Convenient preparation of 4-arylmethyl- and 4-hetarylmethyl thiazoles by regioselective cycloaddition reactions of 3-sulfanyl- and selanylpropargyl alcohols

DOI: 10.1016/j.tet.2010.08.015

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Tetrahedron p. 7975 - 7987 (2010)

Update date:2022-09-26

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Authors:

Yoshimatsu, Mitsuhiro

Matsui, Miki

Yamamoto, Teruhisa

Sawa, Arisa

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Article abstract of DOI:10.1016/j.tet.2010.08.015

Complete details of thiazole syntheses by scandium-catalyzed cycloaddition reactions of 1-aryl- and 1,1-bisaryl-3-phenylsulfanylpropargyl alcohols with thioamides are described. Reactions of 1,1-bisarylpropargyl alcohols with thioamides and selenamide in

Full text of DOI:10.1016/j.tet.2010.08.015

Tetrahedron 66 (2010) 7975e7987

Contents lists available at ScienceDirect

Tetrahedron

journal homepage: w ww.elsevier.com/locate/tet

Convenient preparation of 4-arylmethyl- and 4-hetarylmethyl thiazoles by

regioselective cycloaddition reactions of 3-sulfanyl- and selanylpropargyl alcohols

Mitsuhiro Yoshimatsu , Miki Matsui, Teruhisa Yamamoto, Arisa Sawa

Department of Chemistry, Faculty of Education, Gifu University, Yanagido 1-1, Gifu 501-1193, Japan

a r t i c l e i n f o

a b s t r a c t

Article history:

Received 14 April 2010

Received in revised form 9 August 2010

Accepted 10 August 2010

Available online 13 August 2010

Complete details of thiazole syntheses by scandium-catalyzed cycloaddition reactions of 1-aryl- and

1,1-bisaryl-3-phenylsulfanylpropargyl alcohols with thioamides are described. Reactions of 1,1-bisar-

ylpropargyl alcohols with thioamides and selenamide in MeNO₂/H₂O resulted in 4-bisarylmethyl-1,

3-thiazoles 4aaeic and 4H-4,4-bisaryl-1,3-thiazines 5eaega in high yields. Reactions in MeNO₂/D₂O

resulted in 4-bisaryldeuteriomethyl-1,3-thiazoles 10caeia with high deuterium purity. Reactions of di-

alkyl and alkyl aryl propargyl alcohols are also described.

Keywords:

Thiazoles

Ó 2010 Published by Elsevier Ltd.

Cycloaddition

Thioamide

Propargyl alcohol

Scandium

1. Introduction

The excellent regioselectivity of these reactions is due to

a combination of the remarkable solvent effect of MeNO₂/H₂O/

Bu₄NHSO₄and the g-substituent effect of the sulfur or selenium

Hantzsch thiazole synthesis¹is one of the best and most widely

used routes to thiazoles, consisting of cyclization between a SeCeN

fragment and a CeC fragment. The most common reagents pro-

viding SeCeN fragments²are the readily available and very stable

starting materials, thioureas or thioamides. Useful reagents for

functional groups on the propargyl alcohols.¹⁰However, details of

the reaction mechanism for 1,3-thiazole synthesis were not

completely understood. In addition, reactions of disubstituted

propargyl alcohols, such as 1,1-bisarylpropargyl alcohols and 1-

ethynylcycloalkanols, were far more complex than those of the

mono-aryl propargyl alcohols.⁹To clarify the mechanisms and

limitations of these cycloaddition reactions, we performed cyclo-

additions of 1,1-bisarylpropargyl alcohols and 1,1-bisalkyl de-

rivatives. Here, we report the complete details of efﬁcient

scandium-catalyzed cycloaddition reactions in MeNO₂/H₂O.

providing CeC fragments are

pounds.⁴Other reagents providing CeC fragments, acceptors of

thioamides, have been reported as alkynyliodonium salts,⁵

-halo-

acetonitriles,⁶-diazoketones,⁷and propargyl bromides.⁸Recently,

-halo ketones³and similar com-

we reported a highly regioselective thiazole synthesis by cycload-

dition reactions of 3-sulfanyl propargyl alcohols 1 with thioamides

under mild scandium-catalyzed conditions (Scheme 1).⁹

2. Results and discussion

SPh

First, we investigated the reactions of 1,1-bisaryl and 1,1-bis

(hetaryl) propargyl alcohols 3, which were easily obtained by re-

actions of phenylsulfanyl and phenylselanylethynes and the cor-

responding bisaryl or bis(hetaryl) ketones with thiobenzamide,

thioacetamide, and benzselenamide (Table 1). Reaction of

1,1-diphenyl-3-(phenylsulfanyl)propargyl alcohol 3a with thio-

acetamide resulted in 4-diphenylmethyl-2-methyl-5-(phenyl-

sulfanyl)-1,3-thiazole 4aa in 78% yield (entry 1). The structure of

4aa was determined from the spectral features: the ¹H

SPh

R¹

PhCSNH₂, 5 mol% Sc(OTf)₃

R¹

MeNO₂-H₂O (10:1)

2a (R¹=p-MeOC₆H₄), 2b (3,4-(MeO)₂C₆H₃), 2c (3,4-(OCH₂O)C₆H₃),

2d (p-F-C₆H₄), 2e (2-thienyl)

Scheme 1. Synthesis of thiazoles from propargyl alcohols.

NMR spectrum shows a benzylic proton at

spectrum shows a benzylic carbon at 49.7 ppm, and the mass

spectrum shows a molecular ion peak at m/z 373. Reaction of 3a

5.93 ppm, the ¹³C NMR

* Corresponding author. E-mail address: yoshimae@gifu-u.ac.jp (M. Yoshimatsu).

0040-4020/$ e see front matter Ó 2010 Published by Elsevier Ltd.

doi:10.1016/j.tet.2010.08.015

7976

M. Yoshimatsu et al. / Tetrahedron 66 (2010) 7975e7987

Table 1

thioamides and selenamide exclusively provided thiazoles 4ha,

4ia, 4ib, and 4ic (entries 11e14), regioselectively.

Scandium-catalyzed cycloaddition of propargyl alcohol in MeNO₂/H₂O

R¹

1) R³CY²NH₂

2) Bu₄NHSO₄

R¹

Next, we investigated the reactions of 1,1-dialkylpropargyl alco-

hols with thioamides (Scheme 2). Reaction of 1-(phenyl-

sulfanylethynyl)cyclohexanol 3j treated with thiobenzamide under

the same conditions resulted in two types of spiro compounds, 6ja

and 5ja, by 5-exo-mode cycloaddition of the propargyl cation and 6-

Y¹Ph

R¹

Y¹Ph

R²

Y²

3) Sc(OTf)₃

4) MeNO₂-H₂O (10:1)

R³

endo-mode cycloaddition of the

a-sulfanyl allenyl cation in-

Entry Alcohol R¹

R²

Y¹R³Y²Products (% Yields)

Me 4aa (78)

Se Ph Se 4ba (55)

termediates, respectively. Product structures of both 6ja and 5ja

were conﬁrmed as described above. The identiﬁcation of compound

6ja was demonstrated by conversion to 4-methylene-1-thia-3-

azaspiro[4.5]dec-2-ene 9ja and observation of the spectral features,

p-FC₆H₄

Se Ph

4bb (75)

4ca (77)

4cb (99)

4da (88)

4ea (9)

p-FC₆H₄

which show exo-methylene at

5.15 (d, J¼1 Hz) and 5.27 (d, J¼1 Hz).

Se Ph

p-MeOC₆H₄p-MeOC₆H₄Se Ph

Desulfanylation of 5ja was achieved by successive transmetalation

with MeLi in ether via 4-tributylstannyl-2-phenyl-3-thia-1-azaspiro

[5.5]undec-2-ene to provide 8ja, whose structure was determined by

p-MeOC₆H₄p-MeOC₆H₄

5ea (70)

4fa (35) 5fa (35)

4ga (78)

2-Thienyl

4ga (18)^a5ga (44)

4ha (66)

the characteristic vicinal protons at

5.80 and 6.41 ppm (J¼10 Hz)

because of thiazine. However, both products 6ja and 5ja contain

other unknown compounds that might be regioisomers or E- and Z-

stereoisomers. Reaction in Sc(OTf)₃/MeNO₂/H₂O is ineffective for

regioselective cycloaddition of the dialkyl derivatives. We in-

vestigated reaction conditions for the cycloaddition of cyclohexanol

3j with thiobenzamide by varying the Lewis acid (e.g., BF₃/Et₂O, Yb

(OTf)₃, Sc(OTf)₃, Hf(OTf)₄, Cu(OTf)₂, Sn(OTf)₂, Ln(OTf)₃, TMSOTf, .),

solvent (MeNO₂, CH₂Cl₂, ClCH₂CH₂Cl, DMF, DMSO with or without

H₂O), and reaction temperature. Surprisingly, the best combination

of the conditions for conversion of bicyclic compounds 6ja and 5ja to

spirothiazoles is reﬂux for 10 min in hafnium triﬂate (5 mol

%)/ClCH₂CH₂Cl (entry 7 of Table 2). These optimized conditions also

apply to the reactions of other cycloalkanols and the undecanol 3k

(Scheme 2 and Table 3). Reaction of 3j with thioacetamide exclu-

sively provided (E)- and (Z)-2-methyl-4-(phenylsulfanylmethylene)-

1-thia-3-azaspiro[4.5]dec-2-ene 6jb in 65% yield (entry 1). Reactions

of cyclopentanol 3l resulted in spiro compounds 6la and 6lb in good

Se Me

Se Ph

4ia (57)

4ib (68)

Se Ph Se 4ic (68)

The reaction in the absence of H₂O gave 4,5-Dihydro-5-methyl-2,5-diphenyl-4-

(phenylsulfanylmethylene)-1,3-thiazole (6ga) in 35% yield.

with benzselenamide under approximately same conditions

resulted in the corresponding 4-diphenylmethyl 1,3-selenazole

4ba as the sole product (entry 2). Reactions of bisarylpropargyl

alcohols 3c and 3h and selenium derivatives 3d and 3i resulted in

bisarylmethyl-1,3-thiazoles (entries 2e8, 10e13), respectively.

However, reactions of bis(p-methoxyphenyl)propargyl alcohols 3e

and 3f resulted in a mixture of two compounds, the targeted

cycloadduct and an unexpected cycloadduct. To determine the

structures of the two cycloadduct products, we performed desul-

fanylation by treating 4ea with tributyltin hydride/AIBN in toluene

under reﬂux conditions. The reaction resulted in two products:

4,4-bis(p-methoxyphenyl)-4,4-dihydro-2-phenyl-1,3-thiazin 8ea

yields. Thiazole formation proceeded without formation of b-elimi-

nation products to provide 1-thia-3-azaspiro[4.4]non-2-enes 6la and

6lb. Selenium analogs 6m and spirocyclododecane 6n were also

obtained in moderate yield.

and

4-[bis(p-methoxyphenyl)methyl]-2-phenyl-5-(tributyl-

stannyl)-1,3-thiazole, which upon transmetalation with MeLi

easily provided 4-[bis(p-methoxyphenyl)methyl]-2-phenyl-1,3-

thiazole 7ea (Fig. 1). The result demonstrates that the reaction of

4ea produces both 1,3-thiazole 4ea and the unexpected thiazine

5ea via different pathways: 5-exo- or 6-endo-mode cyclization. In

particular, entry 7 contains a dramatically increased proportion of

1,3-thiazine 5ea. These different selectivities are undoubtedly re-

sponsible for the electronic natures of the propargylic carboca-

tions. In contrast, although the reaction of alcohol 3g (R¹¼phenyl;

R²¼methyl) also provided phenylethyl derivative 4ga (entry 9) in

good yield, the reaction without H₂O provided compounds 4ga,

5ga, and 6g (entry 10). These products were conﬁrmed by the same

desulfanylation reaction that resulted in thiazine 8ga and thiazole

9ga (Fig. 1). Reactions of thienyl derivatives 3h and 3i with

SPh

NH₂

Bu₄NHSO₄

Sc(OTf)₃

5ja (30%)

6ja (29%)

MeNO₂/reflux/10 min

1) Bu₃SnH/AIBN

2) MeLi/Et₂O

Bu₃SnH/AIBN

9ja (93%)

8ja (79%)

SPh

n-pent

OMe

MeO

n-pent

NH₂

Bu₄NHSO₄

Sc(OTf)₃

ClCH₂CH₂Cl-H₂O/reflux

6k (54%)

MeO

Scheme 2. Reaction of 1,1-dialkylpropargyl alcohols with thiobenzamides.

MeO

8ea

We also investigated studied the reactions of propargyl alcohols

3 with thioamides in MeNO₂/D₂O (10:1) as a mechanistically

intriguing and powerful approach to thiazole synthesis from

propargyl alcohols (Table 4). Reaction of 3c with thiobenzamide in

MeNO₂/D₂O resulted in the deuterated product 1,1-bis(p-ﬂuo-

rophenyl)methyl-5-phenylsulfanyl-1,3-thiazole 10ca (entry 1) in

75% yield with 87% deuterium purity. Reactions of 3c and 3d with

thioacetamides and benzselenamide produced various thiazoles

7ea

9ga

8ga

Figure 1.

M. Yoshimatsu et al. / Tetrahedron 66 (2010) 7975e7987

7977

Table 2

reaction medium, such as MeNO₂/H₂O fully stabilizes both the in-

termediates. Therefore, thioamides regioselectively attack the

Discovering reaction conditions for cycloaddition of cyclohexanol 3j with

thiobenzamide

sulfanyl allenyl cation 14⁰, which is thermodynamically more stable

than 14, and intramolecular cyclization then occurs in 5-exo mode

to provide 1,3-thiazole 16 (path a). In contrast, because dialkyl 14 is

not stabilized by aromatic substituents, the reactions of di-

alkylpropargyl alcohols (R¹¼R²¼alkyl) proceed via both in-

termediate 14 and 14⁰to give two types of products, thiazole 19

(through path b) and thiazine 17 (through path a). Thus, we

attempted to control the reaction path by which cycloalkanols react

with thioamides by using chlorinated solvents, such as CH₂Cl₂or

1,2-dichloroethane, which could activate the propargyl cation 14. In

the ﬁnal step, reaction by intramolecular 5-exo-mode cyclization of

iminyl propadienyl sulﬁde 18 results in 4-methylene-1,3-thiazole

19. Biaryl derivatives (R¹¼R²¼aryl) undergo smooth 5-exo-mode

attack of the nitrogen of intramolecular imine 15, providing 16

because of the strong stabilizing effect of the one or two aromatic

groups on the benzylic anions. This mechanism for the formation of

thiazoles is supported by the fact that protonation in the anionic

cyclization of imine 15 would occur with both the higher deuterium

purity and the exclusive deuteration on the 4-benzylic position of

the thiazoles. These would be the most suitable mechanisms for

formation of thiazoles. It is very interesting that the cycloadditions

of dialkyl allenyl imine 15 (R¹¼R²¼alkyl) exclusively undergo

6-endo-mode cyclization to provide thiazine 17.

SPh

PhC(=S)NH₂

Lewis Acid (5 mol%)

Bu₄NHSO₄(10 mol%)

SPh

reflux, 10 min

5ja

6ja

Entry

Condition

5ja (% yield)

6ja (% yield)(Z:E)

Sc(OTf)₃, MeNO₂

33 (10:1)

25 (8:1)

21 (3:1)

11 (5:3)

24 (9:1)

28 (13:1)

56 (99:1)

45 (99:1)

37 (99:1)

BF₃-Et₂O, MeNO₂/H₂O (10:1)

Yb(OTf)₃, MeNO₂/H₂O (10:1)

Cu(OTf)₂, MeNO₂/H₂O (10:1)

Y(OTf)₃, MeNO₂/H₂O (10:1)

Hf(OTf)₄, MeNO₂/H₂O (10:1)

Hf(OTf)₄, ClCH₂CH₂Cl

Hf(OTf)₄, ClCH₂CH₂Cl/H₂O (10:1)

Hf(OTf)₄, CHCl₃/H₂O (10:1)

Table 3

Reactions of phenylsulfanyl and phenylselanyl cycloalkanols in ClCH₂CH₂Cl

YPh

R¹

YPh

NH₂

Bu₄NHSO₄

Hf(OTf)₄

( )_n

( )

ⁿS

ClCH₂CH₂Cl/reflux/10 min

YPh

R²

R¹

Entry

Cycloalkanol 3 (Y/n¼)

Amide (R¹)

6ja (% yield)(Z:E)

3j (S/2)

3l (S/1)

3m (Se/2)

3n (S/8)

6jb (65) (88:12)

6la (43) (99:1)

6lb (47) (99:1)

6m (50) (99:1)

6n (43) (77:23)

YPh

R²

R¹

10cb and selenazole 10cc (entries 2e4 of Table 4). Cycloaddition

reactions of the monoaryl derivatives provided 11aa and 11ea in

high yields but with lower deuterium purity than that for the

bisaryl derivatives (entries 5 and 6). Reactions of most of the di-

substituted alcohols provided deuterated products 10ea, 10bec,

and 10ia with high deuterium purity (entries 7e11). Our previous

ﬁndings suggest that cycloaddition may be a stepwise process

(Scheme 3). Reaction of propargyl alcohol 12 by activation and

YPh

R²

R¹

HO Sc

Bu₄NHSO₄

R²

R¹

YPh

R¹

R²

YPh

14'

Bu₄NOH

R¹=R²=Ar

departure of its hydroxyl group resulted in intermediates a-sulfanyl

R³

and selanylpropargyl cation 14 and propadienyl cation 14⁰. In the

case of the alcohol (R¹¼R²¼aryl), the latter intermediate 14⁰is

H₂O or

DHO

D₂O

path a

R²

R¹

YPh

R³

5-exo

NH₂

stabilized by both two aromatic groups and an a-sulfanyl group. A

6-endo

R¹=R²=alkyl

YPh

R³

YPh

Table 4

R¹

Scandium-catalyzed cycloaddition of propargyl alcohol in MeNO₂/D₂O

path b

YPh

R₃

1) R³CY²NH₂

2) Bu₄NHSO₄

R¹

R²

R¹

R²

Y²Ph

( )n

5-exo

R¹

Y¹Ph

R²

R³

Scheme 3. Mechanism for formations of thiazoles and thiazines.

3) Sc(OTf)₃

4) MeNO₂-D₂O (10:1)

10, 11

1, 3

R³

Entry Alcohol R¹

R²

Y¹R³Y²Product (% yields/D%)

Finally, we examined the alkylation reactions of 4-benzylth-

p-FC₆H₄

p-MeOC₆H₄

p-FC₆H₄

10ca (75/87)

10cb (62/91)

iazoles with n-BuLi/alkyl halides, some of which were reported in

the previous communication (Table 5) to investigate the trans-

formation of the thiazoles obtained. First, we reacted lithiated

1,3-thiazoles with some electrophiles (entries 1e6). Reaction of 4-

p-methoxybenzyl-5-phenylsulfanyl-1,3-thiazole 2a with n-BuLi at

ꢀ78 ^ꢁC easily resulted in a versatile lithiated 1,3-thiazole. Reactions

with alkyl halides, such as methyl iodide, ethyl iodide, benzyl

bromide, and isopropyl iodide provided alkylated products 20aed

in moderate to high yields. Reaction of lithiated 2a with methanol-

Ph Se 10cc (43/88)

Se Ph

10da (80/88)

11aa (70/46)

11ea (90/49)

10ea (49/90)

10ha (59/90)

10hb (54/92)

p-MeOC₆H₄p-MeOC₆H₄

2-Thienyl

Ph Se 10hc (57/85)

10ia (59/90)

Se Ph

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M. Yoshimatsu et al. / Tetrahedron 66 (2010) 7975e7987

Table 5

Alkylations of lithiated thiazoles with alkyl halides

R²

R¹

SPh

R¹

SPh

R¹

1) n-BuLi/THF/-78 ^o

2) R²X

1) Bu₃SnH/AIBN

2) MeLi/ether

R₃

2,4

Entry

Thiazole

R¹

R²

n-BuLi (equiv)

R³X (equiv)

Product (% yield)

Product (% yield)^a

4aa

p-MeOC₆H₄

3,4-(MeO)₂C₆H₃

p-FC₆H₄

p-MeOC₆H₄

MeI (10)

EtI (1.5)

CD₃OD (10)

i-PrI (3)

MeI (10)

Bn (3)

20a (Me) (79)

20b (Et) (87)

20c (D) (69)

20d (i-Pr) (69)

20e (Me) (63)

20f (Bn) (50)

20g (Bn) (78)

20h (Me) (63)

20i (Me) (74)

21a (69/72)

1.5

1.2

1.5

1.2

21e (58/74)

Bn (3)

MeI (10)

21h (96/75)

21i (93/75)

The yields of both stannylation and transmetalation are, respectively, shown.

d₄resulted in mono deuterated thiazole 20c in almost pure form.

Some 4-benzylthiazoles also underwent lithiation and alkylation to

provide a wide variety of substituted thiazoles in good yields. In

contrast, alkylation of 4-bisarylmethyl-1,3-thiazole 4aa did not

proceed under some conditions. Next, we examined the desulfa-

nylation of methylated thiazoles, because neither sulfanyl nor

selanyl functional groups are necessary to provide other useful

compounds. Methylated thiazoles underwent desulfanylation to

provide thiazoles 21aei by the two-step process described above. A

representative example is described as follows. The desulfanylation

of 20a by using tributyltin hydride/AIBN, one of the usual methods

for the desulfanylation and deselanylation of bis(aryl) sulﬁdes and

bis(aryl) selenides, failed to hydrate the thiazoles, forming stan-

nylated thiazoles instead. Therefore, we performed transmetalation

of the stannanes using MeLi. The same procedures for the alkylated

thiazoles 20e, 20h, and 20i were also examined, as shown in entries

5, 8, and 9. These investigations demonstrate that the thiazole of

propargyl alcohols bearing sulfur and selenium functional groups

with thioamides is one of the most practical leading compounds

because of its useful functionalities.

tetramethylsilane as the internal standard. Splitting patterns are

designated as follows: s, singlet; d, doublet; t, triplet; q, quartet. IR

spectra were recorded with a JASCO FT-IR 460PLUS infrared spec-

trometer and are expressed in reciprocal centimeters. EI mass

spectra (MS) were obtained using a JEOL MS-700 spectrometer

with a direct-insertion probe at 70 eV. All high-resolution mass

spectra were obtained using a JMSD300 JMA2000 on-line system.

4.2. Preparations of 2-phenylthiazole (2aee)

Preparations of 4-(4-methoxybenzyl)-2-phenyl-5-(phenylsulfanyl)

thiazole (2a). Typical procedure. To a nitromethane (0.5 ml)/water

(0.05 ml) solution of 1-(p-methoxyphenyl)-3-(phenylsulfanyl)

prop-2-yn-1-ol (1a) (50 mg, 0.18 mmol) was added thiobenzamide

(50 mg, 0.37 mmol) and tetrabutylammonium hydrogensulfate

(6 mg, 0.018 mmol). Then scandium triﬂate (4 mg, 0.009 mmol)

was added to a mixture. The whole was stirred under a reﬂux

condition for 10 min and poured into a saturated NaHCO₃(50 ml).

The organic layer was separated and the aqueous layer was

extracted with ether. The combined organic layer was dried over

MgSO₄. The solvent was removed under reduced pressure. The

residue was puriﬁed by preparative TLC on silica gel eluting with

AcOEt/n-hexane (1:20) to give the title compound 2a (65 mg, 93%)

as a yellow oil.

3. Conclusion

In conclusion, we demonstrated a useful thiazole synthesis by

reaction of 3-sulfanyl and selanylpropargyl alcohols with some

thioamides and selenamides. 1-Aryl and 1,1-bis(aryl)propargyl al-

cohols resulted in 4-benzyl and 4-bisarylmethyl-1,3-thiazoles in

good-to-high yields. 1,1-Dialkyl derivatives provided two types of

products, by 5-exo- or 6-endo-mode cyclization reactions, which

we could control by choosing an appropriate solvent. We further

investigated cyclization reactions in MeNO₂/D₂O and showed de-

tails of the mechanisms for scandium-catalyzed cycloaddition re-

actions of 3-sulfanyl and selanylpropargyl alcohols with thioamides

and selenamide.

Compound 2a: IR (KBr, cm^ꢀ1

) n 3063, 3031, 2999, 2951, 2930,

2909, 2832, 1610, 1582, 1510, 1478, 1454, 1440, 1427, 1301, 1245,

1175, 1107, 1082, 1070, 1036, 1001, 985, 847, 817, 763, 741, 687, 661,

620; ¹H NMR (600 MHz, CDCl₃)

d 3.75 (3H, s, OMe), 4.19 (2H, s, CH₂),

6.77 (2H, d, J¼9 Hz, ArH), 7.14e7.17 (3H, m, ArH), 7.22e7.24 (4H, m,

ArH), 7.40e7.41 (3H, m, ArH), 7.90e7.91 (2H, m, ArH); ¹³C NMR

(150 MHz, CDCl₃)

34.7 (t), 55.2 (q),113.7 (dꢂ2), 120.9 (s), 126.2 (d),

126.5 (dꢂ2), 127.1 (dꢂ2), 128.9 (dꢂ2), 129.1 (dꢂ2), 129.9 (dꢂ2),

130.4 (d), 131.1 (s), 133.4 (s), 137.3 (s), 158.0 (s), 162.3 (s), 170.5 (s);

MS m/z 389 (M^þ), 374 (M^þꢀMe), 312 (M^þꢀPh), 280 (M^þꢀPhS).

Anal. Calcd for C₂₃H₁₆NOS₂: C, 70.92; H, 4.92; N, 3.60. Found: C,

70.79; H, 4.98; N, 3.60.

4. Experimental

4.1. General

4.2.1. 4-[(3,4-Dimethoxybenzyl)-2-phenyl-5-(phenylsulfanyl)-thia-

zole (2b). IR (KBr, cm^ꢀ1

)

2930, 1515, 1478, 1464, 1454, 1261, 1235,

Melting points were determined on a J-Science Labo micro-

melting point apparatus and uncorrected. Elemental analyses were

performed at the Center of Instrumentation of Gifu University. ¹H

and ¹³C NMR spectra were determined with JEOL ECA600

(600 MHz) spectrometer at Gifu University. Chemical shift are

expressed in parts par million (ppm) with respect to

1154, 1140, 1029, 764, 741, 689; ¹H NMR (600 MHz, CDCl₃)

3.65

(3H, s, MeO), 3.73 (3H, s, MeO), 4.11 (2H, s, CH₂), 6.65 (1H, d, J¼9 Hz,

ArH), 6.77 (1H, d, J¼9 Hz, ArH), 6.78 (1H, s, ArH), 7.02e7.16 (6H, m,

ArH), 7.31e7.33 (2H, m, ArH), 7.82 (2H, dd, J¼3 and 7 Hz, ArH); ¹³C

NMR (150 MHz, CDCl₃)

d 35.1 (t), 55.6 (q), 55.8 (q), 111.1 (d), 112.3

(d), 120.7 (s), 120.9 (d), 126.2 (d), 126.4 (dꢂ2), 127.0 (dꢂ2), 128.9

M. Yoshimatsu et al. / Tetrahedron 66 (2010) 7975e7987

7979

(dꢂ2), 129.1 (dꢂ2), 130.4 (d), 131.5 (s), 133.4 (s), 137.3 (s), 147.4 (s),

148.7 (s), 162.3 (s), 170.6 (s); MS m/z 419 (M^þ), 342 (M^þꢀPh), 310

(M^þꢀSPh). Anal. Calcd for C₂₄H₂₁S₂O₂N: C, 68.71, H, 5.05; N, 3.34.

Found: C, 68.52; H, 5.10; N, 3.30.

130.1 (s), 144.4 (sꢂ2); MS m/z 316 (M^þ), 299 (M^þꢀOH), 239

(M^þꢀPh), 207 (M^þꢀSPh). Anal. Calcd for C₂₁H₁₆OS: C, 79.71; H, 5.10.

Found: C, 79.98; H, 5.31.

4.3.2. 1,1-Diphenyl-3-(phenylselanyl)prop-2-yn-1-ol (3b). A yellow

4.2.2. 4-(3,4-Methylenedioxybenzyl)-2-phenyl-5-(phenyl-sulfanyl)

oil, IR (KBr, cm^ꢀ1

)

3433 (OH), 3059, 2170, 1953, 1577, 1490, 1477,

1449, 1440, 1327, 1179, 1162, 1058, 1031, 1021, 997, 918, 890, 776,

890, 642; ¹H NMR (600 MHz, CDCl₃)

2.95 (1H, br s, OH), 7.23e7.28

thiazole (2c). White powders, mp 63e65 ^ꢁC, IR (KBr, cm^ꢀ1

)

2886,

1712,1581,1502,1487,1442,1361,1245,1185,1039, 929, 978, 764, 740,

689; ¹H NMR (600 MHz, CDCl₃)

4.15 (2H, s, CH₂), 5.86 (2H, s, CH₂),

(5H, m, ArH), 7.31e7.34 (4H, m, ArH), 7.46e7.47 (2H, m, ArH), 7.62

6.65 (1H, d, J¼8 Hz, ArH), 6.74 (1H, d, J¼8 Hz, ArH), 6.83 (1H, d,

J¼1 Hz, ArH), 7.14e7.16 (3H, m, ArH), 7.21e7.24 (2H, m, ArH),

7.39e7.40 (3H, m, ArH), 7.89e7.91 (2H, m, ArH); ¹³C NMR (150 MHz,

(4H, br d, J¼8 Hz, ArH); ¹³C NMR (100 MHz, CDCl₃)

d 68.3 (s), 75.5

(s), 106.0 (s), 126.1 (dꢂ4), 127.2 (d), 127.8 (dꢂ2), 128.3 (dꢂ4), 128.5

(s), 129.1 (dꢂ2), 129.5 (dꢂ2), 144.6 (sꢂ2); MS m/z 364 (M^þ). Anal.

Calcd for C₂₁H₁₆OSe: C, 66.12; H, 4.44. Found: C, 66.36; H, 4.27.

CDCl₃) d 35.2 (t),100.7 (t),108.0 (d),109.5 (d),121.1 (s),121.9 (d),126.3

(d),126.5 (dꢂ2),127.1 (dꢂ2),128.9 (dꢂ2),129.1 (dꢂ2),130.4 (d),132.6

(s), 133.4 (s), 137.2 (s), 145.9 (s), 147.4 (s), 162.0 (s), 170.5 (s); MS m/z

403(M^þ), 326 (M^þꢀPh), 294(M^þꢀSPh). Anal. CalcdforC₂₃H₁₉O₂S₂N:

C, 68.46, H, 4.25; N, 3.47. Found: C, 68.04; H, 4.36; N, 3.44.

4.3.3. 1,1-Bis(p-ﬂuorophenyl)-3-(phenylsulfanyl)prop-2-yn-1-ol

(3c). Yield 69%, a yellow oil, IR (KBr, cm^ꢀ1

)

3419 (OH), 3063, 2359,

2175, 1602, 1505, 1478, 1441, 1412, 1228, 1193, 1082, 999, 902, 836,

771, 740, 688, 638, 610; ¹H NMR (600 MHz, CDCl₃)

2.86 (1H, br s,

OH), 7.01e7.04 (4H, m, ArH), 7.22e7.36 (5H, m, ArH), 7.56e7.58 (4H,

m, ArH); ¹³C NMR (100 MHz, CDCl₃)

4.2.3. 4-(4-Fluorobenzyl)-2-phenyl-5-(phenylsulfanyl)thiazole

(2d). A yellow oil, IR (KBr, cm^ꢀ1

)

3060, 2922, 1602, 1581, 1508,

1489, 1478, 1454, 1440, 1427, 1222, 1157, 1052, 1023, 986, 853, 835,

822, 778, 763, 739, 668, 661, 620; ¹H NMR (600 MHz, CDCl₃)

4.20

74.5 (s), 100.3 (s), 115.2 (dꢂ2),

115.3 (dꢂ2), 126.5 (dꢂ2), 126.9 (d), 127.9 (dꢂ2), 128.0 (dꢂ2), 129.4

(dꢂ2),132.1 (s),140.3 (sꢂ2),161.6 (s),163.2 (sꢂ2); MS m/z 352 (M^þ),

335 (M^þꢀOH). Anal. Calcd for C₂₁H₁₄F₂OS: C, 71.58; H, 4.00. Found:

C, 71.32; H, 4.11.

(2H, s, CH₂), 6.88 (2H, d, J¼8 Hz, ArH), 7.13 (2H, d, J¼8 Hz, ArH),

7.14e7.16 (1H, m, ArH), 7.19e7.26 (4H, m, ArH), 7.39e7.40 (3H, m,

ArH), 7.88e7.90 (2H, m, ArH); ¹³C NMR (150 MHz, CDCl₃)

d 34.7 (t),

114.9 (d), 115.1 (d), 121.2 (s), 126.3 (dꢂ2), 126.5 (dꢂ2), 127.1 (dꢂ2),

128.9 (dꢂ2), 129.1 (dꢂ2), 130.3 (d), 130.4 (d), 130.5 (d), 133.3 (s),

137.1 (s), 161.5 (d, J¼244 Hz), 161.7 (s), 170.6 (s); MS m/z 377 (M^þ),

300 (M^þꢀPh), 268 (M^þꢀPhS). Anal. Calcd for C₂₂H₁₆NFS₂: C, 67.00;

H, 4.27; N, 3.71. Found: C, 69.86; H, 4.29; N, 3.69.

4.3.4. 1,1-Bis(p-Fluorophenyl)-3-(phenylselanyl)propargyl

(3d). IR (KBr, cm^ꢀ1

3405, 3063, 2186, 1897, 1603, 1505, 1440, 1411,

1327, 1227, 1158, 1071, 998, 903, 838, 736, 687, 581; ¹H NMR

(600 MHz, CDCl₃)

2.99 (1H, br s, OH), 6.99e7.02 (4H, br t, J¼9 Hz,

ArH), 7.25e7.28 (3H, m, ArH), 7.45e7.47 (2H, m, ArH), 7.55e7.57

(4H, m, ArH); ¹³C NMR (150 MHz, CDCl₃)

69.0 (s), 74.5 (s), 105.3

alcohol

)

4.2.4. 2-Phenyl-5-(phenylsulfanyl)-4-(2-thienylmethyl)thiazole

(s), 115.1 (dꢂ2), 115.2 (dꢂ2), 127.4 (d), 127.9 (dꢂ2), 128.0 (dꢂ2),

128.1 (s), 129.2 (dꢂ2), 129.6 (dꢂ2), 140.4 (sꢂ2), 161.5 (sꢂ2); MS m/z

400 (M^þ), 305 (M^þꢀC₆H₄F), 243 (M^þꢀSePh). Anal. Calcd for

C₂₁H₁₄F₂OSe: C, 63.17; H, 3.53. Found: C, 62.95; H, 3.63.

(2e). White prisms, from CH₂Cl₂/n-hexane, mp 63e64 ^ꢁC, IR (KBr,

cm^ꢀ1

) n 3104, 3064, 2914, 2901, 2852, 1713, 1579, 1579, 1504, 1491,

1476,1454, 1439, 1419, 1359, 1308, 1284, 1237, 1177, 1156, 1120, 1075,

1050, 1026, 1000, 985, 923, 903, 849, 830, 763, 744, 687, 659, 625;

¹H NMR (600 MHz, CDCl₃)

4.43 (2H, s, CH₂), 6.87 (2H, d, J¼3 Hz,

ArH), 7.10e7.25 (5H, m, ArH), 7.39e7.41 (3H, m, ArH), 7.90e7.93

(2H, m, ArH); ¹³C NMR (150 MHz, CDCl₃)

30.0 (t), 121.6 (s), 124.1

4.3.5. 1,1-Bis(p-Methoxyphenyl)-3-(phenylsulfanyl)propargyl alcohol

(3e). IR (KBr, cm^ꢀ1

)

3449, 2933, 2837, 2179, 1604,1508,1463, 1417,

1305, 1252, 1171, 1082, 1033, 833, 770, 741; ¹H NMR (600 MHz,

CDCl₃)

(d), 125.6 (d), 126.4 (d), 126.5 (dꢂ2), 126.6 (d), 127.3 (dꢂ2), 128.9

(dꢂ2), 129.1 (dꢂ2), 130.5 (d), 133.3 (s), 137.0 (s), 141.0 (s), 160.7 (s),

170.6 (s); MS m/z 365 (M^þ), 280 (M^þꢀthienyl), 256 (M^þꢀPhS). Anal.

Calcd for C₂₀H₁₄NS₃: C, 65.90; H, 3.87; N, 3.84. Found: C, 65.75; H,

4.20; N, 3.80.

3.10 (1H, br s, OH), 3.78 (6H, s, OMe), 6.84 (4H, d, J¼9 Hz,

ArH), 7.17e7.20 (1H, m, ArH), 7.24e7.28 (2H, m, ArH), 7.35e7.36

(2H, m, ArH), 7.50 (4H, d, J¼9 Hz, ArH); ¹³C NMR (150 MHz, CDCl₃)

55.2 (q), 55.4 (q), 74.0 (s), 76.8 (s), 101.6 (s), 113.5 (dꢂ4), 126.2

(dꢂ2), 126.5 (d), 127.4 (dꢂ4), 129.2 (dꢂ2), 130.7 (s), 137.1 (sꢂ2),

159.1 (sꢂ2); MS m/z 375 (M^þꢀ1), 359 (M^þꢀOH), 267 (M^þꢀSPh).

Anal. Calcd for C₂₃H₂₀O₃S: C, 73.38; H, 5.35. Found: C, 73.17; H, 5.39.

4.3. Preparations of 1,1-bis(aryl)propargyl alcohols

4.3.1. 1,1-Diphenyl-3-(phenylsulfanyl)prop-2-yn-1-ol (3a). Typical

procedure. n-BuLi was added dropwise to a THF (10 ml) solution of

ethynyl phenyl sulﬁde (0.40 g, 2.98 mmol) at 0 ^ꢁC under an Ar at-

mosphere. After stirring for 10 min, benzophenone (0.65 g,

3.58 mmol) in THF (5 ml) was added to the mixture. The whole was

stirred 2 h at room temperature and poured into water (100 ml).

The organic layer was separated and the aqueous layer was

extracted with ether. The combined organic layer was dried over

MgSO₄. The solvent was removed under reduced pressure. The

residue was puriﬁed by preparative TLC on silica gel eluting with

AcOEt/n-hexane (1:10) to give the title compound (0.437 g, 46%) as

a yellow oil.

4.3.6. 1,1-Bis(p-Methoxyphenyl)-3-(phenylselanyl)propargyl alcohol

(3f). IR (KBr, cm^ꢀ1

)

3438, 2933, 2837, 2170, 1604, 1508, 1462, 1417,

1305, 1252, 1169, 1070, 1032, 998, 929, 835, 771, 738, 687; ¹H NMR

(600 MHz, CDCl₃) 2.81 (1H, br s, OH), 3.79 (6H, br s, MeO), 6.85

(4H, d, J¼9 Hz, ArH), 7.24e7.27 (3H, m, ArH), 7.47e7.49 (2H, m,

ArH), 7.51 (4H, d, J¼9 Hz, ArH); ¹³C NMR (150 MHz, CDCl₃)

d 55.3

(qꢂ2), 67.2 (s), 74.9 (s), 106.6 (s), 113.6 (dꢂ4), 126.9 (d), 127.3 (dꢂ4),

128.5 (s), 128.8 (dꢂ2), 129.4 (d), 132.1 (d), 137.2 (sꢂ2), 158.8 (sꢂ2);

MS m/z 424 (M^þ), 267 (M^þꢀSePh). Anal. Calcd for C₂₃H₂₀O₃Se: C,

65.25; H, 4.76. Found: C, 65.04; H, 4.93.

4.3.7. 1-Methyl-1-phenyl-3-(phenylsulfanyl)prop-2-yn-1-ol (3g). IR

IR (KBr, cm^ꢀ1

)

3542, 3426, 3060, 3028, 2955, 2870, 2170, 1953,

(KBr, cm^ꢀ1

)

3335 (OH), 3060, 2984, 2360, 2173, 1703, 1583, 1479,

1442, 1363, 1228, 1164, 1092, 1071, 1024, 963, 921, 903, 764, 740,

700; ¹H NMR (600 MHz, CDCl₃)

1.85 (3H, s, Me), 2.53 (1H, br s,

OH), 7.19e7.24 (1H, m, ArH), 7.29e7.33 (3H, m, ArH), 7.36e7.41 (4H,

m, ArH), 7.61e7.68 (2H, m, ArH); ¹³C NMR (150 MHz, CDCl₃)

32.9

1886,1809,1582,1490,1478,1449,1329,1179,1098,1065,1032, 999,

919, 890, 741, 699, 669, 643, 595, 532, 495, 464, 436; ¹H NMR

(600 MHz, CDCl₃)

7.25e7.30 (4H, m, ArH), 7.33e7.38 (6H, m, ArH), 7.62e7.64 (4H, m,

ArH); ¹³C NMR (100 MHz, CDCl₃)

73.8 (s), 74.9 (s), 101.3 (s), 125.7

(dꢂ2), 125.8 (dꢂ4), 126.2 (d), 127.3 (dꢂ2), 127.9 (dꢂ4), 128.9 (dꢂ2),

d 42.93 (1H, br s, OH), 7.20e7.21 (1H, m, ArH),

(q), 70.7 (s), 71.8 (s), 101.7 (s), 124.9 (dꢂ2), 126.2 (dꢂ2), 126.6 (d),

127.9 (d), 128.4 (dꢂ2), 129.3 (dꢂ2), 132.4 (s), 145.1 (s); MS m/z 254

7980

M. Yoshimatsu et al. / Tetrahedron 66 (2010) 7975e7987

(M^þ), 239 (M^þꢀMe), 177 (M^þꢀPh), 145 (M^þꢀSPh). Anal. Calcd for

2925,1713,1599,1577, 1478, 1447, 1360,1309, 1221, 1178, 1078, 1031,

998, 944, 917, 893, 841, 762, 737, 719, 701, 663, 633, 615; ¹H NMR

C₁₆H₁₄OS: C, 75.56; H, 5.55. Found: C, 75.35; H, 5.81.

(600 MHz, CDCl₃)

5.99 (1H, br s, CH), 7.15e7.46 (18H, m, ArH),

51.6 (s), 121.2

4.3.8. 1,1-Bis(2-thienyl)-3-(phenylsulfanyl)propargyl alcohol (3h). IR

7.81e7.85 (2H, m, ArH); ¹³C NMR (150 MHz, CDCl₃)

(KBr, cm^ꢀ1

)

3525, 3310, 2170, 1700, 1582, 1515, 1477, 1414, 1361,

1297, 1231, 1140, 1088, 1033, 967, 838, 786, 739, 704; ¹H NMR

(600 MHz, CDCl₃)

(s), 126.3 (dꢂ2), 127.0 (dꢂ2), 127.6 (d), 128.1 (dꢂ4), 128.9 (dꢂ2),

129.2 (dꢂ4), 129.3 (dꢂ2), 130.4 (dꢂ2), 130.4 (d), 133.0 (s), 136.3 (s),

143.0 (sꢂ2), 163.2 (s), 177.8 (s); MS m/z 531 (M^þ), 454 (M^þꢀPh), 374

(M^þꢀSePh). Anal. Calcd for C₂₈H₂₁NSe₂: C, 56.77; H, 3.57; N, 2.36.

Found: C, 56.59; H, 3.57; N, 2.38.

3.55 (1H, br s, OH), 6.93 (2H, dd, J¼4 and 5 Hz,

ArH), 7.18 (2H, dd, J¼4 and 1 Hz, ArH), 7.19e7.23 (1H, m, ArH), 7.27

(2H, dd, J¼4 and 5 Hz, ArH), 7.30e7.31 (2H, m, ArH), 7.40 (2H, br d,

J¼7 Hz, ArH); ¹³C NMR (150 MHz, CDCl₃)

d 70.2 (s), 74.5 (s), 99.3 (s),

125.5 (dꢂ2), 126.0 (dꢂ2), 126.5 (dꢂ2), 126.5 (dꢂ2), 126.8 (d), 129.3

(dꢂ2), 131.8 (s), 148.7 (sꢂ2); MS m/z 328 (M^þ), 219 (M^þꢀSPh). Anal.

Calcd for C₁₇H₁₂OS₃: C, 62.20; H, 3.68. Found: C, 61.87; H, 3.92.

4.4.3. 4-(Diphenylmethyl)-2-phenyl-5-(phenylselanyl)-1,3-thiazole

(4bb). Yield 75%, white powders, mp 124e130 ^ꢁC, IR (KBr, cm^ꢀ1

) n

3060, 3025,1948,1599,1577,1477,1453,1313,1241,1179,1156,1074,

1020, 910, 842, 762, 734, 688, 656, 619; ¹H NMR (600 MHz, CDCl₃)

4.3.9. 1,1-Bis(2-thienyl)-3-(phenylselanyl)propargyl alcohol (3i). IR

5.99 (1H, br s, CH), 7.12 (5H, m, ArH), 7.21e7.29 (6H, m, ArH),

7.35e7.37 (7H, m, ArH), 7.90e7.91 (2H, m, ArH); ¹³C NMR (150 MHz,

CDCl₃)

(KBr, cm^ꢀ1

)

3403, 3072, 2924, 2169, 1704, 1613, 1577, 1477, 1439,

1362, 1230, 1143, 1067, 1033, 999, 964, 903, 851, 738, 707; ¹H NMR

(600 MHz, CDCl₃)

3.46 (1H, br s, OH), 6.92 (2H, dd, J¼4 and 5 Hz,

ArH), 7.17 (2H, dd, J¼4 and 1 Hz, ArH), 7.23e7.30 (5H, m, ArH),

7.50e7.52 (2H, m, ArH); ¹³C NMR (150 MHz, CDCl₃)

68.2 (s), 70.3

51.0 (d), 115.3 (s), 126.3 (dꢂ2), 126.5 (dꢂ2), 127.0 (dꢂ2),

128.1 (dꢂ4), 128.8 (dꢂ2), 129.2 (dꢂ4), 129.3 (dꢂ2), 130.3 (dꢂ2),

132.1 (s), 133.5 (s), 142.8 (sꢂ2), 163.1 (s), 171.4 (s); MS m/z 483 (M^þ),

406 (M^þꢀPh), 326 (M^þꢀSePh). Anal. Calcd for C₂₈H₂₁NSSe: C,

69.70; H, 4.39; N, 2.90. Found: C, 69.69; H, 4.48; N, 2.90.

(s), 104.2 (s), 125.5 (dꢂ2), 126.0 (dꢂ2), 126.5 (dꢂ2), 127.3 (d), 128.0

(s),129.3 (dꢂ2),129.6 (dꢂ2),148.8 (sꢂ2); MS m/z 299 (M^þꢀPh), 219

(M^þꢀSePh). Anal. Calcd for C₁₇H₁₂OS₂Se: C, 54.40; H, 3.22. Found: C,

54.49; H, 3.35.

4.4.4. 4-[Bis(p-ﬂuorophenyl)methyl]-2-methyl-5-(phenylsulfanyl)-

1,3-thiazole (4ca). Yield 77%, orange powders, mp 81e86 ^ꢁC, IR (KBr,

cm^ꢀ1

)

3465, 3062, 1715, 1603, 1581, 1506, 1478, 1440, 1290, 1226,

1181,1158,1097,1050,1016,998,839,798,786,755,740, 689,619,573,

528,502;¹HNMR(600 MHz,CDCl₃)

2.67(3H,s, Me),5.86(1H, s,CH),

6.90e6.93 (4H, m, ArH), 7.03e7.04 (2H, m, ArH), 7.11e7.20 (7H, m,

ArH); ¹³C NMR (150 MHz, CDCl₃)

4.3.10. 3-n-Pentyl-3-(phenylsulfanyl)oct-1-yn-3-ol (3k). Yield 96%,

a yellow oil, IR (KBr, cm^ꢀ1

)

3412, 3061, 2932, 2170, 1708, 1584,

1479, 1378, 1140, 1023, 946, 737, 687; ¹H NMR (600 MHz, CDCl₃)

0.91 (6H, t, J¼7 Hz, Meꢂ2), 1.32e1.35 (8H, m, CH₂), 1.52e1.60 (4H,

20.0 (q), 48.2 (d),115.0 (dꢂ2),115.1

m, CH₂), 1.67e1.76 (4H, m, CH₂), 2.02 (1H, br s, OH), 7.22 (1H, br t,

J¼7 Hz, ArH), 7.32 (2H, br t, J¼8 Hz, ArH), 7.40e7.42 (2H, m, ArH);

(dꢂ2),121.2 (s),126.2 (d),127.1 (dꢂ2),129.0 (dꢂ2),130.5 (dꢂ2),130.5

(dꢂ2),137.0 (s),138.0 (sꢂ2),161.5 (dꢂ2, J¼244 Hz),161.9 (s),169.7 (s);

MS m/z 409 (M^þ), 300 (M^þꢀSPh). Anal. Calcd for C₂₃H₁₇F₂NS₂: C,

67.50; H, 4.18; N, 3.42. Found: C, 67.39; H, 4.30; N, 3.37.

¹³C NMR (150 MHz, CDCl₃)

14.0 (qꢂ2), 22.6 (tꢂ2), 24.1 (tꢂ2), 32.0

(tꢂ2), 42.0 (tꢂ2), 70.6 (s), 72.4 (s), 102.1 (s), 126.1 (dꢂ2), 126.4 (d),

129.1 (dꢂ2), 132.9 (s); MS m/z 304 (M^þ), 287 (M^þꢀOH), 195

(M^þꢀSPh). Anal. Calcd for C₁₉H₂₈OS: C, 74.95; H, 9.27. Found: C,

74.70; H, 9.26.

4.4.5. 4-[Bis(p-ﬂuorophenyl)methyl]-2-phenyl-5-(phenylsulfanyl)-

1,3-thiazole (4cb). Yield 99%, a yellow oil, IR (KBr, cm^ꢀ1

) n 3062,

1714, 1603, 1581, 1506, 1479, 1455, 1431, 1295, 1227, 1158, 1098,

4.4. Syntheses of 1,3-thiazoles from 1,1-bis(aryl)-3-

(phenylsulfanyl)propargyl alcohols

1048,1016,1001, 917, 838, 791, 762, 740, 688, 608, 573, 529; ¹H NMR

(600 MHz, CDCl₃)

7.08e7.19 (6H, m, ArH), 7.27e7.29 (4H, m, ArH), 7.39e7.41 (2H, m,

ArH), 7.89e7.90 (2H, m, ArH); ¹³C NMR (150 MHz, CDCl₃)

48.5 (d),

d 5.89 (1H, s, CH), 6.91e6.94 (4H, m, ArH),

Scandium triﬂate (4 mg, 0.008 mmol) was added to a MeNO₂

(0.50 ml)/H₂O (0.10 ml) solution of 3a (50 mg, 0.16 mmol), thio-

acetamide (24 mg, 0.32 mmol), and tetrabutylammonium hydro-

gensulfate (11 mg, 0.032 mmol). The reaction mixture was reﬂuxed

for 10 min and poured into a saturated NaHCO₃(50 ml). The organic

layer was separated and the aqueous layer was extracted with

ether. The combined organic layer was dried over MgSO₄. The

solvent was removed under reduced pressure. The residue was

puriﬁed by preparative TLC on silica gel eluting with AcOEt/n-

hexane (1:50) to give 4-diphenylmethyl-2-methyl-5-(phenyl-

sulfanyl)-1,3-thiazole (4aa) (46 mg, 78%) as a yellow oil.

114.9 (dꢂ2), 115.1 (dꢂ2), 122.1 (s), 126.5 (dꢂ2), 126.5 (dꢂ2), 127.4

(dꢂ2), 128.9 (dꢂ2), 129.1 (dꢂ2), 130.5 (dꢂ2), 130.6 (dꢂ2), 133.4 (s),

136.8 (s), 138.1 (sꢂ2), 160.8 (s), 162.4 (s), 162.7 (s), 170.6 (s); MS m/z

471 (M^þ), 362 (M^þꢀSPh). Anal. Calcd for C₂₈H₁₉NF₂S₂: C, 71.31; H,

4.06; N, 2.97. Found: C, 71.26; H, 4.25; N, 2.95.

4.4.6. 4-[Bis(p-ﬂuorophenyl)methyl]-2-phenyl-5-(phen_ꢀy₁lselanyl)-

) n 3422,

1,3-thiazole (4da). Yield 88%, mp 76e80 ^ꢁC, IR (KBr, cm

3060, 1889, 1713, 1603, 1577, 1506, 1478, 1453, 1438, 1361, 1302,

1225, 1158, 1097, 1068, 1020, 1000, 981, 943, 917, 879, 839, 790, 762,

736, 688, 607; ¹H NMR (600 MHz, CDCl₃)

d 5.93 (1H, s, CH),

4.4.1. 4-(Diphenylmethyl)-2-methyl-5-(phenylsulfanyl)-1,3-thiazole

6.90e6.93 (4H, m, ArH), 7.13e7.19 (3H, m, ArH), 7.21e7.28 (6H, m,

(4aa). IR (KBr, cm^ꢀ1

) n 3429, 3060, 3025, 2922, 1947, 1878, 1803,

ArH), 7.39e7.40 (3H, m, ArH), 7.89e7.90 (2H, m, ArH); ¹³C NMR

1733, 1600, 1581, 1495, 1478, 1440, 1373, 1308, 1254, 1180, 1129,

(150 MHz, CDCl₃)

49.4 (d), 114.9 (dꢂ2), 115.1 (dꢂ2), 115.3 (s), 126.5

1077,1049,1024, 999, 912, 844, 785, 740, 699. 637, 624, 582, 548; ¹H

(dꢂ2), 127.1 (d), 128.9 (dꢂ2), 129.4 (dꢂ2), 130.2 (dꢂ2), 130.5 (d),

130.5 (dꢂ2), 130.6 (dꢂ2), 131.9 (s), 133.3 (s), 138.4 (s), 138.4 (s),

160.5 (dꢂ2, J¼246 Hz), 162.6 (s), 171.7 (s); MS m/z 519 (M^þ). Anal.

Calcd for C₂₈H₁₉F₂NSSe: C, 64.86; H, 3.69; N, 2.70. Found: C, 64.47;

H, 3.80; N, 2.68.

NMR (600 MHz, CDCl₃)

7.06e7.07 (2H, m, ArH), 7.10e7.27 (13H, m, ArH); ¹³C NMR

(150 MHz, CDCl₃) 20.2 (q), 49.7 (d), 121.0 (s), 126.1 (d), 126.4

d 2.66 (3H, s, Me), 5.93 (1H, s, CH),

(dꢂ2), 127.2 (dꢂ2), 128.2 (dꢂ4), 129.0 (dꢂ2), 129.2 (dꢂ4), 137.2 (s),

142.4 (sꢂ2), 162.4 (s), 169.4 (s); MS m/z 373 (M^þ) 296 (M^þꢀPh) 264

(M^þꢀSPh). Anal. Calcd for C₂₃H₁₉NS₂: C, 74.00; H, 5.13; N, 3.75.

Found: C, 73.64; H, 5.14; N, 3.48.

4.4.7. 4-[Bis(p-methoxyphenyl)methyl]-2-phenyl-5-(phenylsulfanyl)-

1,3-thiazole (4ea) and 4,4-bis(p-methoxyphenyl)-4,4-dihydro-2-

phenyl-6-(phenylsulfanyl)-1,3-thiazine

(5ea). Compounds 4ea/

4.4.2. 4-(Diphenylmethyl)-2-phenyl-5-(phenylselanyl)-1,3-selena-

5ea¼1:8, white powders, mp 79e83 ^ꢁC, IR (KBr, cm^ꢀ1

) n 3434, 3059,

zole (4ba). Yield 55%, a yellow oil, IR (KBr, cm^ꢀ1

)

3059, 3025,

2928, 2834, 2359, 1772, 1685, 1606, 1580, 1508, 1475, 1459, 1441, 1302,

M. Yoshimatsu et al. / Tetrahedron 66 (2010) 7975e7987

7981

1250, 1173,1083,1036, 995, 961, 906, 888, 830, 805, 767, 745, 690, 609;

¹H NMR (600 MHz, CDCl₃)

3.76 (s, 4-Me), 3.77 (s, 5-Me), 5.85 (br s, 4-

¹H NMR (600 MHz, CDCl₃)

3.78 (3H, s, OMe), 5.64 (1H, s, CH),

6.69 (1H, s, oleﬁnic H), 6.84 (2H, d, J¼8 Hz, ArH), 7.13 (2H, d, J¼8 Hz,

CH), 6.57 (s, 5-oleﬁnic H), 6.78 (br d, J¼8 Hz, ArH), 6.84 (br d, J¼8 Hz,

ArH), 7.38e7.40 (3H, m, ArH), 7.91e7.93 (2H, m, ArH); ¹³C NMR

ArH), 7.13e7.42 (m, ArH), 7.87 (br d, J¼7 Hz, ArH); ¹³C NMR (150 MHz,

(150 MHz, CDCl₃)

52.1 (d), 55.2 (q), 113.7 (dꢂ2), 116.0 (d), 126.6

CDCl₃)

48.4 (4-d), 55.2 (4- and 5-q), 71.2 (5-s),113.5 (d),113.5 (d),125.7

(dꢂ2), 128.8 (dꢂ2), 130.0 (dꢂ2), 133.8 (s), 135.4 (s), 158.1 (sꢂ2),

(s), 127.5 (d),128.4 (d), 128.5 (d), 129.1 (d), 130.3 (d), 131.1 (d), 132.2 (d),

133.3 (s), 135.2 (s), 137.2 (s), 138.9 (s), 155.5 (s), 158.4 (s); MS m/z 495

(M^þ), 386 (M^þꢀSPh). Anal. Calcd for C₃₀H₂₅NO₂S₂: C, 72.70; H, 5.08; N,

2.83. Found: C, 72.49; H, 5.06; N, 2.83.

160.7 (s); MS m/z 387 (M^þ).

4.5.2. 4,4-Bis(p-methoxyphenyl)-4,4-dihydro-2-phenyl-1,3-thiazine

(8ea). IR (KBr, cm^ꢀ1

)

2954, 2930, 1607, 1579, 1508, 1463, 1445,

1302, 1249, 1114, 1069, 1036, 984, 956, 830, 811, 767, 961; ¹H NMR

(600 MHz, CDCl₃)

4.4.8. 4-[Bis(p-methoxyphenyl)methyl]-2-phenyl-5-(phenylselanyl)-

1,3-thiazole (4fa) and 4,4-bis(p-methoxyphenyl)-4,4-dihydro-2-phe-

nyl-6-(phenylselanyl)-1,3-thiazine (5fa). Compounds 4fa/5fa¼1:1,

3.77 (6H, s, OMe), 6.13 (1H, d, J¼10 Hz, oleﬁnic

H), 6.67 (1H, d, J¼10 Hz, oleﬁnic H), 6.83 (4H, d, J¼8 Hz, ArH), 7.32

(4H, d, J¼8 Hz, ArH), 7.25e7.44 (3H, m, ArH), 7.96 (2H, d, J¼7 Hz,

a yellow oil, IR (KBr, cm^ꢀ1

)

3449, 3060, 3000, 2953, 2904, 2833,

ArH); ¹³C NMR (150 MHz, CDCl₃)

55.2 (qꢂ2), 67.4 (d), 113.4 (dꢂ2),

2366, 1699, 1607, 1578, 1508, 1477, 1462, 1439, 1302, 1250, 1174,

117.7 (dꢂ4), 117.8 (d), 126.8 (d), 127.3 (dꢂ2), 128.4 (dꢂ2), 128.6

(dꢂ4), 130.8 (d), 137.8 (s),139.4 (sꢂ2),154.2 (s), 158.2 (sꢂ2); MS 387

(M^þ), 380 (M^þꢀp-MeOC₆H₄). Anal. Calcd for C₂₄H₂₁NO₂S: C, 74.39;

H, 5.46; N, 3.61. Found: C, 73.71; H, 5.66; N, 3.53.

1086, 1036, 988, 906, 832, 789, 765, 738, 689, 611; ¹H NMR

(600 MHz, CDCl₃) d 3.75 (s, OMe), 3.77 (s, OMe), 5.88 (s, 4-CH), 6.62

(s, 5-CH), 6.78 (d, J¼8 Hz, ArH), 6.82 (d, J¼8 Hz, ArH), 7.15e7.53 (m,

ArH), 7.87 (d, J¼8 Hz, ArH), 7.91 (br d, J¼4 Hz, ArH); ¹³C NMR

(150 MHz, CDCl₃)

49.4 (d, 4-CH), 55.2 (q), 55.2 (q), 70.8 (s, 5-C),

4.5.3. 4-(1-Phenylethyl)-2-phenyl-5-(phenylsulfanyl)-1,3-thiazole

113.5 (d), 113.5 (d), 114.7 (s), 118.9 (s), 126.5 (d), 126.9 (d), 127.4 (d),

127.9 (d),128.4 (d),128.5 (d),128.8 (d),129.3 (d),129.3 (d),130.0 (d),

130.2 (d), 131.0 (d), 132.7 (d), 133.1 (d), 133.5 (s), 135.4 (s), 135.4 (s),

137.2 (s), 139.0 (s), 155.6 (s),158.0 (s), 163.7 (s),171.4 (s); MS m/z 543

(M^þ), 528 (M^þꢀMe), 436 (M^þꢀMeOC₆H₄). Anal. Calcd for

C₃₀H₂₅NO₂SSe: C₃₀H₂₅NO₂SSe: C, 70.58; H, 4.94; N, 2.74. Found: C,

70.79; H, 4.94; N, 2.68.

(4ga). Yield 78%, a yellow oil, IR (KBr, cm^ꢀ1

) n 3060, 3026, 2969,

2928, 2868, 2360, 1946, 1801, 1581, 1478, 1450, 1371, 1316, 1242,

1179, 1157, 1076, 1025, 1001, 792, 914, 840, 763, 738, 713, 688, 662,

610; ¹H NMR (600 MHz, CDCl₃)

1.73 (3H, d, J¼7 Hz, Me), 4.63 (1H,

q, J¼7 Hz, CH), 7.07e7.23 (8H, m, ArH), 7.39e7.47 (5H, m, ArH),

7.93e7.95 (2H, m, ArH); ¹³C NMR (150 MHz, CDCl₃)

21.8 (q), 39.2

(d), 119.7 (s), 126.1 (d), 126.2 (d), 126.5 (dꢂ2), 127.0 (dꢂ2), 127.8

(dꢂ2), 128.2 (dꢂ2), 128.8 (dꢂ2), 129.0 (dꢂ2), 130.3 (d), 133.6 (s),

137.4 (s), 144.5 (s), 166.0 (s), 170.3 (s); MS m/z 373 (M^þ), 358

(M^þꢀMe), 264 (M^þꢀSPh). Anal. Calcd for C₂₃H₁₉NS₂: C, 73.96; H,

5.13; N, 3.75. Found: C, 73.65; H, 5.15; N, 3.75.

4.4.9. Pure 5fa. IR (KBr, cm^ꢀ1

1462, 1440, 1303, 1249, 1173, 1089, 1036, 989, 960, 906, 861, 829,

767, 740, 690; ¹H NMR (600 MHz, CDCl₃)

3.78 (3H, s, OMe), 6.62

) n 3058, 2928, 2834, 1606, 1578, 1507,

(1H, s, oleﬁnic H), 6.82 (4H, d, J¼8 Hz, ArH), 7.27 (4H, m, ArH),

7.30e7.31 (2H, m, ArH), 7.35e7.38 (2H, m, ArH), 7.42e7.43 (1H, m,

ArH), 7.53e7.54 (2H, m, ArH), 7.87e7.88 (2H, br d, J¼8 Hz, ArH); ¹³C

4.5.4. 4H-4-Methyl-2,4-diphenyl-6-(phenylsulfanyl)-1,3-thiazole

(5ga). IR (KBr, cm^ꢀ1

) n 3059, 3024, 2975, 2883, 1954, 1685, 1617,

NMR (150 MHz, CDCl₃)

55.2 (qꢂ2), 70.8 (s), 113.5 (dꢂ4), 118.9 (s),

1580, 1476, 1445, 1368, 1312, 1275, 1230, 1178, 1072, 1026, 1001, 948,

127.5 (dꢂ2), 127.9 (d), 128.4 (dꢂ2), 128.5 (dꢂ4), 129.3 (s and dꢂ2),

131.0 (d), 132.7 (dꢂ2), 133.1 (d), 137.2 (s), 139.0 (sꢂ2), 155.6 (s),

158.3 (sꢂ2); MS m/z 511 (M^þ). Anal. Calcd for C₂₄H₂₁NO₂S: C, 66.41;

H, 4.64; N, 2.58. Found: C, 66.22; H, 4.68; N, 2.58.

893, 829, 764, 741, 689, 664, 629, 609; ¹H NMR (600 MHz, CDCl₃)

1.84 (3H, s, Me), 6.44 (1H, s, oleﬁnic H), 7.30e7.50 (12H, m, ArH),

7.87 (2H, d, J¼7 Hz, ArH); ¹³C NMR (150 MHz, CDCl₃)

d 29.6 (q), 65.7

(s), 124.9 (s), 125.9 (dꢂ2), 126.9 (d), 127.3 (d), 127.5 (d), 128.3 (dꢂ2),

128.5 (dꢂ2), 129.1 (dꢂ2), 129.8 (dꢂ2), 131.1 (d), 133.6 (d), 137.2 (s),

133.6 (s), 146.6 (s), 156.4 (s); MS m/z 373 (M^þ), 358 (M^þꢀMe), 296

(M^þꢀPh), 264 (M^þꢀSPh). High-resolution mass calcd for

C₂₃H₁₉NS₂: 373.0959, found m/z: 373.0964.

4.5. Structure determination by reaction of 4fa and 5fa with

tributyltin hydride/AIBN

A toluene (1.5 ml) solution of 4fa and 5fa (33 mg, 0.07 mmol),

tributyltin hydride (0.17 ml, 0.70 mmol), and AIBN (2 mg) was stir-

redunder reﬂuxcondition for 4 h. The solvent was evaporated under

reduced pressure. The residue was puriﬁed by preparative TLC on

silica gel eluting with AcOEt/n-hexane (1:40) to give 4-[bis(p-

methoxyphenyl)methyl]-2-phenyl-5-(tributylstannyl)-1,3-thiazole

(24 mg, 55%) as a yellow oil and 4,4-bis(p-methoxyphenyl)-4,4-

dihydro-2-phenyl-1,3-thiazine (8 mg, 32%) as a yellow oil.

4.5.5. 4H-6-Methyl-2,4-diphenyl-6-tributylstannyl-1,3-thiazine. A

colorless oil, IR (KBr, cm^ꢀ1

)

2956, 2925, 2852, 2360, 2341, 1601,

1578, 1558, 1490, 1457, 1446, 1417, 1376,1287, 1232, 1177, 1073,1028,

952, 939, 881, 839, 764, 691, 668; ¹H NMR (600 MHz, CDCl₃)

0.89

(9H, t, J¼7 Hz, Meꢂ3), 1.06e1.09 (6H, m, CH₂), 1.32e1.37 (6H, m,

CH₂), 1.55e1.59 (6H, m, CH₂), 6.02 (1H, s, oleﬁnic H), 7.20e7.22 (1H,

m, ArH), 7.29e7.39 (2H, m, ArH), 7.39e7.45 (4H, m, ArH), 7.51 (2H,

br d, J¼9 Hz, ArH), 7.95 (2H, br d, J¼8 Hz, ArH); ¹³C NMR (150 MHz,

4.5.1. 4-[Bis(p-methoxyphenyl)methyl]-2-phenyl-5-(tributylstannyl)-

CDCl₃)

10.3 (tꢂ3), 13.7 (qꢂ3), 27.2 (tꢂ3), 28.9 (tꢂ3), 29.2 (q), 62.0

1,3-thiazole. IR (KBr, cm^ꢀ1

)

2955, 2928, 2852, 1608, 1509, 1478,

1302, 1250, 1176, 1110, 1074, 1038, 962, 831, 811, 790, 762, 690; ¹H

NMR (600 MHz, CDCl₃)

(s), 126.2 (dꢂ2), 126.4 (d), 127.4 (dꢂ2), 127.9 (dꢂ2), 128.4 (dꢂ2),

130.3 (s), 130.5 (d), 135.8 (d), 138.2 (s), 147.7 (s), 158.1 (s); MS m/z

540 (M^þꢀBu).

0.85 (9H, t, J¼7 Hz, Meꢂ3), 1.25e1.30

(12H, m, CH₂), 1.47e1.52 (6H, m, CH₂), 3.76 (6H, s, OMeꢂ2), 5.26

(1H, s, CH), 6.80 (4H, d, J¼8 Hz, ArH), 7.26 (4H, d, J¼8 Hz, ArH),

7.25e7.38 (3H, m, ArH), 7.95 (2H, d, J¼8 Hz, ArH); ¹³C NMR

4.5.6. 4H-6-Methyl-2,4-diphenyl-1,3-thiazine (8ga). A yellow oil, IR

(KBr, cm^ꢀ1

)

3083, 3058, 3025, 2971, 2924, 2860, 1633, 1577, 1490,

1445, 1368, 1254, 1220, 1178, 1157, 1093, 1073, 930, 878, 765, 730,

691, 655; ¹H NMR (600 MHz, CDCl₃)

1.78 (3H, s, Me), 6.01 (1H, d,

(150 MHz, CDCl₃)

11.2 (tꢂ3), 13.6 (qꢂ3), 29.0 (tꢂ3), 53.5 (d), 55.2

(qꢂ2), 113.4 (dꢂ4), 125.1 (s), 126.6 (dꢂ2), 128.6 (dꢂ2), 129.3 (d),

129.9 (dꢂ4), 134.3 (s), 136.6 (sꢂ2), 157.9 (sꢂ2), 164.9 (s), 172.3 (s);

MS m/z 676 (small M^þ), 620 (M^þꢀBu).

J¼10 Hz, oleﬁnic H), 6.50 (1H, d, J¼10 Hz, oleﬁnic H), 7.22e7.24 (1H,

m, ArH), 7.32e7.35 (2H, m, ArH), 7.40e7.47 (3H, m, ArH), 7.51e7.52

(2H, m, ArH), 7.93e7.95 (2H, m, ArH); ¹³C NMR (150 MHz, CDCl₃)

The compound underwent transmetalation by MeLi in ether at

ꢀ78 ^ꢁC to give 4-bis(p-methoxyphenyl)methyl-2-phenyl-1,3-thia-

zole (7ea) (36%) as a yellow oil.

29.3 (q), 61.9 (s), 117.0 (d), 125.9 (dꢂ2), 126.7 (d), 127.2 (d), 127.3

(dꢂ2), 128.2 (dꢂ2), 128.5 (dꢂ2), 130.8 (d), 137.8 (s), 147.2 (s), 155.0

7982

M. Yoshimatsu et al. / Tetrahedron 66 (2010) 7975e7987

(s); MS m/z 265 (M^þ), 250 (M^þꢀMe). Anal. Calcd for C₁₇H₁₅NS: C,

3430, 3065, 2924, 2853, 2388, 2349, 2285, 1712, 1631, 1577, 1477,

1437, 1361, 1316, 1222, 1178, 1068, 1039, 1020, 1000, 980, 920, 853,

763, 737, 689, 637, 617; ¹H NMR (600 MHz, CDCl₃)

6.44 (1H, br s,

76.94; H, 5.70; H, 5.28. Found: C, 76.47; H, 5.81; N, 5.24.

4.5.7. 4,5-Dihydro-5-methyl-2,5-diphenyl-4-(phenylsulfanyl-

CH), 6.87 (2H, br t, J¼4 Hz, ArH), 6.96 (2H, br s, ArH), 7.18 (5H, br t,

methylene)-1,3-thiazole (6ga). A yellow oil, IR (KBr, cm^ꢀ1

) n 2925,

J¼5 Hz, ArH), 7.31 (2H, br t, J¼4 Hz, ArH), 7.38e7.41 (3H, m, ArH),

2854, 2360, 2342, 1610, 1579, 1541, 1491, 1478, 1447, 1368, 1313, 1256,

7.96e7.97 (2H, m, ArH); ¹³C NMR (150 MHz, CDCl₃)

d 42.4 (d), 114.9

1177, 1160, 1132, 1070, 1027, 953, 840, 765, 741, 689, 669; ¹H NMR

(s), 125.0 (dꢂ2), 125.8 (dꢂ2), 126.2 (dꢂ2), 126.6 (dꢂ2), 127.2 (d),

128.9 (dꢂ2), 129.4 (dꢂ2), 130.4 (dꢂ2), 130.5 (d), 131.8 (s), 133.3 (s),

145.8 (sꢂ2), 161.9 (s), 172.1 (s); MS m/z 495 (M^þ), 338 (M^þꢀSePh).

High-resolution mass calcd for C₂₄H₁₇NS₃Se: 494.9703, found m/z:

494.9688.

(600 MHz, CDCl₃) d 1.96 (3H, s, Me), 6.06 (1H, s, oleﬁnic H), 7.15e7.16

(3H, m, ArH), 7.23e7.28 (2H, m, ArH), 7.28e7.34(1H, m,ArH),7.41e7.45

(4H, m, ArH), 7.49e7.51 (1H, m, ArH), 7.90e7.91 (2H, m, ArH); ¹³C NMR

(150 MHz, CDCl₃)

27.8 (q), 86.8 (s), 111.8 (d), 125.8 (dꢂ2), 126.4 (d),

127.6 (d), 128.0 (dꢂ2), 128.3 (dꢂ2), 128.5 (dꢂ2), 128.6 (dꢂ2), 128.7

(dꢂ2),129.1(dꢂ2),131.6 (d),132.8 (s),135.7(s),143.8 (s),154.9 (s),162.2

(s); MS m/z 373 (M^þ), 358 (M^þꢀMe), 296 (M^þꢀPh); high resolution

mass calcd for C₂₃H₁₉NS₂: 373.0955, found m/z 373.0941.

4.5.13. 4-[Bis(2-thienyl)methyl]-2-phenyl-5-(phenylselanyl)-1,3-se-

lenazole (4ic). Yield 68%, white prisms, mp 119e124 ^ꢁC, IR (KBr,

cm^ꢀ1

)

3448, 3067, 2925, 2853, 2388, 2349, 2285, 1712, 1625, 1577,

1507, 1476, 1455, 1437, 1361, 1279, 1227, 1177, 1069, 1021, 999, 943,

851, 762, 736, 689, 619; ¹H NMR (600 MHz, CDCl₃)

6.46 (1H, br s,

4.5.8. 4,5-Dihydro-5-methyl-2,5-diphenyl-4-(tributylstannyl-methy-

lene)-1,3-thiazole. A yellow oil, IR (KBr, cm^ꢀ1

)

2956, 2926, 2853,

CH), 6.87 (2H, br d, J¼3 Hz, ArH), 6.88 (2H, br s, ArH), 7.31e7.53 (6H,

1606, 1579, 1561, 1492, 1448, 1417, 1375, 1339, 1312, 1256, 1217, 1176,

m, ArH), 7.88 (2H, dd, J¼2 and 4 Hz, ArH); ¹³C NMR (150 MHz,

1134, 1073, 1028, 1001, 956, 864, 765, 690, 657, 628; ¹H NMR

CDCl₃)

43.0 (d), 120.6 (s), 125.0 (dꢂ2), 126.2 (dꢂ2), 127.1 (dꢂ2),

(600 MHz, CDCl₃)

0.87 (9H, t, J¼7 Hz, Meꢂ3), 0.99 (6H, t, J¼7 Hz,

127.2 (d), 128.6 (s), 128.9 (dꢂ2), 129.4 (dꢂ2), 130.4 (dꢂ2), 130.6 (d),

136.1 (s), 145.9 (sꢂ2), 162.0 (s), 178.6 (s); MS m/z 543 (M^þ). Anal.

Calcd for C₂₄H₁₇NS₂Se₂: C, 53.20; H, 3.16; N, 2.59. Found: C, 53.24;

H, 2.95; N, 2.56.

CH₂ꢂ3), 1.27e1.31 (6H, m, CH₂ꢂ3), 1.47e1.52 (6H, m, CH₂ꢂ3), 5.87

(1H, s, oleﬁnic H), 7.24e7.26 (1H, m, ArH), 7.31e7.35 (2H, m, ArH),

7.41e7.48 (10H, m, ArH), 7.86e7.87 (2H, m, ArH); ¹³C NMR (150 MHz,

CDCl₃)

9.9 (tꢂ3),13.7 (qꢂ3), 27.3 (tꢂ3), 28.2 (q), 29.1 (tꢂ3), 88.3 (s),

118.9 (d), 125.9 (dꢂ2), 127.1 (d), 128.2 (dꢂ3), 128.5 (dꢂ2), 131.3 (d),

4.6. Reactions of phenylsulfanylethynylcycloalkanols with

thiobenzamide

133.5 (s), 144.7 (s), 163.0 (s), 165.1 (s); MS m/z 496 (M^þꢀBu).

4.5.9. 4,5-Dihydro-5-methyl-2,5-diphenyl-4-methylene-1,3-thiazole

4.6.1. Reaction of phenylsulfanylethynylcyclohexanol (3j) with thio-

benzamide. Typical procedure. Haffnium triﬂate (33 mg, 0.04 mmol)

was added to a 1,2-dichloroethane (1.0 ml)/H₂O (0.10 ml) solution

of 3j (50 mg, 0.22 mmol), thiobenzamide (59 mg, 0.43 mmol), and

tetrabutylammonium hydrogensulfate (15 mg, 0.04 mmol) at room

temperature. The reaction mixture was heated under reﬂux con-

dition for 20 min. The cooled mixture was poured into a saturated

NaHCO₃(50 ml). The organic layer was separated and the aqueous

layer was extracted with ether. The combined organic layer was

dried over MgSO₄. The solvent was removed under reduced pres-

sure. The residue was puriﬁed by preparative TLC on silica gel eluting

with CH₂Cl₂/n-hexane (1:10) to give (Z)-2-phenyl-4-(phenyl-

sulfanylmethylene)-1-thia-3-azaspiro[4.5]dec-2-ene (6ja)（0.034 g,

45%） as a yellow oil and 2-phenyl-4-phenylsulfanyl-3-thia-1-aza-

spiro[5.5]undec-2-ene (5ja) (8.0 mg, 11%) as a yellow oil.

(9ga). A yellow oil, IR (KBr, cm^ꢀ1

)

3059, 3027, 2979, 2928, 2851,

2382, 2349, 2316, 1603, 1578, 1493, 1447, 1258, 1131, 1073, 1028,

956, 921, 866, 767, 690, 627; ¹H NMR (600 MHz, CDCl₃)

1.91 (3H, s,

Me), 5.13 (1H, d, J¼2 Hz, oleﬁnic H), 5.37 (1H, d, J¼2 Hz, oleﬁnic H),

7.26e7.29 (2H, m, ArH), 7.33e7.36 (2H, m, ArH), 7.42e7.49 (4H, m,

ArH), 7.86 (2H, br d, J¼7 Hz, ArH); ¹³C NMR (150 MHz, CDCl₃)

d 28.1

(q), 87.0 (s), 106.0 (t), 125.6 (dꢂ2), 127.4 (d), 128.2 (dꢂ2), 128.4

(dꢂ2), 128.6 (dꢂ2), 131.4 (d), 133.1 (s), 144.3 (s), 155.6 (s), 162.7 (s);

MS m/z 265 (M^þ), 250 (M^þꢀMe). High resolution mass calcd for

C₁₇H₁₅NS: 265.0925, found m/z 265.0898.

4.5.10. 4-[Bis(2-thienyl)methyl]-2-phenyl-5-(phenylsulfanyl)-1,3-thi-

azole (4ha). White prisms, mp 119e123 ^ꢁC, IR (KBr, cm^ꢀ1

) n 3064,

2919, 2360, 1716, 1579, 1505, 1477, 1455, 1433, 1320, 1230, 1178,

1074, 1047, 1023, 1001, 987, 919, 853, 763, 740, 688, 615. 524; ¹H

NMR (600 MHz, CDCl₃)

6.41 (1H, br s, CH), 6.88 (2H, dd, J¼3 and

4.6.1.1. (E)- and (Z)-4-(phenylsulfanylmethylene)-1-thia-3-azas-

5 Hz, ArH), 6.93e7.01 (2H, m, ArH), 7.14e7.23 (6H, m, ArH),

piro[4.5]dec-2-ene (6ja). IR (KBr, cm^ꢀ1

) n 3436, 3060, 3025, 2930,

7.36e7.51 (4H, m, ArH), 7.96e7.97 (2H, m, ArH); ¹³C NMR (150 MHz,

2853, 1614, 1580, 1478, 1446, 1313, 1281, 1252, 1178, 1157, 1115, 1087,

1025, 968, 944, 904, 870, 834, 765, 740, 689, 643, 615, 470, 445, 420;

CDCl₃)

41.2 (d), 121.7 (s), 125.0 (dꢂ2), 125.9 (dꢂ2), 126.3 (dꢂ2),

126.5 (d), 126.6 (dꢂ2), 127.6 (dꢂ2), 128.9 (dꢂ2), 129.1 (dꢂ2), 130.6

(d), 133.4 (s), 136.7 (s), 145.4 (sꢂ2), 161.8 (s), 170.8 (s); MS m/z 447

(M^þ); Anal. Calcd for C₂₄H₁₇NS₄: C, 64.40; H, 3.83; N, 3.13. Found: C,

64.07; H, 3.82; N, 3.11.

¹H NMR (600 MHz, CDCl₃)

d 1.40e1.44 (m, E- and Z-CH₂), 1.63e1.74

(m, E- and Z-CH₂), 1.87e2.04 (m, E- and Z-CH₂), 6,14 (s, Z-oleﬁnic H),

6.97 (s, E-oleﬁnic H), 7.18e7.7.21 (m, ArH), 7.30e7.31 (m, ArH),

7.40e7.47 (m, ArH), 7.84e7.92 (m, ArH); ¹³C NMR (150 MHz, CDCl₃)

of Z-5a

23.3 (tꢂ2), 26.0 (t), 39.9 (tꢂ2), 85.6 (s), 108.0 (d), 126.2 (d),

4.5.11. 4-[Bis(2-thienyl)methyl]-2-methyl-5-(phenylselanyl)-1,3-thi-

128.0 (dꢂ2), 128.2 (dꢂ2), 128.5 (dꢂ2), 129.1 (dꢂ2), 131.1 (d), 133.4

(s), 136.1 (s), 157.7 (s), 158.6 (s); MS m/z 351 (M^þ) 242 (M^þꢀSPh).

Anal. Calcd for C₂₁H₂₁NS₂: C, 71.75; H, 6.02; N, 3.98. Found: C, 71.57;

H, 6.03; N, 4.01.

azole (4ia). Yield 57%, a yellow oil, IR (KBr, cm^ꢀ1

) n 3442, 3069, 2922,

2359, 1793, 1734, 1616, 1577, 1503, 1476, 1438, 1415, 1361, 1275, 1229,

1176, 1067, 1020, 983, 853, 785, 736, 700, 614, 537; ¹H NMR (600 MHz,

CDCl₃)

7.16e7.18 (5H, m, ArH), 7.26e7.27 (2H, m, ArH); ¹³C NMR (150 MHz,

CDCl₃)

(dꢂ2), 127.1 (d), 129.3 (dꢂ2), 130.3 (dꢂ2), 131.9 (s), 145.6 (sꢂ2), 160.9

(s), 170.9 (s); MS m/z 433 (M^þ), 276 (M^þꢀSePh). Anal. Calcd for

C₁₉H₁₅NS₃Se: C, 52.80; H, 3.50; N, 3.24. Found: C, 52.61; H, 3.48; N, 3.04.

d 2.70 (3H, s, Me), 6.40 (1H, br s, CH), 6.87e6.89 (4H, m, ArH),

4.6.1.2. 4-Phenylsulfanyl-2-phenyl-3-thia-1-azaspiro[5.5]undec-

2-ene (5ja). IR 3060, 2930, 2854, 2663, 1735, 1617, 1580, 1476, 1445,

1301, 1228, 1195, 1176, 1142, 1103, 1070, 1025, 979, 941, 904, 886,

822, 761, 740, 689, 671, 527, 469, 431, 405; ¹H NMR (600 MHz,

19.8 (q), 42.0 (d), 114.1 (s), 124.9 (dꢂ2), 125.9 (dꢂ2), 126.4

CDCl₃)

d 1.55e1.61 (4H, m, CH₂), 1.79e1.86 (4H, m, CH₂), 1.93e1.94

(2H, m, CH₂), 6.23 (1H, s, oleﬁnic H), 7.22e7.25 (1H, m, ArH),

7.28e7.37 (6H, m, ArH), 7.40e7.53 (1H, m, ArH), 7.80e7.81 (2H, m,

4.5.12. 4-[Bis(2-thienyl)methyl]-2-phenyl-5-(phenylselanyl)-1,3-t_ꢀh₁i-

azole (4ib). Yield 68%, white prisms, mp 132e135 ^ꢁC, IR (KBr, cm

)

ArH); ¹³C NMR (150 MHz, CDCl₃) 5ja

21.8 (tꢂ2), 25.8 (t), 36.0

M. Yoshimatsu et al. / Tetrahedron 66 (2010) 7975e7987

7983

(tꢂ2), 63.1 (s), 124.1 (s), 127.0 (d), 127.6 (dꢂ2), 128.5 (dꢂ2), 128.8

(dꢂ2), 129.1 (dꢂ2), 129.2 (dꢂ2), 130.9 (d), 134.1 (s), 137.3 (s), 155.1

(s); MS m/z 351 (M^þ) 238 (M^þꢀPh). High-resolution mass calcd for

C₂₁H₂₁NS₂: 351.1115, found m/z: 373.1093.

3060, 3026, 2959, 2868, 2386, 2349, 2284, 1609, 1581, 1478, 1447,

1316, 1256, 1207, 1176, 1157, 1087, 1024, 1000, 953, 887, 826, 765,

740, 689, 613, 522, 501, 470, 435, 411; ¹H NMR (600 MHz, CDCl₃)

1.92 (4H, m, CH₂), 2.04e2.07 (2H, m, CH₂), 2.19e2.21 (2H, m, CH₂),

6.19 (1H, s, oleﬁnic H), 7.20e7.21 (1H, m, ArH), 7.29e7.31 (4H, m,

ArH), 7.40e7.46 (3H, m, ArH), 7.82 (2H, d, J¼7 Hz, ArH); ¹³C NMR

4.7. Desulfanylation of 6ja with tributyltin hydride

(150 MHz, CDCl₃)

25.6 (tꢂ2), 43.4 (tꢂ2), 92.2 (s), 107.6 (d), 126.3

IR (KBr, cm^ꢀ1

1177, 1156, 1051, 970, 953, 921, 850, 764, 709, 689, 642, 615, 569; ¹H

NMR (600 MHz, CDCl₃) 1.38e1.44 (1H, m, CH₂), 1.52e1.57 (2H, m,

)

2930, 2853, 1607, 1579, 1490, 1446, 1395, 1252,

(d), 128.0 (dꢂ2), 128.1 (dꢂ2), 128.5 (dꢂ2), 129.1 (dꢂ2), 131.1 (d),

133.1 (s), 136.0 (s), 156.9 (s), 159.4 (s); MS m/z 259 (M^þꢀ1), 228

(M^þꢀSPh). Anal. Calcd for C₂₀H₁₉NS₂: C, 71.18; H, 5.67; N, 4.15.

Found: C, 71.13; H, 5.81; N, 3.95.

CH₂),1.69e1.71 (2H, m, CH₂),1.83e1.88 (3H, m, CH₂),1,94e2.00 (2H,

m, CH₂), 5.15 (1H, d, J¼1 Hz, oleﬁnic H), 5.27 (1H, d, J¼1 Hz, oleﬁnic

H), 7.40e7.46 (3H, m, ArH), 7.80e7.82 (2H, m, ArH); ¹³C NMR

4.8.4. (Z)-2-Methyl-4-(phenylsulfanylmethylene)-1-thia-3-azaspiro-

[4.4]ron-2-ene (6lb). Z:E¼99:1, a orange oil, IR (KBr, cm^ꢀ1

) n 3422,

(150 MHz, CDCl₃)

23.5 (tꢂ2), 26.0 (t), 39.6 (tꢂ2), 85.4 (s), 102.2 (t),

3058, 2959, 2869, 1639, 1582, 1478, 1440, 1371, 1303, 1206, 1150,

128.1 (dꢂ2), 128.4 (dꢂ2), 130.1 (d), 133.6 (s), 157.5 (s), 159.2 (s); MS

m/z 243 (M^þ). Anal. Calcd for C₁₅H₁₇NS: C, 74.00; H, 7.04; N, 5.76.

Found: C, 73.93; H, 6.95; N, 5.73.

1086, 1068, 1024, 1000, 974, 945, 903, 889, 823, 740, 690, 615; ¹H

NMR (600 MHz, CDCl₃) d 1.82e1.88 (4H, m, CH₂), 1.97e1.99 (2H, m,

CH₂), 2.04e2.07 (2H, m, CH₂), 2.27 (3H, s, Me), 6.11 (1H, s, oleﬁnic

H), 7.18e7.21 (1H, m, ArH), 7.27e7.31 (4H, m, ArH); ¹³C NMR

4.8. Reaction of 5ja with tributyltin hydride and the following

MeLi

(150 MHz, CDCl₃)

20.5 (q), 25.5 (tꢂ2), 43.2 (tꢂ2), 91.7 (s), 107.1

(d), 126.3 (d), 127.9 (dꢂ2), 129.1 (dꢂ2), 135.9 (s), 158.0 (s), 158.4

(s); MS m/z 275 (M^þ). Anal. Calcd for C₁₅H₁₇NS₂: C, 65.41; H, 6.22;

N, 5.09. Found: C, 65.03; H, 6.19; N, 4.21.

A toluene (2.0 ml) solution of 5ja (200 mg, 0.57 mmol), tribu-

tyltin hydride (0.75 ml, 2.84 mmol), and AIBN (19 mg, 0.11 mmol)

was heated under reﬂux condition for 1.5 h. The evaporated mix-

ture was puriﬁed by preparative TLC on silica gel eluting with

CH₂Cl₂/n-hexane (1:4) to give a mixture of 8a and 2-phenyl-10-

tributylstannyl-3-thia-1-azaspiro[5.5]undec-2-ene (0.20 g).

4.8.5. (Z)-2-Phenyl-4-(phenylselanylmethylene)-1-thia-3-azaspiro-

[4.5]dec-2-ene (6m). Z:E¼99:1, a yellow oil, IR (KBr, cm^ꢀ1

) n 3448,

3059, 3029, 2930, 2853, 1614, 1577, 1476, 1446, 1313, 1281, 1252,

1220, 1178, 1157, 1107, 1070, 1022, 968, 943, 904, 859, 817, 764, 736,

688, 642, 616, 525, 491, 469, 417; ¹H NMR (600 MHz, CDCl₃)

IR (KBr, cm^ꢀ1) 3650, 3526, 3447, 2929, 2361, 1716, 1654, 1602,

1559, 1507, 1457, 1418, 1361, 1295, 1219, 1176, 1074, 976, 939, 766,

1.37e1.43 (1H, m CH₂), 1.59e1.66 (2H, m, CH₂), 1.71e1.73 (2H, m,

691; ¹H NMR (600 MHz, CDCl₃)

0.90 (9H, t, J¼7 Hz, Me), 1.04e1.07

CH₂), 1.86e1.91 (3H, m, CH₂), 1.96e2.04 (2H, m, CH₂), 6.42 (1H, s,

oleﬁnic H), 7.21e7.29 (3H, m, ArH), 7.39e7.46 (5H, m, ArH),

(6H, m, CH₂), 1.32e1.36 (6H, m, CH₂), 1.54e1.57 (8H, m, CH₂),

1.61e1.94 (6H, m, CH₂), 5.78 (1H, s, oleﬁnic H), 7.26e7.41 (3H, m,

7.83e7.84 (2H, m, ArH); ¹³C NMR (150 MHz, CDCl₃)

23.3 (tꢂ2),

ArH), 7.89 (2H, d, J¼8 Hz, ArH); ¹³C NMR (150 MHz, CDCl₃)

d 10.2

25.9 (t), 39.8 (tꢂ2), 85.4 (s), 103.4 (d), 126.8 (d), 128.2 (dꢂ2), 128.5

(dꢂ2), 129.3 (dꢂ2), 130.7 (dꢂ2), 131.1 (d), 131.4 (s), 133.4 (s), 158.2

(s), 160.2 (s); MS m/z 399 (M^þ). Anal. Calcd for C₂₁H₂₁NS₂: C, 63.31;

H, 5.31; N, 3.52. Found: C, 63.47; H, 5.37; N, 3.51.

(tꢂ3), 13.6 (qꢂ3), 22.2 (tꢂ2), 26.1 (t), 27.2 (tꢂ3), 28.9 (tꢂ3), 35.5

(tꢂ2), 59.2 (s), 127.5 (dꢂ2), 128.3 (dꢂ2), 129.1 (s), 130.3 (d), 135.9

(s), 138.4 (d), 156.6 (s); MS m/z 533 (small M^þ). The mixture of 5ja

and tributylstannylated product was not further puriﬁed and used

in the next step.

4.8.6. (E)- and (Z)- 2-Phenyl-4-(phenylsulfanylmethylene)-1-thia-3-

azaspiro[4.11]-dec-2-ene (6n). Z:E¼77:23, a orange oil, IR (KBr,

cm^ꢀ1

) n 3589, 3453, 3369, 3197, 3060, 2937, 2852, 2360, 1734, 1715,

4.8.1. 2-Phenyl-3-thia-1-azaspiro[5.5]undec-2-ene (8ja). IR (KBr,

cm^ꢀ1

)

3430, 3060, 2929, 2854, 1716, 1623, 1489, 1446, 1333, 1228,

1177, 1075, 973, 931, 851, 765, 736, 690, 611, 411; ¹H NMR (600 MHz,

CDCl₃) 1.54e1.56 (4H, m.CH₂), 1.72e1.74 (2H, m, CH₂), 1.84e1.85

1685, 1580, 1471, 1445, 1352, 1258, 1218, 1025, 1000, 940, 899, 764,

742, 690; ¹H NMR (600 MHz, CDCl₃)

1.39e1.42 (m, CH₂), 1.56e1.60

(m, CH₂), 1.75e1.80 (m, CH₂), 1.89e1.94 (m, CH₂) 6.13(s, E-oleﬁnic

H), 6.19 (s, Z-oleﬁnic H), 7.23e7.26 (m, ArH), 7.29e7.36 (m, ArH),

7.40e7.45 (m, ArH), 7.77.81 (m, ArH); ¹³C NMR (150 MHz, CDCl₃) of

(4H, m, CH₂), 5.80 (1H, d, J¼10 Hz, oleﬁnic H), 6.41 (1H, d, J¼9 Hz,

oleﬁnic H), 7.36e7.44 (3H, m, ArH), 7.88e7.90 (2H, m, ArH); ¹³C

NMR (150 MHz, CDCl₃)

21.8 (tꢂ2), 25.9 (t), 36.0 (tꢂ2), 59.3 (s),

Z-7e

19.0 (tꢂ2), 22.2 (tꢂ2), 22.7 (tꢂ2), 26.1 (t), 26.5 (tꢂ2), 32.7

116.7 (d), 127.5 (dꢂ2), 128.4 (dꢂ2), 130.6 (d), 138.0 (s); MS m/z 243

(M^þ). High resolution mass could not be measured by the same

peak of the standard PFK.

(tꢂ2), 66.1 (sꢂ2), 123.3 (s), 127.0 (d), 127.5 (dꢂ2), 128.4 (dꢂ2), 129.1

(dꢂ2), 129.3 (dꢂ2), 130.8 (d), 134.0 (d), 137.4 (sꢂ2); MS m/z 435

(M^þ) 358 (M^þꢀPh), 326 (M^þꢀSPh). High-resolution mass calcd for

C₂₇H₃₃NS₂: 435.2054, found m/z: 435.2040.

4.8.2. (E)- and (Z)-2-Methyl-4-(phenylsulfanylmethylene)-1-thia-3-

azaspiro[4.5]dec-2-ene (6lb). E/:Z¼1:7, a orange oil, IR (KBr, cm^ꢀ1

)

4.9. Reaction of 3k with thiobenzamide

3073, 2930, 2854, 2359, 1734, 1646, 1582, 1507, 1478, 1440,

1373, 1261, 1160, 1086, 1024, 976, 941, 904, 876, 830, 741, 689,

4.9.1. Reaction of 5-phenylsulfanylethynyl-5-undecanol with thio-

benzamide (3k).

637, 602; ¹H NMR (600 MHz, CDCl₃)

1.31e1.36 (m, E- and Z-

CH₂), 1.52e1.57 (m, E- and Z-CH₂), 1.69e1.71 (m, E- and Z-CH₂),

1.80e1.87 (m, E- and Z-CH₂), 2.22 (s, Z-Me), 2.28 (s, E-Me), 6.05

(s, E-oleﬁnic H), 6.19 (s, Z-oleﬁnic H), 7.26e7.30 (m, ArH); ¹³C

4.9.1.1. 5-Methyl-4,5-dihydro-2,5-diphenyl-4-(phenyl-

sulfanylmethyl-ene)-1,3-thiazole (6k). IR (KBr, cm^ꢀ1

) n 3419, 3062,

2930, 2857,1715,1627,1581, 1458,1377, 1227,1154, 1073,1025,1001,

NMR (150 MHz, CDCl₃) of Z-6lb

20.8 (q), 23.2 (tꢂ2), 25.7 (t),

941, 885, 763, 739, 689, 661, 617; ¹H NMR (600 MHz, CDCl₃)

39.5 (tꢂ2), 85.3 (s), 107.4 (d), 126.2 (d), 127.8 (dꢂ2), 129.0 (dꢂ2),

136.0 (s), 157.7 (s), 158.9 (s); MS m/z 289 (M^þ) 180 (M^þꢀSPh).

High-resolution mass calcd for C₁₆H₁₉NS₂: 289.0957, found m/z:

289.0938.

0.86e0.92 (6H, t, J¼7 Hz, Meꢂ2), 1.24e1.36 (12H, m, CH₂),

1.62e1.67 (2H, m, CH₂), 1.81e1.86 (2H, m, CH₂), 6.05 (1H, s, oleﬁnic

H), 7.15e7.43 (8H, m, ArH), 7.75e7.76 (2H, m, ArH); ¹³C NMR

(150 MHz, CDCl₃)

14.1 (qꢂ2), 22.6 (tꢂ2), 24.1 (tꢂ2), 32.3 (tꢂ2),

41.6 (tꢂ2), 66.6 (s), 123.1 (s), 126.8 (dꢂ2), 127.0 (d), 128.4 (dꢂ2),

129.1 (dꢂ2), 129.4 (dꢂ2), 130.6 (d), 132.3 (d), 133.8 (s), 137.8 (s),

154.1 (s); MS m/z 352 (M^þꢀ(CH₂)₄Me), 313 (M^þꢀPhSH).

4.8.3. (Z)-2-Phenyl-4-(phenylsulfanylmethylene)-1-thia-3-azaspiro

[4.4]non-2-ene (6la). Z:E¼99:1, a yellow oil, IR (KBr, cm^ꢀ1

) n 3442,

7984

M. Yoshimatsu et al. / Tetrahedron 66 (2010) 7975e7987

4.10. Reactions of 1-aryl- and 1,1-bisaryl-3-(phenylsulfanyl)

propargyl alcohols 1 and 3 with thiobenzamide in MeNO₂/D₂O

4.10.1.4. 4-(p-Methoxyphenyldeuteriomethyl)-2-phenyl-5-(phe-

nylsulfanyl)-1,3-thiazo_ꢀle₁(11aa). Yield 70%, 46%

D purity, mp

66e69 ^ꢁC, IR (KBr, cm

) n 3060, 3001, 2931, 2833, 1610, 1582, 1510,

4.10.1. Bis(p-ﬂuorophenyl)-3-(phenylsulfanyl)propargyl

ALCOHOL

1478, 1454, 1440, 1301, 1246, 1177, 1108, 1067, 1037, 1001, 971, 916,

(3c) with thiobenzamide in MeNO₂/D₂O. Typical procedure. Scan-

dium triﬂate (3.5 mg, 0.007 mmol) was added to a mixture of 3c

(50 mg, 0.14 mmol), benzthioamide (39 mg, 0.28 mmol), and

Bu₄NHSO₄(10 mg, 0.03 mmol) in MeNO₂(0.50 ml)/D₂O (0.1 ml).

The reaction mixture was heated under reﬂux condition for 10 min

and poured into a saturated NaHCO₃(50 ml). The work-up pro-

cedure gave 4-[bis(p-ﬂuorophenyl)deuteriomethyl]-2-phenyl-5-

(phenylsulfanyl)-1,3-thiazole (10ca) (50 mg, 75%).

843, 809, 764, 740, 689, 620, 583, 566; ¹H NMR (600 MHz, CDCl₃)

3.73 (s, OMe), 4.17 (s, CH₂), 4.19 (s, CHD), 6.77 (d, J¼8 Hz, ArH),

7.13e7.16 (m, ArH), 7.21e7.24 (m, ArH), 7.38e7.39 (m, ArH),

7.89e7.92 (m, ArH); ¹³C NMR (150 MHz, CDCl₃)

34.4 (d, J¼20 Hz),

34.7 (t, CH₂), 55.2 (q), 113.7 (dꢂ2), 120.8 (s), 126.2 (d), 126.5 (dꢂ2),

127.1 (dꢂ2), 128.9 (dꢂ2), 129.1 (dꢂ2), 129.9 (dꢂ2), 130.4 (d), 131.0

(s),133.4 (s),137.3 (s),158.0 (s),162.3 (s),170.5 (s); MS m/z 472 (M^þ),

363 (M^þꢀSPh). Anal. Calcd for C₂₃H₁₈DNOS₂: 70.70; 4.65; N, 3.59.

Found: C, 70.71; H, 5.02; N, 3.57.

Compound 10ca: yield 75%, 87% D purity, a yellow oil, IR (KBr,

cm^ꢀ1

)

3062, 2925, 1887, 1603, 1581, 1507, 1478, 1453, 1440, 1313,

1300, 1280, 1227, 1179, 1159, 1098, 1071, 1048, 1023, 1000, 981, 917,

838, 784, 761, 739, 688, 658, 608; ¹H NMR (600 MHz, CDCl₃)

5.89

4.10.1.5. 4-(2-Thienyldeuteriomethyl)-2-phenyl-5-(phenyl-

sulfanyl)-1,3-thiazole (11ea). Yield 90%, 49% D purity, a yellow oil, IR

(s, a trace of benzyl H), 6.91e6.94 (m, ArH), 7.08e7.19 (m, ArH),

(KBr, cm^ꢀ1

) n 3446, 3062, 2925, 2363, 1713, 1636, 1580, 1541, 1506,

7.24e7.30 (m, ArH), 7.39e7.41 (m, ArH), 7.90e7.91 (m, ArH); ¹³C

1488, 1478, 1455,1439, 1362, 1317, 1229, 1177, 1157, 1072, 1052, 1024,

NMR (150 MHz, CDCl₃)

114.9 (dꢂ2), 115.1 (dꢂ2), 121.9 (s), 126.4

1001, 988, 968, 918, 850, 763, 740, 688, 623, 577, 529; ¹H NMR

(d), 126.5 (dꢂ2), 127.3 (dꢂ2), 128.9 (dꢂ2), 129.1 (dꢂ2), 130.5 (dꢂ2),

130.5 (dꢂ2), 130.6 (d), 133.4 (s), 136.8 (s), 138.1 (s), 161.1 (dꢂ2,

J¼244 Hz), 162.7 (s), 170.6 (sꢂ2), 171.1 (s); MS m/z 472 (M^þ), 395

(M^þꢀPh), 363 (M^þꢀSPh). High-resolution mass calcd for

C₂₈H₁₈DF₂NS₂: 472.0990, found m/z: 472.0991.

(600 MHz, CDCl₃)

4.41 (br s, CH₂), 4.44 (br s, CHD), 6.88 (d, J¼3 Hz,

ArH), 7.11e7.12 (m, ArH), 7.15e7.18 (m, ArH), 7.22e7.25 (m, ArH),

7.40e7.41 (m, ArH), 7.91e7.92 (m, ArH); ¹³C NMR (150 MHz, CDCl₃)

29.7 (t, J¼18 Hz, CDH), 29.9 (t, CH₂), 121.6 (s), 124.1 (d), 125.5 (d),

126.4 (d), 126.5 (dꢂ2), 126.6 (d), 127.3 (dꢂ2), 128.9 (dꢂ2), 129.1

(dꢂ2), 130.5 (d), 133.3 (s), 137.0 (s), 140.9 (s), 160.7 (s), 170.7 (s); MS

m/z 366 (M^þ), 257 (M^þꢀSPh). Anal. Calcd for C₂₀H₁₄DNS₂: C, 65.50;

H, 3.85; N, 3.82. Found: C, 65.25; H, 4.20; N, 3.82.

4.10.1.1. 4-[Bis(p-ﬂuorophenyl)deuteriomethyl]-2-methyl-5-(phe-

nyl-sulfanyl)-1,3-thiazole (10cb). _ꢀY₁ield 62%, 91% D purity, white

prisms, mp 79e84 ^ꢁC, IR (KBr, cm

) n 3421, 3060, 2924, 1889, 1603,

1581, 1507, 1478, 1440, 1374, 1290, 1227, 1178, 1159, 1098, 1075, 1017,

4.10.1.6. 4-[Bis(p-methoxyphenyl)deuteriomethyl]-2-phenyl-5-

838, 780, 740, 689, 638, 611, 570, 553, 526; ¹H NMR (600 MHz,

(phenyl-sulfanyl)-1,3-thiazole (10ea). Yield 49%, 90% D purity, mp

CDCl₃)

H- and D-ArH), 7.03e7.04 (m, D- and H-ArH), 7.10e7.20 (m, ArH);

¹³C NMR (150 MHz, CDCl₃)

2.68 (br s, D- and HeMe), 5.86 (br s, HeCH), 6.90e6.93 (m,

133e135 ^ꢁC, IR (KBr, cm^ꢀ1

) n 3431, 3060, 3000, 2925, 2853, 1608,

1580, 1509, 1477, 1440, 1298, 1248, 1177, 1113, 1071, 1036, 1000, 982,

20.0 (q), 115.0 (dꢂ2), 115.1 (dꢂ2), 121.1

835, 809, 783, 763, 741, 717, 688, 658, 627, 608, 583, 548; ¹H NMR

(s), 126.3 (d), 127.1 (dꢂ2), 129.0 (dꢂ2), 130.5 (dꢂ2), 130.5 (dꢂ2),

137.0 (s), 137.9 (s), 161.5 (dꢂ2, J¼246 Hz), 161.9 (s), 169.7 (sꢂ2); MS

m/z 410 (M^þ), 301 (M^þꢀSPh). Anal. Calcd for C₂₃H₁₆DF₂NS₂: C,

67.50; H, 4.18; N, 3.42. Found: C, 67.39; H, 4.30; N, 3.37.

(600 MHz, CDCl₃) d 3.75 (s, D-OMe), 3.78 (s, H-OMe), 5.84 (s, CH),

6.79 (d, J¼8 Hz, D-ArH), 6.84 (d, J¼8 Hz, H-ArH), 7.11e7.20 (m, ArH),

7.24e7.31 (m, ArH), 7.34e7.42 (m, ArH), 7.87e7.92 (m, ArH); ¹³C

NMR (150 MHz, CDCl₃)

55.2 (qꢂ2), 113.5 (dꢂ4),121.3 (s), 126.2 (d),

126.5 (dꢂ2), 127.3 (dꢂ2), 128.8 (dꢂ2), 129.1 (dꢂ2), 130.0 (dꢂ4),

130.4 (d), 133.6 (s), 135.1 (sꢂ2), 137.2 (s), 158.0 (sꢂ2), 163.9 (s), 170.3

(s); MS m/z 496 (M^þ), 310 (M^þꢀPhꢀSPh). Anal. Calcd for

C₃₀H₂₄DNO₂S₂: C, 72.60; H, 4.87; N, 2.82. Found: C, 72.42; H, 4.89;

N, 2.81.

4.10.1.2. 4-[Bis(p-ﬂuorophenyl)deuteriomethyl]-2-phenyl-5-(phe-

nyl-sulfanyl)-1,3-selenazole (10cc). Yield 43%, 88% D purity, white

powders, mp 108e113 ^ꢁC, IR (KBr, cm^ꢀ1

) n 3434, 3060, 1888, 1602,

1581, 1507, 1479, 1439, 1301, 1277, 1227, 1158, 1097, 1065, 1023, 987,

954, 835, 780, 761, 739, 689, 661, 586, 560, 524, 500; ¹H NMR

(600 MHz, CDCl₃)

5.90 (br s, HeCH), 6.92e6.95 (m, D- and H-ArH),

4.10.1.7. 4-[Bis(2-thienyl)deuteriomethyl]-2-phenyl-5-(phenyl-

7.15e7.17 (m, D- and H-ArH), 7.19e7.22 (m, D- and H-ArH),

7.27e7.30 (m, D- and H-ArH), 7.36e7.44 (m, D- and H-ArH),

sulfanyl)-1,3-thiazole (1_ꢀ0₁ha). Yield 59%, 90%

purity, mp

126e129 ^ꢁC, IR (KBr, cm

) n 3343, 3063, 2923, 2853, 1656, 1579,

7.81e7.83 (m, D- and H-ArH); ¹³C NMR (150 MHz, CDCl₃)

114.9

1478, 1453, 1432, 1314, 1232, 1158, 1080, 1040, 1024, 1001, 978, 917,

(dꢂ2), 115.0 (dꢂ2), 126.4 (d), 127.0 (dꢂ2), 127.4 (dꢂ2), 128.4 (d),

129.0 (dꢂ2), 129.1 (dꢂ2), 130.5 (dꢂ2), 130.6 (dꢂ2), 130.8 (d), 136.2

(s), 137.7 (s), 138.3 (s), 161.5 (dꢂ2, J¼244 Hz), 163.1 (s), 177.3 (s); MS

m/z 520 (M^þ), 411 (M^þꢀSPh). Anal. Calcd for C₂₈H₁₈DF₂NSSe: C,

64.74; H, 3.49; N, 2.70. Found: C, 64.87; H, 3.72; N, 2.54.

849, 763, 740, 688, 613; ¹H NMR (600 MHz, CDCl₃)

6.41 (br s, CH),

6.88 (dd, J¼4 and 5 Hz, ArH), 6.97e6.98 (m, ArH), 7.14e7.22 (m,

ArH), 7.40e7.41 (m, ArH), 7.96e7.97 (m, ArH); ¹³C NMR (150 MHz,

CDCl₃)

121.7 (s), 125.0 (dꢂ2), 125.9 (dꢂ2), 126.3 (dꢂ2), 126.5

(dꢂ2), 126.6 (dꢂ2), 127.6 (dꢂ2), 128.9 (dꢂ2), 129.1 (dꢂ2), 130.6 (d),

133.4 (s), 136.7 (s), 145.3 (sꢂ2), 161.8 (s), 170.8 (s); MS m/z 448 (M^þ).

Anal. Calcd for C₂₄H₁₆DNS₄: C, 64.30; H, 3.59; N, 3.12. Found: C,

63.94; H, 3.65; N, 3.11.

4.10.1.3. 4-[Bis(p-ﬂuorophenyl)deuteriomethyl]-2-phenyl-5-(phe-

nylselanyl)-1,3-thiazole (10da). Yield 80%, 88% D purity, a yellow oil,

IR (KBr, cm^ꢀ1

)

3062, 1888, 1603, 1577, 1507, 1476, 1438, 1300, 1273,

1227, 1159, 1098, 1063, 1019, 980, 917, 838, 783, 762, 735, 713, 688,

648, 606, 571, 523; ¹H NMR (600 MHz, CDCl₃)

5.93 (s, H-CH),

4.10.1.8. 4-[Bis(2-thienyl)deuteriomethyl]-2-methyl-5-(phenyl-

sulfanyl)-1,3-thiazole (10hb). Yield 54%, 92% D purity, IR (KBr, cm^ꢀ1

)

6.90e6.93 (m, D- and H-ArH), 7.13e7.28 (m, D- and H-ArH),

3430, 3103, 3071, 2922, 2853, 1733, 1617, 1580, 1500, 1478, 1439,

1415, 1360, 1290, 1233, 1179, 1081, 1067, 1042, 1023, 997, 900, 849,

830, 785, 740, 699, 616, 549; ¹H NMR (600 MHz, CDCl₃)

2.70 (br s,

7.39e7.40 (m, D- and H-ArH), 7.89e7.91 (m, D- and H-ArH); ¹³C

NMR (150 MHz, CDCl₃) of D-14da

49.4 (d), 114.9 (dꢂ2), 115.1

(dꢂ2), 115.2 (s), 126.5 (dꢂ4), 127.1 (d), 128.9 (dꢂ2), 129.4 (dꢂ2),

130.2 (d), 130.4 (dꢂ2), 130.5 (dꢂ2), 131.9 (s), 133.3 (sꢂ2), 138.3 (s),

161.5 (sꢂ2, J¼245 Hz), 162.6 (s), 171.7 (s); MS m/z 520 (M^þ), 443

(M^þꢀPh). Anal. Calcd for C₂₈H₁₈DF₂NSSe: C, 64.74; H, 3.49; N, 2.70.

Found: C, 64.44; H, 3.52; N, 2.72.

D- and H-Me), 6.36 (br s, H-CH), 6.88 (dd, J¼3 and 5 Hz, D- and H-

ArH), 6.91 (d, J¼3 Hz, D- and H-ArH), 7.12e7.24 (m, D- and H-ArH),

7.68e7.69 (m, HeArH), 7.90e7.91 (m, H-ArH); ¹³C NMR (150 MHz,

CDCl₃)

20.0 (q),124.9 (dꢂ2),126.0 (dꢂ2),126.4 (dꢂ2),127.4 (dꢂ2),

127.9 (d),129.1 (dꢂ2),133.1 (s),133.5 (s),136.8 (s),145.2 (sꢂ2),160.9

M. Yoshimatsu et al. / Tetrahedron 66 (2010) 7975e7987

7985

(s), 170.0 (s); MS m/z 386 (M^þ), 277 (M^þꢀSPh). Anal. Calcd for

C₁₉H₁₄DNS₄: C₁₉H₁₄DNS₄: C, 59.00; H, 3.65; N, 3.62. Found: C,

58.82; H, 3.86; N, 3.14.

3.75 (3H, s, OMe), 4.26 (1H, t, J¼7 Hz, CH), 6.76 (2H, d, J¼9 Hz, ArH),

7.08e7.21 (5H, m, ArH), 7.34 (2H, d, J¼9 Hz, ArH), 7.42e7.44 (3H, m,

ArH), 7.96 (2H, dd, J¼2 and 7 Hz, ArH); MS m/z 417 (M^þ), 388

(M^þꢀEt). Anal. Calcd for C₂₄H₂₁NS₂: C, 74.38; H, 5.46; N, 3.61.

Found: C, 74.43; H, 5.37; N, 3.71.

4.10.1.9. 4-[Bis(2-thienyl)deuteriomethyl]-2-phenyl-5-(phenyl-

sulfanyl)-1,3-selenazole (10hc). Yield 57%, 85%

D purity, mp

113e118 ^ꢁC, IR (KBr, cm^ꢀ1

)

3421, 3062, 2924, 2852, 1793, 1712,

4.11.1.2. 4-(1-Deutrio-4-methoxybenzyl)-2-phenyl-5-(phenyl-

1580, 1505, 1479, 1454, 1437, 1310, 1232, 1177, 1075, 1023, 1000, 953,

sulfanyl)-thiazole (20c). White powders, mp 60e62 ^ꢁC, IR (KBr,

917, 850, 761, 740, 688, 664, 597, 513; ¹H NMR (600 MHz, CDCl₃)

cm^ꢀ1

)

2925, 2854, 1714, 1512, 1478, 1465, 1441, 1362, 1247, 1221,

6.43 (br s, H-CH), 6.89 (dd, J¼6 and 8 Hz, ArH), 6.98 (dd, J¼2 and

1177, 1036, 764, 689; ¹H NMR (600 MHz, CDCl₃)

3.74 (s, MeO), 4.16

6 Hz, ArH), 7.18 (d, J¼5 Hz, ArH), 7.21e7.22 (m, ArH), 7.31e7.42 (m,

(s, CH₂), 4.19 (s, CHD), 6.77 (d, J¼8 Hz, ArH), 7.14e7.16 (m, ArH),

ArH), 7.90e7.91 (m, ArH); ¹³C NMR (150 MHz, CDCl₃) of D-14hc

7.21e7.24 (m, ArH), 7.39e7.40 (m, ArH), 7.90e7.91 (m, ArH); ¹³C NMR

41.9 (d, H-CH), 125.0 (dꢂ2), 125.8 (dꢂ2), 126.2 (dꢂ2), 126.5 (d),

(150 MHz, CDCl₃)

34.5 (t, J¼20 Hz, CHD), 34.7 (t), 55.2 (q), 113.7

127.1 (dꢂ2), 127.6 (dꢂ2), 127.9 (s), 129.0 (dꢂ2), 129.1 (dꢂ2), 130.8

(d), 136.2 (s), 137.6 (s), 145.6 (sꢂ2), 162.1 (s), 177.6 (s); MS m/z 496

(M^þ). Anal. Calcd for C₂₄H₁₆DNS₃Se: C, 58.20; H, 3.25; N, 2.83.

Found: C, 58.03; H, 3.28; N, 2.82.

(dꢂ2), 120.8 (s), 126.2 (d), 126.5 (dꢂ2), 127.1 (dꢂ2), 128.9 (dꢂ2),

129.1 (dꢂ2),129.9 (dꢂ2),130.4 (d),131.0 (s),133.4 (s),137.3 (s),158.0

(s), 162.3 (s), 170.5 (s); MS m/z 390 (M^þ), 375 (M^þꢀMe), 313

(M^þꢀPh), 312 (M^þꢀPh), 281 (M^þꢀSPh), 280 (M^þꢀSPh). High-res-

olution mass calcd for C₂₃H₁₈S₂NOD: 390.0971, found m/z 390.0896.

4.10.1.10. 4-[Bis(2-thienyl)deuteriomethyl]-2-phenyl-5-(phenyl-

selanyl)-1,3-thiazole (10ia). Yield 59%, 90%

136e140 ^ꢁC, IR (KBr, cm^ꢀ1

3066, 2925, 2855, 2382, 2348, 2300,

1577, 1504, 1477, 1453, 1436, 1313,1232, 1179, 1157, 1074, 1020,1000,

978, 916, 849, 763, 736, 688, 615; ¹H NMR (600 MHz, CDCl₃)

6.44

purity, mp

4.11.1.3. 4-[1-(4-Methoxyphenyl)-2-methylpropyl]-2-phenyl-5-

)

(phenyl-sulfanyl)thiazole (20d). A yellow oil, IR (KBr, cm^ꢀ1

)

2956,

2927, 2855, 2361, 2343, 1610, 1582, 1510, 1479, 1440, 1247, 1177, 762,

739, 688; ¹H NMR (600 MHz, CDCl₃)

0.81 (3H, d, J¼7 Hz, Me), 0.84

(br s, H-CH), 6.87 (dd, J¼4 and 5 Hz, D- and H-ArH), 6.96 (dd, J¼1

and 3 Hz, D- and H-ArH), 7.17e7.23 (m, D- and H-ArH), 7.30e7.31

(m, D- and H-ArH), 7.40e7.41 (m, D- and H-ArH), 7.96e7.98 (m, D-

(3H, d, J¼7 Hz, Me), 2.68e2.70 (1H, m, CH), 3.74 (3H, s, MeO), 3.94

(1H, d, J¼11 Hz, CH), 6.76 (2H, d, J¼9 Hz, ArH), 7.07e7.08 (2H, m,

ArH), 7.11e7.13 (1H, m, ArH), 7.17e7.19 (4H, m, ArH), 7.36 (2H, d,

J¼8 Hz, ArH), 7.42e7.44 (3H, m, ArH), 7.96e7.47 (4H, m, ArH); ¹³C

and H-ArH); ¹³C NMR (150 MHz, CDCl₃)

114.7 (s), 125.0 (dꢂ2),

125.8 (dꢂ2), 126.3 (dꢂ2), 126.6 (dꢂ2), 127.2 (dꢂ2), 128.9 (dꢂ2),

129.4 (dꢂ2), 130.4 (dꢂ2), 130.5 (d), 131.8 (s), 133.3 (s), 145.6 (sꢂ2),

161.8 (s), 172.0 (s); MS m/z 496 (M^þ). Anal. Calcd for C₂₄H₁₆NS₃Se: C,

58.17; H, 3.25; N, 2.83. Found: C, 57.84; H, 3.31; N, 2.82.

NMR (150 MHz, CDCl₃) d 21.2 (q), 21.7 (q), 33.4 (d), 52.4 (d), 55.1 (q),

113.4 (dꢂ2), 120.0 (s), 126.0 (d), 126.5 (dꢂ2), 127.0 (dꢂ2), 128.9

(dꢂ2), 128.9 (dꢂ2), 129.7 (dꢂ2), 130.3 (d), 133.8 (s), 135.0 (s), 137.6

(s), 157.9 (s), 165.5 (s), 170.0 (s); MS m/z 431(M^þ), 388 (M^þꢀCH

(CH₂)₂), 322 (M^þꢀSPh). Anal. Calcd for C₂₆H₂₅NOS₂: C, 72.35; 5.84;

N, 3.25. Found: C, 72.07; H, 5.79; N, 3.23.

4.11. Alkylations of 4-benzyl-2-phenyl-5-(phenylsulfanyl)-1,3-

thiazoles 2 and 4 with n-BuLi/electrophiles

4.11.1.4. 4-[1-(3,4-Dimethoxyphenyl)ethyl]-2-phenyl-5-(phenyl-

4.11.1. Reaction of p-methoxyphenyl-2-phenyl-5-phenylsulfanyl-1,3-

thiazole (2a) with n-BuLi/methyl iodide. Typical procedure. n-BuLi

(0.15 ml of 2.6 M n-hexane solution, 0.39 mmol) was added drop-

wise to a THF (1.0 ml) solution of 2a (0.05 g, 0.13 mmol) at ꢀ78 ^ꢁC

under an Ar atmosphere. The reaction mixture was stirred for

10 min. Methyl iodide (0.18 g, 1.30 mmol) in THF (1.0 ml) was added

to the mixture. The whole was stirred for 10 min and poured into

water (50 ml). The organic layer was separated and the aqueous

layer was extracted with ether. The combined organic layer was

dried over MgSO₄. The solvent was removed under reduced pres-

sure. The residue was puriﬁed by preparative TLC on silica gel

eluting with n-hexane/EtOAc (50:1) to give 4-[1-(4-methox-

yphenyl)ethyl]-2-phenyl-5-(phenylsulfanyl)thiazole (20a) (42 mg,

79%) as a yellow oil.

sul-fanyl)thiazole (20e). white powder, mp 46e48 ^ꢁC, IR (KBr,

cm^ꢀ1

)

2960, 2930, 1583, 1515, 1478, 1463, 1450, 1440, 1261, 1235,

1156, 1143, 1029, 764, 741, 689; ¹H NMR (600 MHz, CDCl₃)

1.72

(3H, d, J¼7 Hz, Me), 3.75 (3H, s, MeO), 3.82 (3H, s, MeO), 4.59 (1H, q,

J¼7 Hz, CH), 6.73 (1H, d, J¼8 Hz, ArH), 6.96 (1H, d, J¼8 Hz, ArH),

6.98 (1H, s, ArH), 7.07 (2H, d, J¼8 Hz, ArH), 7.11e7.13 (1H, m, ArH),

7.16e7.19 (2H, m, ArH), 7.40e7.41 (3H, m, ArH), 7.94e7.95 (2H, m,

ArH); ¹³C NMR (150 MHz, CDCl₃)

d 21.9 (q), 38.7 (d), 55.6 (q), 56.0

(q), 110.9 (d), 111.2 (d), 119.0 (s), 119.5 (d), 126.0 (d), 126.4 (dꢂ2),

126.7 (dꢂ2), 128.8 (dꢂ2), 129.0 (dꢂ2), 130.3 (d), 133.6 (s), 137.1 (s),

137.5 (s),147.3 (s),148.5 (s),166.4 (s),170.4 (s); MS m/z 433(M^þ), 418

(M^þꢀMe), 356 (M^þꢀPh), 324 (M^þꢀSPh). High-resolution mass

calcd for C₂₅H₂₃S₂O₂N: 433.1170, found m/z 433.1177.

Compound 20a: IR (KBr, cm^ꢀ1

1478, 1460, 1440, 1264, 1245, 1177, 1036, 763, 739, 688; ¹H NMR

(600 MHz, CDCl₃)

)

2962, 2927, 1610, 1582, 1511,

4.11.1.5. 4-[1-(3,4-Dimethoxyphenyl)-2-phenylethyl]-2-phenyl-5-

(phenylsulfanyl)thiazole (20f). white powders, mp 130e132 ^ꢁC, IR

1.70 (3H, d, J¼7 Hz, Me), 3.75 (3H, m, MeO), 6.77

(KBr, cm^ꢀ1

)

2925, 1714, 1516, 1362, 1262, 1222, 1142, 1030, 765,

(2H, q, J¼7 Hz, CHMe), 6.77 (2H, d, J¼7 Hz, ArH), 7.08e7.21 (5H, m,

742, 691; ¹H NMR (600 MHz, CDCl₃)

3.33 (1H, dd, J¼6 and 13 Hz,

ArH), 7.33 (2H, d, J¼9 Hz, ArH), 7.41e7.44 (2H, m, ArH), 7.94e7.96

CH₂), 3.68 (1H, dd, J¼10 and 13 Hz, CH), 3.78 (3H, s, OMe), 3.81 (3H,

s, MeO), 4.66 (1H, dd, J¼6 and 10 Hz, CH₂), 6.74e6.78 (3H, m, ArH),

7.03e7.08 (7H, m, ArH), 7.12e7,17 (3H, m, ArH), 7.43e7.44 (3H, m,

(2H, m, ArH); ¹³C NMR (150 MHz, CDCl₃)

d 22.0 (q), 38.4 (q), 55.2

(d), 113.6 (dꢂ2), 119.3 (s), 126.1 (d), 126.5 (dꢂ2), 126.9 (dꢂ2), 128.7

(dꢂ2), 128.9 (dꢂ2), 129.0 (dꢂ2), 130.3 (d), 133.7 (s), 136.8 (s), 137.5

(s), 158.0 (s), 166.5 (s), 170.4 (s); MS m/z 403 (M^þ), 388 (M^þꢀMe),

326 (M^þꢀPh), 294 (M^þꢀSPh). High-resolution mass calcd for

C₂₄H₂₁S₂NO: 403.1064, found m/z 403.0996.

ArH), 7.98e8.00 (2H, m, ArH); ¹³C NMR (150 MHz, CDCl₃)

d 42.6 (t),

46.9 (d), 55.6 (q), 55.8 (q), 111.0 (d), 111.5 (d), 120.3 (d), 121.0 (s),

125.9 (d), 126.4 (dꢂ2), 126.9 (dꢂ2), 128.1 (dꢂ2), 128.9 (dꢂ5), 129.1

(dꢂ2), 130.3 (d), 133.7 (s), 135.6 (s), 137.2 (s), 140.2 (s), 147.5 (s),

148.5 (s), 164.2 (s), 170.2 (s); MS m/z 509 (M^þ), 418 (M^þꢀCH₂Ph),

310 (M^þꢀPhSꢀCH₂Ph), 308 (M^þꢀPhSꢀCH₂Ph). High-resolution

mass calcd for C₃₁H₂₇S₂O₂N: 509.1483, found m/z 509.1515.

4.11.1.1. 4-[1-(4-Methoxyphenyl)propyl]-2-phenyl-5-(phen_ꢀy₁l-

sulfanyl)-thiazole (20b). White prisms, mp 59e61 ^ꢁC, IR (KBr, cm

)

2925, 2854, 1714, 1611, 1583, 1511, 1478, 1455, 1441, 1362, 1247,

1221, 1177, 1036, 764, 740, 689; ¹H NMR (600 MHz, CDCl₃)

0.83

4.11.1.6. 4-[1-(Benzodioxol-5-yl)-2-phenylethyl]-2-phenyl-5-

(3H, t, J¼7 Hz, Me), 2.07e2.12 (1H, m, CH₂), 2.23e2.27 (1H, m, CH₂),

(phenyl-sulfanyl)thiazole (20g). white powders, mp 113e114 ^ꢁC, IR

7986

M. Yoshimatsu et al. / Tetrahedron 66 (2010) 7975e7987

(KBr, cm^ꢀ1

)

1714, 1503, 1486, 1454, 1441, 1362, 1247, 1223, 1040,

m, CH₂ꢂ3), 1.48e1.54 (6H, m, CH₂ꢂ3), 1.74 (3H, d, J¼7 Hz, Me), 3.83

933, 764, 741, 699, 689; ¹H NMR (600 MHz, CDCl₃)

3.29 (1H, dd, J¼6

(3H, s, MeO), 3.87 (3H, s, MeO), 4.04 (1H, q, J¼7 Hz, ArH), 6.77 (1H, d,

J¼8 Hz,ArH), 6.91(1H, d,J¼8 Hz,ArH),7.14(1H, s,ArH), 7.34e7.37 (1H,

m, CH), 7.39e7.42 (2H, m, ArH), 8.00 (2H, d, J¼8 Hz, ArH); ¹³C NMR

and 13 Hz, CH₂), 3.65 (1H, dd, J¼10 and 13 Hz, CH₂), 4.63 (1H, dd, J¼6

and 10 Hz, CH), 5.88 (2H, dd, J¼1 and 10 Hz, CH₂), 6.65 (1H, d, J¼8 Hz,

ArH), 6.75e6.78 (3H, m, ArH), 6.85 (1H, d, J¼8 Hz, ArH), 7.07e7.23

(8H, m, ArH), 7.42e7.47 (3H, m, ArH), 7.99e8.00 (2H, m, ArH); ¹³C

(150 MHz, CDCl₃)

11.1 (tꢂ3), 13.6 (qꢂ3), 24.0 (d), 27.2 (tꢂ3), 29.0

(tꢂ3), 43.6 (q), 55.7 (q), 55.8 (d),110.8 (d),112.1 (d),119.5. (d),123.3(s),

126.4 (dꢂ2), 128.7 (dꢂ2), 129.3 (d), 134.3 (s), 138.8 (s), 147.2 (s), 148.6

(s), 167.3 (s), 172.2 (s); MS m/z 558 (M^þꢀBu), 556 (M^þꢀBu), 444

(M^þꢀ3ꢂBu), 351 (M^þꢀPhꢀMe-3ꢂBu). Anal. Calcd forC₃₁H₄₅NO₂SSn:

C, 60.60, H, 7.38; N, 2.28. Found: C, 60.38; H, 7.35; N, 2.27.

NMR (150 MHz, CDCl₃)

d 42.7 (t), 47.1 (d), 100.8 (t), 108.0 (d), 108.6

(d), 121.3 (d), 125.9 (d), 126.0 (d), 126.5 (dꢂ2), 127.1 (dꢂ2), 128.2

(dꢂ2),128.9 (dꢂ4),129.2 (dꢂ2),130.4 (d),133.7(s),137.0(s),137.1 (s),

140.2 (s),146.0 (s),147.4 (s),163.9 (s),170.2 (s); MS m/z 493 (M^þ), 402

(M^þꢀCH₂Ph), 294 (M^þꢀPhSꢀCH₂Ph). Anal. Calcd for C₃₀H₂₃S₂O₂N:

C, 72.99, H, 4.70; N, 2.84. Found: C, 72.87; H, 4.71; N, 2.83.

4.12.3. 2-Phenyl-4-[1-(2-thienyl)ethyl]-5-(tributylstannyl)thiazole. IR

(KBr, cm^ꢀ1

)

2957, 2927, 2871, 2852, 1716, 1508, 1482, 1463, 1376,

1231, 1074, 1046, 1023, 1007, 962, 868, 849, 763, 690, 604; ¹H NMR

(600 MHz, CDCl₃)

4.11.1.7. 4-[1-(4-Fluorophenyl)ethyl]-2-phenyl-5-(phenyl-

sulfanyl)-thiazole (20h). IR (KBr, cm^ꢀ1

)

3061, 2970, 2928, 1603,

1582, 1508, 1478, 1449, 1440, 1429, 1224, 1158, 1054, 1041, 1024,

1001, 973, 837, 763, 738, 688; ¹H NMR (600 MHz, CDCl₃)

1.70 (3H,

0.88 (9H, t, J¼7 Hz, Meꢂ3), 1.14e1.17 (6H, m,

CH₂), 1.28e1.36 (6H, m, CH₂), 1.48e1.66 (6H, m, CH₂), 1.80 (3H, d,

J¼7 Hz, Me), 4.34 (1H, d, J¼7 Hz, CH), 6.86e6.87 (1H, m, ArH), 6.88

(1H, dd, J¼4 and 5 Hz, ArH), 7.26 (2H, s, ArH), 7.35e7.42 (2H, m, ArH),

d, J¼7 Hz, Me), 4.60 (1H, q, J¼7 Hz, CH), 6.86e6.89 (1H, m, ArH),

7.04e7.05 (2H, m, ArH), 7.08e7.10 (1H, m, ArH), 7.14e7.16 (2H, m,

ArH), 7.33e7.37 (5H, m, ArH), 7.92e7.93 (3H, m, ArH); ¹³C NMR

7.99 (2H, d, J¼7 Hz, ArH); ¹³C NMR (150 MHz, CDCl₃)

11.1 (tꢂ3),12.3

(qꢂ3), 24.5 (d), 27.2 (tꢂ3), 29.0 (tꢂ3), 39.8 (d), 123.4 (s), 123.5 (dꢂ2),

126.1 (d),126.5 (dꢂ2),128.6 (dꢂ2),129.3 (d),137.2 (s),149.7 (s),166.4

(s), 172.5 (s); MS m/z 504 (M^þꢀBu), 502 (M^þꢀBu), 379

(M^þꢀSPhꢀMeꢀBu). Anal. Calcd for C₂₇H₃₉S₂SnN: C, 57.87, H, 7.01; N,

2.50. Found: C, 57.61; H, 6.97; N, 2.48.

(150 MHz, CDCl₃)

d 22.0 (q), 38.4 (d), 114.8 (d), 114.9 (d), 119.6 (s),

126.1 (d), 126.4 (dꢂ2), 126.8 (dꢂ2), 128.8 (dꢂ2), 129.0 (dꢂ2), 129.1

(d), 129.2 (d), 130.4 (d), 133.5 (s), 137.2 (s), 140.1 (s), 161.3 (s), 165.8

(s), 170.5 (s); MS m/z 391 (M^þ), 376 (M^þꢀMe), 314 (M^þꢀPh), 282

(M^þꢀSPh). Anal. Calcd for C₂₃H₁₈FNS₂: C, 70.56; H, 4.63; N, 3.58.

Found: C, 70.33; H, 4.67; N, 3.49.

4.12.4. 4-[1-(4-Fluorophenyl)ethyl]-2-phenyl-5-(tributylstannyl)-

thiazole. IR (KBr, cm^ꢀ1

)

2957, 2926, 2871, 2852, 1716, 1602, 1508,

1480,1463,1430,1376,1223,1158,1074,1051,1009, 962, 876, 835, 762,

739, 689, 667, 602; ¹H NMR (600 MHz, CDCl₃)

4.11.1.8. 2-Phenyl-5-(phenylsulfanyl)-4-[1-(2-thienyl)ethyl]thia-

zole (20i). A yellow oil, IR (KBr, cm^ꢀ1

)

1714,1581,1488,1478, 1449,

1439, 1431, 1361, 1220, 1024, 764, 740, 689; ¹H NMR (600 MHz,

CDCl₃)

0.87 (9H, t, J¼7 Hz,

Meꢂ3), 1.09e1.17 (6H, m, CH₂ꢂ3), 1.30e1.34 (6H, m, CH₂ꢂ3),

1.50e1.51 (6H, m, CH₂ꢂ3), 1.74e1.75 (3H, d, J¼6 Hz, Me), 4.09 (1H, q,

J¼6 Hz, CH), 6.89e6.95(2H, m, ArH), 7.33e7.40 (5H, m, ArH), 8.00 (2H,

1.76 (3H, d, J¼7 Hz, Me), 4.93 (1H, q, J¼7 Hz, CH), 6.86e6.87

(2H, m, ArH), 7.12e7.18 (3H, m, ArH), 7.23e7.26 (3H, m, ArH),

7.42e7.43 (3H, m, ArH), 7.95 (2H, dd, J¼3 and 6 Hz, ArH); ¹³C NMR

d, J¼7 Hz, ArH); ¹³C NMR (150 MHz, CDCl₃)

11.1 (tꢂ3), 13.6 (qꢂ3),

(150 MHz, CDCl₃)

23.0 (q), 34.9 (d), 119.9 (s), 123.7 (d), 123.9 (d),

23.9 (d), 27.2 (tꢂ3), 29.0 (tꢂ3), 43.3 (d), 114.7 (d), 114.9 (d), 123.5 (s),

126.5 (dꢂ2),128.7 (dꢂ2),129.0 (d),129.0 (d),129.3 (d),134.2 (s),141.7

(s), 161.3 (d, J¼244 Hz), 166.8 (s), 172.8 (s); MS m/z 516 (M^þꢀBu), 458

(M^þꢀ2ꢂBu), 324 (M^þꢀPhꢀBu). Anal. Calcd for C₂₉H₄₀FNSSn: C,

60.85; H, 7.04; N, 2.45. Found: C, 60.91; H, 6.58; N, 2.51.

126.2 (dꢂ2), 126.4 (dꢂ2), 127.0 (dꢂ2), 128.8 (dꢂ2), 129.0 (dꢂ2),

130.3 (d),133.4 (s), 137.2 (s),147.9 (s),165.1 (s), 170.6 (s); MS m/z 379

(M^þ), 364 (M^þꢀMe), 302 (M^þꢀPh), 269 (M^þꢀSPh). Anal. Calcd for

C₂₁H₁₇S₃N: C, 66.45, H, 4.51; N, 3.69. Found: C, 65.66; H, 4.53; N, 3.66.

4.12. Desulfanylation of methylated 1,3-thiazoles 20

4.13. Destannylation of 4-[1-(4-methoxyphenyl)ethyl]-2-

phenyl-5-(tributylstannyl)thiazole

Typical procedure. A mixture of 20a (70 mg, 0.17 mmol) and

AIBN (12 mg, 0.07 mmol) in toluene (1.0 ml) was reﬂuxed for 7 h.

The cooled mixture was evaporated under reduced pressure. The

residue was puriﬁed by preparative TLC on silica gel eluting with

AcOEt/n-hexane (1:50) to give 4-[1-(4-methoxyphenyl)ethyl]-2-

phenyl-5-(tributylstannyl)thiazole (68 mg, 69%) as a colorless oil.

Typical procedure. MeLi (1 M, 0.45 ml, 0.50 mmol) in ether was

added dropwise to a THF (1.0 ml) solution of 4-[1-(4-methoxy-

phenyl)ethyl]-2-phenyl-5-(tributylstannyl)thiazole (56 mg, 0.10

mmol) at ꢀ72 ^ꢁC under an Ar atmosphere. The reaction mixturewas

stirred for 10 min and poured into a saturated NH₄Cl (50 ml) solu-

tion. The organic layer was separated and the aqueous layer was

extracted with ether. The combined organic layer was dried over

MgSO₄. The solvent was removed under reduced pressure. The

residue was puriﬁed by preparative TLC on silica gel eluting with

AcOEt/n-hexane (1:30) to give 21a (21 mg, 76%) as a yellow oil.

4.12.1. 4-[1-(4-Methoxyphenyl)ethyl]-2-phenyl-5-(tributylstannyl)-

thiazole. IR (KBr, cm^ꢀ1

)

2956, 2926, 2871, 2852, 1611, 1510, 1480,

1463, 1303, 1245, 1177, 1074, 1038, 1008, 962, 830, 762, 689, 667,

602; ¹H NMR (600 MHz, CDCl₃)

0.87 (9H, t, J¼7 Hz, Meꢂ3),

1.10e1.14 (6H, m, CH₂ꢂ3), 1.27e1.35 (6H, m, CH₂ꢂ3), 1.44e1.53 (6H,

m, CH₂ꢂ3), 1.73 (3H, d, J¼7 Hz, Me), 3.75 (3H, s, MeO), 4.06 (1H, q,

J¼7 Hz, CH), 6.81 (2H, d, J¼9 Hz, ArH), 7.33e7.41 (5H, m, ArH), 8.00

4.13.1. 4-[1-(4-Methoxyphenyl)ethyl]-2-phenylthiazole

(KBr, cm^ꢀ1

1611,1511,1497,1462,1439,1302,1247,1178,1035,1002,

832, 766, 690; ¹H NMR (600 MHz, CDCl₃)

(21a). IR

)

(2H, d, J¼9 Hz, ArH); ¹³C NMR (150 MHz, CDCl₃)

11.1 (tꢂ3), 13.6

1.70 (3H, d, J¼7 Hz, Me),

(qꢂ3), 23.9 (d), 27.2 (tꢂ3), 29.0 (tꢂ3), 43.2 (t), 55.2 (q), 113.5 (dꢂ2),

123.1 (s), 126.5 (dꢂ2), 128.5 (dꢂ2), 128.7 (dꢂ2), 129.2 (d), 134.3 (s),

138.3 (s), 157.8 (s), 167.4 (s), 172.1 (s); MS m/z 528 (M^þꢀBu), 526

(M^þꢀBu), 470 (M^þꢀ2Bu). Anal. Calcd for C₃₀H₄₃SnSNO: C, 61.66; H,

7.42; N, 2.40. Found: C, 61.32; H, 7.32; N, 2.39.

3.78 (3H, s, MeO), 4.31 (1H, q, J¼7 Hz, CH), 6.75 (1H, s, CH), 6.86 (2H,

dd, J¼2 and 7 Hz, ArH), 7.26 (2H, dd, J¼2 and 7 Hz, ArH), 7.38e7.42

(3H, m, ArH), 7.92e7.94 (2H, m, ArH); ¹³C NMR (150 MHz, CDCl₃)

21.7 (q), 41.6 (d), 55.2 (q), 113.0 (d), 113.8 (dꢂ2), 126.5 (dꢂ2), 128.6

(dꢂ2), 128.8 (dꢂ2), 129.7 (d), 133.9 (s), 137.0 (s), 158.1 (s), 162.8 (s),

167.5 (s); MS m/z 295 (M^þ), 280 (M^þꢀMe). Anal. Calcd for

C₁₈H₁₇NOS: C, 73.19; H, 5.80; N, 4.74. Found: C, 73.11; H, 5.86; N, 4.68.

4.12.2. 4-[1-(3,4-Dimethoxyphenyl)ethyl]-2-phenyl-5-(tributyl-

stannyl)thiazole. IR (KBr, cm^ꢀ1

)

2956, 2926, 2871, 2853, 1517, 1480,

1464,1261,1234,1155,1144,1031, 763, 690;¹H NMR (600 MHz, CDCl₃)

0.88 (9H, t, J¼7 Hz, Meꢂ3),1.10e1.18 (6H, m, CH₂ꢂ3),1.29e1.37 (6H,

4.13.2. 4-[1-(3,4-Dimethoxyphenyl)ethyl]-2-phenylthiazole (21e). IR

(KBr, cm^ꢀ1

) n 2963, 2930, 1591, 1516, 1463, 1417, 1259, 1236, 1160,

M. Yoshimatsu et al. / Tetrahedron 66 (2010) 7975e7987

7987

1143, 1030, 1005, 982, 767, 691; ¹H NMR (600 MHz, CDCl₃)

1.71

References and notes

(3H, d, J¼7 Hz, Me), 3.83 (3H, s, OMe), 3.89 (3H, s, OMe), 4.29 (1H, q,

J¼7 Hz, CH), 6.77 (1H, s, ArH), 6.81 (1H, d, J¼8 Hz, ArH), 6.86e6.88

(1H, m, ArH), 6.92 (1H, d, J¼2 Hz, ArH), 7.35e7.41 (3H, m, ArH),

1. Metzger, J. V. In Comprehensive Heterocyclic Chemistry; Katrizky, A. R., Rees, C.

W., Eds.; Pergamon: Oxford, 1984; Vol. 6, pp 235e331; Dondoni, A.; Merino, P.

In Comprehensive Heterocyclic Chemistry II; Katrizky, A. R., ReesC.W., Scriven, E.

F. V., Eds.; Elsevier Science: Oxford, 1996; Vol. 3, pp 373e474; Hantzsch, A. R.

Justus Liebigs Ann. Chem. 1888, 249, 1e6; Hantzsch, A. R.; Weber, J. H. Ber. Dtsch.

Chem. Ges. 1887, 20, 3118e3132.

7.92e7.94 (2H, m, ArH); ¹³C NMR (150 MHz, CDCl₃)

d 21.6 (q), 41.7

(d), 55.7 (q), 55.7 (q), 110.9 (d), 111.0 (d), 112.9 (d), 119.3 (d), 126.3

(dꢂ2), 128.7 (dꢂ2), 129.6 (d), 133.7 (s), 137.3 (s), 147.4 (s), 148.6 (s),

162.5 (s), 167.4 (s); MS m/z 403 (M^þ), 388 (M^þꢀMe), 326 (M^þꢀPh),

294 (M^þꢀSPh). High-resolution mass calcd for C₁₉H₁₉NO₂S:

325.1136, found m/z 325.1072.

2. Kikelj, D.; Urleb, U. Sci. Synth. 2001, 11, 643e645.

3. Prijs, B.; Ostertag, J.; Erlenmeyer, H. Helv. Chim. Acta 1947, 30, 2110e2113;

Taurins, A.; Blaga, A. J. Heterocycl. Chem. 1970, 7, 1137e1141; Tanaka, K.;

Nomura, H.; Oda, H.; Yoshida, S.; Mitsuhashi, K. J. Heterocycl. Chem. 1991, 28,

907e911; Wilson, W.; Woodger, R. J. Chem. Soc. 1955, 2943e2948; Ohkubo,

M.; Kuno, A.; Nakanishi, I.; Takasugi, H. Chem. Pharm. Bull. 1995, 43,

1497e1504; Friedman, B. S.; Sparks, M.; Adams, R. J. Am. Chem. Soc. 1937, 59,

2262e2264; Conover, L. H.; Tarbell, D. S. J. Am. Chem. Soc. 1950, 72,

5221e5225; Clarke, H. T.; Gurin, S. J. Am. Chem. Soc. 1935, 57, 1876e1881;

Vernin, G.; Metzger, J. Bull. Soc. Chim. Fr. 1963, 2498e2503; Benkoe, A.;

Levente, A. Justus Liebigs Ann. Chem. 1968, 717, 148e153; Ried, W.; Kaiser, L.

Justus Liebigs Ann. Chem. 1976, 395e399.

4. Moriarty, R. M.; Vaid, B. K.; Ducan, M. P.; Levy, S. G.; Prakash, O.; Goyal, S.

Synthesis 1992, 845e846; Penz, G.; Zbiral, E. Chem. Ber. 1985, 118, 4131e4133;

Varma, R. S.; Kumar, D.; Liesen, P. J. J. Chem. Soc., Perkin Trans. 1 1998,

4093e4096; Iriuchijima, S.; Hasegawa, K. JP 7777061, 1975. Chem. Abstr. 1977,

87, 201513; Erlenmeyer, H.; Weber, O.; Schmidt, P.; Kuenig, G.; Zinsstag, C.; Prijs,

B. Helv. Chim. Acta 1948, 31, 1142e1158; Erlenmeyer, H.; Becker, C.; Sorkin, E.;

Bloch, H.; Suter, E. Helv. Chim. Acta 1947, 30, 2058e2062.

5. Wipf, P.; Venkartraman, S. J. Org. Chem. 1996, 61, 8004e8005.

6. Zaleska, B.; Ciez, D.; Falk, H. Monatsh. Chem. 1996, 127, 1251e1257; Tayler,

E. C.; Anderson, J. A.; Berchtold, G. A. J. Am. Chem. Soc. 1955, 77,

5444e5445; Land, A. H.; Ziegler, C.; Sprague, J. M. J. Org. Chem. 1946, 11,

617e623.

7. Kim, H.-S.; Kwon, I.-C.; Kim, O.-H. J. Heterocycl. Chem. 1995, 32, 937e939;

Lardicci, L.; Battistini, C.; Menicagli, R. J. Chem. Soc., Perkin Trans. 1 1974,

344e346.

4.13.3. 4-[1-(4-Fluorophenyl)ethyl]-2-phenylthiazole (21h). IR (KBr,

cm^ꢀ1

)

3063, 2970, 2930, 2872, 1603, 1508, 1461, 1437, 1223, 1159,

1052, 1003, 979, 915, 836, 766, 690, 609, 597, 548; ¹H NMR

(600 MHz, CDCl₃)

1.70 (3H, d, J¼8 Hz, Me), 4.31e4.34 (1H, q,

J¼8 Hz, CH), 6.77 (1H, s, ArH), 6.97e7.01 (2H, m, ArH), 7.28e7.30

(2H, m, ArH), 7.36e7.41 (3H, m, ArH), 7.91e7.93 (2H, m, ArH); ¹³C

NMR (150 MHz, CDCl₃)

d 21.7 (q), 41.5 (d), 113.1 (d), 115.0 (d), 115.2

(d), 126.5 (dꢂ2), 128.8 (dꢂ2), 129.0 (d), 129.1 (d), 129.8 (d), 133.8 (s),

140.5 (s), 161.4 (d, J¼244 Hz), 162.1 (s), 167.7 (s); MS m/z 284 (M^þ),

283, 269 (M^þꢀMe), 268 (M^þꢀMe). High-resolution mass calcd for

C₁₇H₁₄FNS: 283.0831, found m/z 283.0828.

4.13.4. 4-[1-(2-Thienyl)ethyl]-2-phenylthiazole (21i). IR (KBr, cm^ꢀ1

)

2971, 2928, 1713, 1510, 1497, 1458, 1437, 1362, 1222, 1002, 766,

690; ¹H NMR (600 MHz, CDCl₃)

1.80 (3H, d, J¼8 Hz, Me), 4.64 (1H,

q, J¼7 Hz, CH), 6.87 (1H, d, J¼8 Hz, ArH), 6.94e6.95 (2H, m, ArH),

8. Coen, S.; Ragonnet, B.; Vieillescazes, C.; Roggero, J.-P. Heterocycles 1985, 23,

1225e1228; Sankyo, UK 951885, 1964; Chem. Abtsr. 1964, 61, 5657.

9. Yoshimatsu, M.; Yamamoto, T.; Sawa, A.; Kato, T.; Tanabe, G.; Muraoka, O. Org.

Lett. 2009, 11, 2952e2955.

10. Yoshimatsu, M.; Otani, T.; Matsuda, S.; Yamamoto, T.; Sawa, A. Org. Lett. 2008,

10, 4251e4254.

7.17 (2H, dd, J¼2 and 4 Hz, ArH), 7.37e7.42 (3H, m, ArH), 7.94e7.95

(1H, m, ArH); ¹³C NMR (150 MHz, CDCl₃)

d 22.6 (q), 37.7 (d), 113.2

(d), 123.6 (d), 124.0 (d), 126.5 (dꢂ3), 128.8 (dꢂ2), 129.8 (d), 133.8 (s),

148.4 (s), 161.7 (s), 167.7 (s); MS m/z 271 (M^þ), 256 (M^þꢀMe). High

resolution mass calcd for C₁₅H₁₃NS₂: 271.0489, found m/z 271.0409.

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