz, 2H), 1.67 (p, J = 7.5 Hz, 2H), 1.57−1.37

(m, 2H), 1.16 (t, J = 7.2 Hz, 3H), 1.10 (t, J = 7.1 Hz, 3H); ¹³C{¹H}

NMR (100 MHz, CDCl₃) δ 171.8, 42.0, 40.2, 33.9, 33.0, 32.8, 28.2,

24.6, 14.5, 13.3; TLC R_f= 0.17 (30% EtOAc/hexanes). Next, a

mixture of 6-bromo-N,N-diethylhexanamide (3 g, 12 mmol) was

added to a solution of NaI (2.16 g, 14.4 mmol) in acetone (20 mL),

and the mixture was stirred overnight at 65 °C. Then, the reaction

mixture was cooled to room temperature, the precipitate ﬁltered, and

the ﬁltrate evaporated. Then, Et₂O (50 mL) was added to the residue

[(6-Chlorohexyl)peroxy]triisopropylsilane. 6-Chlorohexyl metha-

nesulfonate (3.64 g, 17.0 mmol) was subjected to general procedure

C, using 12:1 MeOH/H₂O (0.3 M) as the solvents, for 18 h. Silica

ﬂash chromatography provided 1-chloro-6-hydroperoxyhexane (1.317

g, 51% yield) as a clear, colorless oil: ¹H NMR (500 MHz, CDCl₃) δ

8.16 (s, 1H), 4.02 (t, J = 6.5 Hz, 2H), 3.53 (t, J = 6.7 Hz, 2H), 1.84−

1.73 (m, 2H), 1.71−1.60 (m, 2H), 1.51−1.34 (m, 4H); ¹³C{¹H}

NMR (126 MHz, CDCl₃) δ 77.0, 45.1, 32.6, 27.5, 26.8, 25.3; IR

(neat) 3381 (b), 2937, 2861, 1461, 1367, 1309, 109, 763, 648 cm⁻¹;

TLC R_f= 0.52 (30% EtOAc/hexanes). Next, 1-chloro-6-hydro-

peroxyhexane (763 mg, 5 mmol) was subjected to general procedure

E for 3 h. Silica ﬂash chromatography provided [(6-chlorohexyl)-

peroxy]triisopropylsilane (1.278 g, 83% yield) as a clear, colorless oil:

¹H NMR (400 MHz, CDCl₃) δ 3.97 (t, J = 6.5 Hz, 2H), 3.51 (t, J =

6.7 Hz, 2H), 1.88−1.70 (m, 2H), 1.65−1.55 (m, 2H), 1.50−1.32 (m,

4H), 1.30−1.11 (m, 3H), 1.07 (d, J = 7.0 Hz, 18H); ¹³C{¹H} NMR

(126 MHz, CDCl₃) δ 75.6, 44.2, 31.6, 26.8, 26.2, 25.9, 24.6, 17.1,

10.7; LRMS (ESI) mass fragmentation 336.1 (11), 308.1 (55), 276.0

(16), 267.1 (29), 250.0 (10), 217.9 (14), 190.4 (8), 178.0 (41), 147.0

(100); IR (neat) 2942, 2865, 1463, 1366, 1015, 882, 781, 676, 661

cm⁻¹; TLC R_f= 0.66 (5% EtOAc/hexanes).

Methyl 8-Bromohexanoate. A mixture of 8-bromohexanoic acid

(2.2 g, 10 mmol) and concentrated H₂SO₄(0.3 mL) in methanol (20

mL) was reﬂuxed for 5 h. Then, the volatile was evaporated. The

mixture was poured into H₂O (30 mL) and extracted with EtOAc (3

× 30 mL). The combined organic layer was washed with a saturated

NaHCO₃solution (30 mL) and a brine solution (30 mL) and dried

over anhydrous MgSO₄. After the solvent had evaporated, methyl 8-

bromohexanoate was isolated (1.94 g, 82%) with high purity as a

colorless oil that matched the reported spectra:⁴⁰¹H NMR (500

MHz, CDCl₃) δ 3.65 (s, 3H), 3.38 (t, J = 6.8 Hz, 2H), 2.29 (t, J = 7.5

Hz, 2H), 1.89−1.78 (m, 2H), 1.69−1.56 (m, 2H), 1.52−1.37 (m,

2H), 1.35−1.29 (m, 4H); TLC R_f= 0.4 (20% EtOAc/hexanes).

Methyl 8-Iodomohexanoate. A mixture of methyl 8-bromohex-

anoate (1.91 g, 8.06 mmol) was added to a solution of NaI (3.6 g,

24.2 mmol) in acetone (15 mL), and the mixture was stirred for 2 h at

65 °C. After 2 h, the reaction mixture was cooled to room

temperature, the precipitate ﬁltered, and the ﬁltrate evaporated.

Then, Et₂O (50 mL) was added to the residue and washed with

saturated aqueous Na₂S₂O₃(1 × 50 mL), H₂O (1 × 50 mL), and

brine (1 × 50 mL). The organic solution was dried over anhydrous

MgSO₄. After evaporation of the solvent, methyl 8-iodohexanoate was

isolated (2.15 g, 94%) with high purity as a colorless oil that matched

the reported spectra:⁴¹¹H NMR (500 MHz, CDCl₃) δ 3.65 (s, 3H),

3.17 (t, J = 7.0 Hz, 2H), 2.29 (t, J = 7.5 Hz, 2H), 1.80 (p, J = 7.1 Hz,

2H), 1.68−1.55 (m, 2H), 1.43−1.35 (m, 2H), 1.31 (p, J = 3.6 Hz,

4H); TLC R_f= 0.41 (20% EtOAc/hexanes).

Methyl 8-Hydroperoxyoctanoate. Methyl 8-iodohexanoate (1.586

g, 6.19 mmol) was subjected to general procedure D for 2 h. Silica

ﬂash chromatography provided methyl 8-hydroperoxyoctanoate

1

hexanoate (810 mg, 69% yield) as a clear, colorless oil: H NMR

(400 MHz, CDCl₃) δ 8.20 (s, 1H), 3.99 (ddd, J = 8.4, 5.4, 1.8 Hz,

2H), 3.66 (s, 3H), 2.42−2.10 (m, 2H), 1.61 (dd, J = 9.5, 4.8 Hz, 4H),

1.36−1.25 (m, 6H); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 175.0, 77.1,

51.8, 34.2, 29.1, 29.1, 27.6, 25.8, 24.9; TLC R_f= 0.34 (30% EtOAc/

hexanes); HRMS (ESI) calcd for C₉H₁₈O₄Na [M + Ma]⁺213.1097,

found 213.1097; IR (neat) 3400, 2933, 2857, 1736, 1715, 1437, 1363,

1252, 1203,1171, 1104, 855, 726 cm⁻¹.

Methyl 8-[(Triisopropylsilyl)peroxy]hexanoate. Methyl 8-hydro-

peroxyoctanoate (0.790 g, 4.157 mmol) was subjected to general

procedure E for 3 h. Silica ﬂash chromatography provided methyl 8-

[(triisopropylsilyl)peroxy]hexanoate (978 mg, 68% yield) as a clear,

colorless oil: ¹H NMR (400 MHz, CDCl₃) δ 3.96 (t, J = 6.6 Hz, 2H),

3.65 (s, 3H), 2.29 (t, J = 7.5 Hz, 2H), 1.59 (dt, J = 13.5, 6.9 Hz, 4H),

1.31 (d, J = 4.1 Hz, 6H), 1.25−1.11 (m, 3H), 1.08 (d, J = 7.0 Hz,

18H); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 174.4, 76.8, 51.6, 34.2,

29.2, 29.2, 27.9, 26.1, 25.0, 18.2, 11.7; HRMS (ESI) calcd for

C₁₈H₃₈O₄NaSi [M + Na]⁺369.2432, found 369.2434; IR (neat) 2941,

G

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The Journal of Organic Chemistry

Article

and washed with saturated aqueous Na₂S₂O₃(1 × 50 mL), H₂O (1 ×

50 mL), and brine (1 × 50 mL). The organic solution was dried over

anhydrous MgSO₄. After the solvent had evaporated, N,N-diethyl-6-

iodohexanamide was isolated (2.2 g, 62%) as a brown liquid, which

matched previously reported spectra.⁴⁴Without further puriﬁcation,

(q, J = 273.5 Hz), 65.5, 33.3, 30.2, 28.6, 25.1, 6.7; ¹⁹F NMR (376

MHz, CDCl₃) δ −62.83; LRMS (GCMS) mass fragmentation 273.1

(34), 210.1 (10), 191.1 (37), 173.1 (100), 145.1 (75), 125.1 (10),

83.2 (63), 55.2 (30), 41.1 (10); IR (neat) 2934, 2858, 1721, 1617,

1441, 1333, 1247, 1166, 1123, 1086, 1071, 920, 819, 756, 693, 650,

602 cm⁻¹; TLC R_f= 0.52 (20% EtOAc/hexanes). Finally, 6-iodohexyl

3-(triﬂuoromethyl)benzoate (2 g, 5 mmol) was subjected to general

procedure D for 2 h. Silica ﬂash chromatography provided 6-

hydroperoxyhexyl 3-(triﬂuoromethyl)benzoate (550 mg, 36% yield)

as a clear, colorless oil: ¹H NMR (400 MHz, CDCl₃) δ 8.29 (s, 1H),

8.22 (d, J = 7.8 Hz, 1H), 8.02 (s, 1H), 7.81 (d, J = 7.7 Hz, 1H), 7.58

(t, J = 7.8 Hz, 1H), 4.36 (t, J = 6.6 Hz, 2H), 4.03 (t, J = 6.4 Hz, 2H),

1.80 (p, J = 6.7 Hz, 2H), 1.68 (p, J = 6.7 Hz, 2H), 1.51−1.41 (m,

4H); ¹³C{¹H} NMR (126 MHz, chloroform-d) δ 165.6, 132.9, 131.4,

131.2 (q, J = 32.8 Hz), 129.6 (q, J = 3.7 Hz), 129.2, 126.6 (q, J = 3.9

Hz), 123.8 (q, J = 173.9 Hz), 77.02, 65.70, 28.71, 27.63, 25.97, 25.74;

¹⁹F NMR (376 MHz, CDCl₃) δ −62.85; HRMS (ESI) calcd for

C₁₄H₁₇F₃O₄Na [M + Na]⁺329.0971, found 329.0974; IR (neat)

3414, 2939, 2863, 1721, 1617, 1334, 1248, 1166, 1123, 1087, 1071,

979, 920, 821, 757, 693, 650 cm⁻¹; TLC R_f= 0.35 (20% EtOAc/

hexanes).

6-[(Triisopropylsilyl)peroxy]hexyl 3-(Triﬂuoromethyl)benzoate.

6-Hydroperoxyhexyl 3-(triﬂuoromethyl)benzoate (496 mg, 1.62

mmol) was subjected to general procedure E for 2 h. Silica ﬂash

chromatography provided 6-[(triisopropylsilyl)peroxy]hexyl 3-

(triﬂuoromethyl)benzoate (480 mg, 65% isolated as pure) as a

clear, colorless oil: ¹H NMR (400 MHz, CDCl₃) 8.29 (d, J = 2.2 Hz,

1H), 8.22 (d, J = 7.8 Hz, 1H), 7.81 (d, J = 7.7 Hz, 1H), 7.58 (t, J = 7.8

Hz, 1H), 4.35 (t, J = 6.7 Hz, 2H), 4.00 (t, J = 6.5 Hz, 2H), 1.80 (p, J =

6.8 Hz, 2H), 1.64 (p, J = 6.7 Hz, 2H), 1.49−1.40 (m, 4H), 1.29−1.13

(m, 3H), 1.14−0.93 (m, 18H); ¹³C{¹H} NMR (126 MHz,

chloroform-d) δ 165.4, 132.9, 131.5, 131.2 (q, J = 34.0 Hz), 129.5

(q, J = 3.7 Hz), 129.2, 126.6 (q, J = 3.9 Hz), 123.9 (q, J = 272.2 Hz),

76.64, 65.71, 28.77, 27.88, 26.05, 26.02, 18.13, 11.72; ¹⁹F NMR (376

MHz, CDCl₃) δ −62.87; HRMS (ESI) calcd for C₂₃H₃₇F₃O₄SiNa [M

+ Na]⁺485.2305, found 485.2307; IR (neat) 2943, 2867, 1726, 1464,

1335, 1250, 1169, 1132, 1086, 1072, 920, 883, 757, 694 cm⁻¹; TLC R_f

= 0.38 (5% EtOAc/hexanes).

6-Hydroperoxyhexyl Acetate. 6-Iodohexyl acetate (1.37 g, 5.10

mmol) was subjected to general procedure D for 2 h. Silica ﬂash

chromatography provided 6-hydroperoxyhexyl acetate (267 mg, 30%

yield) as a clear, colorless oil: ¹H NMR (400 MHz, CDCl₃) δ 8.32 (s,

1H), 4.05 (t, J = 6.7 Hz, 2H), 4.01 (t, J = 6.5 Hz, 2H), 2.04 (s, 3H),

1.70−1.58 (m, 4H), 1.46−1.32 (m, 4H); ¹³C{¹H} NMR (100 MHz,

CDCl₃) δ 171.6, 77.0, 64.6, 28.6, 27.5, 25.8, 25.6, 21.1; LRMS

(GCMS) mass fragmentation 115.1 (13), 98.1 (12), 80.1 (10), 69

(20), 61.1 (50), 55.1 (40), 43.1 (100); IR (neat) 3401, 2939, 2862,

1737, 1718, 1389, 1367, 1240, 1036 cm⁻¹; TLC R_f= 0.2 (20%

EtOAc/hexanes).

6-[(Triisopropylsilyl)peroxy]hexyl Acetate. 6-Hydroperoxyhexyl

acetate (260 mg, 1.47 mmol) was subjected to general procedure E

for 2 h. Silica ﬂash chromatography provided 6-[(triisopropylsilyl)-

peroxy]hexyl acetate (330 mg, 68% isolated as pure) as a clear,

colorless oil: ¹H NMR (400 MHz, CDCl₃) δ 4.02 (t, J = 6.7 Hz, 2H),

3.96 (t, J = 6.5 Hz, 2H), 2.01 (s, 3H), 1.63−1.55 (m, 4H), 1.35 (p, J =

3.6 Hz, 4H), 1.24−1.11 (m, 3H), 1.10−1.03 (m, 18H); ¹³C{¹H}

NMR (100 MHz, CDCl₃) δ 171.3, 76.7, 64.6, 28.6, 27.8, 26.0, 21.1,

18.1, 11.7; HRMS (EI) calcd for C₁₄H₂₉O₄Si [M − C₃H₇]⁺289.1830,

found 289.1827; IR (neat) 2942, 2866, 1741, 1463, 1365, 1233, 1037,

919, 882, 781, 677, 606, 462 cm⁻¹; TLC R_f= 0.41 (10% EtOAc/

hexanes).

1

we proceeded to the next step: H NMR (400 MHz, CDCl₃) δ 3.37

(q, J = 7.1 Hz, 2H), 3.30 (q, J = 7.1 Hz, 2H), 3.20 (t, J = 7.0 Hz, 2H),

2.30 (t, J = 7.5 Hz, 2H), 1.85 (p, J = 7.1 Hz, 2H), 1.76−1.57 (m, 2H),

1.52−1.38 (m, 2H), 1.17 (t, J = 7.1 Hz, 3H), 1.10 (t, J = 7.1 Hz, 3H);

TLC R_f= 0.21 (30% EtOAc/hexanes).

N,N-Diethyl-6-[(triisopropylsilyl)peroxy]hexanamide. N,N-Dieth-

yl-6-iodohexanamide (1.1 g, 3.7 mmol) was subjected to general

procedure D for 2 h. Silica ﬂash chromatography provided N,N-

diethyl-6-hydroperoxyhexanamide with another mixture. We pro-

ceeded to the next step with the impure N,N-diethyl-6-hydro-

peroxyhexanamide. The mixture with N,N-diethyl-6 hydroperoxyhex-

anamide was subjected to general procedure E with TIPSOTf (0.71

mL, 2.64 mmol) and lutidine (0.506 mL, 2.64 mL) for 2 h. Silica ﬂash

chromatography provided N,N-diethyl-6-[(triisopropylsilyl)peroxy]-

hexanamide (278 mg, 21%, after two steps) as a clear, colorless oil: ¹H

NMR (400 MHz, CDCl₃) δ 3.96 (t, J = 6.5 Hz, 2H), 3.34 (q, J = 7.1

Hz, 2H), 3.27 (q, J = 7.1 Hz, 2H), 2.37−2.14 (m, 2H), 1.74−1.52 (m,

4H), 1.44−1.31 (m, 2H), 1.24−1.10 (m, 6H), 1.11−1.02 (m, 21H);

¹³C{¹H} NMR (100 MHz, CDCl₃) δ 172.1, 76.6, 42.0, 40.1, 33.0,

27.8, 26.1, 25.4, 18.1, 14.5, 13.2, 11.6; LRMS (GC) decomposed in

GCMS; IR (neat) 3395, 2970, 2932, 2863, 1616, 1459, 1431, 1379,

1260, 1220, 1140, 1071, 1055, 605 cm⁻¹; TLC R_f= 0.32 (20%

EtOAc/hexanes).

6-Hydroperoxyhexyl 3-(Triﬂuoromethyl)benzoate. To a ﬂame-

dried round-bottom ﬂax equipped with a stir bar was added 6-

bromohexan-1-ol (2.6 mL, 20 mmol); 50 mL of dry DCM was then

added via syringe. Then, 3-(triﬂuoromethyl)benzoyl chloride (3.01

mL, 20 mmol) was added dropwise. Then, triethylamine (3.1 mL, 22

mmol) was added to the mixture dropwise (15 min) with constant

stirring. The total reaction mixture was stirred at room temperature

overnight. After the reaction had reached completion, 10 mL of water

was added to it. The DCM layer was separated with a separatory

funnel. The DCM layer was washed with saturated NaHCO₃(20 mL)

and a saturated NaCl solution. Then, the ﬁnal organic portion was

passed through anhydrous MgSO₄and dried in rotavap. With the

concentrated organic portion as 6-bromohexyl 3-(triﬂuoromethyl)-

benzoate (6.4 g, 91%, ∼90% pure), we proceeded to the next step

without any further puriﬁcation: ¹H NMR (400 MHz, CDCl₃) δ 8.29

(s, 1H), 8.22 (d, J = 7.8 Hz, 1H), 7.81 (d, J = 7.8 Hz, 1H), 7.58 (t, J =

7.9 Hz, 1H), 4.36 (t, J = 6.6 Hz, 2H), 3.42 (t, J = 6.7 Hz, 2H), 1.98−

1.75 (m, 4H), 1.62−1.42 (m, 4H); ¹³C{¹H} NMR (100 MHz,

CDCl₃) δ 165.4, 132.9, 131.3, 131.1 (q, J = 32.0 Hz), 129.5 (q, J = 4.0

Hz), 129.1, 126.5 (q, J = 4.0 Hz), 123.8 (q, J = 272.5 Hz), 65.6, 33.8,

32.7, 28.6, 27.9, 25.4; ¹⁹F NMR (376 MHz, CDCl₃) δ −62.84; LRMS

(GCMS) mass fragmentation 235.0 (3), 233.0 (3), 191.1 (40), 173.1

(100), 162.1 (40), 164.1 (40), 145.1 (75), 125.1 (10), 95.1 (10), 83.2

(45), 69.2 (10), 55.2 (25), 41.2 (10); IR (neat) 2937, 2860, 1721,

1617, 1440, 1333, 1300, 1248, 1166, 1123, 1086, 1071, 921, 820, 756,

693, 649, 561 cm⁻¹; TLC R_f= 0.5 (20% EtOAc/hexanes). In the next

step, a mixture of 6-bromohexyl 3-(triﬂuoromethyl)benzoate (5.36 g,

15.2 mmol) was added to a solution of NaI (2.5 g, 16.7 mmol) in

acetone (45 mL) and the mixture was stirred overnight at 65 °C.

Then, the reaction mixture was cooled to room temperature, the

precipitate ﬁltered, and the ﬁltrate evaporated. Then, Et₂O (50 mL)

was added to the residue and washed with saturated aqueous Na₂S₂O₃

(1 × 50 mL), H₂O (1 × 50 mL), and brine (1 × 50 mL). The organic

solution was dried over anhydrous MgSO₄. After the solvent had

evaporated, 6-iodohexyl 3-(triﬂuoromethyl)benzoate was isolated (4.2

g, 68%, ∼90% pure) as a brown liquid. Without any further

6-Iodohexyl Methanesulfonate. 6-Iodohexan-1-ol (1.71 g, 7.5

mmol) was subjected to general procedure A for 14 h. After the

workup procedure, the crude material was isolated with high purity.

We moved to the next step without any further puriﬁcation (1.94 g,

85% yield): ¹H NMR (400 MHz, CDCl₃) δ 4.21 (t, J = 6.5 Hz, 2H),

3.18 (t, J = 6.9 Hz, 2H), 2.99 (d, J = 1.1 Hz, 3H), 1.90−1.67 (m, 4H),

1.52−1.36 (m, 4H); HRMS (ESI) calcd for C₇H₁₅IO₃SNa [M + Na]⁺

328.9679, found 328.9679; IR (neat) 2935, 2858, 1347, 1331, 1206,

1

puriﬁcation, we proceeded to the next step: H NMR (400 MHz,

CDCl₃) δ 8.28 (s, 1H), 8.21 (d, J = 7.8 Hz, 1H), 7.79 (d, J = 7.8 Hz,

1H), 7.57 (t, J = 7.8 Hz, 1H), 4.35 (t, J = 6.6 Hz, 2H), 3.18 (t, J = 6.9

Hz, 2H), 1.82 (dt, J = 19.1, 6.8 Hz, 4H), 1.47 (p, J = 3.5 Hz, 4H);

¹³C{¹H} NMR (100 MHz, CDCl₃) δ 165.3, 132.8, 131.3, 131.0 (q, J

= 32.3 Hz), 129.3 (q, J = 4.0 Hz), 129.1, 126.5 (q, J = 3.9 Hz), 123.7

H

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The Journal of Organic Chemistry

Article

1169, 971, 938, 908, 827, 718, 526, 459 cm⁻¹; TLC R_f= 0.4 (30%

EtOAc/hexanes).

solution was cooled to 0 °C. 1,7-Heptanediol (4.2 mL, 30 mmol) in

15 mL of THF was added via syringe. The reaction mixture was

warmed to room temperature for 30 min and then cooled to 0 °C.

Triisopropylsilyl chloride (6.4 mL, 30 mmol) in 15 mL of THF was

added via syringe, and the reaction mixture was allowed to stir for 40

min at 0 °C and then overnight at rt. The reaction was quenched by

the addition of water, and the mixture was extracted three times with

diethyl ether. The combined organic layers were dried over MgSO₄

and concentrated in vacuo. The desired product was isolated by silica

ﬂash chromatography (2.93 g, 34% yield) as a colorless oil that

matched previously reported spectra:⁴⁶¹H NMR (400 MHz, CDCl₃)

δ 3.76−3.53 (m, 4H), 1.56 (m, 5H), 1.36 (m, 6H), 1.13−0.99 (m,

21H); HRMS (ESI) calcd for C₁₆H₃₇O₂Si [M − H]⁺289.2557, found

289.2559; IR (neat) 3327, 2933, 2891, 2864, 1462, 1382, 1366, 1247,

1101, 1059, 1012, 994, 918, 881, 840, 791, 716, 677, 657 cm⁻¹; TLC

R_f= 0.47 (20% EtOAc/hexanes).

[(7-Iodoheptyl)oxy]triisopropylsilane. A ﬂame-dried ﬂask equip-

ped with a stir bar was charged with PPh₃(4.7 g, 7.2 mmol),

imidazole (1.2 g, 7.2 mmol), and I₂(4.5 g, 7.2 mmol) under N₂.

Anhydrous DCM (0.2 M) was added; the ﬂask was cooled in an ice

bath, and the mixture was stirred for 10 min. Alcohol (1.728 g, 6

mmol), diluted in a 5:1 ratio in DCM, was added dropwise at 0 °C,

and the reaction mixture was stirred at 0 °C for 1 h. After 1 h, the

reaction mixture was allowed to warm to room temperature and

stirred for an additional 12 h. The reaction mixture was concentrated

under reduced pressure, diluted with 25% EtOAc in hexanes, and

ﬁltered through a plug of silica. The ﬁltrate was concentrated under

reduced pressure, and silica ﬂash chromatography provided [(7-

iodoheptyl)oxy]triisopropylsilane (1.48 g, 62% yield) as a clear,

colorless oil: ¹H NMR (400 MHz, CDCl₃) δ 3.67 (t, J = 6.5 Hz, 2H),

3.18 (t, J = 7.0 Hz, 2H), 1.82 (p, J = 7.1 Hz, 2H), 1.53 (p, J = 6.7 Hz,

2H), 1.44−1.27 (m, 6H), 1.05 (d, J = 4.3 Hz, 21H); ¹³C{¹H} NMR

(101 MHz, CDCl₃) δ 63.5, 33.7, 33.0, 30.6, 28.5, 25.8, 18.2, 12.1, 7.3;

HRMS (ESI) calcd for C₁₆H₃₆OISi [M + H]⁺399.1575, found

399.1576; IR (neat) 2931, 2891, 2863, 1461, 1382, 1245, 1103, 994,

918, 881, 789, 717, 678, 654 cm⁻¹; TLC R_f= 0.49 (5% EtOAc/

hexanes).

6-Hydroperoxyhexyl Methanesulfonate. 6-Iodohexyl 4-methyl-

benzenesulfonate (0.915 g, 3 mmol) was subjected to general

procedure D for 2 h. Silica ﬂash chromatography provided 6-

hydroperoxyhexyl methanesulfonate (265 mg, 42% yield) as a clear,

colorless oil: ¹H NMR (400 MHz, CD₃OD) δ 4.87 (s, 1H), 4.38 (t, J

= 6.4 Hz, 2H), 4.07 (t, J = 6.4 Hz, 2H), 3.20 (s, 3H), 1.94−1.86 (m,

2H), 1.78 (p, J = 6.7 Hz, 2H), 1.67−1.45 (m, 4H); ¹³C{¹H} NMR

(100 MHz, CD₃OD) δ 76.0, 70.4, 35.7, 28.7, 27.2, 25.1, 24.9; HRMS

(ESI) calcd for C₇H₁₆O₅SNa [M + Na]⁺235.0611, found 235.0609;

IR (neat) 3428, 2940, 2864, 1344, 1168, 973, 952, 926, 820, 528

cm⁻¹; TLC R_f= 0.5 (50% EtOAc/hexanes).

6-[(Triisopropylsilyl)peroxy]hexyl Methanesulfonate. 6-Hydro-

peroxyhexyl methanesulfonate (248 mg, 1.17 mmol) was subjected

to general procedure E for 2 h. Silica ﬂash chromatography provided

6-[(triisopropylsilyl)peroxy]hexyl methanesulfonate (295 mg, 68%) as

1

a clear, colorless oil: H NMR (400 MHz, CDCl₃) δ 4.18 (t, J = 6.5

Hz, 2H), 3.95 (t, J = 6.4 Hz, 2H), 2.96 (s, 3H), 1.80−1.67 (m, 2H),

1.63−1.53 (m, 2H), 1.45−1.33 (m, 4H), 1.25−1.10 (m, 3H), 1.10−

0.98 (m, 18H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 76.5, 70.1, 37.4,

29.1, 27.7, 25.7, 25.4, 18.1, 11.6; HRMS (ESI) calcd for

C₁₆H₃₆O₅SSiNa [M + Na]⁺391.1945, found 391.1949; IR (neat)

2942, 2866, 1464, 1354, 1174, 972, 955, 924, 882, 855, 815, 781, 678,

664, 528 cm⁻¹; TLC R_f= 0.63 (30% EtOAc/hexanes).

(5-Iodopentyl)benzene. A mixture of (5-bromopentyl)benzene

(909 mg, 4 mmol) was added to a solution of NaI (2 g, 12 mmol) in

acetone (10 mL), and the mixture was stirred overnight at 65 °C.

Then, the reaction mixture was cooled to room temperature, the

precipitate ﬁltered, and the ﬁltrate evaporated. Then, Et₂O (30 mL)

was added to the residue and washed with saturated aqueous Na₂S₂O₃

(1 × 20 mL), H₂O (1 × 20 mL), and brine (1 × 50 mL). The organic

solution was dried over anhydrous MgSO₄. After the solvent had

evaporated, (5-iodopentyl)benzene was isolated (1.01 g, 93%) as a

brown liquid. Without any further puriﬁcation, we proceeded to the

next step:⁴⁵¹H NMR (400 MHz, CDCl₃) δ 7.29 (dd, J = 8.6, 6.6 Hz,

2H), 7.24−7.13 (m, 3H), 3.19 (t, J = 7.0 Hz, 2H), 2.63 (t, J = 7.7 Hz,

2H), 1.87 (p, J = 7.2 Hz, 2H), 1.75−1.61 (m, 2H), 1.51−1.35 (m,

2H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 142.5, 128.6, 128.5, 126.0,

35.9, 33.7, 30.6, 30.4, 7.2; TLC R_f= 0.5 (5% EtOAc/hexanes).

(5-Hydroperoxypentyl)benzene. (5-Iodopentyl)benzene (1 g, 3.6

mmol) was subjected to general procedure D for 1.5 h. Silica ﬂash

chromatography provided (5-hydroperoxypentyl)benzene (279 mg,

[(7-Hydroperoxyheptyl)oxy]triisopropylsilane. [(7-Iodoheptyl)-

oxy]triisopropylsilane (1.3 g, 3.2 mmol) was subjected to general

procedure D for 2 h. Silica ﬂash chromatography provided [(7-

hydroperoxyheptyl)oxy]triisopropylsilane (340 mg, 35% yield) as a

clear, colorless oil: ¹H NMR (400 MHz, CDCl₃) δ 7.97 (s, 1H), 4.02

(t, J = 6.6 Hz, 2H), 3.67 (t, J = 6.6 Hz, 2H), 1.67−1.59 (m, 2H), 1.54

(p, J = 6.6 Hz, 2H), 1.44−1.30 (m, 6H), 1.15−0.99 (m, 21H);

¹³C{¹H} NMR (126 MHz, CDCl₃) δ 77.3, 63.6, 33.0, 29.0, 27.6, 26.1,

1

43% yield) as a clear, colorless oil: H NMR (400 MHz, CDCl₃) δ

7.88 (s, 1H), 7.33−7.25 (m, 2H), 7.22−7.15 (m, 3H), 4.02 (t, J = 6.6

Hz, 2H), 2.63 (t, J = 7.7 Hz, 2H), 1.78−1.54 (m, 4H), 1.52−1.35 (m,

2H); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 142.6, 128.6, 128.5, 125.9,

77.2, 36.0, 31.4, 27.6, 27.3, 25.7; TLC R_f= 0.33 (20% EtOAc/

hexanes); LRMS (GCMS, mass fragmentation) 162.1 (100), 144

(83), 133.1 (31), 129.1 (54), 120.0 (42), 118.1 (37), 117.1 (25),

105.1 (12), 92.1 (37), 91.0 (4); IR (neat) 3376, 3025, 2933, 2856,

1602, 1495, 1452, 1367, 1030, 745, 697, 493 cm⁻¹.

25.9, 18.2, 12.2; HRMS (ESI) calcd for C₁₆H₃₇O₃Si [M + H]⁺

305.2506, found 305.2508; IR (neat) 3357, 2938, 2864, 1462, 1382,

1366, 1248, 1101, 1067, 1013, 995, 918, 881, 792, 717, 679, 657, 460

cm⁻¹; TLC R_f= 0.11 (5% EtOAc/hexanes).

3,3,14,14-Tetraisopropyl-2,15-dimethyl-4,5,13-trioxa-3,14-disila-

hexadecane. [(7-Iodoheptyl)oxy]triisopropylsilane (330 mg, 1.08

mmol) was subjected to general procedure E for 2 h. Silica ﬂash

chromatography provided 3,3,14,14-tetraisopropyl-2,15-dimethyl-

4,5,13-trioxa-3,14-disilahexadecane (355 mg, 72% yield) as a clear,

colorless oil: ¹H NMR (400 MHz, CDCl₃) δ 3.98 (t, J = 6.6 Hz, 2H),

3.66 (t, J = 6.6 Hz, 2H), 1.56 (ddd, J = 22.2, 10.4, 4.3 Hz, 4H), 1.39−

1.28 (m, 6H), 1.28−1.14 (m, 3H), 1.15−1.02 (m, 39H); ¹³C{¹H}

NMR (126 MHz, CDCl₃) δ 76.9, 63.6, 33.1, 29.5, 27.9, 26.3, 25.9,

18.2, 18.1, 12.2, 11.7; HRMS (EI) calcd for C₂₅H₅₇O₃Si₂[M]⁺

459.3684, found 459.3686; IR (neat) 2940, 2865, 1462, 1382,

1366, 1248, 1101, 1069, 1013, 996, 919, 881, 783, 677, 459 cm⁻¹;

TLC R_f= 0.7 (5% EtOAc/hexanes).

5-[(Triisopropylsilyl)oxy]pentan-1-ol. To a round-bottom ﬂask

equipped with a stir bar was added sodium hydride (60% dispersion

in mineral oil, 1 g, 25 mmol). The sodium hydride was washed three

times with hexanes and dried under an argon atmosphere. Thirty

millilitersof THF was then added, and the resulting heterogeneous

solution was cooled to 0 °C. 1,5-Pentanediol (2.6 mL, 25 mmol) in

15 mL of THF was added via syringe. The reaction mixture was

warmed to room temperature for 30 min and then cooled to 0 °C.

Triisopropyl[(5-phenylpentyl)peroxy] silane. (5-

Hydroperoxypentyl)benzene (0.180 g, 1.5 mmol) was subjected to

general procedure E for 3 h. Silica ﬂash chromatography provided

triisopropyl[(5-phenylpentyl)peroxy]silane (201 mg, 40% yield) as a

1

clear, colorless oil: H NMR (400 MHz, CDCl₃) δ 7.36−7.27 (m,

2H), 7.24−7.17 (m, 3H), 4.03 (t, J = 6.6 Hz, 2H), 2.65 (t, J = 7.7 Hz,

2H), 1.80−1.59 (m, 4H), 1.44 (dddd, J = 14.8, 9.3, 6.6, 3.4 Hz, 2H),

1.32−1.18 (m, 3H), 1.14 (d, J = 6.9 Hz, 18H); ¹³C{¹H} NMR (101

MHz, CDCl₃) δ 142.7, 128.6, 128.4, 125.8, 76.8, 36.0, 31.5, 27.9, 26.0,

18.3, 18.2, 18.2, 11.7; HRMS (EI) calcd for C₁₇H₂₉O₂Si [M − C₃H₇]⁺

293.1931, found 293.1933; IR (neat) 2940, 2865, 1495, 1462, 1382,

1366, 1250, 1050, 1014, 997, 919, 882, 849, 783, 744, 696, 676, 569,

462 cm⁻¹; TLC R_f= 0.6 (5% EtOAc/hexanes).

7-[(Triisopropylsilyl)oxy]heptan-1-ol. To a round-bottom ﬂask

equipped with a stir bar was added sodium hydride (60% dispersion

in mineral oil, 1.2 g, 30 mmol). The sodium hydride was washed three

times with hexanes and dried under an argon atmosphere. Thirty

milliliters of THF was then added, and the resulting heterogeneous

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Article

Triisopropylsilyl chloride (5.3 mL, 50 mmol) in 15 mL of THF was

added via syringe, and the reaction mixture was allowed to stir for 40

min at 0 °C and then overnight at rt. The reaction was quenched by

the addition of water, and the mixture was extracted three times with

diethyl ether. The combined organic layers were dried over MgSO₄

and concentrated in vacuo. The desired product was isolated by silica

ﬂash chromatography (2.73 g, 42% pure isolated) as a colorless oil

that matched the reported spectra:⁴⁷¹H NMR (400 MHz, CDCl₃) δ

3.67 (t, J = 6.3 Hz, 2H), 3.63 (t, J = 7.1 Hz, 2H), 1.64−1.51 (m, 4H),

1.46−1.37 (m, 2H), 1.03 (m, 21H); IR (neat) 3330, 2939, 2864,

1462, 1382, 1248, 1102, 1069, 994, 918, 881, 790, 718, 678, 656

cm⁻¹; TLC R_f= 0.45 (20% EtOAc/hexanes).

the ﬁltrate evaporated. Then, Et₂O (30 mL) was added to the residue

and washed with saturated aqueous Na₂S₂O₃(1 × 20 mL), H₂O (1 ×

20 mL), and brine (1 × 50 mL). The organic solution was dried over

anhydrous MgSO₄. After the solvent had evaporated, [(6-

iodoohexyl)oxy](tert-butyl)diphenylsilane was isolated (871 mg,

87%) as a brown liquid. Without any further puriﬁcation, we

proceeded to the next step:⁴⁹¹H NMR (400 MHz, CDCl₃) δ 7.75−

7.55 (m, 4H), 7.39 (m, 6H), 3.66 (t, J = 6.4 Hz, 2H), 3.39 (q, J = 6.7

Hz, 2H), 1.83 (q, J = 7.0 Hz, 2H), 1.54 (m, 2H), 1.47−1.33 (m, 4H),

1.04 (s, 9H); TLC R_f= 0.6 (5% EtOAc/hexanes).

tert-Butyl[(6-hydroperoxyhexyl)oxy]diphenylsilane. [(6-

Iodoohexyl)oxy](tert-butyl)diphenylsilane (800 mg, 1.7 mmol) was

subjected to general procedure D for 2 h. Silica ﬂash chromatography

provided tert-butyl[(6-hydroperoxyhexyl)oxy]diphenylsilane (505 mg,

5-[(Triisopropylsilyl)oxy]pentyl Methanesulfonate. 5-

[(Triisopropylsilyl)oxy]pentan-1-ol (2.33 g, 8.87 mmol) was sub-

jected to general procedure A for 14 h. After the workup procedure,

the crude material was isolated with high purity. We moved to the

1

47% yield) as a clear, colorless oil: H NMR (400 MHz, CDCl₃) δ

8.04 (s, 1H), 7.65−7.53 (m, 4H), 7.44−7.23 (m, 6H), 3.90 (t, J = 6.6

Hz, 2H), 3.58 (t, J = 6.5 Hz, 2H), 1.58−1.42 (m, 4H), 1.27 (ddt, J =

14.5, 12.7, 5.0 Hz, 4H), 0.97 (s, 9H); ¹³C{¹H} NMR (100 MHz,

CDCl₃) δ 135.7, 134.2, 129.6, 127.7, 77.2, 64.0, 32.5, 27.7, 27.0, 25.8,

25.7, 19.4; HRMS (ESI) calcd for C₂₂H₃₃O₃Si [M + H]⁺373.2193,

found 373.2195; IR (neat) 3363, 2931, 2857, 1472, 1427, 1389, 1187,

1108, 1093, 822, 739, 700, 688, 613, 503, 488 cm⁻¹; TLC R_f= 0.26

(10% EtOAc/hexanes).

3,3-Diisopropyl-2,14,14-trimethyl-13,13-diphenyl-4,5,12-trioxa-

3,13-disilapentadecane. tert-Butyl[(6-hydroperoxyhexyl)oxy]-

diphenylsilane (270 mg, 0.72 mmol) was subjected to general

procedure E for 2 h. Silica ﬂash chromatography provided 3,3-

diisopropyl-2,14,14-trimethyl-13,13-diphenyl-4,5,12-trioxa-3,13-disila-

pentadecane (273 mg, 72% isolated as pure) as a clear, colorless oil:

¹H NMR (400 MHz, CDCl₃) δ 7.89−7.57 (m, 4H), 7.55−7.29 (m,

6H), 4.10−3.89 (m, 2H), 3.73−3.54 (m, 2H), 1.72−1.47 (m, 4H),

1.35 (m, 4H), 1.29−1.16 (m, 3H), 1.10 (m, 18H), 1.06 (s, 9H);

¹³C{¹H} NMR (126 MHz, CDCl₃) δ 135.7, 134.3, 129.7, 127.8, 76.9,

64.1, 32.6, 28.0, 27.1, 2618, 25.9, 19.4, 18.2, 18.2, 12.2, 11.7; HRMS

(ESI) calcd for C₃₁H₅₃O₃Si₂[M + H]⁺529.3528, found 529.3528; IR

(neat) 2939, 2864, 1462, 1427, 1385, 1362, 1257, 1106, 997, 882,

822, 781, 738, 700, 684, 613, 503, 487 cm⁻¹; TLC R_f= 0.63 (10%

EtOAc/hexanes).

Triisopropyl(pent-4-en-1-ylperoxy)silane (34). TIPSOOH (284

mg, 1.5 mmol, 1 equiv) was subjected to general procedure F using 5-

iodo-1-pentene (0.55 mL, 4.5 mmol, 3 equiv). Silica ﬂash

chromatography provided 34 (164.9 mg, 42% yield) as a clear,

colorless oil: ¹H NMR (400 MHz, CDCl₃) δ 5.81 (ddt, J = 16.9, 10.2,

6.6 Hz, 1H), 5.03 (dd, J = 17.1, 1.8 Hz, 1H), 4.97 (dd, J = 10.1, 1.8

Hz, 1H), 4.00 (t, J = 6.5 Hz, 2H), 2.12 (q, J = 7.1 Hz, 2H), 1.71 (p, J

= 7.6, 6.8, 6.8 Hz, 2H), 1.29−1.14 (m, 3H), 1.10 (d, J = 7.1 Hz,

18H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 138.2, 115.0, 76.1, 30.4,

27.2, 18.1, 11.7; LRMS (GCMS) mass fragmentation 171.2 (15),

169.2 (15), 141.2 (15), 129.2 (25), 105.1 (30), 103.1 (30), 77.1

(100), 76.1 (40), 61.1 (20), 41.2 (10); IR (neat) 3079, 2943, 2866,

1642, 1463, 995, 911, 882, 676 cm⁻¹; TLC R_f= 0.58 (5% EtOAc/

hexanes).

Hydroperoxycyclopentane. Cylopentyl mesylate (1.96 g, 12

mmol, 1 equiv) was subjected to general procedure C at a

concentration of 0.3 M (12:1 MeOH/H₂O) for 22 h. Silica ﬂash

chromatography provided hydroperoxycyclopentane (539 mg, 44%

yield) as a clear, colorless oil that matched the reported spectra:⁵⁰¹H

NMR (600 MHz, CDCl₃) δ 7.99 (br s, 1H), 4.60 (tt, J = 5.9, 3.1 Hz,

1H), 1.89−1.61 (m, 6H), 1.63−1.48 (m, 2H); TLC R_f= 0.36 (20%

EtOAc/hexanes).

(Cyclopentylperoxy)triisopropylsilane (36). Hydroperoxycyclo-

pentane (322 mg, 3.0 mmol, 1 equiv) was subjected to general

procedure E using triisopropylsilyl chloride (0.65 mL, 3.0 mmol, 1

equiv), Ag₂O (686 mg, 3.0 mmol, 1 equiv), and anhydrous ammonia

as the base (sparge for 10 min and then a balloon atmosphere) for 15

h. The crude mixture was ﬁltered through a silica plug, eluting with

10% EtOAc/hexanes to provide 36 (395 mg, 51% yield) as a clear,

colorless oil: ¹H NMR (400 MHz, CDCl₃) δ 4.54 (dt, J = 5.6, 2.9 Hz,

1H), 1.86−1.73 (m, 2H), 1.72−1.57 (m, 5H), 1.58−1.44 (m, 2H),

1.28−1.13 (m, 2H), 1.08 (d, J = 6.8 Hz, 18H); ¹³C{¹H} NMR (100

1

next step without any further puriﬁcation (2.86 g, 95% yield): H

NMR (400 MHz, CDCl₃) δ 4.24 (t, J = 6.6 Hz, 2H), 3.69 (t, J = 6.1

Hz, 2H), 3.00 (s, 3H), 1.79 (p, J = 6.8 Hz, 2H), 1.63−1.45 (m, 4H),

1.18−0.90 (m, 21H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 70.0, 62.9,

37.3, 32.2, 28.9, 27.1, 21.9, 18.0, 11.9; HRMS (ESI) calcd for

C₁₅H₃₅O₄SSi [M + H]⁺339.2020, found 339.2020; IR (neat) 2941,

2864, 1463, 1351, 1172, 1110, 949, 881, 828, 719, 677, 657, 527, 459

cm⁻¹; TLC R_f= 0.17 (10% EtOAc/hexanes).

[(5-Hydroperoxypentyl)oxy]triisopropylsilane. 5-

[(Triisopropylsilyl)oxy]pentyl methanesulfonate (2.85 g, 8.46

mmol) was subjected to general procedure C, using 12:1 MeOH/

H₂O (0.3 M) and Et₂O (0.8 M) as the solvents, for 44 h. Silica ﬂash

chromatography provided [(5-hydroperoxypentyl)oxy]-

triisopropylsilane (1.19 g, 51% yield) as a clear, colorless oil: ¹H

NMR (500 MHz, CDCl₃) δ 8.12−7.66 (m, 1H), 4.03 (t, J = 6.6 Hz,

2H), 3.69 (t, J = 6.4 Hz, 2H), 1.74−1.63 (m, 2H), 1.62−1.54 (m,

2H), 1.50−1.40 (m, 2H), 1.14−0.91 (m, 21H); ¹³C{¹H} NMR (126

MHz, CDCl₃) δ 77.3, 63.3, 32.8, 27.4, 22.4, 18.2, 12.1; IR (neat)

3333, 2938, 2864, 1462, 1382, 1248, 1102, 1069, 994, 918, 881, 791,

718, 678, 656, 454 cm⁻¹; TLC R_f= 0.1 (5% EtOAc/hexanes).

3,3,12,12-Tetraisopropyl-2,13-dimethyl-4,5,11-trioxa-3,12-disila-

tetradecane. [(5-Hydroperoxypentyl)oxy]triisopropylsilane (1.19 g,

4.31 mmol) was subjected to general procedure E for 2 h. Silica ﬂash

chromatography provided 3,3,12,12-tetraisopropyl-2,13-dimethyl-

4,5,11-trioxa-3,12-disilatetradecane (780 mg, 42% isolated as pure)

as a clear, colorless oil: ¹H NMR (400 MHz, CDCl₃) δ 4.00 (t, J = 6.6

Hz, 2H), 3.68 (t, J = 6.4 Hz, 2H), 1.71−1.51 (m, 4H), 1.48−1.38 (m,

2H), 1.28−1.14 (m, 3H), 1.14−1.01 (m, 39H); ¹³C{¹H} NMR (126

MHz, CDCl₃) δ 76.9, 63.3, 33.0, 27.8, 22.7, 18.2, 18.1, 12.2, 11.7;

HRMS (ESI) calcd for C₂₃H₅₃O₃Si₂[M + H]⁺433.3528, found

433.3530; IR (neat) 2941, 2865, 1462, 1382, 1248, 1102, 1068, 996,

919, 881, 783, 718, 677, 659, 458 cm⁻¹; TLC R_f= 0.7 (5% EtOAc/

hexanes).

[(6-Bromohexyl)oxy](tert-butyl)diphenylsilane. To a round-bot-

tom ﬂask equipped with a stir bar were added 6-bromohexanol (2.6

mL, 30 mmol) and TBDCl (33 mmol, 5.2 mL) in DCM (60 mL).

Then, triethylamine (4.6 mL, 45 mol) was added dropwise. The

reaction mixture was stirred overnight at room temperature. Then, the

reaction was quenched with a 10% NaHCO₃solution (40 mL), and

the solution was diluted with ethyl acetate (40 mL). The organic layer

was extracted; the aqueous layer was washed with ethyl acetate (3 ×

20 mL), and the combined organic layers were dried with MgSO₄and

concentrated in vacuo. The pure desired product was isolated by silica

gel column chromatography using hexane as the eluent. The isolated

pure product (35%, 2.9 g) was a colorless oil that matched previously

reported spectra:⁴⁸¹H NMR (400 MHz, CDCl₃) δ 7.81−7.59 (m,

4H), 7.50−7.34 (m, 6H), 3.66 (t, J = 6.4 Hz, 2H), 3.39 (t, J = 6.8 Hz,

2H), 1.83 (td, J = 8.6, 7.8, 5.9 Hz, 2H), 1.70−1.51 (m, 2H), 1.44−

1.36 (m, 4H), 1.05 (s, 9H); TLC R_f= 0.6 (2% EtOAc/hexanes).

[(6-Iodoohexyl)oxy](tert-butyl)diphenylsilane. A mixture of [(6-

bromohexyl)oxy](tert-butyl)diphenylsilane (900 mg, 2.15 mmol) was

added to a solution of NaI (894 mg, 6 mmol) in acetone (10 mL),

and the mixture was stirred overnight at 65 °C. Then, the reaction

mixture was cooled to room temperature, the precipitate ﬁltered, and

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MHz, CDCl₃) δ 87.1, 31.1, 24.2, 18.2, 11.8; LRMS (GCMS) mass

fragmentation 199.3 (3), 173.2 (3), 147.2 (15), 105.2 (43), 77.2

(100), 76.1 (40), 61.1 (15), 45.2 (10); IR (neat) 2943, 2866, 1463,

1346, 1071, 881, 675 cm⁻¹; TLC R_f= 0.6 (5% EtOAc/hexanes).

(5-Bromopent-1-yn-1-yl)benzene. To phenylacetylene (1.7 mL,

15 mmol) in anhydrous THF (28 mL) was added n-BuLi (2.2 M

solution in hexanes, 22 mmol) dropwise at room temperature over 5

min before the mixture was heated to reﬂux for 2 h. The reaction

mixture was cooled to room temperature before 1,4-diiodobutane (2.0

equiv) was added as a THF solution (0.4 M). The reaction mixture

was reﬂuxed overnight, returned to room temperature, quenched with

H₂O (10 mL), and extracted with Et₂O (3 × 25 mL). The combined

organic extracts were dried (MgSO₄), ﬁltered, and concentrated to

give a residue. Silica ﬂash chromatography provided (5-bromopent-1-

yn-1-yl)benzene (1.66 g, 50%) as a clear, colorless oil, which matched

previously reported spectra:⁵¹¹H NMR (400 MHz, CDCl₃) δ 7.46−

7.33 (m, 2H), 7.32−7.14 (m, 3H), 3.57 (t, J = 6.5 Hz, 2H), 2.59 (td, J

= 6.9, 4.8 Hz, 3H), 2.12 (p, J = 6.7 Hz, 2H).

(5- Iodopent-1-yn-1-yl)benzene. A mixture of (5-bromopent-1-yn-

1-yl)benzene (1.332 g, 6 mmol) was added to a solution of NaI (3 g,

18 mmol) in acetone (20 mL), and the mixture was stirred overnight

at 65 °C. Then, the reaction mixture was cooled to room temperature,

the precipitate ﬁltered, and the ﬁltrate evaporated. Then, Et₂O (40

mL) was added to the residue and washed with saturated aqueous

Na₂S₂O₃(1 × 20 mL), H₂O (1 × 30 mL), and brine (1 × 50 mL).

The organic solution was dried over anhydrous MgSO₄. After the

solvent had evaporated, (5-iodopent-1-yn-1-yl)benzene was isolated

(1.474 g, 91%) as a brown liquid, which matched previously reported

spectra. Without any further puriﬁcation, we proceeded to the next

step:⁵²¹H NMR (400 MHz, CDCl₃) δ 7.41 (ddd, J = 6.2, 4.5, 2.7 Hz,

2H), 7.34−7.09 (m, 3H), 3.37 (t, J = 6.8 Hz, 2H), 2.56 (t, J = 6.7 Hz,

2H), 1.22 (t, J = 7.0 Hz, 2H).

DCM. The combined organic layers were washed with brine, dried

(MgSO₄), ﬁltered, and concentrated by rotary evaporation to provide

4-cyclopropylbutan-1-ol as a clear yellow oil. The product was pure as

determined by ¹H NMR analysis and directly subjected to Appel

conditions. To a 50 mL ﬂask with a stir bar were added

triphenylphosphine (1.835 g, 7.0 mmol, 1 equiv), imidazole (488

mg, 7.0 mmol, 1 equiv), and iodine (1.769 g, 7.0 mmol, 1 equiv). The

ﬂask was placed in an ice bath, and DCM (0.5 M) was added. The

resulting opaque yellow solution was stirred at 0 °C for 50 min. A

solution of the crude alcohol in 2 mL of DCM was added dropwise,

and the reaction mixture was slowly warmed to room temperature

overnight. After 14 h, solvents were removed by rotary evaporation,

providing a viscous yellow oil. This oil was ﬁltered through a pad of

silica, washing with ∼100 mL of hexanes, and then concentrated to

provide (4-iodobutyl)cyclopropane (1.295 g, 82% yield over two

steps) as a clear, colorless oil that did not require further puriﬁcation:

¹H NMR (400 MHz, CDCl₃) δ 3.19 (t, J = 7.1 Hz, 1H), 1.86 (p, J =

7.2 Hz, 1H), 1.50 (ddd, J = 12.5, 8.2, 6.2 Hz, 1H), 1.21 (q, J = 7.2 Hz,

1H), 0.64 (ddt, J = 9.7, 7.2, 3.6 Hz, 1H), 0.50−0.34 (m, 1H), −0.00

(t, J = 4.8 Hz, 1H); ¹³C{¹H} NMR (101 MHz, chloroform-d) δ 33.8,

33.5, 30.7, 10.8, 7.4, 4.6; HRMS (EI) calcd for C₇H₁₃I [M]⁺

224.0056, found 224.0053; IR (neat) 3073, 2998, 2923, 2850,

1455, 1426, 1221, 1179, 1166, 1013, 820, 720, 597, 504 cm⁻¹; TLC R_f

= 0.68 (10% EtOAc/hexanes).

[(4-Cyclopropylbutyl)peroxy]triisopropylsilane (40). TIPSOOH

(288 mg, 1.5 mmol, 1 equiv) was subjected to general procedure F

using (4-iodobutyl)cyclopropane (1.010 g, 4.5 mmol, 3 equiv). Silica

ﬂash chromatography provided 40 (118.0 mg, 27% yield) as a clear,

colorless oil: ¹H NMR (400 MHz, CDCl₃) δ 4.02 (t, J = 6.6 Hz, 2H),

1.64 (dt, J = 8.7, 6.6 Hz, 2H), 1.57−1.40 (m, 2H), 1.35−1.18 (m,

5H), 1.12 (d, J = 6.9 Hz, 18H), 0.81−0.59 (m, 1H), 0.49−0.35 (m,

2H), 0.07 to −0.05 (m, 2H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ

77.0, 34.7, 27.8, 26.3, 18.2, 11.8, 10.9, 4.6; LRMS (GCMS) mass

fragmentation 227.3 (1), 185.2 (10), 183.2 (10), 155.2 (20), 131.2

(20), 105.2 (42), 103.2 (30), 77.2 (100), 76.1 (38), 61.1 (20), 41.2

(10); IR (neat) 2942, 2866, 1463, 1382, 1366, 1256, 1014, 997, 881,

859, 789, 676, 663 cm⁻¹; TLC R_f= 0.69 (5% EtOAc/hexanes).

5-Hydroperoxypent-1-ene. 4-Pentenyl mesylate (1.310 g, 8 mmol,

1 equiv) was subjected to general procedure C at a concentration (of

0.3 M 12:1 MeOH/H₂O) for 20 h. Silica ﬂash chromatography

provided 5-hydroperoxypent-1-ene (380 mg, 46% yield) as a clear,

colorless oil that matched the reported spectra:⁵⁴¹H NMR (400

MHz, CDCl₃) δ 7.88 (s, 1H), 5.82 (ddt, J = 16.9, 10.2, 6.6 Hz, 1H),

5.05 (dd, J = 17.2, 1.8 Hz, 1H), 4.99 (dd, J = 10.2, 1.7 Hz, 1H), 4.04

(t, J = 6.5 Hz, 2H), 2.14 (q, J = 7.1 Hz, 2H), 1.75 (p, J = 7.0 Hz, 2H);

TLC R_f= 0.38 (20% EtOAc/hexanes).

Triisopropyl[(5-phenylpent-4-yn-1-yl)peroxy]silane (38). (5-Iodo-

pent-1-yn-1-yl)benzene (1.458 g, 5.4 mmol) was subjected to general

procedure D for 2 h. Silica ﬂash chromatography provided (5-

hydroperoxypent-1-yn-1-yl)benzene (522 mg, 55% yield) as a clear,

colorless oil: ¹H NMR (400 MHz, CDCl₃) δ 8.50 (s, 1H), 7.45−7.37

(m, 2H), 7.27 (dt, J = 4.7, 2.9 Hz, 3H), 4.16 (t, J = 6.2 Hz, 2H), 2.51

(t, J = 7.0 Hz, 2H), 2.10−1.67 (m, 2H); ¹³C{¹H} NMR (100 MHz,

CDCl₃) δ 131.7, 128.3, 127.8, 123.7, 89.3, 81.3, 75.7, 26.9, 16.1; IR

(neat) 3369, 3059, 2936, 2232, 1709, 1598, 1489, 1441, 1275, 1176,

1069, 1027, 755, 713, 690, 526 cm⁻¹; TLC R_f= 0.27 (20% EtOAc/

hexanes). Next, (5-hydroperoxypent-1-yn-1-yl)benzene (475 mg, 2.7

mmol) was subjected to general procedure E for 2 h. Silica ﬂash

chromatography provided triisopropyl[(5-phenylpent-4-yn-1-yl)-

peroxy]silane (609 mg, 68% isolated as pure) as a clear, colorless

1

oil: H NMR (400 MHz, CDCl₃) δ 7.37 (tt, J = 5.7, 2.3 Hz, 2H),

Hydroperoxytriisopropylsilane (TIPSOOH). To a 100 mL round-

bottom ﬂask with a stir bar were added TIPSCl (4.30 mL, 20 mmol, 1

equiv) and dry Et₂O (1.0 M). The solution was cooled in an ice bath,

and urea/H₂O₂(3.86 g, 40 mmol, 2 equiv) was added in a single

portion. The reaction mixture was sparged with anhydrous ammonia

for 15 min and then left under an atmosphere of NH₃, warming to

room temperature overnight. The next morning, the reaction mixture

was diluted with hexane and water (∼20 mL each). The organic layer

was removed, and the aqueous layer extracted with hexanes (2 × 50

mL). The combined organic layers were washed with brine, dried

(MgSO₄), ﬁltered, and concentrated to provide a clear colorless oil.

Silica ﬂash chromatography provided hydroperoxytriisopropylsilane

(2.021 g, 53%) as a clear, colorless oil: ¹H NMR (400 MHz, CDCl₃)

δ 7.25−7.14 (br s, 1H), 1.26 (sept, J = 7.3 Hz, 3H), 1.11 (d, J = 7.3

Hz, 18H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 18.1, 11.6; IR (neat)

3331, 2944, 2867, 1463, 1384, 998, 881, 733, 676 cm⁻¹; TLC R_f=

0.40 (15% EtOAc/hexanes) (stains brightly with KMnO₄); TLC

silanol side product R_f= 0.34 (15% EtOAc/hexanes) (stains faintly

with KMnO₄)

7.30−7.21 (m, 3H), 4.13 (t, J = 6.1 Hz, 2H), 2.49 (t, J = 7.2 Hz, 2H),

1.98−1.89 (m, 2H), 1.26−1.15 (m, 3H), 1.08 (d, J = 7.1 Hz, 18H);

¹³C{¹H} NMR (126 MHz, CDCl₃) δ 131.7, 131.7, 128.4, 127.8, 89.5,

75.3, 27.4, 27.3, 18.2, 18.2, 16.5, 11.7; LRMS (GCMS) mass

fragmentation 273.1 (27), 231.2 (100), 203.2 (27), 155.2 (7), 115.2

(17), 75.2 (3); IR (neat) 2943, 2865, 1598, 1490, 1463, 1366, 1069,

997, 918, 881, 753, 687 cm⁻¹; TLC R_f= 0.7 (5% EtOAc/hexanes).

(4-Iodobutyl)cyclopropane. To a 50 mL two-neck ﬂask with a stir

bar and a reﬂux condenser were added 5-hexen-1-ol (0.840 mL, 7.0

mmol, 1 equiv), diiodomethane (0.710 mL, 8.75 mmol, 1.25 equiv),

and anhydrous DCM (1.0 M).⁵³While the mixture was being stirred

at room temperature, trimethylaluminum (8.0 mL, 15.4 mmol, 2.2

equiv, 2 M in hexanes) was added dropwise over ∼5 min. The

reaction mixture was stirred at room temperature for 10 min and then

heated to 40 °C overnight. After 14 h, the reaction mixture was cooled

to room temperature and diluted with 10 mL of DCM, and the

reaction carefully quenched with water (dropwise addition of 1 mL of

water, ∼1 drop/10 s). After vigorous bubbling had stopped, the

mixture was transferred to a separatory funnel with DCM and an

additional 3 mL of water was slowly added. Once all bubbling had

stopped, an additional ∼25 mL of water was added. The mixture was

diluted with DCM and 1 M aqueous NaOH (∼50 mL each). The

organic layer was removed and extracted with 3 × 50 mL of aqueous

1-(Methylperoxy)dodecane (3a). To a 25 mL round-bottom ﬂask

with a stir bar were added 1-dodecyl hydroperoxide 391 (404 mg, 2.0

mmol, 1 equiv) and MeOH (0.8 M). The solution was cooled in an

ice bath, and 50 wt % aqueous KOH (225 mg, 2.0 mmol, 1 equiv) and

iodomethane (0.45 mL, 5.0 mmol, 2.5 equiv) were added

K

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The Journal of Organic Chemistry

Article

successively. The reaction mixture was stirred overnight, warming to

room temperature. After 15 h, the mixture was diluted with DCM

(∼25 mL) and water (∼50 mL). The organic layer was removed, and

the aqueous layer extracted with 3 × 25 mL of DCM. The combined

organic layers were washed sequentially with water, potassium

thiosulfate, and brine, dried (MgSO₄), ﬁltered, and concentrated by

rotary evaporation, keeping the water bath below 40 °C. Silica ﬂash

chromatography provided 3a (368 mg, 85% yield) as a clear, colorless

oil: ¹H NMR (600 MHz, CDCl₃) δ 3.97 (t, J = 6.6 Hz, 2H), 3.82 (s,

3H), 1.59 (p, J = 6.8 Hz, 2H), 1.26 (d, J = 4.4 Hz, 18H), 0.88 (t, J =

6.7 Hz, 3H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 74.2, 62.2, 32.1,

29.8, 29.8, 29.7, 29.7, 29.6, 29.5, 28.0, 26.2, 22.8, 14.3; IR (neat)

2922, 2853, 1742, 1466, 1376, 1017 cm⁻¹; TLC R_f= 0.66 (20%

EtOAc/hexanes).

(neat) 2923, 2853, 1250, 879, 732 cm⁻¹; TLC, hydrolyzes on silica

gel.

(Dodecylperoxy)triethylsilane (3f). 1-Dodecyl hydroperoxide 3b

(40.5 mg, 0.5 mmol, 1 equiv) was subjected to general procedure E

using triethylsilyl triﬂate (0.040 mL, 0.18 mmol, 0.9 equiv). The

reaction mixture was diluted with diethyl ether, ﬁltered, and then

concentrated to provide 3f (74.3 mg, 54% yield) as a clear, colorless

oil in ∼85% purity by ¹H NMR with contaminating hydroperoxide. 3f

decomposed under all puriﬁcation attempts and was used without

1

further puriﬁcation: H NMR (600 MHz, CDCl₃) δ 3.97 (t, J = 6.6

Hz, 2H), 1.61 (p, J = 6.8 Hz, 2H), 1.40−1.20 (m, 18H), 1.00 (t, J =

8.0 Hz, 9H), 0.89 (t, J = 7.0 Hz, 3H), 0.70 (q, J = 8.0 Hz, 6H); TLC,

hydrolyzes on silica gel.

(Dodecylperoxy)dimethyl(vinyl)silane (3g). 1-Dodecyl hydroper-

oxide 3b (103.0 mg, 0.5 mmol, 1 equiv) was subjected to general

procedure E using chloro(dimethyl)vinylsilane (0.070 mL, 0.5 mmol,

1 equiv) for 14 h. The reaction mixture was diluted with pentane,

ﬁltered, and then concentrated to provide 3g (102.5 mg, 71% yield)

as a clear, colorless oil in ∼80% purity by ¹H NMR with

contaminating hydroperoxide: ¹H NMR (400 MHz, CDCl₃) δ

6.26−6.03 (m, 2H), 5.87 (dd, J = 19.8, 4.3 Hz, 1H), 3.97 (t, J = 6.6

Hz, 2H), 1.69−1.55 (m, 2H), 1.44−1.15 (m, 18H), 0.88 (t, J = 6.8

Hz, 3H), 0.28 (s, 6H); TLC, hydrolyzes on silica gel.

Dodecyl 2,2,2-Triﬂuoroethaneperoxoate (3c).⁵⁵To a screw-cap

test tube with a stir bar was added 1-dodecyl hydroperoxide 3b (204.5

mg, 1.0 mmol, 1 equiv). The ﬂask was cooled in an ice bath, and

triﬂuoroacetic anhydride (0.140 mL, 1.0 mmol, 1 equiv) was added

dropwise. The reaction mixture was stirred at 0 °C for 2 h, the

reaction quenched with 3 mL of water, and the mixture diluted with

10 mL of DCM. The mixture was washed with saturated aqueous

NaHCO₃, the organic layer removed, and the aqueous layer extracted

with DCM (2 × 10 mL). The combined organic layers were washed

with brine, dried (MgSO₄), ﬁltered, and concentrated by rotary

evaporation to provide 3c (241 mg, 81% yield) as a clear, colorless oil

in 90% purity (dodecanal as the contaminant). The crude product

was used without further puriﬁcation: ¹H NMR (600 MHz, CDCl₃) δ

4.38 (t, J = 6.6 Hz, 2H), 1.72 (p, J = 6.8 Hz, 2H), 1.41 (p, J = 7.0 Hz,

2H), 1.36−1.16 (m, 16H), 0.88 (t, J = 6.7 Hz, 3H); ¹⁹F NMR (376

MHz, CDCl₃) δ −72.43; IR (neat) 2923, 2854, 1785, 1466, 1162, 779

cm⁻¹.

(Dodecylperoxy)triethoxysilane (3d). 1-Dodecyl hydroperoxide 3b

(102.4 mg, 0.5 mmol, 1 equiv) was subjected to general procedure E

using chlorotriethoxysilane (0.10 mL, 0.5 mmol, 1 equiv) and

triethylamine (0.14 mL, 1.0 mmol, 2 equiv) as the base for 15 h. The

reaction mixture was diluted with diethyl ether, ﬁltered, and then

concentrated by rotary evaporation. NMR analysis showed incom-

plete conversion; the crude material was dissolved in DCM (3 mL),

and triethylamine (0.10 mL, 0.72 mmol, 1.5 equiv) was added. The

reaction mixture was stirred for 14 h, ﬁltered, and concentrated to

provide 3d (95.3 mg, 52% yield) in ∼80% purity by ¹H NMR, which

was used without further puriﬁcation: ¹H NMR (600 MHz, CDCl₃) δ

4.03 (t, J = 6.6 Hz, 2H), 3.87 (q, J = 6.8 Hz, 6H), 1.69−1.51 (m, 4H),

1.39−1.18 (m, 25H), 0.88 (t, J = 7.0 Hz, 3H); TLC R_f= 0.50 (15%

EtOAc/hexanes), hydrolyzes on silica gel.

(Dodecylperoxy)(methyl)diphenylsilane (3h). 1-Dodecyl hydro-

peroxide 3b (200.6 mg, 1.0 mmol, 1 equiv) was subjected to general

procedure E using chloro(methyl)diphenylsilane (0.070 mL, 0.5

mmol, 1 equiv) and silver triﬂate (257.0 mg, 1.0 mmol, 1 equiv) for

14 h. To remove residual hydroperoxide, the crude material was

diluted with pentane (3 mL) and ﬂushed through a silica plug,

washing with an additional ∼10 mL of pentane, and concentrated to

1

provide 3h (110.0 mg, 27% yield) as a clear, colorless oil: H NMR

(400 MHz, CDCl₃) δ 7.65 (dt, J = 6.5, 1.6 Hz, 3H), 7.52 (dt, J = 6.7,

1.5 Hz, 1H), 7.47−7.35 (m, 5H), 7.31 (dd, J = 7.9, 6.4 Hz, 1H), 3.93

(t, J = 6.6 Hz, 2H), 1.58−1.47 (m, 2H), 1.40−1.12 (m, 18H), 0.89 (t,

J = 6.7 Hz, 3H), 0.76 (s, 3H); TLC R_f= 0.73 (15% EtOAc/hexanes).

tert-Butyl(dodecylperoxy)dimethylsilane (3i). 1-Dodecyl hydro-

peroxide 3b (120.0 mg, 0.6 mmol, 1 equiv) was subjected to general

procedure E using tert-butyldimethylsilyl triﬂate (0.140 mL, 0.6 mmol,

1 equiv) at a concentration of 0.75 M for 14 h to provide 3i (136.0

mg, 71% yield) as a clear, colorless oil. The crude material was >95%

1

pure as determined by H NMR and did not require puriﬁcation: ¹H

NMR (400 MHz, CDCl₃) δ 3.96 (t, J = 6.6 Hz, 2H), 1.59 (p, J = 6.6

Hz, 2H), 1.40−1.17 (m, 18H), 0.94 (s, 9H), 0.88 (t, J = 6.6 Hz, 3H),

0.16 (s, 6H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 77.2, 32.1, 29.8,

29.8, 29.7, 29.7, 29.6, 29.5, 27.9, 26.4, 26.3, 22.9, 18.3, 14.3, −5.7; IR

(neat) 924, 2854, 1738, 1462, 1250, 835, 733 cm⁻¹.

(Dodecylperoxy)triisopropoxysilane (SI-3k). 1-Dodecyl hydro-

peroxide 3b (103.4 mg, 0.5 mmol, 1 equiv) was subjected to general

procedure E using chlorotriisopropoxysilane⁵⁶(0.14 mL, 0.5 mmol, 1

equiv) and triethylamine (0.14 mL, 1.0 mmol, 2 equiv) as the base for

15 h. The reaction mixture was diluted with diethyl ether, ﬁltered, and

then concentrated by rotary evaporation. NMR analysis showed

incomplete conversion; the crude material was dissolved in DCM (3

mL), and triethylamine (0.10 mL, 0.72 mmol, 1.5 equiv) was added.

The reaction mixture was stirred for 14 h, ﬁltered, and concentrated

to provide SI-3k (138.0 mg, 68% yield) in ∼85% purity by ¹H NMR,

tert-Butyl(dodecylperoxy)diphenylsilane (SI-3l). 1-Dodecyl hy-

droperoxide 3b (203.8 mg, 1.0 mmol, 1 equiv) was subjected to

general procedure E using tert-butyl(chloro)diphenylsilane (0.26 mL,

1.0 mmol, 1 equiv) and silver triﬂate (248.4 mg, 0.97 mmol, 1 equiv)

for 14 h. The reaction mixture was diluted with diethyl ether, ﬁltered,

and then concentrated. Silica ﬂash chromatography provided SI-3l

1

(107.0 mg, 24% yield) as a clear, colorless oil: H NMR (400 MHz,

CDCl₃) δ 7.75 (td, J = 8.7, 7.9, 1.2 Hz, 4H), 7.50−7.31 (m, 6H), 3.92

(t, J = 6.6 Hz, 2H), 1.53−1.44 (m, 2H), 1.37−1.06 (m, 27H), 0.88 (t,

J = 6.7 Hz, 3H); IR (neat) 2926, 2855, 1738, 1462, 1112, 906, 730

cm⁻¹; TLC R_f= 0.73 (15% EtOAc/hexanes).

1

which was used without further puriﬁcation: H NMR (600 MHz,

CDCl₃) δ 4.24 (hept, J = 6.3 Hz, 3H), 3.99 (t, J = 6.7 Hz, 3H), 1.61

(p, J = 6.9, Hz, 2H), 1.36−1.21 (m, 17H), 1.19 (d, J = 6.1 Hz, 18H),

0.86 (t, J = 6.9 Hz, 3H).

Di-tert-butyl(dodecylperoxy)(isobutyl)silane (SI-3m). 1-Dodecyl

hydroperoxide 3b (101.2 mg, 0.5 mmol, 1 equiv) was subjected to

general procedure E using di-tert-butyl-isobutylsilyl triﬂate (0.14 mL,

1.0 mmol, 1 equiv) for 16 h. The reaction mixture was diluted with

diethyl ether, ﬁltered, and then concentrated. Elution through a silica

plug (hexanes) provided SI-3m (18.7 mg, 9% yield) as a clear,

colorless oil: ¹H NMR (400 MHz, CDCl₃) δ 3.98 (t, J = 6.5 Hz, 2H),

2.00 (septet, J = 6.6 Hz, 1H), 1.58 (p, J = 6.9 Hz, 2H), 1.39−1.18 (m,

18H), 1.05 (s, 18H), 0.99 (d, J = 6.5 Hz, 6H), 0.88 (t, J = 6.7 Hz,

3H), 0.68 (d, J = 6.6 Hz, 2H); TLC R_f= 0.79 (5% EtOAc/hexanes).

(2,3-Dimethylbutan-2-yl)(dodecylperoxy)dimethylsilane (SI-3n).

1-Dodecyl hydroperoxide 3b (101.2 mg, 0.5 mmol, 1 equiv) was

subjected to general procedure E using chlorodimethylhexylsilane

(Dodecylperoxy)trimethylsilane (3e). 1-Dodecyl hydroperoxide

3b (102.5 mg, 0.5 mmol, 1 equiv) was subjected to general procedure

E using chlorotrimethylsilane (0.130 mL, 1.0 mmol, 2 equiv) and

pyridine (0.080 mL, 1.0 mmol, 2 equiv) as the base at a concentration

of 0.2 M for 40 min. The reaction mixture was diluted with pentane,

ﬁltered, and then concentrated to provide 3e (74.3 mg, 54% yield) in

>95% purity by ¹H NMR: ¹H NMR (400 MHz, CDCl₃) δ 3.97 (t, J =

6.6 Hz, 2H), 1.60 (p, J = 6.9 Hz, 2H), 1.39−1.18 (s, 19H), 0.88 (t, J =

6.7 Hz, 3H), 0.20 (s, 9H); ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 77.3,

32.1, 29.8, 29.8, 29.7, 29.7, 29.6, 29.5, 27.9, 26.2, 22.8, 14.3, −1.3; IR

L

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The Journal of Organic Chemistry

Article

(0.10 mL, 0.5 mmol, 1 equiv) for 16 h. The reaction mixture was

diluted with diethyl ether, ﬁltered, and then concentrated. Elution

through a silica plug (hexanes) provided SI-3n (24.9 mg, 14% yield)

as a clear, colorless oil: ¹H NMR (400 MHz, CDCl₃) δ 3.95 (t, J = 6.6

Hz, 2H), 1.70−1.49 (m, 2H), 1.38−1.18 (m, 18H), 0.94−0.83 (m,

16H), 0.21 (s, 6H); TLC R_f= 0.71 (5% EtOAc/hexanes).

and concentrated to provide a clear red-orange oil. Silica ﬂash

chromatography provided 1,2-bis(4-methoxyphenyl)disulfane (618

mg, 88% yield) as a clear, viscous yellow oil that matched the reported

spectrum:⁶⁰¹H NMR (600 MHz, CDCl₃) δ 7.40 (d, J = 8.7 Hz, 4H),

6.84 (d, J = 8.8 Hz, 4H); TLC R_f= 0.19 (25% EtOAc/hexanes).

1,2-Bis(4-nitrophenyl)disulfane. The compound was prepared

following the same procedure that was used for 1,2-di(naphthalen-

2-yl)disulfane, using 4-nitrothiophenol (785 mg, 5 mmol). Trituration

with diethyl ether provided 1,2-bis(4-nitrophenyl)disulfane (508 mg,

66% yield) as a light yellow solid that matched the reported

spectrum:⁶⁰¹H NMR (600 MHz, CDCl₃) δ 8.19 (d, J = 8.8 Hz, 4H),

7.62 (d, J = 9.0 Hz, 4H); TLC R_f= 0.50 (25% EtOAc/hexanes).

2,2′-Disulfanediyldibenzoic Acid. The compound was prepared

following the same procedure that was used for 1,2-di(naphthalen-2-

yl)disulfane, using 2-mercaptobenzoic acid (769 mg, 5 mmol).

Trituration with diethyl ether provided 2,2′-disulfanediyldibenzoic

acid (194 mg, 25% yield) as a white solid that matched the reported

spectrum:⁶²¹H NMR (400 MHz, DMSO-d₆) δ 13.55 (br s, 2H), 8.02

(d, J = 7.7 Hz, 2H), 7.69−7.51 (m, 4H), 7.34 (t, J = 7.4 Hz, 2H).

1-(Naphthalen-2-yl)-2-phenyldisulfane.⁶³To a solution of the

1,2-di(naphthalen-2-yl)disulfane (1.0 mmol) in tetrahydrofuran

(THF) (5.0 mL) at 0 °C was added slowly SO₂Cl₂(1.1 mmol).

The reaction mixture was stirred for 1 h at the same temperature. This

solution was used immediately in the next step.

To a solution of the thiophenol (1.0 mmol), triethylamine (2.2

mmol), and water (10 mmol) in THF (4.0 mL) at room temperature

was added the solution from the ﬁrst step (1 mmol of sulfenyl

chloride dissolved in THF) while the mixture was being stirred. The

reaction mixture was stirred for 6 h at room temperature. The

reaction mixture was diluted with DCM (20 mL), washed with a

saturated aqueous NaHCO₃solution and water, and then dried over

anhydrous MgSO₄. The solvent was removed by evaporation, and 1-

(naphthalen-2-yl)-2-phenyldisulfane was puriﬁed by column chroma-

tography using hexanes as the eluent and isolated as a white solid in

35% yield (94 mg), which matched the reported spectrum:⁶⁴¹H

NMR (400 MHz, chloroform-d) δ 7.95 (s, 1H), 7.85−7.77 (m, 2H),

7.75 (d, J = 8.1 Hz, 1H), 7.60 (dd, J = 8.6, 1.9 Hz, 1H), 7.57−7.50

(m, 2H), 7.50−7.41 (m, 2H), 7.29 (dd, J = 8.4, 6.8 Hz, 2H), 7.25−

7.17 (m, 1H).

tert-Butoxy(dodecylperoxy)diphenylsilane (SI-3o). 1-Dodecyl

hydroperoxide 3b (100.6 mg, 0.5 mmol, 1 equiv) was subjected to

general procedure E using tert-butoxy(chloro)diphenylsilane⁵⁷(148.1

mg, 0.5 mmol, 1 equiv) for 14 h. The reaction mixture was diluted

with diethyl ether, ﬁltered, and then concentrated. Silica ﬂash

chromatography provided SI-3o (132.5 mg, 58% yield) as a clear,

1

colorless oil: H NMR (600 MHz, CDCl₃) δ 7.76−7.63 (m, 4H),

7.47−7.39 (m, 2H), 7.38−7.30 (m, 4H), 3.88 (t, J = 6.6 Hz, 2H),

1.49 (p, J = 6.6 Hz, 2H), 1.36 (s, 9H), 1.34−1.10 (m, 18H), 0.89 (t, J

= 6.8 Hz, 3H); TLC R_f= 0.65 (15% EtOAc/hexanes).

(Dodecylperoxy)(isopropoxy)diisopropylsilane (SI-3p). 1-Dodecyl

hydroperoxide 3b (198.9 mg, 1.0 mmol, 1 equiv) was subjected to

general procedure E using chloro(isopropoxy)diisopropylsilane

(216.1 mg, 1.0 mmol, 1 equiv) for 16 h. The reaction mixture was

diluted with pentane, ﬁltered, and then concentrated. Silica ﬂash

chromatography provided SI-3p (143.0 mg, 38% yield) as a clear,

1

colorless oil: H NMR (600 MHz, CDCl₃) δ 4.27 (sept, J = 6.0 Hz,

1H), 4.02 (t, J = 6.6 Hz, 2H), 1.60 (p, J = 6.8 Hz, 2H), 1.39−1.23 (m,

18H), 1.20 (d, J = 6.1 Hz, 6H), 1.13−1.01 (m, 14H), 0.88 (t, J = 6.7

Hz, 3H); TLC R_f= 0.73 (15% EtOAc/hexanes).

1,2-Di(naphthalen-2-yl)disulfane. To a 25 mL ﬂask with a stir bar

were added 2-thionaphthol (807 mg, 5 mmol, 1 equiv) and ethyl

lactate (0.67 M). The reaction mixture was stirred at 60 °C, open to

air.⁵⁸After 16 h, the reaction was quenched with water and the

mixture transferred to a separatory funnel, diluting with ∼50 mL each

of ethyl acetate and water. The organic layer was removed, and the

aqueous layer was extracted with EtOAc (2 × 50 mL). The combined

organic layers were washed with water and then brine, dried

(MgSO₄), ﬁltered, and concentrated by rotary evaporation.

Trituration with diethyl ether provided 1,2-di(naphthalen-2-yl)-

disulfane (377 mg, 47% yield) as an oﬀ-white solid that matched

the reported spectrum:⁵⁸¹H NMR (400 MHz, CDCl₃) δ 7.99 (s,

2H), 7.86−7.68 (m, 6H), 7.62 (dd, J = 8.7, 1.9 Hz, 2H), 7.52−7.38

(m, 4H).

1,2-Bis(3,4-dichlorophenyl)disulfane. The compound was pre-

pared following the same procedure that was used for 1,2-

di(naphthalen-2-yl)disulfane, using 3,4-dichlorothiophenol (0.64

mL, 5 mmol). Trituration with diethyl ether provided 1,2-bis(3,4-

dichlorophenyl)disulfane (353 mg, 39% yield) as an oﬀ-white solid

that matched the reported spectrum:⁵⁹¹H NMR (400 MHz, CDCl₃)

δ 7.55 (s, 2H), 7.37 (d, J = 8.5 Hz, 2H), 7.29 (d, J = 8.5 Hz, 2H).

1,2-Bis(4-bromophenyl)disulfane. The compound was prepared

following the same procedure that was used for 1,2-di(naphthalen-2-

yl)disulfane, using 4-bromothiophenol (383 mg, 2 mmol). Silica ﬂash

chromatography provided 1,2-bis(4-bromophenyl)disulfane (302 mg,

80% yield) as a white solid that matched the reported spectrum:⁵⁸¹H

NMR (400 MHz, CDCl₃) δ 7.42 (d, J = 8.6 Hz, 4H), 7.34 (d, J = 8.5

Hz, 4H); TLC R_f= 0.66 (15% EtOAc/hexanes).

1,2-Bis[4-(triﬂuoromethyl)phenyl]disulfane. The compound was

prepared following the same procedure that was used for 1,2-

di(naphthalen-2-yl)disulfane, using 4-(triﬂuoromethyl)thiophenol

(0.40 mL, 3 mmol). Trituration with diethyl ether provided 1,2-

bis[4-(triﬂuoromethyl)phenyl]disulfane (210 mg, 39% yield) as a

white solid that matched the reported spectrum:⁶⁰¹H NMR (400

MHz, CDCl₃) δ 7.58 (s, 8H); ¹⁹F NMR (376 MHz, CDCl₃) δ

−62.64.

1,2-Bis(4-methoxyphenyl)disulfane. To a 100 mL round-bottom

ﬂask with a stir bar were added silica gel (6.4 g) and water (1 M). The

mixture was stirred for 5 min to hydrate silica, leaving a free-ﬂowing

powder. DCM (0.1 M) and 4-methoxybenzenethiol (0.62 mL, 5

mmol, 1 equiv) were added, and then while the mixture was being

stirred at room temperature, a solution of bromine (0.26 mL, 5.05

mmol, 1.01 equiv) in 5 mL of DCM was added dropwise.⁶¹After 20

min, the reaction mixture was ﬁltered, washing with ∼75 mL of DCM,

1-(4-Methoxyphenyl)-2-phenyldisulfane. To a solution of the 1,2-

bis(4-methoxyphenyl)disulfane (1.0 mmol) in tetrahydrofuran