A photolabile protection strategy for terminal alkynes

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Tina A. Gschneidtner, Kasper Moth-Poulsena

PII:

S0040-4039(13)01312-9

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http://dx.doi.org/10.1016/j.tetlet.2013.07.144

TETL 43342

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Tetrahedron Letters

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21 May 2013

Please cite this article as: Gschneidtner, T.A., Moth-Poulsena, K., A photolabile protection strategy for terminal

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Tetrahedron Letters

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A photolabile protection strategy for terminal alkynes

Tina A. Gschneidtner^a, Kasper Moth-Poulsen^a,

^aDepartment of Chemical and Biological Engineering, Chalmers University of Technology, SE-412 96 Göteborg, Sweden

ARTICLE INFO

ABSTRACT

Article history:

Received

Received in revised form

Accepted

We present a strategy for photolabile protection of terminal alkynes. Several photo-caged

alcohols were synthesized via mild copper(II)-catalyzed substitution between tertiary

propargylic alcohols and 2-nitrobenzyl alcohol to build up robust, base stable o-nitrobenzyl

(NB) photo-cleavable compounds. We compare the new photolabile protecting group with the

commonly used alkyne protecting group, 2-methyl-3-butyn-2-ol and the results show that NB

ethers are stable under the cleaving conditions for the cleavage of methylbutynol protected

alkynes. Additionally, we present the synthesis of photo-cleavable NB derivatives containing

thiol groups that can serve as agents for photoinduced surface functionalization reactions.

Available online

Keywords:

Photolabile protection

Terminal alkynes

o-nitrobenzyl

Terminal alkynes are reactive species in a number of

important chemical reactions such as the 1,3-dipolar

cycloaddition¹between azides and alkynes to give 1,2,3-triazoles

(click-chemistry²), the Sonogashira reaction and its forerunner,

the Stephens-Castro reaction.^3,4Furthermore, alkynes can

undergo the Vollhardt cyclization,⁵alkyne trimerization to form

aromatic compounds,^6,7or can act as dienophiles in Diels-Alder

reactions.⁸A number of protecting groups have been developed

for alkyne chemistry such as trialkylsilyl, benzyl- or phenyl-

substituted alkylsilyl groups and propargylic alcohols. The

development of a photolabile protecting group for terminal

alkynes has, to the best of our knowledge, not been described in

the literature until now, and would add to the portfolio of

possible chemical transformations of terminal alkynes. Such

protected alkynes could also be applied in the modification of

surfaces where it is highly desirable to perform spatially

controlled chemoselective reactions, e.g., by using

chemoselective ―click chemistry‖.⁹

benzoic acid was by Barltrop et al.³¹in 1966, and it was further

developed by Kaplan et al.,¹⁶who used it for the triggered release

of ATP. Photolysis of o-nitrobenzyl-derived ethers releases the

free alcohol and o-nitrosobenzaldehyde, due to proton abstraction

by the light-activated nitro group from the benzylic ether.^13,27,32

NBs are used to release, e.g., phosphoric acids,^33–35thiols,³⁶

amines,³⁷carboxy acids,^38,39and alcohols,²⁹and internal alkynes⁴⁰

via light activation. For an overview of this field we refer to a

review.⁴¹

Herein, we introduce a photolabile protection strategy for

terminal alkynes based on a combination of the photoactive NB

group and tertiary propargyl ethers. The combined NB-propargyl

ether groups are stable under strong alkaline conditions but

release terminal alkynes after irradiation under alkaline

conditions (Scheme 1).

A library of alkynes protected with the NB cage on the tertiary

propargylic alcohol was synthesized (Table 1, compounds 1-7).

Protected, photolabile compounds, the so called caged

compounds,¹⁰have been used in organic synthesis,^11–13surface

science^14,15and biochemistry,¹⁶for DNA-chip fabrication,^17,18

natural product synthesis,¹⁹and the photorelease of biological

substances.²⁰Among photo-cleavable groups such as the

2-Methyl-3-butyn-2-ol was introduced by

a

standard

Sonogashira⁴reaction with precursor molecules (aryl halides)⁴²8,

9 and 12-14 with 2-methyl-3-butyn-2-ol. These products were

converted into the NB-propargylic ethers 1-7 via a copper-

catalyzed nucleophilic substitution reaction with o-nitrobenzyl

alcohol. In this step the tertiary propargylic alcohol was activated

with CuBr₂to react with o-nitrobenzyl alcohol at room

temperature.

nitroindoline (Bni)

group,^21,22

(coumarin-4-yl) methyl

derivatives^23,24and p-hydroxyphenacyl derivatives,^25,26the o-

nitrobenzyl (NB)^27–29group is a very robust and a widely used

group for the protection of primary alcohols.²⁷Photoinduced

reactions of NBs were reported as early as 1901.³⁰The first

reported use of the o-nitrobenzyl group as a protecting group for

———

 Corresponding author. Tel.: +46 (0) 317723403; e-mail: kasper.moth-poulsen@chalmers.se

2

Tetrahedron Letters

The versatility of the copper-catalyzed reaction using tertiary

OH

365 nm

KOH,

toluene

reflux, 12 h

propargylic alcohols to build up NB-propargylic photo-caged

derivatives was also tested on alkynes containing functional

groups, such as ethers (7) or carbamates (5, 6) (Table 1). For

subsequent modification reactions, amine (5) bromide (2) and

alkyne functionalities (4) were introduced. These functional

groups can react, e.g., via cross-coupling reactions, peptide-

coupling strategies or N-alkylation reactions among others. The

synthesis of 3 from 2 via the Sonogashira reaction underlines the

tolerance of the NB group and further modification possibilities

(see Scheme 4).

NO₂

cat. CuBr₂

MeNO₂

rt, 12 h

O

NO₂

OH

R

R=H

8

1

15

Scheme 1. Final step in the synthesis of o-nitrobenzyl NB

compounds. o-Nitrobenzyl alcohol reacts with different tertiary

propargylic alcohols in the presence of catalytic amounts of CuBr₂.

These products can be photo-cleaved under alkaline conditions to

give terminal alkynes.

A wide variety of photo-cleavable derivatives and their further

use can be envisioned. As a proof of principle we synthesized the

surface active compounds 6 and 7 (see Schemes 2 and 3) that can

be applied for self-assembly on gold surfaces and spatially

controlled photoinduced reactions. In the first step, tert-butyl [4-

(3-hydroxy-3-methylbut-1-yn-1-yl)phenyl]carbamate (12) was

obtained via Pd-catalyzed reaction of 1-bromo-4-tert-

Propargylic ethers are interesting building blocks in organic

chemistry^43,44and terminal and secondary propargylic ethers have

been prepared using Lewis acids,^45,46or transition metal

complexes with, e.g. cobalt (the Nicholas reaction),⁴⁷

rhenium,^43,48or ruthenium.⁴⁹However, mild methods for tertiary

ethers are rare, since their synthesis is not trivial. A mild method

recently reported by Huang et al.⁵⁰has been used in this study to

form the propargylic ether via a mild copper(II)-catalyzed (S_N1)

substitution.

butoxycarbonylaminobenzene

and

2-methylbut-3-yn-2-ol

(Scheme 2). Compound 12 was deprotected with tetra-n-butyl

ammonium fluoride (TBAF) to give the free amine.⁵¹An

activated N-C coupling strategy (EDC and DMAP, as used in

peptide synthesis) was used to react 11-(acetylthio)undecanoic

acid (synthesized according to published procedures⁵²) with 12 to

give 6. Irradiation under neutral conditions deprotected 6 and led

to the release of alcohol 13. Irradiation under alkaline conditions

(365 nm, 200 μWatt/cm², in aq. KOH, toluene) hydrolysed the

amide-functionality of photo-caged 6 to give 18, thus the thiol

linker for the gold surface was lost. As a consequence of the

limited stability of compound 6 under basic conditions a more

stable derivative using an ether instead of an amine (7) was

designed (Scheme 3).

The obtained photolabile NB-propargylic ethers were

deprotected via irradiation (365 nm, 200 W/cm²) to form the

alcohols 8-14 and the terminal alkynes 15-19 under alkaline

conditions. Figure 1 illustrates an example of the photo-cleaving

reaction

of

1-[(2-methyl-4-phenylbut-3-yn-2-yl)oxy]-2-

1

nitrobenzene (1) in CDCl₃monitored by H NMR spectroscopy.

The sample was irradiated over a period of 120 minutes

interrupted by short breaks, in which the NMR spectra (10-

minute intervals) were recorded. The conversion of the starting

material (signal a, e) as well as the formation of the two

characteristic products o-nitrosobenzaldehyde (signals c, d) and

2-methyl-4-phenylbut-3-yn-2-ol (signal b) were monitored. The

disappearance of the benzylic proton (e) as well as a shift of the

protons of the methyl group of 2-methylbut-3-yn-2-ol (a to b),

indicated the change from an ether to a free alcohol.

Substrate 7 was synthesized via protection of the alcohol

moiety of 4-bromophenol with 3,4-dihydro-2H-pyran under

weakly acidic conditions (p-TsOH) followed by a Sonogashira

reaction to form 25. Tetrahydropyran 25 was deprotected to give

the free alcohol under acidic conditions and compound 7 was

reacted via etherification with S-(12-bromododecyl) thioacetate

(22) (Scheme 3). The NB ether was deprotected by irradiation

under alkaline conditions to form the terminal alkyne 19. Thus,

we have shown that it is possible to obtain terminal alkynes with

a thiol functionality for self-assembly on gold surfaces.

HO

NO₂

Br

d

a

O

Boc

N

H

Boc

N

12

H

NO₂

b, c, d

O

S

O

N

HN

Boc

5

H

6

5

e

f

NH₂

O

18

HO

N

HO

S

NH

Boc

5

H

13

12

Scheme 2. Synthesis of photolabile compounds 5 and 6. a.

PdCl₂(PPh₃)₂, NEt₃, 2-methyl-3-butyn-2-ol, CuI, PPh₃,THF; b.

TBAF, THF; c. EDC, DMAP, DMF, 11-(acetylthio)

undecanoic acid; d. CuBr₂, MeNO₂, o-nitrobenzyl alcohol; e.

365 nm, KOH, toluene, f. 365 nm, ethyl acetate.

1

Figure 1. H-NMR spectra of 1 in CDCl₃upon irradiation with

UV-light (365 nm, 200 µW/cm²) for 120 minutes. The formation

of 8 and the by-product 2-nitrosobenzaldehyde (Lit. values

NMR³²) were observed.

3

Table 1. Library of photolabile compounds synthesized as shown in Scheme 1.

Photolabile Compounds

Photoreaction

Alkaline Photoreaction

15 (16 h, 70%)

1 (70%)

2 (73%)

3 ^a

8 (96%)

NO₂

O

OH

9 (94%)

16 (5 h, 78%)

17 (12 h, 70%)

17 (12 h, 62%)

18 (10 h, 50%)

Br

NO₂

10 (86%)

11 (88%)

12 (90%)

13 (92%)

14 (94%)

HO

4 ^b

O

OH

O

5 (57%)

6 (42%)

7 (48%)

O

N

H

H₂N

O

N

H

OH

H

N

- (0%)

S

O

19 (14h, 52%)

O

S

O

NO₂

All compounds were deprotected to the propargylic alcohol in CHCl₃in 120 minutes, after irradiation with photons of 365 nm wavelength and 200 W/cm²

intensity. Upon UV-irradiation under alkaline conditions (KOH in toluene (reflux), 5-14 h, see above) these compounds formed terminal alkynes. ^aSynthesized

from compound 2, ^bObtained via deprotection of 3.

NO₂

OH

O

Br

g

f

SH

6

Br

a, b

c

O

c, d, e

Br

a, b

19

14

HO

OH

Br

OTHP

O

OH

2

3

25

f

OH

6

S

O

g

e

HO

d

SH

7

6

Br

9

Scheme 3. Synthesis of an alkyne functionalized linker for

Br

g

surfaces, 19, as well as its photolabile precursor 7. a. p-TsOH,

DCM, 3,4-dihydro-2H-pyran; b. PdCl₂(PPh₃)₂, NEt₃, 2-methyl-3-

butyn-2-ol, CuI, PPh₃,THF; c. p-TsOH, THF/MeOH; d. K₂CO₃,

DMF, S-(12-bromododecyl) thioacetate; e. CuBr₂, MeNO₂, o-

nitrobenzyl alcohol, f. 365 nm, ethyl acetate, g, 365 nm, KOH,

toluene.

16

O₂N

O

10

4

e

OH

f

g

HO

To demonstrate the use of the photolabile protecting group for

terminal alkynes in synthetic organic chemistry, we compared a

conventional 2-methyl-3-butyn-2-ol protected alkyne with the

NB ether protected compound (Scheme 4). We synthesized

compound 3, which contains both the propargylic alcohol

protecting group for alkynes and the photo-caged propargylic

alcohol. To achieve this, 1,4-dibromobenzene was reacted with 2-

methyl-3-butyn-2-ol and o-nitrobenzyl alcohol was introduced to

form photo-caged 2. This was transformed into 3 by Sonogashira

reaction in the dark at 80 °C, which demonstrates the high

stability of this photolabile compound. Alcohol 3 was then

deprotected to give 4 under basic conditions (KOH, toluene,

reflux, dark), leaving the photolabile group intact. Additionally, 3

was deprotected with UV light (365 nm) to form 10 and

irradiation under alkaline conditions gave the terminal alkyne 17.

We showed that the propargylic alkyne protecting group was

removed under traditional alkaline deprotection conditions, while

the NB-propargylic protected alcohol group stayed intact in all

cases.

11

17

Scheme 4. Synthesis of the photolabile ortho-protecting group 3

and a bromo-substituted photo-caged 2. a. PdCl₂(PPh₃)₂, NEt₃, 2-

methyl-3-butyn-2-ol, CuI, PPh₃, THF; b. CuBr₂, MeNO₂o-

nitrobenzyl alcohol; c. PdCl₂(PPh₃)₂, NEt₃, 2-methyl-3-butyn-2-ol,

CuI, PPh₃, THF; d. 365 nm, ethylacetate; e. KOH, toluene, f.

365 nm, ethyl acetate; g. 365 nm, KOH, toluene.

In summary, we have developed a method to synthesize

tertiary propargylic ether NB-photo-cages, which can release

terminal alkynes upon UV-irradiation under alkaline conditions.

These photo-protected propargylic alcohols add to the portfolio

of alkyne protecting groups, and we envision their possible use in

synthetic organic chemistry. The new light-sensitive protection

strategy was applied to synthesize functional photo-cages that

can be used for further post-modification reactions. The

presented thiol-functionalized photocages may serve as agents for

chemoselective, site-specific surface modification reactions on

metal surfaces in future investigations.

4

Tetrahedron

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A photo labile protection strategy for terminal alkynes

Tina A. Gschneidtner,^†Kasper Moth-Poulsen*^†

^†Department of Chemical and Biological Engineering, Chalmers University of Technology, SE-412 96

Göteborg, Sweden.

Supporting Information:

Contents:

page:

General Methods

1

SI-1 Synthesis and Characterization of Compounds 8-14

SI-2 Synthesis and Characterization of the Photo-Cleavable Alkyne

Compounds (1-7)

2-8

9-13

14-15

16-17

18-22

32-33

SI-3 Irradiation of Compounds 1-7 to 8-14

SI-4 Alkaline Irradiation of Compounds 1-7 to 15-19

SI-5 NMR-Characterization

References

1

General Methods:

Characterization. Nuclear magnetic resonance (NMR) measurements were

recorded by an automated Agilent (Varian) MR 400 MHz spectrometer, equipped

with "one-probe" (¹H-Frequency: 399.95 MHz and ¹³C-Frequency: 100.58 MHz) in

CDCl₃as the solvent or on a Varian Unity 500. Chemical shifts () are given in ppm

referring to the signal center using the solvent peak for reference: CDCl₃7.26

ppm/77.0 ppm. UV/Vis-absorption spectra were measured using a Varian Cary 5000

spectrometer. The irradiation experiments were performed with a UV-lamp with

365 nm wavelength and an intensity of 200 µW/cm². HRMS (ESI+/-) was measured

on a LC Agilent 1000 gradient pump, Autosampler CTC PAL, Mass spectrometer

Micromass Q-TOF micro (water) spectrometer at Stenagen Analysislab AB, Sweden.

All samples on the LC Agilent 1000 gradient were prepared by dissolving 1 mg in

1 mL of acetonitrile (ACN). 5µl were injected on a C18 LC system (Agilent XDB-C18

1.8 um 2.1x50 mm, flow rate 0.4 ml/min, gradient 5-95% ACN/water with 0.1%

formic acid). Some samples were recorded on a Bruker Autoflex apparatus at the

department of Chemistry at the University at Copenhagen, in methanol.

Materials. Solvents and reagents were obtained from Sigma-Aldrich (Steinheim,

Germany) except 2-nitrobenzyl alcohol, which was purchased from ABCR (Karlsruhe,

Germany). THF was distilled from sodium/benzophenone shortly prior use. All other

dry solvent were purchased from Aldrich chemical company and used as received.

A PHOTO LABILE PROTECTION STRATEGY FOR TERMINAL ALKYNES: TOWARDS PHOTO-

1

INDUCED SURFACE FUNCTIONALISATION

SI-1 Synthesis and Characterization of Compounds 8-14

HO

2-methyl-4-phenylbut-3-yn-2-ol (8) was synthesized according to published

procedures in a slightly modified procedure.^[8]

2-methylbut-3-yn-2-ol (3.21 g, 38.16 mmol) and 15 mL NEt₃were added to a mixture

of bromobenzene (5.00 g, 31.8 mmol), CuI (181 mg, 954 μmol), PPh₃(996 mg,

3.80 mmol), and PdCl₂(PPh₃)₂(1.34 g, 1.90 mmol) under nitrogen. The reaction

mixture was heated to 80 °C for 12 h. The reaction was quenched with water

(100 mL), extracted with dichloromethane (DCM) (3 x 100 mL). The combined

organic phase was dried over MgSO₄, filtered off, and concentrated under reduced

pressure. The product was obtained as a yellow oil by column chromatography

(silica, hexane/ethyl acetate (4:1), R_f=0.33) (yield: 4.84 g, 95%).

IR (KBr pellet): (Lit.^[9]) _max(cm^-1): 3351 (O-H stretch), 3082 (C-H stretch, aromatic),

3057 (C-H stretch, aromatic), 3035 (C-H stretch, aromatic), 2982 (C-H stretch, alkyl),

2933 (C-H stretch, alkyl), 2230 (C≡C stretch), 1598 (C-C stretch, aromatic), 1573 (C-C

stretch, aromatic), 1489 (C-C stretch, aromatic), 1444 (C-C stretch aromatic), 1376

1

(C-H, alkyl), 1362 (C-H, alkyl), 1272, 1162 (C-O stretch); H-NMR (400 MHz, CDCl₃,

298 K): _H(ppm): 7.44-7.39 (m, 2H, H_arom.), 7.32-7.27 (m, 3H), 1.62 (s, 6H) (cf. Lit.^[10]);

¹³C-NMR (101 MHz, CDCl₃, 298 K): _C(ppm): 131.5, 128.1, 122.6 (C_quart.), 93.6 (C_alkyne),

81.9 (C_alkyne), 65.4 (C_{quart. t-Bu}

/

), 31.3 (CH₃) (cf. Lit.^[11]); UV/VIS (CHCl₃): λ_max(nm), (log ε_λ

(M^-1cm^-1)): 269, (4.35).

OH

Br

4-(4-bromophenyl)-2-methylbut-3-yn-2-ol (9)

2-methylbut-3-yn-2-ol (713 mg, 8.48 mmol), NEt₃(15 mL), and THF (15 mL) were

added to a mixture of 1,4-dibromobenzene (2.00 g, 8.48 mmol), CuI (97 mg,

509 μmol), PPh₃(133 mg, 509 mmol), and PdCl₂(PPh₃)₂(179 mg, 255 μmol) under

nitrogen. The reaction mixture was heated to 75 °C for 12 h. The reaction was

quenched with water (50 mL) and the crude product extracted with DCM (3 x

50 mL). The combined organic phase was dried over MgSO₂, filtered off, and dried

under vacuum. The product was obtained as a yellow oil by column chromatography

(silica, hexane/ethyl acetate (4:1), R_f=0.57) (yield: 1.09 g, 54%).

A PHOTO LABILE PROTECTION STRATEGY FOR TERMINAL ALKYNES: TOWARDS PHOTO-

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INDUCED SURFACE FUNCTIONALISATION

IR (KBr pellet): _max(cm^-1): 2982 (C-H stretch, alkyl), 2929 (C-H stretch, alkyl), 2971 (C-

H stretch, alkyl), 1510 (C-C stretch, aromatic), 1370 (C-H, alkyl), 1280, 1171 (C-O

stretch, tertiary alcohol); UV/VIS (CHCl₃): λ_max(nm), (log ε_λ(M^-1cm^-1)): 251, (4.13);

261, (3.94); ¹H-NMR (400 MHz, CDCl₃, 298 K): _H(ppm): 7.43 (m, 2H, H_arom.), 7.27 (m,

13

2H, H_arom.), 1.61 (s, 6H, CH₃) (cf. Lit.^[13]); C-NMR (101 MHz, CDCl₃, 298 K): _C(ppm):

133.2, 131.6, 122.6 (C_quart.), 121.8 (C_quart.), 95.1 (C_alkyne), 81.2 (C_alkyne), 65.7 (C_{quart. t-Bu}

/

),

31.5 (CH₃) (cf. Lit.^[13]).

HO

O

N

O

H

tert-butyl (4-(3-hydroxy-3-methylbut-1-yn-1-yl)phenyl)carbamate (12)

2-methylbut-3-yn-2-ol (370 mg, 4.41 mmol) and NEt₃(5 mL)were added to a mixture

of 1-bromo-4-t-butoxycarbonylaminobenzene (1 g, 3.67 mmol), CuI (71.6 mg,

370 μmol), PPh₃(115 mg, 440 μmol), and PdCl₂(PPh₃)₂(154 mg, 220 μ mol) under

nitrogen. The reaction was heated to 80 °C and stirred for 12 h. The reaction mixture

was quenched with water (50 mL) and extracted with DCM (3 x 50 mL). The

combined organic phase was dried over MgSO₂, filtered off, and concentrated under

vacuum. The product was obtained as a yellow oil by column chromatography (silica,

DCM/EA (10:1), R_f=0.26) (yield: 889 mg, 88%).

IR (KBr pellet): _max(cm^-1): 3447 (O-H stretch, N-H stretch), 2980 (C-H stretch, alkyl),

2935 (C-H stretch, alkyl), 2823 (C-H stretch, alkyl), 2229 (C≡C stretch), 1704 (C=O

stretch, carbonyl amide), 1610, 1590 (C-C stretch, aromatic), 1520 (N-C=O stretch,

1

amide), 1393 (C-H, alkyl), 1367 (C-H, alkyl), 1159 (C-O stretch, tertiary alcohol); H-

NMR (400 MHz, CDCl₃, 298 K): _H(ppm): 7.32 (m, 4H, H_arom.), 6.57 (s, broad, 1H,

13

H_amide), 2.12 (s, broad, 1H, OH), 1.60 (s, 6H, CH₃), 1.51 (s, 9H, H_t-Bu/BOC); C-NMR

(101 MHz, CDCl₃, 298 K): _C(ppm): 152.4 (C_{quart./carbonyl}), 138.4 (C_quart.), 132.4, 118.0

(C_quart.), 116.9 (C_quart.), 92.9 (C_alkyne), 81.9 (C_alkyne), 80.9 (C_{quart./t-Bu/BOC}), 65.6 (C_{quart. t-Bu}),

/

31.5 (CH₃), 28.3 (CH₃); UV/VIS (CHCl₃): λ_max(nm), (log ε_λ(M^-1cm^-1)): 267, (4.15);

HR/ESI-Mass m/z (MeOH): [C₁₆H₂₁NO₃+Na]⁺: calc.: 298.1414 [M+Na]⁺, exper.

298.1419.

A PHOTO LABILE PROTECTION STRATEGY FOR TERMINAL ALKYNES: TOWARDS PHOTO-

3

INDUCED SURFACE FUNCTIONALISATION

OH

O

S

N

H

O

S-(11-((4-(3-methyl-3-((2-nitrobenzyl)oxy)but-1-yn-1-yl)phenyl)amino)-11-

oxoundecyl) ethanethioate (13)

11-(acetylthio)undecanoic acid (20) (557 mg, 2.14 mmol) was stirred with 1-ethyl-3-

(3-dimethylaminopropyl)carbodiimide (EDC) (410 mg, 2.14 mmol) and 4-dimethyl-

aminopyridine (DMAP) (174 mg, 1.43 mmol) in DMF (20 mL) for 20 min at room

temperature. 4-(4-aminophenyl)-2-methylbut-3-yn-2-ol (21) (250 mg, 1.43 mmol)

was added and the reaction mixture was stirred for 12 h. The reaction was quenched

with water (50 mL) and the crude product extracted with DCM (3 x 30 mL), dried

over MgSO₄, filtered off, and concentrated under reduced pressure. 13 was obtained

after column chromatography (silica, gradient hexane/ethyl acetate (4:1), (1:1), R_f

(hexane/ethyl acetate 4:1)= 0.42) (yield: 555 mg, 93%, yellowish oil).

IR (KBr pellet): _max(cm^-1): 3430 (O-H stretch, N-H stretch), 3200 (O-H stretch), 3096

(C-H stretch, aromatic), 3050 (C-H stretch, aromatic), 2981 (C-H stretch, alkyl), 2928

(C-H stretch, alkyl), 2852 (C-H stretch, alkyl), 2231 (C≡C stretch), 1690 (S-C=O stretch,

amine), 1664 (C=O stretch, amide), 1598 (C-C stretch, aromatic), 1535 (C-C stretch,

aromatic), 1512 (C-C stretch, aromatic), 1361 (C-H, alkyl), 1244 (S-C stretch), 1164 (C-

1

O stretch, tertiary alcohol); H-NMR (400 MHz, CDCl₃, 298 K): _H(ppm): 7.47 (d, 2H,

3

³J_HH=8.5 Hz, H_arom.), 7.35 (d, 2H, J_HH=8.5 Hz, H_arom.), 2.85 (m, 2H), 2.33 (t, 2H,

³J_HH=9.6 Hz), 2.32 (s, 3H, CH₃), 2.08 (s, br., 1H, OH or NH), 2.04 (s, br., 1H, OH or NH).

13

1.71 (m, 2H), 1.61 (s, 6H, CH₃), 1.55 (m, 2H), 1.28 (m, 12H); C-NMR (101 MHz,

CDCl₃, 298 K): _C(ppm): 196.4 (C_quart./SCO), 171.6 (C_{quart./carbonyl}), 138.2 (C_quart.), 132.6,

119.4, 93.5 (C_alkyne), 82.0 (C_alkyne), 65.8 (C_{quart. t-Bu}), 31.7, 30.8, 29.6, 29.6, 29.5, 29.3,

/

29.3, 28.9, 25.6, 25.2; UV/VIS (CHCl₃): λ_max(nm), (log ε_λ(M^-1cm^-1)): 273, (4.04);

HR/ESI-Mass m/z (MeOH): [C₂₄H₃₅NO₃S+Na]⁺: calc.: 440.2230 [M+Na]⁺, exper.

440.2235.

HO

S

O

S-(12-(4-(3-hydroxy-3-methylbut-1-yn-1-yl)phenoxy)dodecyl) ethanethioate (14)

4-(3-hydroxy-3-methylbut-1-yn-1-yl)phenol (23) (430 mg, 2.44 mmol) and S-(12-

bromododecyl) thioacetate (22) (1.58 mg, 4.88 mmol) were stirred with K₂CO₃

(1.69 mg, 12.2 mmol) in DMF (25 mL) for 16 h at 90 °C. The reaction mixture was

A PHOTO LABILE PROTECTION STRATEGY FOR TERMINAL ALKYNES: TOWARDS PHOTO-

4

INDUCED SURFACE FUNCTIONALISATION

washed with water (3 x 50 mL) and extracted with DCM (3 x 40 mL). The combined

organic phase was dried over MgSO₄, filtered off, and concentrated under reduced

pressure. 22 was obtained as a white solid after column chromatography (silica,

hexane/ethyl acetate (4:1), R_f=0.55) (yield: 868 mg, 85%).

IR (KBr pellet): _max(cm^-1): 3460 (OH stretch), 3173 (C-H stretch, aromatic), 2983 (C-H

stretch, alkyl), 2925 (C-H stretch, alkyl), 2852 (C-H stretch, alkyl), 2220 (C≡C stretch),

1692 (C=O stretch, thioacetate), 1606, 1509, 1468, 1354 (C-H, alkyl),

1246 (C-O-C stretch, ether), 1169 (C-O-C stretch, ether), 1135 (C-O-X stretch,

ether/alcohol), 1076 (C-O-X stretch, ether/alcohol); UV/VIS (CHCl₃): λ_max(nm), (log ε_λ

(M^-1cm^-1)): 257, (4.50); ¹H-NMR (400 MHz, CDCl₃, 298 K): _H(ppm): 7.34 (d, 2H, ³J_HH

=

3

8.8 Hz, H_arom.), 6.81 (d, 2H, ³J_HH= 7.7 Hz, H_arom.), 3.94 (t, 2H, J_HH= 6.8 Hz, C_arom.-O-C),

3

3.49 (methanol), 2.86 (m, 4H), 2.32 (s, 3H, CH₃), 1.78 (tt, 2H, J_HH=8.4 Hz,

13

⁴J_HH=6.0 Hz), 1.53 (m, 10H, CH₂+C_t-Bu), 1.26 (m, 12H, CH₂); C-NMR (101 MHz, CDCl₃,

298 K): _C(ppm): 195.9 (C_quart./SCO), 159.1 (C_quart.), 133.0, 114.6, 114.3 (C_quart.), 89.3

(C_alkyne), 84.16 (C_alkyne), 70.9 (C_quart./t-Bu), 68.0 (C_arom.-O-C), 64.6, 50.4 (methanol), 32.2,

30.6, 29.7, 29.5, 29.5, 29.4, 29.4, 29.3, 29.2, 29.1, 28.8, 28.6, 26.0; HR/ESI-Mass m/z

(CH₃CN): [C₂₅H₃₈O₃S+H]⁺: calc.: 419.2614 [M+H]⁺, exper. 419.2620.

O

S

OH

11-acetylthioundecanoic acid (20) was synthesized according to publised

procedures.^[2]

11-bromoundecanoic acid (2.00 g, 7.54 mmol) was stirred for 18 h at 85 °C in CH₃CN

with potassium thioacetate (947 mg, 8.29 mmol). The reaction was quenched with

water 850 mL and the product extracted with diethylether (5 x 75 mL). The organic

phase was dried over MgSO₄, filtered off and concentrated under reduced pressure.

The product was obtained after column chromatography (silica, hexane/ethyl

acetate (1:1), R_f=0.26) (yield: 1.86 g, 95%).

¹H-NMR (400 MHz, CDCl₃, 298 K): _H(ppm): 2.79 (t, 2H, ³J_HH= 7.3 Hz, CH₂S), 2.26 (t+s,

5H, CH₃, CH₂-COOH), 1.54 (m, 4H, CH₂), 1.24 (m, 12H) (cf. Lit.^[3]); ¹³C-NMR (101 MHz,

CDCl₃, 298 K): _C(ppm): 196.1 (C_thioacetate), 179.39 (C_{quart./carbonyl}), 34.0, 30.6, 29.4,

29.3, 29.2, 29.1, 29.1, 29.0, 29.0, 28.7, 24.6.

HO

NH₂

4-(4-aminophenyl)-2-methylbut-3-yn-2-ol (21) was obtained from 12 (500 mg,

1.81 mmol) by an acidic deprotection with TBAF (tetra-n-butylammonium fluoride)

(2.37 g, 9.05 mmol) in THF (35 mL) at 75 °C for 12 h. The reaction mixture was

allowed to cool down and was extracted with DCM (3 x 25 mL), washed with water

A PHOTO LABILE PROTECTION STRATEGY FOR TERMINAL ALKYNES: TOWARDS PHOTO-

5

INDUCED SURFACE FUNCTIONALISATION

and brine (each 3 x 25 mL), dried over MgSO₄, filtered off and dried under vacuum.

The crude was purified by column chromatography (silica, hexane/ethyl acetate

(1:1), R_f=0.32) (yield: 289 mg, 90%, yellowish solid).

IR (KBr pellet):

(cm^-1): 3378 (O-H stretch, N-H stretch), 3035 (C-H stretch,

max

aromatic), 2980 (C-H stretch, alkyl), 2932 (C-H stretch, alkyl), 2980 (C-H stretch,

alkyl), 2222 (C≡C stretch), 1621 (N-H stretch, amine), 1608 (N-H stretch, amine),

1513 (C-C stretch, aromatic), 1376 (C-H, alkyl), 1363 (C-H, alkyl), 1280, 1171 (C-O

1

stretch, tertiary alcohol) (cf. Lit.^[12]); H-NMR (400 MHz, CDCl₃, 298 K): _H(ppm):

7.24-7.19 (m, 2H, H_arom.), 6.61-6.56 (m, 2H, H_arom.), 3.78 (s, broad, NH₂), 1.59 (s, 6H)

13

(cf. Lit.^[12]); C-NMR (101 MHz, CDCl₃, 298 K): _C(ppm): 146.7 (C_quart.), 133.1, 114.8,

112.2 (C_quart.), 91.7 (C_alkyne), 82.7 (C_alkyne), 65.8 (C_{quart. t-Bu}

), 31.8 (CH₃) (cf. Lit.^[12]);

/

UV/VIS (CHCl₃): λ_max(nm), (log ε_λ(M^-1cm^-1)): 241, (3.90), 252 (3.00).

S

Br

O

S-(12-bromododecyl) thioacetate (22)

A mixture of 1,12-dibromododecane (5.00 g, 15.24 mmol) and potassium thioacetate

(1.74 g, 15.24 mmol) was stirred in freshly distilled THF (100 mL) for 6 h at room

temperature. The crude product was extracted with diethylether (5 x 70 mL) and

washed with water and brine (3 x 50 mL). The combined organic phase was dried

over MgSO₄, filtered off and concentrated under reduced pressure. The product was

obtained as a white solid after column chromatography (silica, gradient: hexane;

hexane/ethyl acetate 30:1, hexane/ethyl acetate 10:1, R_f(hexane/ethyl acetate

10:1)=0.6) (yield: 2.07 g, 42%).

3

¹H-NMR (400 MHz, CDCl₃, 298 K): _H(ppm): 3.38 (t, 2H, J_HH= 6.9Hz, CH₂Br), 2.83 (t,

2H, ³J_HH=7.4 Hz, CH₂S), 2.23 (s, 3H, CH₃CO), 1.82 (dt, 2H, ²J_HH=14.7 Hz, ³J_HH=6.9 Hz, S-

CH₂-CH₂), 1.54 (m, 2H, Br-CH₂-CH₂), 1.31 (m, 16H, CH₂) (cf. Lit.^[1]); ¹³C-NMR (101 MHz,

CDCl₃, 298 K): _C(ppm): 195.9 (C_thioacetate), 34.0, 32.8, 30.6, 29.5, 29.5, 29.4, 29.4,

29.4, 29.1, 29.1, 29.1, 28.8, 28.7, 28.1.

HO

OH

4-(3-hydroxy-3-methylbut-1-yn-1-yl)phenol (23)

2-methyl-4-(4-((tetrahydro-2H-pyran-2-yl)oxy)phenyl)but-3-yn-2-ol (24) (960 mg,

3.68 mmol) was stirred for 4 h at room temperature with p-TsOH (175 mg, 921 μmol)

in THF/MeOH (25 mL) (1:2). The crude product was extracted with DCM (3 x 30 mL),

A PHOTO LABILE PROTECTION STRATEGY FOR TERMINAL ALKYNES: TOWARDS PHOTO-

6

INDUCED SURFACE FUNCTIONALISATION

washed with water and brine (each 3 x 30 mL), dried over MgSO₄, filtered off, and

concentrated under reduced pressure. The product was purified by column

chromatography (silica, hexane/ethyl acetate (4:1), R_f=0.2) (yield: 584 mg, 90%,

yellow solid).

IR (KBr pellet): _max(cm^-1): 3359 (O-H stretch), 3279 (C-H stretch, aromatic), 3085 (C-

H stretch, aromatic), 2981 (C-H stretch, alkyl), 2942 (C-H stretch, alkyl), 2870 (C-H

1

stretch, alkyl), 1201 (C-O stretch); H-NMR (400 MHz, CDCl₃, 298 K): _H(ppm): 7.30

(d, 2H, ³J_HH= 8.8 Hz, H_arom.), 6.78 (d, 2H, ³J_HH= 8.8 Hz H_arom.), 1.55 (s, 6H, CH₃/_t-Bu) (cf.

13

Lit.^[7]) (methanol impurity 3.49); C-NMR (101 MHz, CDCl₃, 298 K): _C(ppm): 155.9

(C_quart.), 133.3, 115.4, 114.5 (C_quart.), 88.9 (C_alkyne), 84.4 (C_alkyne), 71.5 (C_{quart. t-Bu}

/

), 28.4

(CH₃) (methanol impurity 50.4).

HO

O

2-methyl-4-(4-((tetrahydro-2H-pyran-2-yl)oxy)phenyl)but-3-yn-2-ol (24)

2-methylbut-3-yn-2-ol (982 mg, 11.7 mmol), 5 mL NEt₃and 20 mL THF were added

to a mixture of 2-(4-bromophenoxy)tetrahydro-2H-pyran (25) (1.00 g, 3.89 mmol),

CuI (44 mg, 233 μmol), PPh₃(61 mg, 233 μmol), and PdCl₂(PPh₃)₂(82 mg, 117 μmol)

under nitrogen. The reaction was heated to 80 °C and stirred for 12 h. The reaction

was quenched with water (50 mL) and extracted with DCM (3 x 50 mL). The

combined organic phase was dried over MgSO₂, filtered off, and concentrated under

reduced pressure. 24 was obtained as a light yellow solid by column chromatography

(silica, hexane/ethyl acetate (4:1), R_f=0.28) (yield: 962 mg, 95%).

IR (KBr pellet): _max(cm^-1): 3299 (O-H stretch), 3279 (C-H stretch, aromatic), 3085 (C-

H stretch, aromatic), 2981 (C-H stretch, alkyl), 2942 (C-H stretch, alkyl), 2870 (C-H

stretch, alkyl), 1228 (C-O-C stretch, ether), 1201 (C-O stretch), 1157 (C-O-C stretch,

1

ether), 1056 (C-O-C stretch, ether); H-NMR (400 MHz, CDCl₃, 298 K): _H(ppm): 7.33

3

4

(d, 2H, J_HH= 8.9 Hz, H_arom.), 6.97 (d, 2H, J_HH= 8.9 Hz, H_arom.), 5.41 (t, 1H, J_HH=

2

3

4

3.3 Hz, OCH), 4.12 (m, 1H, OCH₂CH₂), 3.87 (ddd, 1H, J_HH= 11.3, J_HH= 9.6, J_HH= 3.1

Hz, OCH₂CH₂), 3.61 (m, 1H), 2.00 (m, 2H), 1.85 (m, 1H), 1.67 (m, 2H), 1.60 (s, 6H,

3

13

C(CH₃)OH), 1.26 (t, 1H, J_HH=7.1 Hz) (cf. Lit.^[6]); C-NMR (101 MHz, CDCl₃, 298 K): _C

(ppm): 157.0 (C_quart.), 132.9, 116.3, 115.6 (C_quart.), 96.2 (OCH), 92.41 (C_alkyne), 82.0

(C_alkyne), 65.6 (C_quart./t-Bu), 62.0 (OCH2), 31.6, 30.2, 25.1, 18.7.

A PHOTO LABILE PROTECTION STRATEGY FOR TERMINAL ALKYNES: TOWARDS PHOTO-

7

INDUCED SURFACE FUNCTIONALISATION

Br

O

2-(4-bromophenoxy)tetrahydro-2H-pyran (25) was synthesized following a known

procedure.^[4]

4-bromophenol (5.00 g, 28.9 mmol) and 3,4-dihydro-2H-pyran (4.86 g, 57.8 mmol) in

DCM (50 mL) were stirred for 12 h at room temperature with catalytic amounts of p-

TsOH (20 mg, 116 μmol). The reaction was quenched with water, the product

extracted with DCM (3 x 100 mL), dried over MgSO₄, filtered off, and concentrated

under reduced pressure. The product was purified by column chromatography

(silica, gradient hexane/ethyl acetate (30:1), (10:1), R_f(hexane/ethyl acetate

10:1)=0.1) (yield: 7.06 g, 95%).

IR (KBr pellet): _max(cm^-1): 3082, 2950 (C-H stretch, alkyl), 2870 (C-H stretch, alkyl),

2710 (C-H stretch, alkyl), 2035, 1879, 1755, 1585 (C-C stretch, aromatic), 1579, 1490

(C-H, alkyl), 1450 (C-H, alkyl), 1437 (C-H, alkyl), 1391 (C-H, alkyl), 1353, 1326, 1280,

1237 (C-O-C stretch, ether), 1160 (C-O-C stretch, ether), 1072, 1056 (C-O-C stretch,

1

3

ether) (cf. Lit.^[5]); H-NMR (400 MHz, CDCl₃, 298 K): _H(ppm): 7.37 (d, 2H, J_HH

=

3

9.0 Hz, H_arom.), 6.94 (d, 2H, J_HH= 9.0 Hz, H_arom.), 5.37 (s, 1H, OCH), 3.86 (ddd, 1H,

²J_HH=11.4 Hz, ³J_HH= 9.6 Hz, ³J_HH= 3.2 Hz, OCH₂CH₂), 3.59 (dtd, 1H, ²J_HH= 11.3, ³J_HH= 4.1,

⁴J_HH= 1.5 Hz, OCH₂CH₂), 1.89 (m, 1H), 1.85 (m, 2H), 1.62 (m, 3H) (cf. Lit.^[5]); C-NMR

13

(101 MHz, CDCl₃, 298 K): _C(ppm): 156.1 (C_quart.), 132.2, 118.3, 113.8 (C_quart.), 96.4

(OCH), 62.0 (OCH2), 30.2, 25.1, 18.6 (cf. Lit.^[5]).

A PHOTO LABILE PROTECTION STRATEGY FOR TERMINAL ALKYNES: TOWARDS PHOTO-

8

INDUCED SURFACE FUNCTIONALISATION

SI-2 Synthesis and Characterization of the Photo-Cleavable Alkyne

Compounds (1-7)

General procedure to build up different photo-cleavable molecules via a mild Cu(II)

catalyzed S_N1reaction between different propargylic alcohols and 2-nitrobenzyl

alcohol.

NO₂

O

As an example the synthesis of 1-(((2-methyl-4-phenylbut-3-yn-2-yl)oxy)methyl)-2-

nitrobenzene (1) is described below:

2-nitrobenzyl alcohol (1.00 g, 6.53 mmol), 2-methyl-4-phenylbut-3-yn-2-ol (8)

(348 mg, 2.18 mmol) and CuBr₂(24 mg, 1.09 mmol) in nitromethane (20 mL) were

stirred at room temperature for 12 h in the dark. The crude product was extracted

with DCM (3 x 30 mL), the combined organic phase was washed with water and

brine (each 3 x 30 mL), dried over MgSO₄, filtered off and concentrated under

reduced pressure. 1 was obtained after column chromatography (silica, hexane/ethyl

acetate (4:1), R_f=0.4) as a yellowish oil (yield: 451 mg, 70%).

IR (KBr pellet): _max(cm^-1): 3082 (C-H stretch, aromatic), 3063 (C-H stretch, aromatic),

2984 (C-H stretch, alkyl), 2934 (C-H stretch, alkyl), 2860 (C-H stretch, alkyl), 2230

(C≡C stretch), 1672, 1611, 1598 (C-C stretch, aromatic), 1577 (C-C stretch, aromatic),

1523 (N-O stretch, nitro), 1490 (C-C stretch, aromatic), 1443 (C-C stretch, aromatic),

1379 (C-H, alkyl), 1342 (N-O, nitro), 1284 (C-O-C stretch, ether), 1155 (C-O-C stretch,

ether), 1065 (C-O-C stretch, ether; UV/VIS (CHCl₃): λ_max(nm), (log ε_λ(M^-1cm^-1)): 241,

1

3

(4.53); 252, (4.00); H-NMR (500 MHz, CDCl₃, 298 K): _H(ppm): 8.05 (dd, 1H, J_HH

=

8.2 Hz, ⁴J_HH=1.3 Hz, H_arom.), 7.90 (dd, 1H, J_HH= 8.2, 1.3 Hz H_arom.), 7.64 (td, 1H, J_HH

3

7.6, 1.3 Hz, H_arom.), 7.45-7.39 (m, 1H, H_arom.), 7.39-7.34 (m, 1H, H_arom.), 7.28 (dd, 4H,

13

J_HH= 5.2 Hz, J_HH2.1 Hz, H_arom.), 5.11 (s, 2H), 1.67 (s, 6H, CH₃); C-NMR (125 MHz,

CDCl₃, 298 K): _C(ppm): 147.4 (C_quart.), 136.1 (C_quart.), 133.6, 131.8, 129.3, 128.4,

128.4, 127.8, 124.6, 122.7 (C_quart.), 90.9 (C_alkyne), 85.0 (C_alkyne), 71.6 (C_quart./t-Bu), 63.3

(CH₂), 29.1 (CH₃); HR/ESI-Mass m/z (MeOH): [C₁₈H₁₇NO₃+Na]⁺: calc.: 318.1101,

[M+Na]⁺, exper. 318.1006.

A PHOTO LABILE PROTECTION STRATEGY FOR TERMINAL ALKYNES: TOWARDS PHOTO-

9

INDUCED SURFACE FUNCTIONALISATION

O

NO₂

HN

tert-butyl (4-(3-methyl-3-((2-nitrobenzyl)oxy)but-1-yn-1-yl)phenyl)carbamate 5 was

synthesized according to the general procedure with tert-butyl (4-(3-hydroxy-3-

methylbut-1-yn-1-yl)phenyl)carbamate (12) (500 mg, 1.82 mmol) and 2-nitrobenzyl

alcohol (556 mg, 3.63 mmol).

The product was obtained as a yellowish oil after column chromatography (silica,

hexane/ethyl acetate (4:1), R_f=0.22) (yield: 426 mg, 57%).

IR (KBr pellet): _max(cm^-1): 3331 (N-H stretch, amide), 3173 (C-H stretch, aromatic),

3089 (C-H stretch, aromatic), 2981 (C-H stretch, alkyl), 2934 (C-H stretch, alkyl), 2220

(C≡C stretch), 1731 (C=O stretch, carbonyl), 1709 (C=O stretch, carbonyl amide),

1609, 1585 (C-C stretch, aromatic), 1523 (N-O stretch, nitro), 1407, 1392 (C-H, alkyl),

1367 (C-H, alkyl), 1341 (N-O, nitro), 1230 (C-O-C stretch, ether), 1157 (C-O-C stretch,

ether), 1056 (C-O-C stretch, ether); UV/VIS (CHCl₃): λ_max(nm), (log ε_λ(M^-1cm^-1)): 268,

1

3

(4.60); H-NMR (400 MHz, CDCl₃, 298 K): _H(ppm): 8.02 (dd, 1H, J_HH= 8.2, 1.3 Hz,

3

H_arom.), 7.88 (dd, 1H, J_HH= 8.2, 1.3 Hz H_arom.), 7.61 (td, 1H, J_HH= 7.7, 1.3 Hz, H_arom.),

7.38 (td, 1H, ³J_HH= 7.7, 1.3 Hz, H_arom.), 7.26 (dd, 4H, ³J_HH= 7.6, 1.3 Hz, H_arom.), 6.56 (s,

13

broad, 1H, NH), 5.07 (s, 2H), 1.63 (s, 6H, CH₃), 1.49 (s, 9H, CH₃/_t-Bu); C-NMR (101

MHz, CDCl₃, 298 K): _C(ppm): 152.5 (C_{quart./carbonyl}), 147.4 (C_quart.), 138.6 (C_quart.), 136.1

(C_quart.), 133.6, 132.6, 129.3, 127.7, 124.5, 118.0, 116.9 (C_quart.), 89.9 (C_alkyne), 84.8

(C_alkyne), 81.0 (C_quart./_t-Bu), 71.6 (C_quart./_t-Bu), 63.3 (CH₂), 29.1 (CH₃), 28.4 (CH₃/_t-Bu);

HR/ESI-Mass m/z (MeOH): [C₂₃H₂₆N₂O₅+H]⁺: calc.: 433.1734 [M+Na]⁺, exper.

433.1739 [M+Na]⁺.

O

S

O₂N

O

HN

S-(11-((4-(3-methyl-3-((2-nitrobenzyl)oxy)but-1-yn-1-yl)phenyl)amino)-11-

oxoundecyl) ethanethioate 6 was synthesized according to the procedure given for

1

with S-(11-((4-(3-methyl-3-((2-nitrobenzyl)oxy)but-1-yn-1-yl)phenyl)amino)-11-

oxoundecyl) ethanethioate (13) (100 mg, 242 μmol) and 2-nitrobenzyl alcohol

(74 mg, 485 μmol). The product was obtained as a yellowish oil after column

chromatography (silica, hexane/ethyl acetate (1:1), R_f=0.4) (yield: 56 mg, 42%).

A PHOTO LABILE PROTECTION STRATEGY FOR TERMINAL ALKYNES: TOWARDS PHOTO-

10

INDUCED SURFACE FUNCTIONALISATION

IR (KBr pellet): _max(cm^-1): 3311 (N-H stretch, amide), 3181 (C-H stretch, aromatic),

3100 (C-H stretch, aromatic), 2983 (C-H stretch, alkyl), 2927 (C-H stretch, alkyl), 2854

(C-H stretch, alkyl), 2218 (C≡C stretch), 1691 (S-C=O stretch, amine), 1666 (C=O

stretch, amide), 1592 (C-C stretch, aromatic), 1525 (N-O stretch, nitro), 1465 (C-C

stretch, aromatic), 1341 (N-O, nitro), 1248 (S-C stretch), 1141; UV/VIS (CHCl₃): λ_max

(nm), (log ε_λ(M^-1cm^-1)): 273, (4.57); 286, (4.20); ¹H-NMR (400 MHz, CDCl₃, 298 K): _H

3

(ppm): 8.01 (dd, 1H, J_HH= 8.2, 1.4 Hz, H_arom.), 7.87 (dd, 1H, J_HH= 8.2, 1.4 Hz H_arom.),

3

4

7.61 (td, 1H, J_HH= 7.6 Hz, J_HH=1.3 Hz, H_arom.), 7.47 (m, 2H, H_arom.), 7.38 (m, 1 H,

3

H_arom.), 7.27 (m, 2H), 5.06 (s, 2H), 2.83 (m, 2H), 2.31 (d, 5H, J_H₁_H₃= 5.6 Hz), 1.95 (s,

broad, 1H, NH), 1.63 (s, 8H, CH₃), 1.52 (m, 2H), 1.27 (m, 12H); C-NMR (101 MHz,

CDCl₃, 298 K): _C(ppm): 196.4 (C_quart./SCO), 171.7 (C_{quart./carbonyl}), 147.2 (C_quart.), 138.2

(C_quart.), 135.9 (C_quart.), 133.5,132.4, 129.1, 127.6, 124.4, 119.2, 117.8 (C_quart.), 90.1

(C_{quart./alkyne}), 84.6 (C_{quart./alkyne}), 71.5 (C_{quart. t-Bu}), 63.1 (CH₂), 37.7, 30.7, 29.4, 29.3,

/

29.3, 29.2, 29.2, 29.2, 29.1, 29.1, 29.0, 28.9, 28.8, 28.7, 25.5, 23.5; HR/ESI-Mass m/z

(MeOH): [C₃₁H₄₀N₂O₅S+Na]⁺: calc.: 575.2550 [M+Na]⁺, exper. 575.2556.

Br

O

NO₂

1-(((4-(4-bromophenyl)-2-methylbut-3-yn-2-yl)oxy)methyl)-2-nitrobenzene (2)

2 was synthesized according to the procedure described for compound 1 with 4-(4-

bromophenyl)-2-methylbut-3-yn-2-ol (9) (260.1 mg, 1.09 mmol) and 2-nitrobenzyl

alcohol (334 mg, 2.18 mmol). The product was obtained as a yellowish oil after

column chromatography (silica, hexane/ethyl acetate (4:1), R_f=0.4) (yield: 297 mg,

73%).

IR (KBr pellet): _max(cm^-1): 3085 (C-H stretch, aromatic), 3068 (C-H stretch, aromatic),

2984 (C-H stretch, alkyl), 2933 (C-H stretch, alkyl), 2857 (C-H stretch, alkyl), 2234

(C≡C stretch), 1611, 1578 (C-C stretch, aromatic), 1524 (N-O stretch, nitro), 1487 (C-C

stretch, aromatic), 1393 (C-H, alkyl), 1379 (C-H, alkyl), 1341 (N-O, nitro), 1280 (C-O-C

stretch, ether), 1155 (C-O-C stretch, ether), 1069 (C-O-C stretch, ether); UV/VIS

1

(CHCl₃): λ_max(nm), (log ε_λ(M^-1cm^-1)): 261, (4.46); 252, (4.05); H-NMR (400 MHz,

3

CDCl₃, 298 K): _H(ppm): 8.04 (dd, 1H, J_HH= 8.3, 1.3 Hz, H_arom.), 7.89 (dd, 1H, J_HH

=

3

8.3, 1.3 Hz H_arom.), 7.64 (td, 1H, J_HH= 15.3, 1.3 Hz, H_arom.), 7.40 (m, 3H, H_arom.), 7.22

(d, 2H, ³J_HH= 8.6 Hz, H_arom.), 5.09 (s, 2H), 1.66 (s, 6H, CH₃); ¹³C-NMR (101 MHz, CDCl₃,

298 K): _C(ppm): 147.3 (C_quart.), 135.8 (C_quart.), 133.5, 133.1, 131.5, 129.1, 127.7,

124.4, 122.6 (C_quart.), 121.5 (C_quart.), 91.9 (C_alkyne), 83.8 (C_alkyne), 71.4 (C_{quart. t-Bu}), 63.2

/

(CH₂), 28.8 (CH₃); HR/ESI-Mass m/z (MeOH): [C₁₈H₁₆BrNO₃+Na]⁺: calc.: 396.0206

[M+Na]⁺, exper. 396.0211.

HO

O

NO₂

A PHOTO LABILE PROTECTION STRATEGY FOR TERMINAL ALKYNES: TOWARDS PHOTO-

INDUCED SURFACE FUNCTIONALISATION

11

2-methyl-4-(4-(3-methyl-3-((2-nitrobenzyl)oxy)but-1-yn-1-yl)phenyl)but-3-yn-2-ol

(3)

NEt₃(3 mL) and THF (7 mL) were added to a mixture of 1-(((4-(4-bromophenyl)-2-

methylbut-3-yn-2-yl)oxy)methyl)-2-nitrobenzene (2) (90 mg, 240 μmol), CuI

(2.73 mg, 240 μmol), PPh₃(3.78 mg, 144 μmol), and PdCl₂(PPh₃)₂(5.1 mg, 7.2 μg), 2-

methylbut-3-yn-2-ol (60 mg, 721 μmol) under nitrogen. The reaction mixture was

heated to 80 °C for 12 h. The reaction was quenched with water (25 mL), and

extracted with DCM (3 x 25 mL). The combined organic phase was dried over MgSO₂,

filtered off, and concentrated under reduced pressure. The product was obtained as

an yellow oil by column chromatography (silica, hexane/ethyl acetate (4:1), R_f=0.14)

(yield: 86 mg, 95%).

IR (KBr pellet): _max(cm^-1): 3401 (O-H stretch; N-H stretch, amide), 3081 (C-H stretch,

aromatic), 3041 (C-H stretch, aromatic), 2983 (C-H stretch, alkyl), 2936 (C-H stretch,

alkyl), 2870 (C-H stretch, alkyl), 2229 (C≡C stretch), 1611, 1577 (C-C stretch,

aromatic), 1525 (N-O stretch, nitro), 1378 (C-H, alkyl), 1361 (C-H, alkyl), 1342 (N-O,

nitro), 1275 (C-O-C stretch, ether), 1155, 1065 (C-O-C stretch, ether); UV/VIS (CHCl₃):

1

λ_max(nm), (log ε_λ(M^-1cm^-1)): 270, (4.56); 281, (4.20); H-NMR (400 MHz, CDCl₃,

3

298 K): _H(ppm): 8.03 (dd, 1H, J_HH= 8.2, 1.3 Hz, H_arom.), 7.88 (dd, 1H, J_HH= 8.2, 1.3

Hz H_arom.), 7.63 (td, 1H, ³J_HH= 7.6, 1.3 Hz, H_arom.), 7.40 (ddd, 1H, ³J_HH= 8.7, 7.6, 1.5 Hz

H_arom.), 7.35-7.24 (m, 4 H, H_arom.), 5.08 (s, 2H), 1.65 (s, 6H, CH₃), 1.60 (s, 6H, CH₃); ¹³C-

NMR (101 MHz, CDCl₃, 298 K): _C(ppm): 147.3 (C_quart.), 135.9 (C_quart.), 133.6, 131.6,

131.6, 129.2, 127.8, 124.6, 122.8 (C_quart.), 122.4 (C_quart.), 95.6 (C_{quart./alkyne}), 92.5

(C_{quart./alkyne}), 84.5 (C_{quart./alkyne}), 81.8 (C_{quart./alkyne}), 71.5 (C_{quart. t-Bu}), 65.7 (C_quart./_t-Bu),

/

63.3 (CH₂), 31.5 (CH₃), 29.0 (CH₃); HR/ESI-Mass m/z (MeOH): [C₂₃H₂₃NO₄+Na]⁺: calc.:

400.1519 [M+Na]⁺, exper. 400.1525.

H

O

NO₂

1-(((4-(4-ethynylphenyl)-2-methylbut-3-yn-2-yl)oxy)methyl)-2-nitrobenzene (4)

2-methyl-4-(4-(3-methyl-3-((2-nitrobenzyl)oxy)but-1-yn-1-yl)phenyl)but-3-yn-2-ol (3)

(30 mg, 80 μmol) was stirred for 16 h with KOH (90 mg, 1.6 mmol) in toluene (5 mL)

at 110 °C in the dark. 4 was obtained after column chromatography (silica,

hexane/ethyl acetate (4:1), R_f=0.2) (yield: 20 mg, 80%).

IR (KBr pellet):

(cm^-1): 3291 (C-H stretch, acetylenic), 3059 (C-H stretch,

max

aromatic), 2985 (C-H stretch, alkyl), 2934 (C-H stretch, alkyl), 1611, 1577 (C-C stretch,

aromatic), 1524 (N-O stretch, nitro), 1435 (C-C stretch, aromatic), 1380 (C-H, alkyl),

1341 (N-O, nitro), 1280 (C-O-C stretch, ether), 1184 (C-O-C stretch, ether), 1091 (C-

O-C stretch, ether), 1064 (C-O-C stretch, ether); UV/VIS (CHCl₃): λ_max(nm), (log ε_λ(M^-

¹cm^-1)): 267, (4.34); 279 (4.01); ¹H-NMR (400 MHz, CDCl₃, 298 K): _H(ppm): 8.04 (dd,

3

4

3

1H, J_HH= 8.3 Hz, J_HH=1.6 Hz, H_arom.), 7.88 (d, 1H, J_HH= 8.3 Hz, H_arom.), 7.63 (td, 1H,

³J_HH= 7.7 Hz, ⁴J_HH=1.3 Hz, H_arom.), 7.36 (m, 5H, H_arom.), 5.09 (s, 2H), 3.14 (s, 1H, H_alkyne),

1.65 (s, 6H, CH₃); C-NMR (101 MHz, CDCl₃, 298 K): _C(ppm): 147.2 (C_quart.), 135.8

13

(C_quart.), 133.5, 132.0, 131.6, 129.1, 127.7, 124.5, 123.0 (C_quart.), 122.0 (C_quart.), 92.7

(C_{quart./alkyne}), 84.3 (C_{quart./alkyne}), 83.1 (C_{quart./alkyne}), 78.8 (C_{quart./alkyne}), 71.4 (C_{quart. t-Bu}

/

),

A PHOTO LABILE PROTECTION STRATEGY FOR TERMINAL ALKYNES: TOWARDS PHOTO-

INDUCED SURFACE FUNCTIONALISATION

12

63.2 (CH₂), 28.8 (CH₃); HR/ESI-Mass m/z (MeOH): [C₂₀H₁₇NO₃+Na]⁺: calc.: 342.1101

[M+Na]⁺, exper. 342.1117.

NO₂

O

S

O

S-(12-(4-(3-methyl-3-((2-nitrobenzyl)oxy)but-1-yn-1-yl)phenoxy)dodecyl)

ethanethioate (7)

7 was synthesized according to the procedure described for 1 with S-(12-(4-(3-

hydroxy-3-methylbut-1-yn-1-yl)phenoxy)dodecyl) ethanethioate (14) (250 mg,

598 μmol) and 2-nitrobenzyl alcohol (183 mg, 1.195 mmol). The product was

obtained as a yellowish oil after column chromatography (silica, hexane/ethyl

acetate (4:1), R_f=0.3) (yield: 159 mg, 48%).

IR (KBr pellet): _max(cm^-1): 2925 (C-H stretch, alkyl), 2852 (C-H stretch, alkyl), 2218

(C≡C stretch), 1750, 1692 (C=O, thioacetate), 1602 (C-C stretch, aromatic), 1527 (N-O

stretch, nitro), 1509, 1463 (C-C stretch, aromatic), 1343 (N-O, nitro), 1284 (C-O-C

stretch, ether), 1245 (C-O-C stretch, ether), 1179 (C-O-C stretch, ether), 1134 (C-O-C

stretch, ether), 1107 (C-O-C stretch, ether), 1037 (C-O-C stretch, ether); UV/VIS

1

(CHCl₃): λ_max(nm), (log ε_λ(M^-1cm^-1)): 266, (4.33); 277 (4.00); 297 (shoulder); H-NMR

3

4

(400 MHz, CDCl₃, 298 K): _H(ppm): 8.04 (dd, 1H, J_HH= 8.2 Hz, J_HH= 1.3 Hz, H_arom.),

7.91 (m, 1H, H_arom.), 7.52 (td, 1H, ³J_HH= 7.6 Hz, ⁴J_HH= 1.3 Hz, 7.42 (m, 1H, H_arom.), 7.29

(m, 2H), 6.79 (m, 2H, H_arom.), 5.09 (s, 2H, H_benzyl.), 3.93 (t, 2H, J_HH= 6.6 Hz, C-S-C=O),

3

2.86 (m, 4H, C-S-C=O), 2.32 (s, 3H), 1.74 (m, 4H), 1.65 (s, 6H, C_t-Bu), 1.54 (m, 2H, CH₂),

13

1.32 (m, 12H, CH₂) (methanol impurity 3.49); C-NMR (101 MHz, CDCl₃, 298 K): _C

(ppm): 196.0 (C_{quart./thioacetate}), 159.2 (C_quart.), 147.3 (C_quart.), 136.1 (C_quart.), 133.4,

133.1, 132.2129.1, 127.5, 124.4, 114.4, 114.0 (C_quart.), 89.1 (C_{quart./alkyne}), 84.8

(C_{quart./alkyne}), 71.5 (C_quart./t-Bu), 68.0 (C_arom.-O-C), 63.1 (CH₂), 30.6, 29.5, 29.5, 29.4, 29.3,

29.1, 29.1, 29.0, 28.8, 26.0; HR/ESI-Mass m/z (CH₃CN): [C₃₂H₄₃NO₅S+H]⁺: calc.:

554.2935 [M+H]⁺, exper. 554.2940.

A PHOTO LABILE PROTECTION STRATEGY FOR TERMINAL ALKYNES: TOWARDS PHOTO-

13

INDUCED SURFACE FUNCTIONALISATION

SI-3 Light Irradiation of Compounds 1-7

The light induced deprotection of the photo-caged molecules was done for

compounds 1-7. A general procedure is described for compound 1:

HO

1 (100 mg, 339 μmol) was dissolved in either CHCl₃, THF, methanol or DCM (15 mL)

and stirred for 120 min irradiated by a UV-lamp (365 nm, 200 μWatt/cm²) in a

distance of around 2 cm. If the reaction is performed in CDCl₃, the reaction can be

followed by NMR (see Scheme 1). The crude product was extracted with DCM (3 x

30 mL), washed with water (2 x 25 mL), dried over MgSO₄, filtered off and

concentrated under reduced pressure. The product was obtained after column

chromatography (silica, hexane/ethyl acetate (4:1), R_f=0.33). Compound 8 was

obtained (characterization see above) (yield: 52 mg, 96%).

The byproduct, 2-nitrosobenzaldehyde (Lit:^[15]), can be identified by NMR-

spectroscopy.

Br

OH

9 was obtained according to the above mentioned procedure starting from 2

(characterization see above) (yield: 60 mg, 94%).

OH

HO

4-4´-(1,4-pheynylene)bis(2-methylbut-3-yn-2-ol) (10) was synthesized according to

the above mentioned procedure starting from 3 (yield: 55 mg, 86%).

¹H NMR (400 MHz, CDCl₃) δ 7.35 (m, 4H), 2.04 (s, 2H), 1.60 (s, 12H). ¹³C NMR (100.5

MHz, CDCl₃) δ 131.9, 122.5, 95.5, 81.6, 65.4, 31.4. Comparable with characterization

in Lit.^[16,17]

HO

4-(4-ethynylphenyl)-2-methylbut-3-yn-2-ol (11) was synthesized according to the

above mentioned procedure starting from 4 (yield: 51 mg, 88%).

¹H NMR (400 MHz, CDCl₃) δ 7.43 (d, J = 8.1 Hz, 2H), 7.37 (d, J = 8.1 Hz, 2H), 3.16 (s,

1H), 2.02 (s, 1H), 1.63 (s, 6H). ¹³C NMR (100.5 MHz, CDCl₃) δ 131.9, 131.5, 95.6, 82.7,

81.6, 78.8, 64.8, 31.4. Comparable with characterization in Lit.^[18]

A PHOTO LABILE PROTECTION STRATEGY FOR TERMINAL ALKYNES: TOWARDS PHOTO-

14

INDUCED SURFACE FUNCTIONALISATION

HO

O

N

O

H

12 (tert-butyl (4-(3-hydroxy-3-methylbut-1-yn-1-yl)phenyl)carbamate) was

synthesized according to the above mentioned procedure starting from 5 (yield:

60 mg, 90%) (characterization see above).

OH

O

S

N

H

O

13

(S-(11-((4-(3-methyl-3-((2-nitrobenzyl)oxy)but-1-yn-1-yl)phenyl)amino)-11-

oxoundecyl) ethanethioate) was synthesized according to the above mentioned

procedure starting from 6 (yield: 70 mg, 92%) (characterization see above).

HO

S

O

14 (S-(12-(4-(3-hydroxy-3-methylbut-1-yn-1-yl)phenoxy)dodecyl) ethanethioate)

was synthesized according to the above mentioned procedure starting from 7 (yield:

71 mg, 94%) (characterization see above).

A PHOTO LABILE PROTECTION STRATEGY FOR TERMINAL ALKYNES: TOWARDS PHOTO-

15

INDUCED SURFACE FUNCTIONALISATION

SI-4 Alkaline Irradiation of Compounds 1-7

The light-induced reaction under alkaline conditions leads to terminal alkynes. A

general procedure is given for compound 1 leading to compound 9 is described here.

ethynylbenzene (15)

1 (100 mg, 624 μmol) was dissolved in toluene (10 mL) under nitrogen conditions.

KOH powder (700 mg, 12.5 mmol) was added and the reaction mixture stirred under

reflux (110°C )and irradiation with a UV-lamp (365 nm, 200 μWatt/cm²) for 16 h. The

reaction was quenched by the addition of water. The crude product was extracted

with DCM (3 x 30 mL), dried over MgSO₄, filtered off and concentrated under

reduced pressure. The product was purified by flash chromatography to remove the

side product 2-nitrosobenzaldehyde. (yield: 45 mg, 70%)

¹H-NMR (400 MHz, CDCl₃, 298 K): _H(ppm): 7.48 (m, 2H, H_arom.), 7.30 (m, 3H, H_arom.),

13

3.07 (s, 1H, H_alkyne); C-NMR (101 MHz, CDCl₃, 298 K): _C(ppm): 132.2, 128.6, 128.1

(C_quart.), 122.2 (C_quart.), 83.5 (C_alkyne), 77.3 (C_alkyne); compound known from Lit.^[13,19]

Br

1-bromo-4-ethynylbenzene (16)

2, reaction time: 5 h (yield: 38 mg, 78%)

¹H-NMR (400 MHz, CDCl₃, 298 K): _H(ppm): 7.47 (d, 2H, ³J_HH= 8.5 Hz, H_arom.), 7.36 (d,

3

13

2H, J_HH= 8.5 Hz, H_arom.), 3.14 (s, 1H, H_alkyne); C-NMR (101 MHz, CDCl₃, 298 K): _C

(ppm): 134.1, 132.3, 122.9 (C_quart.), 121.0 (C_quart.), 83.4 (C_alkyne), 77.4 (C_alkyne);

compound known from Lit.^[20,21]

1,4-diethynylbenzene (17)

3, reaction time: 12 h (yield: 23 mg, 70%)

4, reaction time: 12 h (yield: 25 mg, 62%)

¹H-NMR (400 MHz, CDCl₃, 298 K): _H(ppm): 7.43 (s, 4H, H_arom.), 3.17 (s, 2H, H_alkyne);

¹³C-NMR (101 MHz, CDCl₃, 298 K): _C(ppm): 132.7, 123.0 (C_quart.), 84.0 (C_alkyne), 78.4

(C_alkyne); compound known from

Lit.^[16,17]

NH₂

4-ethynylaniline (18)

5, reaction time: 10 h (yield: 14 mg, 50%)

6, reaction time: 12 h (yield: 9 mg, 42%)

¹H-NMR (400 MHz, CDCl₃, 298 K): _H(ppm): 7.31 (d, 2H, ³J_HH= 8.6 Hz, H_arom.), 6.63 (d,

3

13

2H, J_HH= 8.6 Hz, H_arom.), 3.82 (s, 2H, NH₂), 2.98 (s, 1H, H_alkyne); C-NMR (101 MHz,

A PHOTO LABILE PROTECTION STRATEGY FOR TERMINAL ALKYNES: TOWARDS PHOTO-

16

INDUCED SURFACE FUNCTIONALISATION

CDCl₃, 298 K): _C(ppm): 147.1 (C_quart.), 133.6, 114.6, 111.2 (C_quart.), 84.4 (C_{quart./alkyne}),

75.0 (C_{quart./alkyne}); compound known from Lit.^[22–24]

12-(4-ethynylphenoxy)dodecane-1-thiol (19)

7, reaction time: 14 h (yield: 39 mg, 52%)

IR (KBr pellet): _max(cm^-1): 2925 (C-H stretch, alkyl), 2851 (C-H stretch, alkyl), 2220

(C≡C stretch), 1634, 1606, 1509, 1466, 1376 (C-H, alkyl), 1259 (C-O-C stretch, ether),

1169 (C-O-C stretch, ether), 1169 (C-O-X stretch, ether/alcohol), 1078 (C-O-X stretch,

1

ether/alcohol); UV/VIS (CHCl₃): λ_max(nm), (log ε_λ(M^-1cm^-1)): 254, (4.00); H-NMR

3

(400 MHz, CDCl₃, 298 K): _H(ppm): 7.33 (d, 2H, J_HH= 8.9 Hz, H_arom.), 6.79 (d, 2H,

3

³J_HH=8.9 Hz, H_arom.), 3.92 (t, 2H, J_HH= 6.6 Hz, C_arom.-O-C), 2.49 (m, 3H), 1.74 (m, 1H),

13

1.58 (m, 2H, CH₂), 1.29 (m, 17H, CH₂) (methanol impurity 3.49); C-NMR (101 MHz,

CDCl₃, 298 K): _C(ppm): 159.1 (C_quart.), 133.0, 114.6, 114.3 (C_quart.), 89.3 (C_alkyne), 84.2

(C_alkyne), 68.0 (C_arom.-O-C), 63.0, 34.0, 32.8, 32.2, 29.7, 29.5, 29.4, 29.2, 29.1, 29.0,

28.4, 28.4, 26.0, 25.7, 24.6 (methanol impurity 50.41); HR/ESI-Mass m/z

(DMC/MeOH): [C₂₀H₃₀OS-H]⁺: calc.: 317.1945 [M-H]⁺, exper. 317.1723.

A PHOTO LABILE PROTECTION STRATEGY FOR TERMINAL ALKYNES: TOWARDS PHOTO-

17

INDUCED SURFACE FUNCTIONALISATION

SI-5 NMR:

A PHOTO LABILE PROTECTION STRATEGY FOR TERMINAL ALKYNES: TOWARDS PHOTO-

INDUCED SURFACE FUNCTIONALISATION

18

A PHOTO LABILE PROTECTION STRATEGY FOR TERMINAL ALKYNES: TOWARDS PHOTO-

INDUCED SURFACE FUNCTIONALISATION

19

A PHOTO LABILE PROTECTION STRATEGY FOR TERMINAL ALKYNES: TOWARDS PHOTO-

INDUCED SURFACE FUNCTIONALISATION

20

A PHOTO LABILE PROTECTION STRATEGY FOR TERMINAL ALKYNES: TOWARDS PHOTO-

INDUCED SURFACE FUNCTIONALISATION

21

A PHOTO LABILE PROTECTION STRATEGY FOR TERMINAL ALKYNES: TOWARDS PHOTO-

INDUCED SURFACE FUNCTIONALISATION

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650

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f1 (ppm)

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f1 (ppm)

A PHOTO LABILE PROTECTION STRATEGY FOR TERMINAL ALKYNES: TOWARDS PHOTO-

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Article Doi

A photolabile protection strategy for terminal alkynes

DOI: 10.1016/j.tetlet.2013.07.144

Source and publish data:

Authors:

Article abstract of DOI:10.1016/j.tetlet.2013.07.144

Full text of DOI:10.1016/j.tetlet.2013.07.144

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