Regioselective vicinal functionalization of unactivated alkenes with sulfonium iodate(i) reagents under metal-free conditions

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Regioselective vicinal functionalization of unactivated alkenes

with sulfonium iodate(I) reagents under metal‐free condition

Received 00th January 20xx,

Accepted 00th January 20xx

a

a,b

Dodla S. Rao, Thurpu R. Reddy, Kalvacherla Babachary and Sudhir Kashyap*

DOI: 10.1039/x0xx00000x

Metal‐free, molecular iodine‐free direct 1,2‐difunctionalization of unactivated alkenes has been

reported. The sulfonium iodate(I) reagent efficiently promoted the intermolecular vicinal iodo‐

functionalization of diverse range of olefins in stereo and regioselective manner. This method

enables the divergent and straightforward preparation of synthetically useful functionalities; β‐

iodocarboxylates, β‐iodohydrins, and β‐iodoethers in one‐step process. Further interconversion of

iodo‐functionalized derivatives allowing easy access to valuable synthetic intermediates en route

for biologically active molecules.

www.rsc.org/

10

interdisciplinary fields.

Essentially, halofunctionalized

substrates provide possibilities of further functional group

transformations to access diverse and synthetically useful

derivatives.

Introduction

Stereoselective and divergent bisfunctionalization of alkenes

has been recognised as an important transformation to access

versatile synthons en route for pharmaceutically valuable

molecules and active natural products. Recent progress in

The iodocarboxylation of C=C double bond can be carried

1

11a

out by using molecular iodine as oxidant and electrophilic

halogen source with metal salts (copper, silver, thallium,

2

11b‐c

11d

mercury, bismuth),

or ammonium acetate.

Other

transition‐metal catalysis led to rapid development of

attractive and useful techniques for vicinal functionalization of

11e

oxidizing reagent such as ceric ammonium nitrate (CAN),

11f

iodonium‐di‐sym‐collidine

perchlorate

(IDCP),

N‐

and

3

alkenes. Despite the significant advances and fascinating

11g‐h

11i‐j

iodosuccinimide (NIS),

potassium iodate (KIO

3

),

4

applications of transition‐metals in organic chemistry, use of

these reagents are limited in large scale applications and active

pharmaceutical ingredients. The intrinsic drawbacks of

transition‐metal catalysts or heavy metal salts such as toxicity

and use of expensive ligands, additive or co‐catalysts, moisture

sensitive and confront challenges in removal of metal residues,

11k

hydrogen peroxide

in acetic acid as the solvent also

reported for similar transformations. Likewise, the iodoethers,

5

represent useful synthetic intermediates for assembling E‐ or

12

Z‐alkenes,

are generally prepared via intermolecular

cohalogenation of alkenes by employing iodonium source and

13

alcohols. In contrast, access to iodohydrin is generally

6

stimulate to achieving greener and sustainable chemistry.

difficult due to the possibility of reversible addition of iodine

Particularly, halofunctionalization, also ₇known as

7a,14

or hypoiodous acid (IOH generated in situ) on alkenes,

"

cohalogenation" of alkenes, is widely studied and elegant

15

16

hence co‐oxidant as scavengers or metal salts such as

AgNO , HgO, or CuO.HBF are needed to trap the iodine ion.

reaction enabled selective and facile addition of two new

chemical entities in single step. This process generally

proceed through halogenium ion which involves addition of

electrophilic halide, for instance iodate (I ), on olefin then

subsequent opening of cyclic iodonium intermediate with

nucleophile (solvent) stereospecifically generates 1,2‐trans‐

cohalogenated products. Cohalogenation of alkenes

introducing two stereocenters with exclusive anti selectivity to

incorporate vicinal ester

iodohydrin), or alkoxy ( ‐iodoether) moieties have shown

8

3

4

Alternatively, the epoxidation of alkenes by using peracids or

peroxides, and subsequent ring‐opening of oxirane ring with

iodo‐halides or metal‐iodides provide the desired

9

+

7a,13,17

iodohydrin.

18

Notably, large scale preparation of epoxide derivatives

19

and biologically important oxiranes predominantly relies on

the practicability and efficiency of methods developed for

halohydrin intermediates. However, excessive use of toxic

oxidants and expensive metal salts, handling of halogenated

reagents and formation of by‐products such as vicinal dihalides

(

β

‐iodoesters), hydroxy

(β‐

β

broad applications in organic chemistry as well in

2

0

or diols and functional group compatibility of iodinating

reagent system are associated limitations. Therefore, the

developments of convenient and greener approaches for

direct functionalization of alkenes utilizing metal‐free and

environmentally preferred reagents are highly desirable. In this

a.

Department of Chemistry, Malaviya National Institute of Technology, Jaipur‐

3

02017, INDIA. E‐mail: skashyap.chy@mnit,ac,in, skr.kashyap@gmail.com.

INSPIRE Faculty, Department of Science and Technology (DST) and Assistant

Professor, Academy of Scientific and Innovative Research (AcSIR), INDIA.

b.

Electronic Supplementary Information (ESI) available: [Spectral charts are

provided]. See DOI: 10.1039/x0xx00000x

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a

context, hypervalent iodine reagents are surged as versatile Table 1. Screening and optimization of sulfonium bis(acetoxy)iodate (I) reagent system

and attractive alternatives in vicinal bisfunctionalization of

21

olefins.

Halogen source (1.1 equiv)

Oxidant (1.1 equiv)

OAc

2

During our research towards glycochemistry, we recently

demonstrated the preparation of novel sulfonium

bis(acetoxy)iodate(I) reagent and studied its utility in

I

Solvent, additive

room temperature

1a

2a

2

2a

iodoglycosylation of glycals. The exceptional versatility of

metal‐free protocol highlighted for one‐pot and divergent

synthesis of glycosyl carboxylates and glycosyl azides in stereo‐

and regioselective manner. The efficiency and convenience of

present reagent system encourage us to relate this method

mechanistically for bisfunctionalization of unactivated C=C

double bond (Scheme 1).

b

Entry Iodo source

Oxidant/Additive

Solvent

Time

Yield

1

2

3

4

5

6

7

8

9

1

Me

3

SI

PhI(OAc)

‐

2

CH

2

3

Cl

2

12 h

5 h

56%

78%

86%

66%

88%

82%

61%

68%

66%

SI

CN

SI

DCE

SI

/4 Å MS DCE

10 h

15 min

1 h

SI

AcOH

SOI

AcOH

DCE

SI(OAc)

SI

2

7 h

2

‐

AcOH

30 min

1 h

NaIO

4

c

d

e

f

0

1

2

SI

H

2

O

2

24 h

15 min

2 h

traces

48%

Scheme 1. Iodoglycosylation and rational for vicinal functionalization of alkenes with

sulfonium bis(acetoxy)iodate (I) salt .

SI

TBHP

‐ /NH

Herein, we present

a

facile approach for 1,2‐

11a

I

2

4

OAc

82%

cohalogenation of alkenes enabling the stereodivergent

synthesis of vicinal iodoester, iodohydrin, and iodohydrin

derivatives by employing sulfonium‐salt based iodate(I)

reagents. The operationally simple protocol is mild and

promising alternative to toxic metal‐based reagent system and

8a

13

NaI

NH

PhI(OAc)

2

/CBTAB

CH

2

Cl

2

84%

g

11f

14

4

I

H

2

O

2

/Ac

2

O

AcOH/ CH

3

CN 1 h

67%

a

b

Reaction conditions: 1a (1.0 equiv), solvent (1 mL), 25 °C. The isolated yields

c

d

applicable for a diverse range of olefins, switching the solvent after column chromatography. Reaction was performed with 35% aq H

2

O

2

. 70%

e

f

aq TBHP was used. Iodine (1.0 equiv), NH

4

OAc (0.5 equiv). NaI (1.0 equiv),

system

iodofunctionalization of double bond. Further transformations

of ‐iodo derivatives employs nucleophilic substitution with

directed

the

intermolecular

selective

β‐

g

PhI(OAc)

2

(2.0 equiv), CTAB (10 mol%). NH

4

I (1.2 equiv), 50% aq H (1.2 equiv).

2 2

O

β

Further screening employing acetonitrile and 1,2‐

dichloroethane as the solvent resulted improved yields, 78%

and 86% respectively (entries 2,3). Attempt to conduct this

experiment using 4Å molecular sieves led to a decreased yield

sodium azide allowing straightforward access to vicinal azido

analogues, constitutes important sub unit with tremendous

synthetic and biological applications.

(

entry 4). In contrast, acetoxyiodonation of 1a in acetic acid

solvent to delivered the desired 1,2‐iodoacetate 2a in further

increased yields (88%) albeit with shorter reaction time (entry

Results and discussion

The sulfonium bis(acetoxy)iodate (I) [Me

iodate(I) species to realize bisfunctionalization of C=C bond,

could be generated in situ by employing

phenyliodine(III)diacetate (PhI(OAc) ) and trimethylsulfonium

SI). We begin our studies with styrene (1a) as the

3 2

SI(OAc) ], an active

5

). Moreover, switching the iodonium source to

trimethylsulfoxonium iodide (Me SOI) or employing sulfonium

bis(acetoxy)iodate (I) complex, Me₂SI(OAc) directly, prepared

failed to improve the

3

2a

2

by using our previously report,

22a

iodide (Me

3

efficiency of the reaction (Table 1, entries 6‐8). Apparently,

presence of acetic acid as the solvent as well external

nucleophile and in situ preparation of sulfonium iodate salt led

to a better result. Further evaluation of other reagent such as

NaIO , aq. H O , and TBHP as an alternative oxidant to PIDA

4 2 2

resulted poor to moderate yields (entries 9‐11).

model substrate, investigating the outcome of reaction under

different condition by varying solvent, iodonium source,

oxidants, additive, etc., results are illustrated in Table 1. Thus,

treatment of a preformed solution of Me

3 2

SI and PhI(OAc) (1.1

equiv each) in CH Cl with 1a (1.0 equiv) at room temperature

2

for 12 h led to the formation of exclusively a Markovnikov

product, 2‐phenyl‐2‐acetoxy‐1‐iodoethane (2a) in 56% yield

with complete regioselectivity (entry 1).

Notably, the Woodward's reaction conditions utilizing

1

1d

molecular iodine,

rather toxic, corrosive, and sublimable

1

1a

oxidant,

provide lesser yields as compared to present

2

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protocol (entry 12). In contrast, use of other halide salt such as

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3 2

Table 2._aScope of metal‐free iodoacetoxylation of alkenes with Me SI(OAc) in

8

a

NaI in combination with PhI(OAc)

2

produce 2a in 84% yield,

one‐pot

however required twofold excess of oxidant and

cetyltrimethylammonium bromide (CTAB) under critical

concentration (entry 13). On the other hand, ammonium salt

b

Entry

1

Substrate

Product

Yield

such as NH

4

I as electrophilic iodine source and H

2 2

O as oxidant

96%

84%

in the presence of Ac

been reported for oxidative iodoacetoxylation of styrene

albeit with lower yield (entry 14).

2

O in AcOH/CH CN solvent system have

3

11f

1b; R = Cl

2b; R = Cl

2c; R = F

2

3

4

5

1c; R = F

Having established the optimized reaction conditions, the

scope and general applicability of present protocol were

examined for a wide range of electronically and sterically

diverse olefins (Table 2). The styrene derivatives with electron‐

withdrawing groups for instance chloro‐, fluoro‐ as well

electron‐donating substituents such as methyl‐, tert‐butyl‐,

and methoxy‐, were reacted efficiently, affording the

corresponding iodoacetates 2b‐2f in good yields (entries 1‐5).

Furthermore, an electron rich 4‐vinylbiphenyl, a highly

substituted 2,4,6‐trimethylstyrene, and 2‐vinylnaphthalene

preformed well to afford the desired products 2g‐2i

respectively in good yields (entries 6‐8). However, whereas α‐

Me styrene reacted smoothly yielding the corresponding

iodoacetates 2j in complete regioselectivity, diphenylethylene

failed to produce 2k in acceptable yield (entries 9,10).

Encouraged by these results, we next investigated the

1d; R = Me

1e; R = tBu

1f; R = OMe

2d; R = Me

2e; R = tBu

2f; R = OMe

>99%

88%

85%

6

7

8

>99%

87%

92%

1g

2g

1

h

2h

1i

2i

influence of substituent's on

β‐position of terminal styrenes.

Gratifying, (E)‐ ‐methylstyrene underwent regio‐ and

β

9

82%

diastereoselective iodoacetoxylation to afford exclusive trans

product (±)‐3‐acetoxy‐2‐iodo‐3‐phenylpropanoate (2l) in 90%

yield (Table 2, entry 11). Subsequently, the stereoselective

direct vicinal functionalization of α,β‐unsaturated alkenes such

as cinnamic acid (1m), methyl trans‐cinnamate (1n), cinnamyl

alcohol (1o), and cinnamyl acetate (1p) is accomplished

successfully to obtain the desired products 2m‐2p in good

yields (entries 12‐15). In contrast, substrates with strong

1j; R = Me

1k; R = Ph

2j; R = Me

2k; R = Ph

1

0

1

traces

90%

1

l; R = Me

1m; R = CO

1n; R = CO

2l; R = Me

withdrawing groups at

β

‐position in conjugation with double

12

2

H

2m; R = CO

2

H

>99%

87%

bond, for instance trans‐cinnamaldehyde (1q) or trans‐

benzylidenacetone (1r), found to be challenging targets and

failed to give satisfactory yield even after prolonged reaction

time or at high temperature (entries 16,17).

13

2

Me

2n; R = CO

2

Me

14

1o; R = CH

1p; R = CH

2

OH

2o; R = CH

2

OH

81%

15

OAc

2p; R = CH

OAc

98%

On the other hand, internal aromatic olefins such as indene

(

1s) and 1,2‐dihydronaphthalene (1t) were found to be

16

1q; R = CHO

1r; R = COPh

2q; R = CHO

2r; R = COPh

traces

compatible under these conditions. Accordingly, addition of

electrophilic reagent on 1s and 1t resulted vicinal iodoacetates

2

17

OAc

s‐2t with exclusive trans‐diastereoselectivity and good yields

(

entries 18,19). It is pertinent to mention that, an aliphatic

18

75%

94%

I

1

s

bicyclic alkene such as norborn‐2‐ene, produced 7‐syn‐iodo‐2‐

exo‐acetoxybicyclo[2.2.1]heptane (2u, entry 20), involving a

distinct rearrangement of cationic intermediates as observed

2s

1

9

0

23

in previous reports (Figure 1).

1t

2t

2

78%

1u

2u

a

Reaction conditions: Substrate 1 (1.0 equiv), Me

3

2

SI and PhI(OAc) (1.1 equiv

b

each), acetic acid (1 mL), 25 °C, 30‐60 min. The isolated and unoptimized yields

after chromatography.

Figure 1. Probable rearrangement for norbornene iodofunctionalization

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2

5

To further gain the mechanistic insight, we examined the pharmaceutically fascinating molecules.

Despite the

addition of reactive species on cis/trans double bond. synthetic values of these structural motifs, a few scarce

Assuming the cis‐trans isomerization, (E)‐ and (Z)‐stilbenes reports yet employs metal‐based toxic reagent have been

25a

were chosen as mechanistic probes to realize the documented for their preparation. Therefore, our method

stereochemical outcome under present protocol (Scheme 2). offers an appealing and ideal‐green synthesis of 2,5‐diacetoxy‐

Interestingly, reaction of trans‐stilbene 1v in acetic acid with 2,5‐dihydrofuran albeit at room temperature.

sulfonium iodate(I) reagent generated in situ resulted the

erythro‐acetoxyiodide as a single diastereomer (±)‐trans‐2‐

iodo‐1,2‐diphenylethylacetate (2v). Despite the possibility of

isomerization, iodoacetoxylation of cis‐stilbene 1w affording

stereoselective threo product 2w, attributed to stereospecific

24

ring‐opening of putative iodonium intermediate. From

mechanistic point of view, this transformation highlights a

useful aspect of stereoselective (anti addition) vicinal

bisfunctionalization of ‐C=C‐ double bond apart from

regioselectivity (positional selectivity).

Scheme 3. Synthesis of 2,5‐diacetoxy‐2,5‐dihydrofuran and possible transformations to

3 2

bioactive molecules. Reaction conditions: Furan (1.0 equiv), Me SI and PhI(OAc) (1.1

equiv each), acetic acid (1 mL), 25 °C, 30 min.

We next explored the feasibility of non‐conjugated olefin

system and further evaluated the stereochemical information

toward mechanistic studies. Interestingly, eugenol derivative

(

1y), substrate bearing an allylic moiety, yielded a mixture of

regioisomers corresponding to Markovnikov and anti‐

Markovnikov‐type products 2y in good yields (Scheme 4). The

lack of selectivity could be attributed to the variation of charge

density on two carbons leading to non‐regiospecifically ring

opening of iodonium ion intermediate with acetate ion. Same

trend of regioselectivity was observed in the electrophilic

addition of less substituted terminal alkenes such as

allylbenzene (1z) and allylalcohol (1aa), eliminating a free‐

radical pathway. In contrast, geraniol acetate undergo

pronounced chemoselective iodoacetoxylation of terminal

Scheme 2. Stereoselective preparation of β‐iodocarboxylates from stilbenes via anti‐ double bond to obtain notably better regioselectivity in favor

addition and mechanistic illustration of cis‐trans isomerization

of Markovnikov 1,2‐iodoacetae 2ab with a ratio of ∼3:1 in 80%

overall isolated yields.

The stereochemistry of the product is unequivocally

confirmed to be the anti addition and precisely correlated by

1

spectroscopic analyses as well. In the H NMR spectrum of

erythro adduct, the characteristic resonances due to CHOAc

and CHI are identified at δ 5.85 (d, J = 7.4 Hz) and 4.91 (d, J =

7

.4 Hz) respectively. In contrast, threo configuration showed

corresponding chemical shifts at slightly higher values at δ 6.17

and 5.33 with distinctive coupling constant, J = 9.8 Hz between

α

‐protons. Notably, the formation of erthro and threo adduct

in exclusive anti‐diastereoselective manners is consistent with

2

4

previous studies and suggestive an ionic concerted one step

process not a free radical one.

Next, it was of interest to examine the reactivity of

electrophilic reagent on heterocyclic compound to expand the

scope. Interestingly, the reaction of furan (1x), comprising a

diene system with sulfonium bis(acetoxy)iodate (I) generated

in situ delivered completely different adduct, 2,5‐diacetoxy‐

2

,5‐dihydrofuran 2x as 1:1 isomeric mixture in 90% overall

Scheme 4. Scope of allylic double bond and mechanistic investigation: Substrate 1 (1.0

a

yields (Scheme 3). Noteworthy, the scaffolds with 2,5‐ equiv), Me SI and PhI(OAc) (1.1 equiv each), acetic acid (1 mL), 25 °C, 30‐60 min. The

disubstituted dihydrofuran moiety are potential useful isolated and unoptimized yields after chromatography. The ratio is based on H NMR

intermediates

3

2

b

1

spectra.

for

several

natural

products

and

4

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We next sought after developing carboxylic acid variant for the corresponding iodohydrin 4a in good yields (Scheme 6).

the intramolecular hetero‐functionalization by employing aryl, Adopting this protocol, feasibility of various substituted aryl,

aliphatic, and amino acids. For this purpose, the reactive and alicyclic alkenes were tested to extend the scope of the

electrophilic intermediate, sulfonium bis(carboxy)iodate (I) iodohydroxylation reaction.

complex prepared by using our previously described

As summarized in Scheme 6, styrene substrates with

procedure, and utilized for iodocarboxylation step (Scheme various functionalities (4‐Cl, 4‐tert‐butyl, 4‐phenyl), 2‐

). Initially, the reaction of styrene (1a) with Me SI(OBz) in vinylnaphthalene and ‐methyl styrene reacted smoothly

acetonitrile proceeded readily at ambient temperature leading to the desired iodohydrins 4b 4f in good yields with

affording the desired iodobenzoate 3a in 74% isolated yield exclusive Markovnikov selectivity. Indeed, diphenylethylene

2

2a

5

3

2

α

‐

26a

with absolute regioselectivity.

being a challenging substrate, reacted this time to afford the

Subsequently, aromatic acids with halogen(s) at different iodohydrin derivative 4g in satisfactory yields (Scheme 6). The

position reacted smoothly to afford the corresponding versatility of sulfonium iodate(I) system was amply

products 3b‐3d in good yields (Scheme 5). Notably, an electron demonstrated in the anti‐diastereoselective iodohydroxylation

rich and highly substituted substrate such as 3,4,5‐ of indene and a few non‐styrenyl substrates, such as norborn‐

trimethoxybenzoic acid performed equally well to give 3e in 2‐ene, cyclohexnene

(

1ac

)

and dihydropyran

(1ad).

acceptable yield. Significantly, phenyl‐ether bearing substrate, Nonetheless, bicyclo[2.2.1]heptene (1u) resulted the expected

phenoxyacetic acid, which constitute organic herbicides and 2‐exo,7‐syn‐stereoisomer (4i), the most obvious outcome of

2

6b

important chemical tools for clinical pharmacokinetics, was the ionic rearrangement as illustrated in Figure 1.

also tolerated under present protocol affording 2‐iodo‐ We next anticipated that switching the solvent system to

phenoxyacetate product 3f in 83% yield. In addition, alicyclic methanol would enable to realize the synthesis of

carboxylic acid was also suitable to obtain the corresponding iodoethers in straightforward transformation. With sulfonium

β‐

β‐iodocarboxylate 3g in satisfactory yields.

iodate (I) reagent in methanol (nucleophile) prepared in situ by

employing a combination of Me SI and PhI(OAc) , a range of

3

2

aryl, aryl‐alkyl internal alkenes, bicyclic, endo‐cyclic, and enol

ether substrates were depicted to illustrate the stereoselective

difunctionalization (5a‐k, Scheme 6).

a

Scheme 5. Iodocarboxylaion of styrene: Reaction conditions: Me

3

SI and PhI(OAc)

2

(1.1

eq each), carboxylic acid (2.2 eq), CH

3

CN (10 mL), 25 °C, 1 h, azeotroping off the acetic

acid; (ii) CH CN (2 mL), 1a (1.0 eq), 25 °C, 1‐2 h.

3

Considering the biological significances of amino acid

constructs, vicinal iodofunctionalization of 1a with Fmoc‐� ‐ala‐

OMe and Fmoc‐L‐leucine‐OMe accomplished successfully by

employing our reagent system to access the respective

derivatives 3h‐3i in good yields.

We next investigated the possibility of further applications

of sulfonium salt based iodate(I) reagent system in rapid and

direct access of synthetically relevant iodofunctionalized

compounds. We envisioned intramolecular version of hydroxy‐

iodonation of alkenes by employing water as the co‐solvent as

Scheme 6. Scope of Me

3

SI(OAc)

2

mediated regio‐ and stereoselective

SI and

O (1:1; 1 mL) or MeOH (1 mL), 25 °C, 30‐60 min.

a

well alternative nucleophile to the acetic acid enabling iodofunctionalization in one‐pot. Reaction conditions: 1 (1.0 equiv), Me

3

PhI(OAc)

2

(1.1 equiv each), CH

3

CN:H

2

iodohydrin adducts. To our delight, treatment of styrene (1a

)

b

c

1

The isolated yields after chromatography. The ratio is based on H NMR spectra.

with a solution of Me SI(OAc) in acetonitrile‐water (1:1) gives

3

2

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Overall, these results are consistent with the study and

In

a

representative

example,

the

vicinal

reveal the expected stereoselectivity for an ionic process; iodofunctionalization of styrene

(

1a) with electrophilic

addition of electrophilc iodonium reagent from sterically less sulfonium iodate(I) were performed by employing acetic acid,

crowded face of the olefin following intramolecular diaxial acetonitrile:water, and methanol as the solvent(s) respectively.

nucleophilic opening of iodonium intermediate. Particularly, The resulting 2‐iodo‐1‐phenylethyl analogs

2‐4 were then

the protocol tolerates a diverse range of synthetically valuable directed to conventional iodo‐azide transformation using

functionalities establishing the vicinal functionalization of sodium azide in DMF solvent at 50‐60 °C to obtain the

internal, terminal, and various substituted olefins corresponding 2‐azido‐1‐phenylethyl derivatives 6a‐8a in good

2

9

stereo/regioselectively complementary to existing procedures. yields. Likewise, the sequential two steps transformation in

The synthetic versatility of vicinal functionalized azides as one‐pot applied to other styrene derivatives affording valuable

valuable building blocks persuaded us to incorporate an azide functionalized azides in good yields, without isolation of the

group involving nucleophilic substitution of

prefunctionalized substrates. The resulting 1,2‐azidoethers or

azidoalcohols serve as useful precursor for aminoether, amino heterofunctionalized derivatives provide rapid synthesis of

β‐iodo iodo‐adducts (6b‐g

, 8b‐g, Scheme 7).

Additionally, the systematic modification of iodo group in

27

alcohol, aziridine, and heterocylic derivatives, and represent analogues of some known drugs and structurally modified

an important structural motif ₂for assembling active 'drug like' molecules of outmost therapeutic applications

8

30

biomolecules as well approved drugs (Figure 2).

(Figure 3). As illustrated in Scheme 8, incorporating a 1H‐

1

,2,3‐triazole moiety instead of imidazole in antifungal drugs

such as miconazoles analogs by employing click reaction

29b‐c

resulting a new class of antitubercular agents.

Thus,

iodoacetate 2a prepared by in situ iodoacetoxylation step and

subsequent "one‐pot" nucleophilic substitution with

benzotriazole employing DBU as the base in DMSO at room

temperature for 8h afforded the corresponding amination

Figure 2. Biologically relevant molecules with 2‐amino‐1‐phenyl scaffold

product 9 in 78% yield over 2 steps (Scheme 8).

In this premise, we decided to synthesize

β‐azido from

corresponding iodo compounds in a sequential one‐pot

process that employs vicinal iodofunctionalization of an alkene

with our electrophilic reagent system following nucleophilic

displacement with sodium azide (Scheme 7).

Figure 3. Pharmaceutical important imidazoles and triazole molecules.

In addition,

β‐azido compounds (6a,7a,8a), conveniently

prepared from easily accessible starting material, were

successfully coupled with phenylacetylene applying copper‐

catalyzed azide‐alkyne cycloaddition (CuAAC) yielding the

corresponding triazoles 10

Scheme 8).

‐12 in sequential transformation

(

a

Scheme 7. Synthesis of β‐azido derivatives in one‐pot sequential process: Reaction

conditions: See footnote under Table 1. and Scheme 5. for the first step, then DMF (2

mL), NaN3 (1.5 equiv), 60 °C, 5‐8 h.

Scheme 8. Transformations of iodofunctionalized product and rapid access to "drug‐

like" molecules.

6

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ARTICLE

1

dihydrofuran. All the products were fully characterised by H

Conclusions

13

and C spectroscopy and MS spectrometry and were in

complete agreement with the assigned structure and

correlated with literature data.

In conclusion, we have successfully demonstrated an

intramolecular

functionalization

regio/stereoselective

of alkenes. Employing

vicinal

iodo‐

sulfonium

bis(acetoxy)iodate (I) species in different solvents allowing the

facile and divergent synthesis of iodoester, iodohydrin, and

iodoethers in a one‐pot process. The scope and limitation of

the electrophilic reagent system was illustrated with a wide

range of structurally diverse olefins. The protocol is mild and

tolerated various functionalities accessing synthetically useful

heterofunctionalized derivatives under ambient conditions.

The metal‐free method utilizing easily available inexpensive

and environmentally beings substrates/oxidants is potentially

attractive and advantageous over the conventional methods.

Importantly, diacetoxylation of furan is realized with sulfonium

iodate(I) salt which further highlights a green approach

avoiding stoichiometric use of toxic metal reagent. In addition,

13b

1

Compound 2a

CDCl ) δ 7.47‐7.30 (m, 5H), 5.88 (dd, J = 7.7, 5.5 Hz, 1H), 3.48

dd, J = 10.6, 7.7 Hz, 1H), 3.45 (dd, J = 7.7, 2.7 Hz, 1H), 2.13 (s,

;

Oily liquid (271 mg, 88%). H NMR (400 MHz,

3

(

13

3

1

+

3

H). C NMR (101 MHz, CDCl ) δ 169.77, 138.39, 128.71,

28.67, 126.38, 126.11, 75.16, 21.01, 7.73. HRMS (ESI) m/z [M

H] calcd. for C10

+

H

12IO

2

: 290.98765; found: 290.98900. IR

–1

(

CHCl

3

, cm ): 2923, 1731, 1234, 699.

13b

1

Compound 2b

;

Oily liquid (293 mg, 96%). H NMR (500 MHz,

CDCl ) δ 7.46‐7.18 (m, 4H), 5.82 (dd, J = 7.4, 5.6 Hz, 1H), 3.43

m, 2H), 2.12 (s, 3H). C NMR (101 MHz, CDCl

37.42, 130.20, 128.86, 127.83, 74.39, 20.95, 7.26. HRMS (ESI)

m/z [M] calcd. for C10

3

13

(

3

) δ 169.58,

1

+

2

H

11ClIO

: 323.94868; found: 323.95124.

synthetic applicability of prefunctionalized

β‐iodo precursors

–1

IR (CHCl

3

, cm ): 2924, 1728, 1214, 747.

was illustrated by simple organic transformations to access

biologically significant scaffolds. Our investigations towards

understanding mechanistic pathways employing sulfonium

bis(acetoxy)iodate (I) species in new transformations and its

applications in modern organic chemistry are currently in

progress.

1

Compound 2c; Oily liquid (208 mg, 84%). H NMR (400 MHz,

CDCl ) δ 7.40‐7.31 (m, 2H), 7.07‐7.03 (m, 2H), 5.84 (dd, J = 7.6,

.6 Hz, 1H), 3.45 (dd, J = 10.6, 7.7 Hz, 1H), 3.42 (dd, J = 10.6,

.6 Hz, 1H), 2.12 (s, 3H). C NMR (126 MHz, CDCl ) δ 169.26,

3

63.21, 161.24, 134.01, 133.99, 128.01, 127.95, 116.28,

3

5

1

13

+

15.25, 115.07, 74.03, 20.53, 7.49, 1.37. HRMS (ESI) m/z [M]

Experimental

+

calcd. for C10

H

10FIO

2

: 307.97095; found: 307.97225. IR (CHCl

3

,

–1

General consideration: All reactions were performed in flame‐ cm ): 2923, 1732, 1216, 746.

dried round bottom flasks, fitted with rubber septa or glass gas

1

3b

1

adapters, under a positive pressure of nitrogen or argon. Compound 2d

Removal of solvent under reduced pressure refers to CDCl ) δ 7.25‐7.15 (m, 4H), 5.84 (dd, J = 7.9, 5.4 Hz, 1H), 3.46

distillation with a rotary evaporator attached to a vacuum (dd, J = 10.5, 8.5 Hz, 1H), 3.42 (dd, J = 10.5, 5.3 Hz, 1H), 2.33 (s,

;

Oily liquid (166 mg, 99%). H NMR (400 MHz,

3

1

3

pump (~3 mmHg). NMR were recorded on 300, 400 or 500 3H), 2.11 (s, 3H). C NMR (126 MHz, CDCl ) δ 169.68, 138.52,

MHz nuclear magnetic resonance spectrometers. The proton 135.38, 129.28, 126.29, 75.05, 21.16, 20.97, 7.82. HRMS (ESI)

+

resonances are annotated as: chemical shift (δ) relative to m/z [M] calcd. for C11

tetramethylsilane (δ 0.0) using the residual solvent signal as an (CHCl

H

13IO

2

: 303.99602; found: 303.99369. IR

–

1

3

, cm ): 2922, 1730, 1215, 754.

internal standard or tetramethylsilane itself: chloroform‐d (δ

1

7

.26, singlet), multiplicity (s, singlet; d, doublet; t, triplet; q, Compound 2e; Oily liquid (218 mg, 88%). H NMR (400 MHz,

3

quartet; m, multiplet; br, broad), coupling constant (J, Hz), and CDCl ) δ 7.37 (d, J = 8.4 Hz, 2H), 7.27 (d, J = 8.4 Hz, 2H), 5.87

number of protons for a given resonance is indicated by nH. (dd, J = 8.2, 5.1 Hz, 1H), 3.46 (dd, J = 10.5, 8.1 Hz, 1H), 3.43 (dd,

1

3

13

The chemical shifts of C NMR are reported in ppm relative to J = 10.5, 5.1 Hz, 1H), 2.12 (s, 3H), 1.31 (s, 9H). C NMR (101

the central line of the triplet at 77.00 ppm for CDCl

. High MHz, CDCl ) δ 169.46, 151.42, 135.23, 125.94, 125.39, 74.85,

mass 34.42, 31.12, 20.86, 7.76. HRMS (ESI) m/z [M + NH

3

+

resolution mass analyses were performed on

spectrometer using ESI‐TOF techniques.

a

4

] calcd. for

+

–1

C

14

H

28INO

2

: 364.07680; found: 364.07555. IR (CHCl

3

, cm ):

2

925, 1729, 1214, 750.

Representative procedure for the synthesis of 1,2‐

iodoacetaes; A preformed solution of Me

SI (237 mg, 1.16 Compound 2f

mmol, 1.1 equiv) and PhI(OAc)

(374 mg, 1.16 mmol, 1.1 equiv) CDCl ) δ 7.27 (d, J = 7.4 Hz, 2H), 6.88 (d, J = 7.8 Hz, 2H), 5.87‐

in 1 mL acetic acid was treated with alkene

1a, 110 mg, 100 5.80 (m, 1H), 3.79 (s, 3H), 3.51‐3.36 (m, 2H), 2.10 (s, 3H).

uL, 1.05 mmol, 1.0 equiv) at room temperature. After the NMR (101 MHz, CDCl ) δ 169.64, 159.66, 130.34, 127.69,

completion of reaction, the reaction was diluted with EtOAc 113.88, 74.82, 55.15, 20.94, 7.90. HRMS (ESI) m/z [M] calcd.

13b

1

;

Oily liquid (202 mg, 85%). H NMR (500 MHz,

3

2

3

13

1

(

C

3

+

–1

(

10 mL), quenched with saturated NaHCO

aqueous sodium thiosulfate (2 mL) and extracted with EtOAc 2925, 1724, 1214, 748.

3 X 30 mL). The combined organic layers were washed with

brine solution, dried over anhydrous Na SO

, concentrated in Compound 2g; Oily liquid (203 mg, 99%). H NMR (400 MHz,

vacuo and purified by silica gel column chromatography to CDCl ) δ 7.67‐7.46 (m, 4H), 7.46‐7.38 (m, 5H), 5.92 (dd, J = 7.8,

obtain the desired

‐iodoacetates or 2,5‐diacetoxy‐2,5‐ 5.5 Hz, 1H), 3.50 (dd, J = 10.5, 7.8 Hz, 1H), 3.47 (dd, J = 10.5,

3

3 3

(5 mL), saturated for C11H13IO : 319.99094; found: 319.99236. IR (CHCl , cm ):

(

1

2

4

3

β

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Journal Name

1

3

5

1

C

2

.3 Hz, 1H), 2.14 (s, 3H). C NMR (101 MHz, CDCl

3

) δ 169.71, (m, 2H), 4.23 (dd, J = 11.4, 4.7 Hz, 1H), 2.87 (brs, 1H), 2.01 (s,

1

3

41.57, 140.32, 137.26, 128.74, 127.47, 127.34, 127.01, 3H). C NMR (101 MHz, CDCl

26.79, 74.92, 20.98, 7.60. HRMS (ESI) m/z [M] calcd. for 128.31, 126.45, 75.64, 65.41, 36.24, 20.73. HRMS (ESI) m/z

3

) δ 170.61, 140.15, 128.40,

+

–1

+

16

H

15IO

2

: 366.01167; found: 366.00956. IR (CHCl

3

, cm ): [M] calcd. for C11

H

13IO

3

: 319.99094; found: 319.98895. IR

–

1

923, 1730, 1216, 759.

(CHCl

3

, cm ): 3482, 2924, 1737, 1233, 701.

1

3b

1

Compound 2h

;

Oily liquid (219 mg, 87%). H NMR (400 MHz, Compound 2p; Semi solid (193 mg, 98%). H NMR (400 MHz,

) δ 7.42‐7.28 (m, 5H), 5.95 (d, J = 6.3 Hz, 1H), 4.58 (dd, J =

0.4 Hz, 1H), 3.41 (dd, J = 10.7, 5.1 Hz, 1H), 2.42 (s, 6H), 2.23 (s, 12.2, 6.2 Hz, 1H), 4.51 (dd, J = 11.9, 6.3 Hz, 1H), 4.16 (dd, J =

3 3

CDCl ) δ 6.82 (s, 2H), 6.32 (dd, J = 10.2, 5.1 Hz, 1H), 3.66 (t, J = CDCl

1

3

1

4

13

H), 2.10 (s, 3H). C NMR (126 MHz, CDCl

37.23, 136.20, 131.05, 130.02, 72.80, 20.68, 20.62, 20.37, CDCl

.75. HRMS (ESI) m/z [M + H] calcd. for C13H18IO : 333.03460; 65.48, 30.64, 20.93, 20.75. HRMS (ESI) m/z [M + H] calcd. for

2

found: 333.03702. IR (CHCl

3

) δ 169.41, 137.77, 11.9, 5.8 Hz, 1H), 2.14 (s, 3H), 2.06 (s, 3H). C NMR (75 MHz,

) δ 170.51, 169.53, 137.39, 128.78, 128.42, 127.12, 75.35,

3

+

–

1

+

–1

3

, cm ): 2921, 1741, 1232, 742.

C

13

H

16IO

4

: 363.00878; found: 363.01025. IR (CHCl

3

, cm ):

2

923, 2851, 1744, 1456, 1224, 1116.

1

3b

1

Compound 2i

CDCl

.5 Hz, 1H), 6.04 (dd, J = 8.0, 5.3 Hz, 1H), 3.56 (dd, J = 10.5, 7.9 CDCl

;

Oily liquid (204 mg, 92%). H NMR (500 MHz,

2

1a

1

3

) δ 7.85‐7.81 (m, 4H), 7.52‐.7.46 (m, 2H), 7.42 (dd, J = 8.4, Compound 2s

) δ 7.45‐7.27 (m, 4H), 6.38 (d, J = 3.6 Hz, 1H), 4.48 (ddd, J

Hz, 1H), 3.52 (dd, J = 10.5, 5.1 Hz, 1H), 2.15 (s, 3H). C NMR = 6.8, 4.4, 3.7 Hz, 1H), 3.74 (dd, J = 17.0, 6.7 Hz, 1H), 3.33 (dd, J

;

Oily liquid (199 mg, 75%). H NMR (400 MHz,

1

3

1

3

13

(

101 MHz, CDCl

3

) δ 169.73, 135.61, 133.25, 132.95, 128.59, = 17.0, 4.5 Hz, 1H), 2.10 (s, 3H). C NMR (101 MHz, CDCl

3

) δ

1

28.04, 127.67, 126.44, 125.97, 123.55, 75.28, 21.01, 7.60. 170.34, 142.00, 138.51, 129.55, 127.49, 125.72, 124.69, 85.60,

+

HRMS (ESI) m/z [M + Na] calcd. for C14

H

13INaO

2

: 362.98524; 43.32, 24.17, 20.94. HRMS (ESI) m/z [M] calcd. for C11

H

2

11IO :

–1

found: 362.98401. IR (CHCl

71, 748.

3

, cm ): 2924, 1739, 1229, 1048, 301.98037; found: 301.97852. IR (CHCl

1460, 748.

3

, cm ): 2922, 1729,

7

1

1d

1

Compound 2j

CDCl

;

Semi solid (211 mg, 82%). H NMR (400 MHz, Compound 2t; Oily liquid (229 mg, 94%). H NMR (400 MHz,

3

1

) δ 7.42‐7.18 (m, 5H), 3.81 (m, 2H), 2.13 (s, 7H), 1.96 (s, CDCl

H). C NMR (101 MHz, CDCl

27.64, 124.54, 80.72, 26.10, 21.98, 17.26. HRMS (ESI) m/z 2H), 2.09 (s, 3H). C NMR (101 MHz, CDCl

3

) δ 7.33‐7.15 (m, 4H), 6.20 (d, J = 4.2 Hz, 2H), 4.63‐4.50

3

1

3

) δ 169.33, 141.79, 128.41, (m, 1H), 3.06‐2.96 (m, 1H), 2.94‐2.85 (m, 1H), 2.35‐2.10 (m,

) δ 169.89, 135.77,

: 303.99602; found: 303.99398. IR 131.28, 129.96, 128.77, 128.66, 126.41, 74.47, 28.41, 27.77,

1

3

+

2

[

(

M] calcd. for C11

H

13IO

–

1

+

CHCl

3

, cm ): 2960, 2924, 1733, 1447, 1028, 766, 699.

2

27.69, 21.07. HRMS (ESI) m/z [M] calcd. for C12H13IO :

–

1

3

15.99602; found: 315.99850. IR (CHCl

3

, cm ): 2924, 1697,

1

Compound 2l; Yellow oily liquid (231 mg, 90%). H NMR (500 1449, 737.

3

MHz, CDCl ) δ 7.38‐7.31 (m, 5H), 5.86 (d, J = 5.6 Hz, 1H), 4.53‐

1

3

23b

1

4

.30 (m, 1H), 2.14 (s, 3H), 1.83 (d, J = 7.0 Hz, 3H). C NMR (75 Compound 2u

;

Oily liquid (233 mg, 78%). H NMR (400 MHz,

MHz, CDCl

3

) δ 169.34, 137.38, 128.28, 128.13, 126.82, 79.01, CDCl

3

) δ 4.66 (ddd, J = 7.7, 3.7, 1.1 Hz, 1H), 3.76 (t, J = 1.3 Hz,

1H), 2.59 (d, J = 3.3 Hz, 1H), 2.44 (m, 1H), 2.22‐1.89 (m, 1H),

3

, cm ): 2924, 2854, 2.06 (s, 3H), 1.96 (ddd, J = 13.6, 7.7, 1.4 Hz, 1H), 1.64 (ddd, J =

+

2

3

1

2

8.05, 22.88, 20.82. HRMS (ESI) m/z [M] calcd. for C11H13IO :

03.99219; found: 303.99407. IR (CHCl

742, 1454, 1228, 1020.

–

1

3

18.1, 11.3, 7.8 Hz, 1H), 1.60‐ 1.14 (m, 3H). C NMR (126 MHz,

CDCl ) δ 170.70, 76.90, 47.77, 43.81, 38.61, 27.77, 25.21,

Semi solid (113 mg, 99%). H NMR (500 MHz, 25.00, 21.31. IR (CHCl

3

13c

1

–1

Compound 2m

;

3

, cm ): 2924, 2853, 1742, 1459, 1259,

3

CDCl ) δ 7.50‐7.32 (m, 5H), 6.87 (s, 1H), 6.17 (d, J = 10.8 Hz, 1139.

13

1

H), 4.68 (d, J = 10.8 Hz, 1H), 2.02 (s, 3H). C NMR (101 MHz,

1

CDCl

3

) δ 174.47, 168.93, 136.32, 129.31, 128.52, 128.03, 76.68, Compound 2v; Semi solid (91 mg, 89%). H NMR (400 MHz,

+

2

3

2

1.89, 20.70. HRMS (ESI) m/z [M] calcd. for C11

39.97020; found: 339.96895. IR (CHCl

923, 1731, 1232, 1024, 753, 692.

H

11IO

4

:

CDCl

, cm ): 3460, 3029, 7.4 Hz, 1H), 2.11 (s, 3H). C NMR (126 MHz, CDCl

139.02, 137.24, 136.81, 128.61, 128.10, 128.05, 127.98,

27.55, 127.20, 126.96, 126.44, 80.01, 77.00, 21.09. HRMS

3

) δ 7.70‐7.08 (m, 10H), 5.85 (d, J = 7.4 Hz, 1H), 4.91 (d, J =

–

1

13

3

) δ 170.16,

1

11j

1

+

Compound 2n

CDCl

;

2

Semi solid (94 mg, 87%). H NMR (400 MHz, (ESI) m/z [M] calcd. for C16H15IO : 366.01167; found:

–

1

3

) δ 7.42‐7.34 (m, 5H), 6.14 (d, J = 10.7 Hz, 1H), 4.64 (d, J = 366.00985. IR (CHCl

3

, cm ): 2926, 1731, 1232, 753.

1

3

1

0.7 Hz, 1H), 3.80 (s, 3H), 2.00 (s, 3H). C NMR (101 MHz,

1

CDCl

3

) δ 169.76, 168.61, 136.50, 129.14, 128.40, 127.94, 76.64, Compound 2w; Semi solid (167 mg, 82%). H NMR (400 MHz,

+

5

C

2

3

3.05, 22.39, 20.63. HRMS (ESI) m/z [M + H] calcd. for CDCl ) δ 7.30‐7.02 (m, 5H), 6.16 (d, J = 9.9 Hz, 1H), 5.33 (d, J =

+

–1

13

12

H

14IO

4

: 348.99313; found: 348.99541. IR (CHCl

3 3

, cm ): 9.8 Hz, 1H), 2.18 (s, 3H). C NMR (101 MHz, CDCl ) δ 169.53,

924, 1735, 1734, 1215, 753.

139.56, 136.52, 128.50, 128.35, 128.28, 128.21, 127.10, 79.12,

5.68, 21.26. HRMS (ESI) m/z [M + H] calcd. for C16

+

3

H

16IO

2

:

1

1j

1

–1

Compound 2o

;

Semi solid (375 mg, 81%). H NMR (500 MHz, 367.01895; found: 367.01636. IR (CHCl

3

, cm ): 2923, 1735,

3

CDCl ) δ 7.40‐7.27 (m, 5H), 4.91 (d, J = 5.2 Hz, 1H), 4.63‐4.39 1372, 1233, 1052, 769, 699.

8

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2

5b

1

Compound 2x

CDCl

s, 3H), 2.09 (s, 3H). C NMR (126 MHz, CDCl

69.74, 131.26, 130.86, 101.44, 99.97, 21.04, 20.94. IR (CHCl

;

Oily liquid (498 mg, 90%). H NMR (500 MHz, 1.16 mmol, 1.1 equiv) and PhI(OAc)

2

(374 mg, 1.16 mmol, 1.1

3

) δ 7.00 (s, 1H), 6.77 (s, 1H), 6.26 (s, 1H), 6.23 (s, 1H), 2.12 equiv) in 10 mL CH

3

CN was treated with carboxylic acid (BzOH,

) δ 169.88, 284 mg, 2.32 mmol, 1.1 equiv) at room temperature. The

reaction mixture was stirred at room temperature for 1 h.

cm ): 3107, 2926, 2853, 1749, 1748, 1367, 1230, 1099, 987, After evaporation of solution and dried on vacuum, to ensure

14. the complete removal of acetic acid, the resulting residue were

re‐dissolved in CH CN (2 mL) and treated with 1a (110 mg, 100

Compound 2y; Semi solid (90 mg, 94%). H NMR (500 MHz, uL, 1.05 mmol, 1.0 equiv). After the completion of reaction,

CDCl ) δ 6.97 (d, J = 6.1 Hz, 1H), 6.96 (d, J = 6.1 Hz, 1H), 6.86 adjudged by TLC, the reaction was diluted with EtOAc (10 mL),

d, J = 1.7 Hz, 1H), 6.82 (dd, J = 8.0, 1.8 Hz, 1H), 6.80 (d, J = 1.7 quenched with saturated NaHCO (5 mL), saturated aqueous

Hz, 1H), 6.77 (dd, J = 8.0, 1.8 Hz, 1H), 4.92‐4.74 (m, 1H), 4.44‐ sodium thiosulfate (2 mL) and extracted with EtOAc (3 X 30

13

(

1

3

,

–1

8

3

1

3

(

3

4

3

2

.30 (m, 2H), 4.31‐4.23 (m, 1H), 3.88‐3.80 (m, 1H), 3.83 (s, 3H), mL). The combined organic layers were washed with brine

.83 (s, 3H), 3.35 (dd, J = 10.7, 4.9 Hz, 1H), 3.25‐3.15 (m, 2H), solution, dried over anhydrous Na SO , concentrated in vacuo

.98 (dd, J = 13.8, 6.2 Hz, 1H), 2.94 (dd, J = 13.8, 7.0 Hz, 1H), and purified by silica gel column chromatography to obtain the

2

4

1

3

.31 (s, 6H), 2.10 (s, 3H), 2.08 (s, 3H). C NMR (75 MHz, CDCl

3

)

desired β‐iodocarboxylates (3a‐3i) in good yields..

δ 170.11, 169.92, 168.82, 150.89, 138.58, 137.30, 134.88,

2

6a

1

2

3

2

30.11, 127.33, 122.69, 122.64, 121.41, 120.98, 113.34, Compound 3a

13.01, 72.44, 68.27, 55.77, 43.05, 39.64, 28.96, 20.93, 20.67, MHz, CDCl ) δ 8.18‐8.03 (m, 2H), 7.65‐7.32 (m, 8H), 6.10 (dd, J

= 7.7, 5.1 Hz, 1H), 3.62 (dd, J = 10.6, 7.7 Hz, 1H), 3.58 (dd, J =

;

White solid (278 mg, 74%). H NMR (500

3

+

5

0.54, 7.68. HRMS (ESI) m/z [M + H] calcd. for C14H18IO :

–

1

13

93.01934; found: 393.02212. IR (CHCl

959, 1710, 1220, 1040, 752.

3 3

, cm ): 3396, 3020, 10.6, 5.1 Hz, 1H). C NMR (101 MHz, CDCl ) δ 172.33, 138.78,

133.28, 130.18, 129.82, 129.29, 128.71, 128.45, 126.29, 75.50,

.02. HRMS (ESI) m/z [M + H] calcd. for C15

+

8

H

14IO

2

: 353.00330;

1

1c

1

–1

Compound 2z

;

Oily liquid (239 mg, 82%). H NMR (500 MHz, found: 353.00526. IR (CHCl

3

, cm ): 2926, 2853, 1749, 1367,

CDCl

m, 1H), 4.33 (dd, J = 11.7, 5.9 Hz, 1H), 4.26 (dd, J = 11.6, 6.2

Hz, 1H), 3.33 (dd, J = 10.7, 4.9 Hz, 1H), 3.27 (dd, J = 14.4, 6.5 Compound 3b

Hz, 1H), 3.22‐3.16 (m, 2H), 3.00 (dd, J = 13.8, 6.8 Hz, 1H), 2.95 CDCl

3

) δ 7.38‐7.17 (m, 10H), 4.88 (tt, J = 6.5, 5.0 Hz, 1H), 4.38 1230, 1099, 987, 814.

(

2

6a

1

;

Oily liquid (310 mg, 79%). H NMR (500 MHz,

3

) δ 8.18‐8.11 (m, 2H), 7.68‐7.06 (m, 7H), 6.07 (dd, J = 7.7,

dd, J = 13.8, 6.5 Hz, 1H), 2.10 (s, 3H), 2.06 (s, 3H). C NMR 5.1 Hz, 1H), 3.60 (dd, J = 10.6, 7.7 Hz, 1H), 3.57 (dd, J = 10.6,

13

(

1

3

101 MHz, CDCl

3

) δ 170.13, 169.91, 138.44, 137.34, 136.04, 5.1 Hz, 1H). C NMR (101 MHz, CDCl

3

) δ 167.08, 164.55,

1

6

30.13, 129.29, 128.84, 128.49, 128.47, 126.94, 126.85, 72.74, 164.18, 138.29, 137.32, 132.35, 132.26, 130.11, 128.69,

+

8.29, 43.13, 39.86, 20.95, 20.73, 7.66. HRMS (ESI) m/z [M]

128.65, 127.33, 126.18, 125.86, 115.66, 115.44, 75.54, 7.96.

+

calcd. for C11

cm ): 3482, 2924, 2853, 1737, 1223, 1017, 700.

H

13IO

2

: 303.99602; found: 303.99923. IR (CHCl

3

,

HRMS (ESI) m/z [M ‐ H] calcd. for C15

H

11FIO

2

: 368.97932;

–1

found: 368.98123. IR (CHCl

3

, cm ): 3019, 1709, 1214, 743.

1

Compound 2aa; Oily liquid (388 mg, 78%). H NMR (500 MHz, Compound 3c; White solid (351 mg, 76%). H NMR (500 MHz,

CDCl

H), 4.36 (dd, J = 11.8, 7.0 Hz, 1H), 4.33‐4.25 (m, 1H), 3.89‐3.76 7.47‐7.23 (m, 5H), 7.08 (t, J = 7.7 Hz, 1H), 6.09 (dd, J = 7.9, 5.1

m, 4H), 3.40 (dd, J = 10.5, 6.1 Hz, 1H), 3.32 (dd, J = 10.5, 5.6 Hz, 1H), 3.62 (dd, J = 10.6, 8.2 Hz, 1H), 3.58 (dd, J = 10.6, 5.1

3 3

) δ 4.86 (dd, J = 8.2, 3.1 Hz, 1H), 4.48 (dd, J = 11.8, 5.2 Hz, CDCl ) δ 8.23 (s, 1H), 8.03 (d, J = 7.8 Hz, 1H), 7.70‐7.64 (m, 1H),

1

(

1

3

13

3 3

Hz, 1H), 2.13 (s, 3H), 2.12 (s, 3H). C NMR (101 MHz, CDCl ) δ Hz, 1H). C NMR (101 MHz, CDCl ) δ 163.83, 138.05, 137.30,

1

2

C

3

71.16, 170.96, 69.25, 66.95, 65.44, 64.80, 60.39, 31.02, 21.03, 136.11, 132.58, 131.52, 130.10, 129.95, 128.78, 128.67,

+

0.77, 14.17, 8.82. HRMS (ESI) m/z [M + H] calcd. for 128.30, 127.32, 126.21, 122.43, 75.95, 7.60. HRMS (ESI) m/z

+

–1

+

5

H

13INO

3

: 261.99346; found: 261.98005. IR (CHCl

3 2

, cm ): [M ‐ H] calcd. for C15H11BrIO : 428.89926; found: 428.90112.

–1

394, 2923, 1719, 1227, 1017.

IR (CHCl

3

, cm ): 3021, 2252, 1725, 1252, 750.

1

Compound 2ab; Oily liquid (158 mg, 80%). H NMR (400 MHz, Compound 3d; White solid (318 mg, 71%). H NMR (400 MHz,

CDCl

3

) δ 5.42 (td, J = 7.0, 1.2 Hz, 1H), 4.69 (dd, J = 11.2, 2.3 Hz, CDCl

3

) δ 7.94 (d, J = 8.4 Hz, 1H), 7.49 (d, J = 2.0 Hz, 1H), 7.45‐

1

2

H), 4.59 (d, J = 7.3 Hz, 2H), 2.47‐2.35 (m, 1H), 2.06 (s, 3H), 7.32 (m, 6H), 6.11 (dd, J = 7.8, 5.2 Hz, 1H), 3.62 (dd, J = 10.7,

13

.02 (s, 3H), 2.12‐1.74 (m, 1H), 1.71 (s, 3H), 1.65 (s, 3H), 1.58 7.8 Hz, 1H), 3.58 (dd, J = 10.7, 5.1 Hz, 1H). C NMR (101 MHz,

1

3

(

s, 3H), 1.20 (d, J = 2.9 Hz, 2H). C NMR (101 MHz, CDCl

3

) δ CDCl

3

) δ 163.31, 138.72, 137.89, 135.25, 132.84, 131.14,

1

6

71.04, 170.15, 140.83, 140.20, 119.68, 119.06, 83.01, 80.40, 128.94, 128.77, 127.59, 127.08, 126.47, 76.68, 7.35. HRMS

+

2 2

1.14, 45.48, 39.58, 32.83, 25.88, 23.19, 22.29, 21.01, 16.43. (ESI) m/z [M] calcd. for C15H11Cl IO : 419.91808; found:

+

–1

HRMS (ESI) m/z [M] calcd. for C14

3

1

H

23IO

4

: 382.06410; found: 419.92013. IR (CHCl

3

, cm ): 2923, 1701, 1583, 1239, 697.

–1

82.06621. IR (CHCl

024.

3

, cm ): 2926, 2855, 1739, 1370, 1235,

1

Compound 3e; White solid (365 mg, 78%). H NMR (400 MHz,

CDCl

3

) δ 7.46‐7.32 (m, 7H), 6.04 (dd, J = 7.6, 5.2 Hz, 1H), 3.93

Representative procedure for the synthesis of 1,2‐ (s, 6H), 3.92 (s, 3H), 3.63 (dd, J = 10.6, 7.7 Hz, 1H , 3.61 (dd, J =

1

3

3 3

iodocarboxylates; An equimolar mixture of Me SI (237 mg, 10.6, 5.1 Hz, 1H). C NMR (101 MHz, CDCl ) δ 170.91, 164.98,

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J. Name., 2013, 00, 1‐3 | 9

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Organic & Biomolecular Chemistry

Page 10 of 15

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DOI: 10.1039/C6OB01179A

ARTICLE

Journal Name

1

52.93, 138.49, 128.73, 126.19, 124.64, 124.06, 107.37, column chromatography to obtain the desired β‐iodohydrins

+

07.13, 75.56, 60.91, 56.26, 8.19. HRMS (ESI) m/z [M] calcd.

(4a‐4k) or β‐iodoethers (5a‐5k).

+

–1

5 3

for C18H19IO : 442.02772; found: 442.02442. IR (CHCl , cm ):

11j

1

2

939, 1688, 1415, 1126, 763.

Compound 4a

CDCl ) δ 7.38‐7.29 (m, 5H), 4.8 (m, 1H), 3.49 (dd, J = 10.3, 3.6

Compound 3f; Semi solid (337 mg, 83%). H NMR (400 MHz, Hz, 1H), 3.40 (dd, J = 10.3, 8.8 Hz, 1H), 2.53 (s, 1H). C NMR

;

Oily liquid (226 mg, 86%). H NMR (500 MHz,

3

1

13

CDCl

6

2

3

) δ 7.42‐7.21 (m, 7H), 6.99 (dd, J = 10.6, 4.1 Hz, 1H), 6.92‐ (126 MHz, CDCl

.86 (m, 2H), 6.00 (dd, J = 7.9, 5.4 Hz, 1H), 4.70 (q, J = 16.3 Hz, 15.33. HRMS (ESI) m/z [M + NH

H), 3.49 (dd, J = 10.6, 7.9 Hz, 1H , 3.46 (dd, J = 10.6, 5.2 Hz, 266.00363; found: 266.01974. IR (CHCl

3

) δ 141.08, 128.67, 128.35, 125.71, 74.02,

+

4

]

calcd. for C

8

H

13INO :

–

1

3

, cm ): 3361, 2925,

1

3

1

H). C NMR (101 MHz, CDCl

3

) δ 167.70, 157.49, 137.53, 1721, 1451, 771.

1

7

29.41, 128.81, 128.59, 126.27, 121.61, 114.52, 75.89, 65.01,

+

11j

1

.08. HRMS (ESI) m/z [M] calcd. for C16

H

15IO

3

: 382.00659; Compound 4b

;

White solid (290 mg, 81%). H NMR (500

–

1

found: 382.02923. IR (CHCl

3

, cm ): 2925, 1735, 1162, 698.

MHz, CDCl

3

) δ 7.37‐7.33 (m, 2H), 7.33‐.29 (m, 2H), 4.80 (dd, J =

8

.6, 3.6 Hz, 1H), 3.47 (dd, J = 10.4, 3.7 Hz, 1H), 3.36 (dd, J =

1

13

Compound 3g; Semi solid (275 mg, 72%). H NMR (500 MHz, 10.3, 8.7 Hz, 1H), 2.53 (s, 1H). C NMR (101 MHz, CDCl

3

) δ

3

CDCl ) δ 7.40‐.29 (m, 51H), 5.85 (t, J = 6.5 Hz, 1H), 3.46 (d, J = 139.52, 134.05, 128.83, 127.12, 73.25, 15.03. HRMS (ESI) m/z

+

6

1

2

C

2

.5 Hz, 2H), 2.43‐2.33 (m, 1H), 2.05‐1.96 (m, 1H), 1.94‐1.90 (m, [M + 2H] calcd. for C

8

H

10ClIO : 283.94539; found: 283.94752.

–1

H), 1.83‐1.72 (m, 2H), 1.69‐1.60 (m, 1H), 1.55‐1.43 (m, 2H), IR (CHCl

3

, cm ): 3357, 2926, 1492, 1370, 1229, 823.

13

.33‐1.11 (m, 4H). C NMR (75 MHz, CDCl

3

) δ 174.57, 138.72,

1

3g

1

37.42, 130.18, 128.61, 128.53, 126.17, 74.44, 43.15, 29.06, Compound 4c

;

Oily liquid (348 mg, 80%). H NMR (400 MHz,

) δ 7.38 (d, J = 8.3 Hz, 2H), 7.29 (d, J = 8.3 Hz, 2H), 4.80 (d,

3

, cm ): J = 6.7 Hz, 1H), 3.46 (dd, J = 10.3, 3.6 Hz, 1H), 3.41‐3.34 (m,

+

8.83, 25.70, 25.39, 25.32, 8.12. HRMS (ESI) m/z [M] calcd. for CDCl

3

+

–1

15

H

19IO

2

: 358.04297; found: 358.04512. IR (CHCl

1

3

926, 1735, 1162, 699.

1H), 2.54 (s, 1H), 1.31 (s, 9H). C NMR (101 MHz, CDCl

3

) δ

1

51.32, 138.08, 125.54, 125.42, 125.28, 73.88, 34.55, 31.26,

1

+

Compound 3h; White solid (493 mg, 86%). H NMR (400 MHz, 15.21. HRMS (ESI) m/z [M + H] calcd. for C12H18IO :

–

1

CDCl

3

) δ 7.75 (d, J = 7.6 Hz, 2H), 7.57 (d, J = 7.4 Hz, 2H), 7.42‐ 305.03968; found: 305.04122. IR (CHCl

3

, cm ): 3352, 2959,

7

1

.25 (m, 9H), 5.92 (dd, J = 7.0, 5.9 Hz, 1H), 5.30 (t, J = 5.9 Hz, 1510, 1410, 1214, 1084, 832, 755.

H), 4.38 (d, J = 7.0 Hz, 2H), 4.19 (t, J = 6.9 Hz, 1H), 3.53‐3.44

13

1

(

m, 4H), 2.74‐2.55 (m, 1H). C NMR (126 MHz, CDCl

3

) δ Compound 4d; White solid (314 mg, 87%). H NMR (400 MHz,

1

3

71.06, 156.26, 143.87, 141.28, 138.14, 128.91, 128.81, CDCl

3

) δ 7.62‐7.55 (m, 4H), 7.46‐7.42 (m, 4H), 7.36 (t, J = 7.7

27.65, 127.02, 126.27, 125.02, 119.95, 75.64, 66.72, 47.20, Hz, 1H), 4.89 (dd, J = 8.6, 3.1 Hz, 1H), 3.54 (dd, J = 10.3, 2.8 Hz,

+

13

6.53, 34.64, 7.60. MS (ESI) m/z: 542 ([M + H] , 100). IR (CHCl

3

,

1H), 3.44 (dd, J = 10.1, 8.9 Hz, 1H), 2.51 (s, 1H). C NMR (126

MHz, CDCl ) δ 141.30, 140.54, 140.01, 128.80, 127.46, 127.42,

27.06, 126.18, 73.83, 15.30. HRMS (ESI) m/z [M + H] calcd.

–1

cm ): 2923, 2853, 1742, 1626, 1459, 1262, 1163.

3

+

1

2

6a

1

+

–1

Compound 3i

CDCl ) δ 7.76 (m, 2H), 7.67‐7.56 (m, 2H), 7.45‐7.28 (m, 9H), 3020, 2924, 2853, 1722, 1257, 742.

.92‐5.86 (m, 1H), 5.16 (d, J = 7.2 Hz, 1H), 4.54‐4.45 (m, 1H),

.40 (dd, J = 12.4, 5.2 Hz, 2H), 4.22 (dd, J = 12.9, 6.6 Hz, 1H), Compound 4e; White solid (318 mg, 82%). H NMR (400 MHz,

.54‐3.39 (m, 2H), 1.68‐1.52 (m, 2H), 0.99 (d, J = 6.2 Hz, 3H), CDCl ) δ 7.85‐7.71 (m 4H), 7.49‐7.41 (m, 3H), 4.96 (m, 1H), 3.54

.92 (d, J = 6.2 Hz, 3H), 0.96‐0.81 (m, 1H). MS (ESI) m/z: 584 (dd, J = 10.3, 3.7 Hz, 1H), 3.48‐3.40 (m, 1H), 2.67 (s, 1H).

;

3

White solid (270 mg, 96%). H NMR (400 MHz, for C14H14IO : 325.00838; found: 325.011024. IR (CHCl , cm ):

3

5

4

3

0

1

3

13

C

+

(

[M + H] , 10), 606 ([M + Na] , 100). HRMS (ESI) m/z [M] calcd. NMR (101 MHz, CDCl

3

) δ 138.41, 133.19, 133.16, 128.53,

+

–1

for C15

2

H

19IO

2

: 358.04297; found: 358.04008. IR (CHCl

3

, cm ): 128.01, 127.71, 126.38, 126.22, 124.87, 123.36, 74.09, 15.15.

+

957, 1711, 1217, 736.

HRMS (ESI) m/z [M] calcd. for C12H11IO : 297.98456; found:

–1

2

97.98853. IR (CHCl

Representative procedure for the synthesis of 1,2‐ 1017, 747.

iodohydrins and iodoethers; A preformed solution of Me SI

(374 mg, 1.16 Compound 4f

3

, cm ): 3396, 2923, 2852, 1722, 1214,

3

13e

1

(

237 mg, 1.16 mmol, 1.1 equiv) and PhI(OAc)

2

;

Oily liquid (391 mg, 80%). H NMR (400 MHz,

mmol, 1.1 equiv) in

1

3

mL solvent (Method a; 1:1 CDCl ) δ 7.51‐7.42 (m, 2H), 7.35 (t, J = 7.2 Hz, 2H), 7.29 (t, J =

acetonitrile:water, Method b; methanol) was treated with 7.2 Hz, 1H), 3.61 (d, J = 7.4 Hz, 2H), 2.40 (s, 1H), 1.71 (s, 3H).

1

3

alkene

1

(

1a, 110 mg, 100 uL, 1.05 mmol, 1.0 equiv) at room

3

C NMR (101 MHz, CDCl ) δ 144.17, 128.35, 127.40, 124.66,

+

temperature. After the completion of reaction, the reaction 72.59, 28.92, 24.16. HRMS (ESI) m/z [M + 2H] calcd. for

+

–1

was diluted with EtOAc (10 mL), quenched with saturated

9 3

C H13IO : 263.99273; found: 263.97831. IR (CHCl , cm ): 3076,

NaHCO (5 mL), saturated aqueous sodium thiosulfate (2 mL) 2920, 2851, 1733, 1462, 1215, 1065, 757.

3

and extracted with EtOAc (3 X 30 mL). The combined organic

layers were washed with brine solution, dried over anhydrous Compound 4g

1

3a

1

;

Oily liquid (304 mg, 90%). H NMR (500 MHz,

2 4 3

Na SO , concentrated in vacuo and purified by silica gel CDCl ) δ 7.44 (d, J = 7.7 Hz, 4H), 7.33 (d, J = 7.4 Hz, 3H), 7.27 (m

1

3

2

3

H), 4.01 (s, 2H), 2.88 (s, 1H). C NMR (126 MHz, CDCl ) δ

1

0 | J. Name., 2012, 00, 1‐3

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DOI: 10.1039/C6OB01179A

ARTICLE

1

1j

1

43.35, 128.32, 127.61, 126.10, 76.58, 22.36. HRMS (ESI) m/z Compound 5c

;

Oily liquid (402 mg, 88%). H NMR (400 MHz,

+

[

M

+

Na] calcd. for _–

14 3

C H13INaO : 346.99033; found: CDCl ) δ 7.40‐7.35 (m, 2H), 7.28‐7.22 (m, 2H), 4.28 (dd, J = 8.1,

, cm ): 3439, 2923, 2857, 1624, 1488, 4.8 Hz, 1H), 3.37‐3.28 (m, 2H), 3.30 (s, 3H), 1.32 (s, 9H).

NMR (101 MHz, CDCl

3.41, 57.29, 34.61, 31.30, 10.64. HRMS (ESI) m/z [M] calcd.

3

Oily liquid (371 mg, 82%). H NMR (400 MHz, for C13H19IO : 318.04806; found: 318.04584. IR (CHCl , cm ):

1

13

3

1

46.99330. IR (CHCl

3

C

157, 1059, 754, 698

3

) δ 151.39, 136.65, 126.16, 125.57,

+

8

1

1j

1

+

–1

Compound 4h

;

CDCl

3

) δ 7.45‐7.39 (m, 1H), 7.33‐7.20 (m, 3H), 5.40 (m, 1H), 2960, 1461, 1222, 1104, 1083, 953, 832, 735, 604.

4

8

1

.21 (m, 1H), 3.60 (dd, J = 16.2, 7.3 Hz, 1H), 3.31 (dd, J = 16.2,

13

1

.0 Hz, 1H), 2.37 (s, 1H). C NMR (101 MHz, CDCl

3

) δ 142.05, Compound 5d; Semi solid (338 mg, 90%). H NMR (400 MHz,

) δ 7.61‐7.56 (m, 4H), 7.43 (t, J = 7.5 Hz, 2H), 7.38‐7.30

11IO : 261.98436; (m, 3H), 4.33 (dd, J = 7.8, 5.0 Hz, 1H), 3.40‐3.31 (m, 2H), 3.33

40.95, 128.78, 127.50, 124.31, 123.82, 85.02, 42.29, 30.08. CDCl

3

+

HRMS (ESI) m/z [M + 2H] calcd. for C

9

H

–1

13

found: 261.98706. IR (CHCl

214, 752.

3 3

, cm ): 3015, 2922, 2852, 1735, (s, 3H). C NMR (101 MHz, CDCl ) δ 141.18, 140.42, 138.62,

1

128.70, 127.34, 127.28, 126.94, 126.87, 83.16, 57.24, 10.34.

+

HRMS (ESI) m/z [M] calcd. for C15

H

15IO : 338.01676; found:

, cm ): 2927, 2821, 1485, 1221, 1102,

2

3b

1

–1

Compound 4i

CDCl ) δ 3.88‐3.80 (m, 1H), 3.73 (s, 1H), 2.52 (d, J = 3.4 Hz, 1H), 1079, 836, 763, 734, 696.

.45 (s, 1H), 2.04 (d, J = 6.8 Hz, 2H), 1.64‐.54 (m, 2H), 1.28‐1.18

;

Oily liquid (402 mg, 79%). H NMR (400 MHz, 338.01513. IR (CHCl

3

2

1

3

1

(

m, 1H), 1.06‐0.98 (m, 1H). C NMR (101 MHz, CDCl

3

) δ 76.58, Compound 5e; White solid (345 mg, 85%). H NMR (500 MHz,

+

4

9.94, 44.02, 42.65, 30.27, 25.71, 24.91. HRMS (ESI) m/z [M]

CDCl

(dd, J = 7.5, 4.6 Hz, 1H), 3.48‐3.35 (m, 2H), 3.32 (s, 3H).

NMR (101 MHz, CDCl ) δ 137.07, 133.33, 133.12, 128.62,

3

) δ 7.91‐7.78 (m, 3H), 7.76 (s, 3H), 7.53‐7.36 (m, 3H), 4.44

+

13

calcd. for C

cm ): 3395, 2961, 1728, 1723, 1219, 1087.

7

H

11IO : 238.99273; found: 238.99006. IR (CHCl

3

,

C

–1

3

1

27.88, 127.73, 126.33, 126.19, 126.11, 123.71, 83.66, 57.33,

1

3a

1

+

Compound 4j

CDCl ) δ 4.04 (ddd, J = 12.3, 9.7, 4.3 Hz, 1H), 3.66 (m, 1H), 2.48 313.00838; found: 313.00577. IR (CHCl

ddd, J = 13.4, 3.9, 1.9 Hz, 1H), 2.31 (s, 1H), 2.12 (ddd, J = 11.3, 1409, 1219, 1103, 1081, 817, 764, 663.

;

Oily liquid (528 mg, 77%). H NMR (400 MHz, 10.18. HRMS (ESI) m/z [M + H] calcd. for C13

H

14IO :

–

1

3

, cm ): 2929, 1507,

(

5

.7, 3.0 Hz, 1H), 2.08‐2.00 (m, 1H), 1.90‐1.78 (m, 1H), 1.57‐1.20

1

3

13d

1

(

m, 4H). C NMR (126 MHz, CDCl

3

) δ 76.00, 43.46, 38.61, Compound 5f

;

Oily liquid (458 mg, 89%). H NMR (500 MHz,

+

3

C

2

3

3.65, 27.98, 24.44. HRMS (ESI) m/z [M + H] calcd. for CDCl ) δ 7.54‐7.20 (m, 5H), 3.50 (d, J = 10.5 Hz, 1H), 3.43 (d, J =

+

–1

13

6

H

12IO : 226.99273; found: 226.95060. IR (CHCl

3

, cm ): 3382, 10.5 Hz, 1H), 3.13 (s, 3H), 1.70 (s, 3H). C NMR (101 MHz,

926, 2855, 1728, 1214, 749.

CDCl

1

3

) δ 141.25, 128.33, 127.59, 126.13, 76.77, 51.12, 23.82,

9.65. HRMS (ESI) m/z [M + H] calcd. for C10

+

H

14IO :

1

3f

1

–1

Compound 4k

;

Oily liquid (471 mg, 80%). H NMR (500 MHz, 277.00838; found: 277.00658. IR (CHCl

3

, cm ): 2926, 2853,

3

CDCl ) δ 4.91 (d, J = 7.1 Hz, 1H), 4.42 (m, 1H), 4.21 (s, 1H), 4.13‐ 1486, 1214, 1039, 740.

4

2

1

.03 (m, 1H), 4.01 (ddd, J = 10.6, 7.1, 4.4 Hz, 1H), 3.72‐3.56 (m,

H), 3.46 (s, 1H), 2.47 (dd, J = 13.8, 3.7 Hz, 1H), 2.42‐2.31 (m, Compound 5g

13d

1

;

White solid (332 mg, 92%). H NMR (400

3

H), 2.18‐2.07 (m, 2H), 1.92‐1.83 (m, 1H), 1.72‐1.65 (m, 2H), MHz, CDCl ) δ 7.37 (d, J = 7.9 Hz, 3H), 7.30 (t, J = 7.5 Hz, 3H),

13

.61 (ddd, J = 12.0, 9.7, 8.2 Hz, 2H), 1.34‐1.21 (m, 1H). C NMR 7.27‐7.21 (m, 2H), 4.12 (s, 2H), 3.13 (s, 3H). C NMR (101 MHz,

) δ 98.17, 93.11, 65.39, 63.53, 36.37, 34.60, CDCl ) δ 142.82, 128.03, 127.26, 127.00, 80.62, 50.36, 15.84.

(

101 MHz, CDCl

3

+

3

C

2

1.34, 30.71, 27.08, 24.29. HRMS (ESI) m/z [M + H] calcd. for HRMS (ESI) m/z [M + H] calcd. for C15

10IO : 228.97200; found: 228.97098. IR (CHCl

H

16IO : 339.02403;

+

–1

5

H

3

, cm ): 3392, found: 339.02701. IR (CHCl

3

, cm ): 2923, 2854, 1492, 1466,

924, 2852, 1723, 1214, 1065, 951, 750.

1075, 698.

1

1j

1

11j

1

Compound 5a

;

Oily liquid (255 mg, 92%). H NMR (500 MHz, Compound 5h

;

Oily liquid (371 mg, 78%). H NMR (400 MHz,

CDCl

3

) δ 7.41‐7.28 (m, 5H), 4.29 (dd, J = 7.9, 4.8 Hz, 1H), 3.38‐ CDCl

3

) δ 7.42 (d, J = 7.1 Hz, 1H), 7.32‐7.22 (m, 3H), 5.09 (d, J =

1

3

1

.31 (m, 2H), 3.30 (s, 3H). C NMR (126 MHz, CDCl

28.62, 128.36, 126.48, 83.50, 57.24, 10.40. HRMS (ESI) m/z 3.58 (s, 3H), 3.29 (dd, J = 17.0, 4.6 Hz, 1H). C NMR (101 MHz,

3

) δ 139.69, 3.5 Hz, 1H), 4.54‐.44 (m, 1H), 3.74 (dd, J = 17.0, 6.8 Hz, 1H),

13

+

[

(

M] calcd. for C

CHCl

97.

9

H

11IO : 261.98456; found: 261.98612. IR CDCl

3

) δ 141.34, 140.09, 129.08, 127.11, 125.15, 124.70, 93.30,

–

1

+

3

, cm ): 2931, 2822, 1451, 1272, 1106, 1064, 951, 762, 57.58, 43.50, 25.59. HRMS (ESI) m/z [M + H] calcd. for

+

–1

6

C

10

H

12IO : 274.99273; found: 274.99423. IR (CHCl

3

, cm ):

2

897, 1460, 1212, 1074, 743.

1

1j

1

Compound 5b

CDCl ) δ 7.36‐7.32 (m, 2H), 7.28‐7.24 (m, 2H), 4.26 (dd, J = 7.5, Compound 5i

.1 Hz, 2H), 3.36‐3.27 (m, 2H), 3.30 (s, 2H). C NMR (126 MHz, CDCl

CDCl ) δ 138.25, 134.14, 128.87, 127.92, 82.77, 57.32, 9.93. 2.61 (d, J = 1.6 Hz, 1H), 2.40 (m, 1H), 2.08 (dd, J = 11.7, 7.3 Hz,

HRMS (ESI) m/z [M + 2H] calcd. for C

;

Oily liquid (321 mg, 86%). H NMR (400 MHz,

2

3a

1

3

;

Oily liquid (421 mg, 78%). H NMR (400 MHz,

1

3

5

3

) δ 3.72 (d, J = 1.0 Hz, 1H), 3.48‐.38 (m, 1H), 3.30 (s, 3H),

3

+

9

H12ClIO : 297.96104; 1H), 1.82 (dd, J = 13.2, 7.4 Hz, 1H), 1.64‐1.57 (m, 2H), 1.22 (dd,

–1

13

found: 297.95914. IR (CHCl

172, 1088, 823, 750, 723.

3 3

, cm ): 2931, 2823, 1488, 1216, J = 18.8, 10.4 Hz, 1H), 0.98 (m 1H). C NMR (126 MHz, CDCl ) δ

1

84.56, 56.11, 45.52, 43.58, 38.77, 27.67, 25.53, 25.51. HRMS

J. Name., 2013, 00, 1‐3 | 11

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Organic & Biomolecular Chemistry

Page 12 of 15

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DOI: 10.1039/C6OB01179A

ARTICLE

Journal Name

+

–1

(

2

1

ESI) m/z [M + H] calcd. for C

8

H

14IO : 253.00838; found: 219.10078; found: 219.10156. IR (CHCl

3

, cm ): 3021, 2101,

–1

53.01005. IR (CHCl

044, 745.

3

, cm ): 3022, 2985, 1373, 1242, 1217, 1744, 1219, 1037, 746.

1

Compound 6d; Oily liquid (307 mg, 82%). H NMR (400 MHz,

11j

1

Compound 5j

;

3

Oily liquid (545 mg, 875%). H NMR (400 MHz, CDCl ) δ 7.42‐7.36 (m, 2H), 7.29‐7.25 (m 2H), 5.91 (dd, J = 8.3,

3

CDCl ) δ 4.07 (ddd, J = 10.6, 8.7, 4.2 Hz, 1H), 3.41 (s, 3H), 3.9 Hz, 1H), 3.63 (dd, J = 13.1, 8.3 Hz, 1H), 3.42 (dd, J = 13.1,

1

3

2

(

.44.3.36 (m, 1H), 3.29‐3.22 (m, 1H), 2.46‐2.33 (m, 1H), 2.25‐ 3.9 Hz, 1H), 2.13 (s, 3H), 1.31 (s, 9H). C NMR (101 MHz,

.12 (m, 1H), 1.97 (dtd, J = 14.7, 10.9, 3.9 Hz, 1H), 1.87‐1.74 CDCl ) δ 169.92, 151.74, 134.02, 126.18, 125.64, 74.43, 55.06,

3

1

3

+

m, 1H), 1.59‐1.50 (m, 1H), 1.44‐1.22 (m, 2H). C NMR (126 34.59, 31.24, 21.08. HRMS (ESI) m/z [M] calcd. for

+

–1

MHz, CDCl

3

) δ 83.86, 56.77, 37.73, 35.28, 30.22, 27.07, 23.49.

C

14

H

19

N

3

O

2

: 261.14773; found: 261.14701. IR (CHCl

3

, cm ):

+

HRMS (ESI) m/z [M] calcd. for C H13IO : 240.00111; found: 2961, 2099, 1747, 1223, 1041, 830.

2

9

7

–1

40.00298. IR (CHCl

27, 752.

3

, cm ): 2931, 2857, 1446, 1109, 1082,

1

Compound 6e; Oily liquid (153 mg, 98%). H NMR (500 MHz,

CDCl ) δ 7.60‐7.56 (m, 4H), 7.47‐7.41 m, 4H), 7.38‐7.32 (m,

Oily liquid (509 mg, 82%). H NMR (400 MHz, 1H), 5.96 (dd, J = 8.0, 3.8 Hz, 1H), 3.67 (dd, J = 13.1, 8.2 Hz, 1H),

3

1

3f

1

Compound 5k

CDCl

;

1

3

) δ 4.54 (d, J = 5.5 Hz, 1H), 4.07 (ddd, J = 8.3, 5.3, 4.5 Hz, 3.47 (dd, J = 13.1, 3.9 Hz, 1H), 2.16 (s, 3H). C NMR (126 MHz,

1

3

1

H), 4.02‐3.93 (m, 1H), 3.59 (ddd, J = 11.3, 7.7, 3.5 Hz, 1H), CDCl ) δ 169.87, 141.69, 140.40, 136.01, 128.91, 128.87,

.45 (s, 3H), 2.36 (ddd, J = 14.6, 7.3, 3.7 Hz, 1H), 2.11‐1.95 (m, 128.78, 127.52, 127.46, 127.23, 127.18, 127.08, 126.87, 74.39,

3

1

3

+

H), 1.82‐1.69 (m, 1H), 1.65‐1.52 (m, 1H). C NMR (126 MHz, 55.03, 21.05. HRMS (ESI) m/z [M

+

Na] calcd. for

+

–1

CDCl

3

) δ 103.50, 63.40, 55.71, 32.72, 28.94, 25.55. HRMS (ESI)

C

16

H

15

N

3

O

2

Na : 304.10565; found: 304.10335. IR (CHCl

12IO : 242.98765; found: 242.98498. 2924, 2096, 1742, 1219, 1037, 813.

3

, cm ): 2922, 2852, 1461, 1214, 1037, 752.

3

, cm ):

+

m/z [M + H] calcd. for C

IR (CHCl

6

H

–1

1

Compound 6f; Oily liquid (301 mg, 80%). H NMR (500 MHz,

‐azido CDCl ) δ 6.83 (s, 2H), 6.30 (dd, J = 9.8, 4.3 Hz, 1H), 3.89 (dd, J =

β‐iodo 13.2, 9.8 Hz, 1H), 3.29 (dd, J = 13.2, 4.3 Hz, 1H), 2.43 (s, 6H),

Representative procedure for the synthesis of

derivatives; Following the general procedure for

preparation using Me

PhI(OAc) (374 mg, 1.16 mmol, 1.1 equiv) and alkene (1a, 110 138.11, 136.57, 130.19, 129.79, 72.22, 52.51, 20.85, 20.76,

mg, 100 uL, 1.05 mmol, 1.0 equiv) and usual work, the 20.51. HRMS (ESI) m/z [M + H] calcd. for C13

β

3

1

3

3 3

SI (237 mg, 1.16 mmol, 1.1 equiv), 2.24 (s, 3H), 2.10 (s, 3H). C NMR (101 MHz, CDCl ) δ 169.81,

2

+

18 3 2

H N O :

–

1

resulting residues were treated with NaN

3

(104 mg, 1.58 248.13935; found: 248.13679. IR (CHCl

3

, cm ): 2924, 2098,

mmol, 1.5 equiv) in DMF (5 mL) and stirred at 60 °C till the 1743, 1229, 1023, 852.

completion of reaction. Following the usual workup and

2

9b

1

purification by silica gel column chromatography afforded the Compound 6g

corresponding ‐azides (6‐8) in good yields. CDCl

.7 Hz, 1H), 6.08 (dd, J = 8.2, 3.9 Hz, 1H), 3.72 (dd, J = 13.2, 8.2

;

Oily liquid (273 mg, 82%). H NMR (500 MHz,

β

3

) δ 7.91‐7.79 (m, 4H), 7.52‐7.47 (m, 2H), 7.44 (dd, J = 8.4,

1

2

9a

1

13

Compound 6a

CDCl ) δ 7.44‐7.29 (m, 5H), 5.92 (dd, J = 8.2, 3.9 Hz, 1H), 3.62 (101 MHz, CDCl

dd, J = 13.1, 8.2 Hz, 1H), 3.43 (dd, J = 13.1, 3.9 Hz, 1H), 2.14 (s, 128.02, 127.70, 126.49, 125.90, 123.75, 74.73, 55.04, 21.07.

;

Oily liquid (189 mg, 87%). H NMR (400 MHz, Hz, 1H), 3.51 (dd, J = 13.2, 4.0 Hz, 1H), 2.17 (s, 3H). C NMR

3

) δ 169.88, 134.41, 133.30, 133.05, 128.65,

(

1

3

+

3

1

C

2

H). C NMR (101 MHz, CDCl

3 13 3 2

) δ 169.78, 137.06, 128.68, HRMS (ESI) m/z [M] calcd. for C14H N O : 255.10078; found:

26.36, 74.52, 55.05, 20.98. HRMS (ESI) m/z [M] calcd. for 255.09831. IR (CHCl

+

–1

3

, cm ): 3020, 2098, 1742, 1221, 1038,

+

–1

10

H

11

N

3

O

2

: 205.08513; found: 205.08288. IR (CHCl

926, 2103, 1740, 1226, 1038, 754.

3

, cm ): 745.

2

9a

1

Compound 7a

Oily liquid (211 mg, 94%). H NMR (500 MHz, CDCl

;

Oily liquid (56 mg, 85%). H NMR (400 MHz,

) δ 7.48‐7.29 (m, 5H), 4.88 (dd, J = 7.9, 4.1 Hz, 1H), 3.48

2

9a

1

Compound 6b

;

3

CDCl ) δ 7.39‐7.32 (m, 2H), 7.32‐7.26 (m, 2H), 5.87 (dd, J = 7.9, (dd, J = 12.6, 7.9 Hz, 1H), 3.44 (dd, J = 12.6, 4.1 Hz, 1H), 2.39 (s,

1

3

4

1

3

.1 Hz, 1H), 3.60 (dd, J = 13.1, 7.9 Hz, 1H), 3.42 (dd, J = 13.1, 1H). C NMR (101 MHz, CDCl ) δ 140.51, 128.69, 128.36,

13

+

.1 Hz, 1H), 2.14 (s, 3H). C NMR (126 MHz, CDCl

3

) δ 169.65, 125.88, 73.44, 58.09. HRMS (ESI) m/z [M] calcd. for

+

–1

35.58, 134.52, 128.89, 128.79, 127.80, 73.82, 54.81, 20.90.

C

8

H

10

N

3

O : 164.08184; found: 164.07989. IR (CHCl

3

, cm ):

+

HRMS (ESI) m/z [M] calcd. for C10

H

10ClN

3

O

2

: 239.04623; 3432, 2923, 2853, 2100, 1258, 1062, 757, 699.

–1

found: 239.04453. IR (CHCl

040, 747.

3

, cm ): 2924, 2101, 1743, 1223,

2

9c

1

Compound 8a

;

Oily liquid (170 mg, 90%). H NMR (500 MHz,

CDCl ) δ 7.46‐7.29 (m, 5H), 4.36 (dd, J = 8.5, 3.6 Hz, 2H), 3.49

3

2

9a

1

Compound 6c

;

Oily liquid (232 mg, 96%). H NMR (400 MHz, (dd, J = 13.0, 8.5 Hz, 1H), 3.31 (s, 3H), 3.21 (dd, J = 13.0, 3.6 Hz,

1

3

CDCl

3

) δ 7.27‐7.21 (m, 2H), 7.17 (d, J = 8.0 Hz, 2H), 5.88 (dd, J = 1H). C NMR (126 MHz, CDCl

3

) δ 138.37, 128.70, 128.41,

+

8

1

.2, 4.0 Hz, 1H), 3.61 (dd, J = 13.1, 8.2 Hz, 1H), 3.40 (dd, J = 126.66, 83.16, 56.93, 56.60. HRMS (ESI) m/z [M] calcd. for

13

+

–1

3.1, 4.0 Hz, 1H), 2.34 (s, 3H), 2.12 (s, 3H). C NMR (126 MHz,

9 11 3 3

C H N O : 177.09021; found: 177.08798. IR (CHCl , cm ):

CDCl

13 3 2

1.08, 20.98. HRMS (ESI) m/z [M] calcd. for C11H N O :

3

) δ 169.78, 138.51, 134.09, 129.33, 126.34, 74.42, 54.99, 2922, 2853, 2101, 1218, 1120, 746.

+

2

1

2 | J. Name., 2012, 00, 1‐3

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Page 13 of 15

Journal Name

Orga Pn l iec a s& e Bd oi o nmo ot al ed cj uu sl ta mr Ca rhg ei nms istry

View Article Online

DOI: 10.1039/C6OB01179A

ARTICLE

2

9c

1

Compound 8b

CDCl

.7 Hz, 1H), 3.45 (dd, J = 13.0, 8.2 Hz, 1H), 3.30 (s, 3H), 3.19 temperature for 8 h. Following the usual workup and

;

Oily liquid (224 mg, 85%). H NMR (400 MHz, (152 mg, 1.27 mmol, 1.2 equiv) and DBU (320 mg/315uL, 2.1

3

) δ 7.41‐7.31 (m, 2H), 7.32‐7.22 (m, 2H), 4.34 (dd, J = 8.2, mmol, 1.5 equiv) in DMSO (2 mL) and stirred at room

3

1

3

(

1

(

2

dd, J = 13.0, 3.7 Hz, 1H). C NMR (126 MHz, CDCl

3

) δ 137.08, purification by silica gel column chromatography afforded 9 in

1

34.14, 128.87, 127.99, 127.89, 82.46, 56.94, 56.34. HRMS 82% yield over 2 steps. Semi solid (80 mg, 82%). H NMR (400

+

ESI) m/z [M] calcd. for C

9

H

10ClN

3

O : 211.05124; found: MHz, CDCl

, cm ): 2930, 2095, 1279, 1106, 821.

3

) δ 7.87 (d, J = 3.0 Hz, 1H), 7.85 (d, J = 3.0 Hz, 1H),

7.50‐7.31 (m, 7H), 6.50 (dd, J = 9.5, 3.9 Hz, 1H), 5.12 (dd, J =

3.8, 9.5 Hz, 1H), 4.97 (dd, J = 13.8, 3.9 Hz, 1H), 1.97 (s, 3H).

–1

11.03188. IR (CHCl

3

1

2

9c

1

13

Compound 8c

;

Oily liquid (290 mg, 89%). H NMR (400 MHz,

3

C NMR (101 MHz, CDCl ) δ 169.47, 144.51, 136.60, 128.91,

CDCl

3

) δ 7.26‐7.17 (m, 5H), 4.32 (dd, J = 8.5, 3.6 Hz, 1H), 3.47 128.63, 126.58, 118.10, 74.00, 60.49, 20.84. HRMS (ESI) m/z

+

(

dd, J = 13.0, 8.5 Hz, 1H), 3.29 (s, 3H), 3.18 (dd, J = 12.9, 3.6 Hz, [M] calcd. for C16

H

15

N

3

O

2

: 281.11643; found: 281.11354. IR

13

–1

1

H), 2.36 (s, 3H). C NMR (101 MHz, CDCl

3

) δ 138.17, 135.48, (CHCl

3

, cm ): 2923, 2857, 1742, 1433, 1374, 1229, 1023, 746.

1

29.35, 126.59, 82.93, 56.75, 56.58, 21.13. HRMS (ESI) m/z [M

+

Na] calcd. for C10

H

13

N

3

ONa : 214.09508; found: 214.09811. Representative procedure for copper‐catalyzed azide‐alkyne

, cm ): 2925, 2092, 1252, 1105, 812. cycloaddition; Following the general procedure for ‐azido

and usual work, the resulting residues were treated with

Oily liquid (287 mg, 86%). H NMR (500 MHz, phenylacetylene (130 mg/140 uL, 1.27 mmol, 1.2 equiv), CuI

) δ 7.44‐7.33 (m, 2H), 7.31‐7.17 (m, 2H), 4.34 (dd, J = 8.6, (400 mg, 2.1 mmol, 1.5 equiv) and N,N‐diisopropylethylamine

.5 Hz, 1H), 3.48 (dd, J = 13.0, 8.7 Hz, 1H), 3.31 (s, 3H), 3.19 (407 mg/550 uL, 3.15 mmol, 3 equiv) in CH CN (2 mL) and

dd, J = 13.0, 3.5 Hz, 1H), 1.32 (s, 10H). C NMR (126 MHz, stirred at room temperature for 3 h. Following the usual

CDCl ) δ 151.37, 135.43, 126.32, 125.55, 82.93, 56.88, 56.60, workup and purification by silica gel column chromatography

–1

IR (CHCl

3

β

2

9c

1

Compound 8d

CDCl

3

;

3

1

3

(

3

+

3

2

1

4.57, 31.30. HRMS (ESI) m/z [M] calcd. for C13

19.15281; found: 219.15393. IR (CHCl

266, 1106, 829.

H

19

N

3

O : afforded the triazoles 10‐12 in good yields over 3 sequential

–

1

3

, cm ): 2961, 2094, steps.

1

Compound 10; White solid (85 mg, 78%). Mp. 119‐121 °C. H

Compound 8e; Oily liquid (248 mg, 88%). H NMR (500 MHz, NMR (500 MHz, CDCl ) δ 7.779‐7.77 (m, 2H), 7.64 (s, 1H), 7.48‐

CDCl ) δ 7.62‐7.58 (m, 4H), 7.51‐7.41 (m, 2H), 7.41 ‐7.29 (m, 7.28 (m, 8H), 6.17 (dd, J = 7.5, 4.9 Hz, 1H), 4.78‐4.68 (m, 2H),

2

3

1

3

13

H), 4.41 (dd, J = 8.5, 3.6 Hz, 1H), 3.52 (dd, J = 13.0, 8.5 Hz, 1H), 2.06 (s, 3H). C NMR (126 MHz, CDCl

3

) δ 169.36, 147.57,

.35 (s, 3H), 3.25 (dd, J = 13.0, 3.6 Hz, 1H). C NMR (126 MHz, 136.18, 130.30, 128.91, 128.81, 128.72, 128.08, 126.28,

) δ 141.38, 140.58, 137.53, 128.79, 127.43, 127.09, 125.59, 120.25, 73.71, 54.34, 20.77. MS (ESI) m/z: 308 ([M +

13

CDCl

3

+

1

C

2

27.08, 82.92, 56.99, 56.56. HRMS (ESI) m/z [M] calcd. for H] , 100), 330 ([M + Na] , 50). HRMS (ESI) m/z [M] calcd. for

+

–1

+

–1

15

H

15

N

3

O : 253.12151; found: 253.12406. IR (CHCl

3

, cm ):

C

18

H

17

N

3

O

2

: 307.13208; found: 307.13409. IR (CHCl

2922, 2852, 1744, 1462, 1372, 1226, 1028, 764, 696.

3

, cm ):

922, 2852, 2100, 1215, 749.

2

9c

1

30b

1

Compound 8f

;

Oily liquid (230 mg, 76%). H NMR (400 MHz, Compound 11

;

White solid (87 mg, 78%). Mp. 105‐107 °C. H

CDCl

3

) δ 6.83 (s, 1H), 4.80 (dd, J = 10.2, 4.0 Hz, 1H), 3.55 (t, J = NMR (500 MHz, CDCl

3

) δ 7.79 (s, 1H), 7.78‐7.70 (m, 2H), 7.46‐

1

6

1

0.4 Hz, 1H), 3.31 (dd, J = 10.6, 4.0 Hz, 1H), 3.25 (s, 3H), 2.35 (s, 7.27 (m, 8H), 5.24 (dd, J = 8.8, 3.2 Hz, 1H), 4.65 (dd, J = 14.0,

13

H), 2.25 (s, 3H). C NMR (101 MHz, CDCl

3

) δ 137.45, 136.65, 3.2 Hz, 1H), 4.45 (dd, J = 14.0, 8.9 Hz, 1H). C NMR (126 MHz,

) δ 147.36, 140.14, 130.29, 128.79, 128.47, 128.10,

31.74, 130.33, 81.14, 56.87, 20.79, 20.44, 7.48. HRMS (ESI) CDCl

3

+

m/z [M] calcd. for C12

IR (CHCl

H

17

N

3

O : 219.13716; found: 219.13842. 125.87, 125.61, 121.20, 72.88, 57.51. MS (ESI) m/z: 266 ([M +

–1

+

–1

3

, cm ): 2923, 2099, 1255, 1112, 851.

H] ). IR (CHCl

3

, cm ): 3307, 2922, 2852, 1712, 1462, 1221,

1

065, 770, 693.

2

9c

1

Compound 8g

CDCl

;

Oily liquid (248 mg, 84%). H NMR (400 MHz,

1

3

) δ 7.90‐7.83 (m, 3H), 7.78 (s, 1H), 7.55‐7.47 (m, 2H), 7.43 Compound 12; White solid (92 mg, 82%). Mp. 98‐100 °C. H

(

dd, J = 8.4, 1.7 Hz, 1H), 4.52 (dd, J = 8.5, 3.6 Hz, 1H), 3.58 (dd, J NMR (400 MHz, CDCl

3

) δ 7.86‐7.81 (m, 2H), 7.83 (s, 1H), 7.49‐

=

13.0, 8.5 Hz, 1H), 3.35 (s, 3H), 3.28 (dd, J = 13.0, 3.6 Hz, 1H). 7.29 (m, 8H), 4.68‐4.55 (m, 2H), 4.50‐4.40 (m, 1H), 3.22 (s, 3H).

1

3

13

C NMR (101 MHz, CDCl

3

) δ 135.95, 133.36, 133.19, 128.62,

3

C NMR (126 MHz, CDCl ) δ 147.40, 137.65, 130.70, 128.87,

1

5

27.88, 127.73, 126.36, 126.22, 126.09, 124.00, 83.28, 56.99, 128.75, 127.98, 126.60, 125.66, 121.09, 82.29, 56.96, 56.19.

+

13 3

6.50. HRMS (ESI) m/z [M] calcd. for C13H N O : 227.10586; MS (ESI) m/z: 280 ([M + H] , 100), 302 ([M + Na] , 25). HRMS

–1

+

found: 227.10794. IR (CHCl

8

3

, cm ): 2927, 2095, 1255, 1105, (ESI) m/z [M + Na] calcd. for C17

H

17

N

3

NaO : 302.12638; found:

–1

18, 744, 666.

302.12898. IR (CHCl

107, 766, 683.

3

, cm ): 2923, 2852, 1726, 1461, 1217,

1

Synthesis of benzotriazole derivative; Following the general

procedure for ‐iodo preparation using Me SI (237 mg, 1.16

mmol, 1.1 equiv), PhI(OAc) (374 mg, 1.16 mmol, 1.1 equiv)

β

3

Acknowledgements

2

and 1a (110 mg, 100 uL, 1.05 mmol, 1.0 equiv) and usual work,

the resulting residues were treated with 1‐H‐benzotriazole

SK gratefully acknowledge the Department of Science and

Technology, India for the INSPIRE Faculty award (IFA12‐CH‐54)

J. Name., 2013, 00, 1‐3 | 13

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DOI: 10.1039/C6OB01179A

ARTICLE

Journal Name

8

9

1

(a) P. Pandit, K. S. Gayen, S. Khamarui, N. Chatterjee and D.

K. Maiti, Chem. Commun., 2011, 47, 6933; (b) C. Zhang, C.

Tang and N. Jiao, Chem. Soc. Rev., 2012, 41, 3464; (c) K. H.

Jensen, J. D. Webb and M. S. Sigman, J. Am. Chem. Soc.,

and Start‐up Research Grant for Young Scientists (SB/FT/CS‐

0

24/2014). KB acknowledges CSIR, New Delhi for research

fellowship.

2

010, 132, 17471.

(a) H. Tera, S. Zawadzki and A. Zwierzak, Tetrahedron, 1981,

37, 2675; (b) A. Klepacz and A. Zwierzak, Tetrahedron Lett.,

Notes and references

2

001, 42, 4539; (c) W. Z. Yu, F. Chen, Y. A. Cheng and Y.‐Y.

1

(a) The Chemistry of Double Bonded Functional Groups; S.

Patai, Ed.; Wiley: Chichester, 1997; (b) P. Phukan, P.

Chakraborty and D. J. Kataki, J. Org. Chem., 2006, 71, 7533;

Yeung, J. Org. Chem., 2015, 80, 2815, and references cited

therein.

0 (a) R. E. Erickson, in Marine Natural Products, ed. P. J.

Scheuer, Academic Press, New York, 1986, vol. 5, p. 131; (b)

P. A. Bartlett, in Asymmetric Synthesis, ed. J. D. Morrison,

Academic Press, New York, 1984, vol. 3, p. 411; (b) S. D.

Stamatov and J. Stawinski, Eur. J. Org. Chem., 2008, 2635; (c)

T. Moriuchi, M. Yamaguchi, K. Kikushima and T. Hirao,

Tetrahedron Lett., 2007, 48, 15; (d) D. Urankar, I. Rutar, B.

Modec and D. Dolenc, Eur. J. Org. Chem., 2005, 2349.

1 (a) H. Togo and S. Iida, Synlett, 2006, 2159; (b) R. C. Cambie,

R. C. Hayward, J. L. Roberts, and P. S. Rutledge, J. Chem. Soc.

Chem. Commun. 1973, 359; (c) R. C. Cambie, R. C. Hayward,

J. L. Roberts, and P. S. Rutledge, J. Chem. Soc., Perkin Trans 1

(c) T. B. Kakule, S. Zhang, J. Zhan and E. W. Schmidt, Org.

Lett., 2015, 17, 2295; (d) T. B. Kakule, Z. Lin and E. W.

Schmidt, J. Am. Chem. Soc., 2014, 136, 17882.

For selected references, see: (a) H. Egami and M. Sodeoka,

Angew. Chem. Int. Ed., 2014, 53, 8294; (b) S. R. Chemler and

M. T. Bovino, ACS Catal., 2013, 3, 1076; (c) K. Muñiz and C.

2

MartÍnez, J. Org. Chem., 2013, 78, 2168; (d) S.‐X. Huang and

K.‐L. Ding, Angew. Chem. Int. Ed., 2011, 50, 7734; (e) A.

Minatti and K. Muñiz, Chem. Soc. Rev., 2007, 36, 1142; (f) D.

J. Chen, C. Timmons, H. X. Wei and G. G. Li, J. Org. Chem.,

1

2

003, 68, 5742.

3

Transition‐metal catalyzed difunctionalization of alkenes

such as dioxygenation, oxyamination, diamination,

aminohalogenation, azidohydroxylation, azidocynation,

oxyphopshorylation, etc have been documented. For

selected examples, see; (a) X.‐F. Xia, S.‐L. Zhu, Z. Gu, H.

1

2

974, 1858; (d) Yi Yi Myint and M. A. Pasha, Symm. Comm.,

004, 34, 4477, and refences cited therein; (e) W. R. Roush,

S. Narayan, C. E. Bennett and K. Briner, Org. Lett., 1999, 1,

8

1

95; (f) R. W. Friesen and S. J. Danishefsky, J. Am. Chem. Soc.,

989, 111, 6656; (g) J. Thiem, H. Karl and J. Schwentner,

Wang, W. Li, X. Liu and Y.‐M. Liang, J. Org. Chem., 2015, 80

572; (b) G. A. Abeykoon, S. Chatterjee and J. S. Chen, Org.

Lett., 2014, 16, 3248; (c) Q. Xue, J. Xie, P. Xu, K. Hu, Y. Cheng

and C. Zhu, ACS Catal., 2013, , 1365; (d) L. Legnani and B.

,

Synthesis, 1978, 696; (h) M. Adinolfi, M. Parrilli, G. Barone, G.

Laonigro and L. Mangoni, Tetrahedron Lett., 1976, 40, 3661;

5

(i) L. Mangoni, M. Adinolfi, G. Barone and M. Parrilli,

3

Tetrahedron Lett. 1973, 14, 4485; (j) M. K. Agrawal, S.

Adimurthy, B. Ganguly and, P. K. Ghosh, Tetrahedron, 2004,

65, 2791; (k) D. W. Gammon, H. H. Kinfe, D. E. De Vos, P. A.

Jacobs and B. F. Sels, Tetrahedron Lett., 2004, 45, 9533; J.

Carbohydr. Chem., 2007, 26, 141.

2 (a) Y. Guindon, B. Guérin, C. Chabot, H. Mackintosh and W.

W. Olgivie, Synlett, 1995, 449; (b) K. Maeda, H. Shinokubo

and K. Oshima, J. Org. Chem., 1996, 61, 6770.

3 (a) N. Chakraborty, S. Santra, S. K. Kundu, A. Hajra, G. V.

Zyryanovbd and A. Majee, RSC Adv., 2015, 5, 56780, and

references cited therein; (b) T. K. Achar, S. Maiti and P. Mal,

Org. Biomol. Chem., 2016, 14, 4654; (c) N. Anand, M. Kapoor,

Koul, S.; S. C. Taneja, R. L. Sharma and, G. N. Qazi

Tetrahedron Asymmetry, 2004, 15, 3131; (d) M. S. Yusubov,

R. Y. Yusubova, V. D. Filimonov and K.‐W. Chi, Synth.

Commun. 2004, 34, 443; (e) Rodrigo da S. Ribeiro, P. M.

Morandi, Angew. Chem., Int. Ed., 2016, 55, 2248; (e) P. H.

Fuller, J.‐W. Kim and S. R. Chemler, J. Am. Chem. Soc., 2008,

1

30, 17638; (f) M. C. Paderes, J. B. Keister and S. R. Chemler,

J. Org. Chem., 2013, 78, 506; (g) H. Du, W. Yuan, B. G. Zhao

and Y. A. Shi, J. Am. Chem. Soc., 2007, 129, 11688; (h) P. A.

Sibbald and F. E. Michael, Org. Lett., 2009, 11, 1147; (i) S. R.

1

Chemler and M. T. Bovino, ACS Catal., 2013,

3, 1076; (j) X. Ji,

H. Huang, W. Wu and H. Jiang, J. Am. Chem. Soc., 2013, 135

,

5

9

286; (k) W. Wei and J. Ji, Angew. Chem., Int. Ed., 2011, 50

097; (l) S.‐F. Zhou, D.‐P. Li, K. Liu, J.‐P. Zou and O. T. J.

Asekun, Org. Chem., 2015, 80, 1214; (m) L. Xu, X.‐Q. Mou, Z.‐

M. Chen and S.‐H. Wang, Chem. Commun., 2014, 50, 10676.

(a) E. ‐i. Negishi, Angew. Chem., Int. Ed., 2011, 50, 6738; (b)

A. Suzuki, Angew. Chem., Int. Ed., 2011, 50, 6722; (c) C. C. C.

J. Seechurn, M. O. Kitching, T. J. Colacot and V. Snieckus,

Angew. Chem., Int. Ed., 2012, 51, 5062.

4

Esteves and M. C. S. de Mattos, Tetrahedron Lett. 2007, 48

,

5

(a) D. Nair, J. Scarpello, L. White, L. Freista dos Santos, I.

8

747; (f) B. Sels, P. Levecque, R. Brosius, D. De Vos, P. Jacobs,

Vankelecom and A. Livingston, Tetrahedron Lett., 2001, 42

219; (b) The European Agency for the Evaluation of

Medicinal Products, Committee for Proprietary Medicinal

,

D. W. Gammon and H. H. Kinfe, Adv. Synth. Catal., 2005, 347

,

8

89; (g), H. Nakayama and A. Itoh, Tetrahedron Lett. 2007,

4

8, 1131.

Products; London, 2002; (c) J. Rivera‐Utrilla, I. Bautista‐ 14 G. K. Dewkar, S. V. Narina and A. Sudalai, Org. Lett., 2003,

5

,

Toledo, M. Ferro‐Garcia, C. Moreno‐Catilla, Carbon, 2003,

4501.

4

3

1

, 323; (d) C. Garett and K. Prasad, Adv. Synth. Catal., 2004, 15 (a) M. Parrilli, G. Barone, M. Adinolfi and L. Mangoni,

Tetrahedron Lett., 1976, 17, 207; (b) R. Antonioletti, M.

46, 889.

D'Auria, A. De Mico, G. Piancatelli and A. Scettri,

6

7

For selected reviews, see: (a) P. T. Anastas, J. C. Warner,

Green Chemistry: Theory and Practice; Oxford University

Press: New York, 1998; (b) C.‐J. Li and B. M. Trost, Proc. Natl.

Acad. Sci. U.S.A., 2008, 105, 13197; (c) P. J. Dunn, Chem. Soc.

Rev., 2012, 41, 1452; (d) Regulatory guidelines for metal

content. Doc. Ref. CPMP/SWP/QWP/4446/00.

Tetrahedron, 1983, 39, 1765

.

1

6 (a) J. C. R. Bougault, Acad. Sci., 1900, 130, 1766; (b) J. C. R.

Bougault, Acad. Sci., 1900, 131, 528; (c) J. Barluenga, M. A.

Rodriguez, P. J. Campos and G. Asensio, J. Chem. Soc., Chem.

Commun., 1987, 1491.

7 (a) J. G. Smith and M. Fieser, in Fieser and Fieser's Reagent

for Organic Synthesis, John Wiley and Sons, New York, vol.

1–12, 1990; (b) H. Sharghi, A. R. Massah, H. Eshghi and K.

Niknam, J. Org. Chem., 1998, 63, 1455; (c) K. Otsubo, J.

Inagana and M. Yamaguchi, Tetrahedron Lett., 1987, 28,

4435; (d) P. Sarmah and N. C. Barua, Tetrahedron Lett., 1988,

(a) J. Rodriguez and J.‐P. Dulcère, Synthesis, 1993, 1173; (b)

C. Liu, M. Zhu, W. Wei, D. Yang, H. Cui, X. Liu and H. Wang,

Org. Chem. Front., 2015,

2

, 1356; (c) N. O. Ilchenko, M. A.

, 447; (d) L. Song,

Cortés and K. J. Szabó, ACS Catal., 2016,

6

S. Luo, and J.‐P. Chengab, Org. Chem. Front., 2016,

and references cited therein.

3

, 447,

1

4 | J. Name., 2012, 00, 1‐3

Please do not adjust margins

Page 15 of 15

Orga Pn l iec a s& e Bd oi o nmo ot al ed cj uu sl ta mr Ca rhg ei nms istry

View Article Online

DOI: 10.1039/C6OB01179A

Journal Name

ARTICLE

2

7

9

0

, 5815; (e) B. C. Ranu and S. Banerjee, J. Org. Chem., 2005,

, 4517.

1

2

8 Weissermel, K. Industrial Organic Chemistry; Wiley‐VCH:

Wienheim, 1997; p. 266–267.

9 (a) J. Marco‐Contelles, M. T. Molina and S. Anjum, Chem.

Rev., 2004, 104, 2857.

0 (a) C. Bonini and G. Righi, Synthesis, 1994, 225; (b) G.

Majetich, R. Hicks and S. Reister, J. Org. Chem., 1997, 62

,

4

321.

2

1 For selected references, see: (a) A. Kirschning, C. Plumeier

and L. Rose, Chem. Commun., 1998, 33; (b) A. Kirschning, M.

A. Hashem, H. Moneneschein, L. Rose and K.‐U. Schöning, J.

Org. Chem., 1999, 64, 6522; (c) A.; Kirschning, M. Jesberger

and A. Schönberger, Org. Lett., 2001, 3, 3623.

2

2 (a) T. R. Reddy, D. S. Rao, K. Babachary and S. Kashyap, Eur. J.

Org. Chem., 2016, 291; (b) G. Kundoor, D. S. Rao and S.

Kashyap, Asian J. Org. Chem., 2016, 5, 264; (c) S. K. Battina

and S. Kashyap, Tetrahedron Lett., 2016, 57, 811; (d) S.

Chittela, T. R. Reddy, P. Radha Krishna and S. Kashyap, J. Org.

Chem., 2015, 80, 7108; (e) T. R. Reddy, D. S. Rao and S.

Kashyap, RSC Adv., 2015,

Reddy, S. Kashyap, Carbohydr. Res., 2015, 406, 86; (g) T. R.

Reddy, S. Chittela and S. Kashyap, Tetrahedron, 2014, 70

224; (h) S. Chittela, T. R. Reddy, P. Radha Krishna and S.

Kashyap, RSC Adv., 2014, , 46327.

3 (a) J. H. Schauble, E. A. Trauffer, P. P. Deshpande and R. D.

Evans, Synthesis, 2005, 1333; (b) R. C. Cambie, B. G. Lindsay,

P. S. Rutledge and P. D. Woodgate, J. Chem. Soc., Perkin

Trans., 1 1976, 845

5, 28338‐28343; (f) B. Srinivas, T. R.

,

9

4

2

4 M. F. Ruasse, G. Lo Moro, B. Galland, R. Bianchini, C. Chiappe

and G. Bellucci, J. Am. Chem. Soc. 1997, 119, 12492‐12502.

5 (a) N. Elming and N. Claason‐Kaas, Acta Chem. Scand., 1952,

6

, 535; (b) C. W. Holzapfel and D .B. G. Williams,

Tetrahedron, 1995, 51, 8555; (c) D. B. G. Williams and S. J.

Evans, Tetrahedron Lett., 2004, 45, 7189; (d) B. M. Trost and

Z. Shi, J. Am. Chem. Soc., 1996, 118, 3037.

2

6 (a) A. R. Reddy, P. L. Sangwan, P. K. Chinthakindi, S. Farooq,

V. Siddaiah and S. Koul, Helv. Chim. Acta 2013, 96, 131; (b) C.

Timchalk,Toxicology, 2004, 200, 1.

7 For selected articles, see: (a) J. S. Yadav, B. V. S. Reddy, B.

Jyothirmai and M. S. R. Murty, Tetrahedron Lett., 2005, 46

,

6

2

559; (b) S. Chiba, Y.‐J. Xu and Y.‐F. Wang, J. Am. Chem. Soc.,

009, 131, 12886; (c) C. François‐Endelmond, T. Carlin, P.

Thuery, O. Loreau and F. Taran, Org. Lett., 2010, 12, 40; (d) X.

Sun, X. Li, S. Song, Y. Zhu, Y.‐F. Liang and N. Jiao, J. Am.

Chem. Soc. 2015, 137, 6059.

8 (a) https://pubchem.ncbi.nlm.nih.gov/, PubChem Bioassay

number AID504832; (b) S. Faizi, F. Farooqi, S. Zikr‐Ur‐

Rehman, A. Naz, F. Noor, F. Ansari, A. Ahmad and S. A. Khan,

Tetrahedron, 2009, 65, 998; (c) R. I. Kureshy, A. Das, N. H.

Khan, S. H. R. Abdi, S. Saravan and H. C. Bajaj, ACS Catal.,

2

011, 1, 1529; (d) P. J. Desjardins and R. G. Berlin, Br. J. Clin.

Pharmacol., 2007, 64, 555.

9 (a) A. Kamal, A. A. Shaik, M. Sandbhor and M. S. Malik,

2

3

Tetrahedron Asymmetry, 2004,

A. E. Diaz‐Alvarez and P. Diner, Tetrahedron, 2013, 69, 753;

c) G. Fumagalli, P. T. G. Rabet, M. F. Greaney and S. Boyd,

5, 935; (b) L. Mesas‐Sanchez,

(

Angew. Chem. Int. Ed., 2015, 54, 11481.

0 (a) A. Ramírez‐Villalva, D. González‐Calderón, C. Gonzalez‐

Romero, M. Morales‐Rodríguez, B. Jauregui‐Rodríguez, E.

Cuevas‐Yáñez and A. Fuentes‐Benítes, Eur. J. Med. Chem.,

2

015, 97, 275; (b) K. Pericherla, P. Khedar, B. Khungar and A.

Kumar, Tetrahedron Lett., 2012, 53, 6761; (c) S. Kim, S. ‐N.

Cho, T. Ohc and P. Kim, Bioorg. Med. Chem. Lett., 2012, 22

844.

,

6

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Regioselective vicinal functionalization of unactivated alkenes with sulfonium iodate(i) reagents under metal-free conditions

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