ƘƲk”™Wǯ 5ɢĦǸʙÇöşBȁȓ Research on Catalytic Reductions with Organosilanes

ƘƲk”™Wǯ5ɢĦǸʙÇöşBȁȓ

Research on Catalytic Reductions with Organosilanes

2014 Ň 2 Ɨ

ƎȒǰĠīĠīʮ ÉʑǫłīȁȓȎ éīšǮĄéīĸƀ éīýŨǂȁȓ

ƣƠ ĿŔ

Takehiko MATSUMURA

ǵɮɔ

Ar : aryl

aq. : aqueous

Bn : benzyl

Bu : butyl

cat. : catalytic amount

cod : 1,5-cyclooctadiene

Cy : cyclohexyl

dba : dibenzylideneacetone

DIPEA : N,N-diisopropylethylamine

DMAP : 4-dimethylaminopyridine

DMF : N,N-dimethylformamide

DMSO : dimethyl sulfoxide

dppf : 1,1’-bis(diphenylphosphino)ferrocene

equiv : equivalent

Et : ethyl

mCPBA : m-chloroperbenzoic acid

Me : methyl

Mes : 2,4,6-trimethylphenyl

mp : melting point

N.R. : no reaction

Ph : phenyl

Pr : propyl

PTLC : preparative thin-layer chromatography

quant. : quantitative

Rf : retention factor rt : room temperature

sat. : saturated

temp : temperature

TES : triethylsilyl

Tf : trifluoromethanesulfonyl

THF : tetrahydrofuran

TMS : trimethylsilyl

o-tol : o-tolyl

Hhmpbta : 2-(2’-hydroxy-5’-methylphenyl)benzotriazole

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I1ØƛBƫɥ@";methyl 2-naphthyl sulfide ¹⁵⁾#Q{…s—™FBĝŸöş@9

;üȑʗȏʣĽɢĦ=y•^u–k”™WǯSöşWȣƧ.5(Table 2-1)THFǔ Ħ¤”l\ɢĦ=.;Pd/CWǯ5Ęý@CIJǐ80Õ<CǺǸBǮŨǤ<S {…s—™$Ƕʂʢȃɬ<%5BJ<85ˏentry 1ː$öşƒʪ˖ƒʪ<C67%<Ś S*=$<%5ˏentry 2ːɢĦ=.;”l\†”vdWǯ5Ęý@C19ƒʪř

<,!MǶʂʢB{…s—™$ɠǑ,T5BJ<85(entries 3 and 4)I5Pd(OAc)2W ǯ5Ęý@MPd/CWǯ5Ęý=þȐŊB÷ǩ<ǺǸǤW¡!ˏentry 5ː”l\

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Ȯ;•a™zBƫɥWɒ85Pd(PPh3)4ˏentry 7ːNPd(PCy3)2Cl2ˏentry 8ː"PE Pd(dppf)Cl2•CH2Cl2ˏentry 9ːWǯ5Ęý@CöşCʑɒ.?ȭƥ=?85 Pd2(dba)3

=X-PhosWǯ5Ęý@C25%<ǺǸB{…s—™W¡!5

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ɒ.ǺǸǤW÷ǩ90ˎ<¡!5«#Qę達l\¤B ȦǤ$öş@ʫ¡.;S ŧŠC?MB=ȹ!QTSˏentry 12ː°BʗȏʣĽ<SRhClˏentry 13ːN3 PtClˏentry 2

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Table 2-1. Reduction of methyl 2-naphthyl sulfide with TESH with different catalysts

Ȯ;ǔĦBƫɥ=.;öşƒʪW80Õ=.ę達l\ɢĦĨēŸmethyl 2- naphthyl sulfideWĖʀ=.;TESHWǯ;öşWɒ85ˏTable 2-2ːTHFWǔĦ=.;

ǯ5Ęý@C80Õ<öşCĭȭ.5ˏentry 1ː$y–^™WǔĦ=.;ǯ5Ęý

@C80Õř<CñƇ$ƵR %B÷ǩ=?85ˏentry 2ːI5dioxaneWǯ5Ęý

@MñƇCƵĨ.÷ǩC75%=?85ˏentry 3ːMeCNWǯ5Ęý@MñƇCƵĨ.

ǺǸǤ<S{…s—™B÷ǩC75ˎ=?85ˏentry 4ːDMFWǯ5Ęý@M80Õ<

CöşCĭȭ21{…s—™B÷ǩC82ˎ@ǴI85ˏentry 5ː²žBȭƥPRǔ Ħ=.;CTHF$ʖ.;S«$ȇĈ,T5

SMe Et₃SiH (2.1 equiv) catalyst (3 mol%)

THF, rt

H

1a 2a

Entry Catalyst Time Yield^a (%)

1 Pd/C^b 80 min trace

2 Pd/C^b 5 h 67

3 Pd black 80 min trace

4 Pd black 19 h trace

5 Pd(OAc)2 6 h 79

6 - 24 h 0

7 Pd(PPh3)4 80 min 0

8 Pd(PCy3)2Cl2 80 min 0

9 Pd(dppf)Cl2•CH2Cl2 80 min 0

10 Pd2(dba)3, X-Phos^c 80 min 25

11 PdCl2 80 min 96

12 PdCl2d

60 min 90

13 RhCl3 24 h 0

14 PtCl2 24 h 0

15 Ni(COD)2 24 h 0

a Isolated yields.

b 10 % wt of Pd/C including 3 mol% of p alladium was used.

c 1.5 mol% of Pd2(dba)3 and 3 mo l% of X-Phos was used.

d PdCl2 (99.999%) was used.

Table 2-2. Reductive desulfurization of methyl 2-naphthyl sulfide with Et3SiH and PdCl2 in different solvent

ę達l\=TESH=Böş<CƼȨam=y•^u–k•–d˜”[zˏTESClː ˑ¾B”l\$Ǯ/S«$ėĂ,T;S¹⁶⁾3*<TESCl$ƞʙÇöş@ʫ¡.

;SB<C?#=ȹ!k”™Bȑ˅=Y–b–k•–d˜”[zBnjåBƫɥWɒ 85ˏTable 2-3ːTHFǔĦ¤3 mol%Bę達l\ĨēŸmethyl 2-naphthyl sulfide

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•–d˜”[zˏTMSCl, 1.0ŒʢːWnjå.5Ęý@CöşƒʪC10ÕF=,Q@Ȁȱ ,T÷ǩM97ˎF=Āž.5ˏentry 3ː*B«#QȖ¹ʵijBöşʎŊFBŕʿCĠ

%MB=ȹ!QTSTMSClˏ1.0ŒʢːĨēŸTESHBʢW1.5ŒʢF=ǏQ.5Ę ý<CñƇC45Õ<ljĢ.94ˎ<ǺǸǤ$ŚQT;%5ˏentry 4ː,Q@TESHBʢ WǏQ.1.2Œʢ=.5Ęý@CöşCĭȭ2124ƒʪřMñƇ$ƵĨ.ǺǸǤB÷

ǩC83%=?85ˏentry 5ː1.2ŒʢBTESHWǯ;Möş$ĭȭ.?#85«#Q ę達l\Wˑ¾F=ʙÇ0SÕ@å!”l\‚z•zȑBĬįéI5CdžŢ éB5L@TESH$Şɜ<SúȾŢM.'C”l\ɢĦ@PRTESH$ļ.19 Õɡ.;SúȾŢ$ȹ!QTSȃɬB5L1.2țʢBTESHWǯ;TMSClWnjå 21@öşWɒ85=*U24ƒʪřB÷ǩCentry 5@ƹG¸Ÿ.58%=?85ˏentry 6ː

*BȭƥCTMSCl$Ǟ5Lentry 5@ƹGsp²ǜȨȂˍȭýBÖƈ$ʒ'3BÕ6 (TESHBÕɡ$ʑɒ.5«WȇĈ.;S

y•^ybkk”™Wǯ5Ęý@CöşCʑɒ0SMBBöşBʑɒCʒ'4ƒʪ

<62%= ȭƥ=?Rˏentry 7ː…]|–k”™Wǯ5Ęý@CöşCÍ'ʑɒ.

?ȭƥ=?85ˏentry 8ː°BʙÇÞ=.;ⁿBu3SnHWǯ5Ęý@CTMSClBnj åʼnjå@ʫVQ1öşCʑɒ.?ȭƥ=?85ˏentries 9 and 10ːI5ƼȨʺĐ

SMe

Et₃SiH (2.1 equiv) PdCl₂ (3 mol%) solvent, rt, 80 min

H

1a 2a

Entry Solvent Yield^a (%)

1 THF 96

2 toluene 68^b

3 dioxane 75^b

4 MeCN 75^b

5 DMF 82^b

a Isolated yields.

b Starting material remained.

ƻŸ<öşWɒ85$ę達l\Wǯ5Ęý"PEPd/C=TMSClWǯ5Ęý 1TMöşCʑɒ.?ȭƥ=?85ˏentries 11 and 12ː*TQBȭƥ#QƞöşB ʑɒ@CTESH$Şˁ<S«$ȇĈ,T5

Table 2-3.Reaction of methyl 2-naphthyl sulfide with PdCl2 (3 mol%) and reducing agent in THF at room temperature

SMe

reducing agent PdCl₂ (3 mol%) additive (1.0 equiv)

THF, rt

H

1a 2a

Entry Reducing Agent (equiv) Additive Time Yield^a (%)

1 Et3SiH (2.1) - 80 min 91

2 Et3SiH (2.1) TESCl 50 min 96

3 Et3SiH (2.1) TMSCl 10 min 97

4 Et3SiH (1.5) TMSCl 45 min 94

5 Et3SiH (1.2) TMSCl 24 h 83^b

6 Et3SiH (1.2) - 24 h 58^b

7 (EtO)3SiH (2.1) - 4 h 62^b

8 Ph3SiH (2.1) - 24 h 0^b

9 ⁿBu3SnH (2.1) - 24 h 0^b

10 ⁿBu3SnH (2.1) TMSCl 24 h 0^b

11 H2 atmosphere - 24 h 0^b

12 H2 atmosphere^c TMSCl 24 h 0^b

a Isolated yields.

b Starting material remained.

c 10 % wt of Pd/C including 3 mol% of p alladium was used instead of PdCl2.

I5Pd/CWǯ5Ęý@MTMSClˏ1.0ŒʢːBnjå@PRöş$Àʑ,T80ÕB öşƒʪ<ǺǸǤW÷ǩ97ˎ<¡!5ˏentry 2, Table 2-4ːę達l\#Qɱə.5 ˑ¾B”l\Wǯ5Ęý@";Cę達l\Wǯ5Ęý@ƹGöşBʑ ɒ$ʒ'?R80Õř<CǶʂʢBǺǸǤ.#ŚQT124ƒʪřMǺǸǤB÷ǩC21ˎ

=?85ˏentries 4 and 5ːI5ɢĦ=.;Ni(COD)2Wǯ5Ęý@CTMSClBnjå BƘǞ@##VQ1öşCʑɒ.?ȭƥ<85ˏentries 6 and 7ː²žBƫɥȭƥ#

Qƞöş@"(STMSClBåʎèƥ$ȃɬ,T5

Table 2-4. Reduction methyl 2-naphthyl sulfide with TESH with different catalysts

SMe Et₃SiH (2.1 equiv) catalyst (3 mol%)

THF, rt

H

1a 2a

Entry Catalyst Time Yield^a (%)

1 Pd/C^b 80 min trace

2 Pd/C^b, TMSCl (1.0) 80 min 97

3 PdCl2 80 min 96

4 Pd*(0)^e 80 min trace

5 Pd*(0)^e 24 h 21

6 Ni(COD)2 24 h 0

7 Ni(COD)2, TMSCl (1.0) 24 h 0

a Isolated yields.

b 10 % wt of Pd/C including 3 mol% of palladium was used.

e Pd*(0) prepared from PdCl2 and TESH was used after pumped up.

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@PR¬ʠȭý@"(SßöşBʑɒ$ŭÜ,T5«Wȇ.;S

I5TMSClWnjå@PSƞöşBÚBǥŜWʋGSY–b–ˆw˜Y•›–m–…

Zz1m-1pWĖʀ=.;ǯ5Ęýˏentries 12B-15Bː@CTMSClBnjå@PRöş$

ʑɒ.?ȭƥ=?85"3Q'*TCĖʀBƘ0Sˆw˜ǭBȕȨñħBęĖŢ$ñ ď<ñƇ$TMSCl=ęWœŨ.55L6=ȹ!QTS*TQBȭƥCGrahamQėĂ.

5Y–b–ˆw˜Y•›–m–…ZzBʙÇǸÖƈöşBöşơ³=ǼɘǸ@?S=ȹ!

QTS¹⁴⁾

Table 2-5. The reaction of alkyl aryl sulfides with PdCl₂ (3 mol%) and TESH (2.1 equiv) in the absence of TMSCl (A) and in the presence of TMSCl (1.0 equiv) (B) in THF

Entry Substrate Temp. Time Product Yield^a (%)

1A 1B

2A^b 2B^b 3A 3B

4A 4B

5A 5B 6A 6B 7A 7B

8A 8B 9A 9B

MeS

SMe

MeS

Me MeS

F MeS

Cl MeS

OMe MeS

CO₂Me

MeS NO₂

H

H

H

Me H

F H

Cl H

OMe H

CO₂Me

H NO₂

EtS SO₂Me

1b²⁶⁾

1c

1d

1e

1f

1g

1h

1i

1j

2b

2b

2d

2e

2f

2g

2h

2i

2j rt

rt

rt

rt

rt

rt

rt

reflux rt

rt

80 min 60 min

99 97

22 h 14 h

74 79 135 min

100 min

83 86

45 min 15 min

84 90

H SO₂Me

30 min 10 min

80 min 30 min

20 min 10 min 4d 15 min 40 min 15 min

94 93

86 92 97 96

35^c 92

89 98 H

CO₂Et MeS

CO₂Et

MeS H

NMe N

SMe

O N

SMe S N

SMe

N Me

H 1k

1l

1m²⁷⁾

1n²⁸⁾

1o²⁸⁾

2k

2l

2m

2n

2o

2p 1p

10A 10B 11A 11B 12A^b 12B^f 13A^b 13B^f 14A^b 14B^f 15A 15B

NMe N

H

O N

H S N

H

N Me

SEt

rt

rt

reflux 50 ºC reflux 50 ºC reflux 50 ºC

rt

70 min 70 min 2 h 2 h 7 d 7 d 7 d 7 d 7 h 7 h

2 h 24 h

62^d 87 70 79 44^e 0^e 55^e 0^e trace^e 0^e 72^e 0^e

a Isolated yields.

b 4.2 equiv. of TESH was used.

c 44% of 8 remained. The amine corresponding to 8p (25%) was formed.

d Methyl hydrocinnamete (35%) was formed.

e Starting material remained.

f 2.0 equiv.of TMSCl was used.

ș˕Ȝ öşƲƯBȹĶ

öşƲƯɡƤB5L'9#BİˈWɒ85TES-SEtBǮŨ$éýǤ1jˏˏTable 2-5ː BöşřBǔNJB¹H NMR@PRɠǑ,T5ˏFigure 2-1ː

Scheme 2-1. Reaction of 1j in C6D6

Figure 2-1. ¹³C NMR spectrum of reaction mixture of 1j

I52-(2-naphthylsulfanyl)ethyl phenyl sulfone 1q²⁹⁾Böş@";řÓǫř@{…s—

™ˏ÷ǩ90ˎː=u_›–3qˏ÷ǩ72ˎːˏScheme 2-1ːW¡!…]|–m–…Z™ʟ CÍ'ɠǑ,T?#85ˏScheme 2-2ː

Scheme 2-2. Reaction of 2-(2-naphthylsulfanyl)ethyl phenyl sulfone 1q

TMSCl@PSééýǤ1aBǜȨ-ȂˍȭýBdžŢéWɱGS5LNMRBǑįWɒ85

$chemical shiftBĝé$Ǟ«#QĖʀWdžŢé.;?«$ȇĈ,T5ˏFigure 2-2ː

EtS SO₂Me SO₂Me EtS Si

Et₃SiH (2.1 equiv) PdCl₂ (3 mol%) C₆D₆, rt, 40 min

1j 2j

S SO2Ph HS

SO₂Ph 3q 72 % Et3SiH (2.1 equiv)

PdCl₂ (3 mol%) THF, rt, 30 min

H

2a 90 % 1q

Scheme 2-3. NMR analysis of 1a with TMSCl

²žBƫɥȭƥ#Q”l\ɢĦ@PSY–b–Y•›–m–…ZzBǜȨ-Ȃˍȭ ýBÖƈ$sp³ǜȨ-Ȃˍȭý<?'sp²ǜȨ-Ȃˍȭý<ʁ*Rķş0SY—›™=k

•–é,T5u_›–W¡!S«I5öş@PRÖƈ,T5Y–b–u_Ė$k•–é ,T;ǮŨ.řÓǫ@PRåƼÕɡWù(;u_›–W¡!S«Wȇ.;S

I5*TI<BƅǨėĂ@";ƘƲk”™=”l\ɢĦ#QB”l\‚

z•zȑǮŨBŷĉ³⁰⁾NǮŨ.5”l\‚z•zȑ$öş0SʴB-‘sokmƲ ƯBŵį³¹⁾#QƞöşBöşƲƯWƴBP @ŵį.5ˏFigure 2-2ː

0?V7ę達l\$Y–b–k”™@PRʙÇ,Tˑ¾B”l\$ǮŨ 0SȮ;Y–b–k”™=BʟéǸ±å$ʑɒ.”l\‚z•zȑWǮŨ0S

‘sokm@PRC(sp²)-Sȭý$Öƈ,TS-Siȭý$ǮŨ0Sƶʲ<TMSClBf[

Ȩ$¤ʪ¹BȂˍñħBʻħĵŊWŸ)ǜȨȂˍȭýWdžŢé0S«<öş$Àʑ,T S‘sokm@PRk•–Y–b–u_^›w–$Ǯ/Ɩř@ʙÇǸɀʹWȬ;Y

—›™$ǮŨ0S

Figure 2-2. Proposed reaction mechanism

SMe TMSCl (1.0 equiv) THF-d8

rt, 30 min

No chemical shift change

1H, ¹³C NMR analysis of reaction mixture 1a

Pd(0)

Pd H R₃Si

R₃SiH

R₃Si S Ar

Pd Akyl

H

S Alkyl Ar Pd

Ar H

R₃Si S Alkyl Ar H

PdCl₂ R₃SiH

Pd(0)

Pd H R₃Si

R₃SiH

R₃Si S Ar

Pd alkyl

H

alkyl S Ar Pd

Ar H

R₃Si S alkyl

Ar H

PdCl₂ R₃SiH

R₃Si Cl

S SiMe₃ Pd

Ar H alkyl

TMSCl

oxidative addition reductive

elimination

σ-metathesis

TMSCl

oxidative addition reductive

elimination

σ-metathesis

ș˔ȗ Y–b–Y•›–m–‹bkzBʙÇöş@ʫ0Sȁȓ ș˒Ȝ ʼnɳ

m–‹bkzCȂˍñħž@ Ɔ¤ŝ$Ĩē.ŚS*=#Q ƆɘçĖ=.;ǯS

«$úȾ<S.5$8;ȟ¿#9ĮȾĖʘŮǸ?m–‹bkzBĝŸõEʯòWɒ «$<%TDƘƲýŨéīǸ@Ƙǯ<S

Y–b–Y•›–m–‹bkz#Qķş0SɇˆǭFBĝŸöşCRaney nickelWǯ

5ơ³³²⁾NțʢBNi(OAc)2NNiCl2Wǯ5ơ³³³⁾$ǿQT;S$ÝȺCžʋ.5

P ?ĮȾĖʘŮŢB¸,NöşBĭȭ@ʓàʢWŞɜ=0S«3.;3TɁ¹BǷǚ Ţ#QøRŬ@ƳǝWƘ.řȺCƼȨé{y•\NGrignardɩɐWǯS*=#Q ęĖŢơ³@ Ĭį?ĖʀWǯS«$<%?= Üʭ$S3B5Lǐą#9

¤Ţơ³Ÿ<BöşBʩǷ$ƽLQT;S3*<ʗȏʣĽ=ƘƲk”™WǯSöş ơ³Wƫɥ.5ƫɥBȭƥ”l\ɢĦĨēŸTESHWǯǐą#9ȟ¿?ūǂ WɝÔ0«$<%55L²Ÿ@ɪȩWʋGS

ș˓Ȝ öşơ³BƖʖé

ș˓ȗ<Ɩʖé,T5ơ³@ķş0Sơ³Wǯ;methyl 2-naphthyl sulfoxide³⁴⁾Wǯ

;ƫɥWɒ85=*Um–‹bkz$ʙÇ,T5{…s—™=methyl 2-naphthyl sulfide

$3T4T÷ǩ80ˎ÷ǩ4ˎ<ŚQT;%5ˏScheme 3-1ː

Scheme 3-1. Pd-catalyzed reduction of methyl 2-naphthyl sulfoxide

3B5Lơ³BƖʖé@PRY–b–Y•›–m–…Zz#Qķş0SY—›™m

–…Zz3T4TFʘŮǸ@ʙÇ0S«$úȾ=ȹ!ƫɥWɒ85I1IJǐŸTHF

ǔĦ¤methyl 2-naphthyl sulfoxideWĖʀ=.;ȑB”l\ɢĦWǯ;{…s—

™FBʙÇöşBƫɥWɒ85ˏTable 3-1ːę達l\WɢĦ=.;ǯTMSClW njå21@öşWɒ85=*UöşƒʪCȀȱ.öşƒʪ80Õ<{…s—™W¡!5

ˏentry 1ː3*<Ȯ'ƫɥMTMSClWnjå21@ɒ85ɢĦ=.;ʝʟ”l\W

ǯ5Ęý<C,Q@öşƒʪ$Ȁȱ.50Õ<{…s—™W97ˎB÷ǩ<¡!5ˏentry 2ːPd2(dba)3Wǯ5Ęý<C100Õ86ˎ÷ǩ<ǺǸǤW¡!5ˏentry 3ːPd/CWɢĦ

=.;ǯ5Ęý@C24ƒʪř<MǺǸǤB÷ǩC67%<85ˏentry 4ːPdCl2(PPh3)2

NPd(PPh3)4?>B•a™zWǯ5Ęý@CöşBʑɒCʼŅ@ʒ'24ƒʪřB÷ǩ

C3T4T10ˎ57ˎ=?85ˏentries 5 and 6ːI5”l\ɢĦWnjå21@ö şWɒ85$3BĘý@CöşCʑɒ.?ȭƥ=?85ˏentry 7ː²žBƫɥBȭƥ PRƞöş@C”l\ɢĦ$Şˁ<R¤<Mʝʟ”l\$ʖÖ<S*=

$ȃɬ,T5I5‹m…Z™•a™zBnjå@PRöşʎŊ$ʒ'?S«$ȇ,T5

SMe

Et₃SiH (3.1 equiv) PdCl₂ (3 mol%) TMSCl (1.0 equiv)

THF, rt, 24 h

H O

SMe

4a 2a 80% 1a 4%

Table 3-1. Reduction of methyl 2-naphthyl sulfoxide with various palladium catalysts

9&@methyl 2-naphthyl sulfoxideWĖʀ=.;ʝʟ”l\ɢĦĨēŸTESHW ǯ;ȑBǔĦWƫɥ.5l^u–^›w–Wǯ;öşWɒ85Ęý@C21ƒʪř MH=X>öşCʑɒ21ǶʂʢBǺǸǤ$ɠǑ,T5BJ<85ˏTable 3-2, entry 2ː ld˜˜‘s™WǔĦ=.;ǯ5Ęý@C2ƒʪ<öşCĭȭ.{…s—™W98%B

÷ǩ<¡!5ˏentry 3ːy–^™Wǯ5Ęý@C21ƒʪ<öşCĭȭ.ǺǸǤW93ˎ B÷ǩ<¡!5ˏentry 4ːYoy|y•–Wǯ5Ęý@CöşC2ƒʪ<ĭȭ.{…s

—™W92ˎB÷ǩ<¡!5ˏentry 5ː*TQBƫɥȭƥ#Qöşƒʪ@ǾǺ.THFW ƞöşBƖʖǔĦ=.5

Table 3-2. Reduction of methyl 2-naphthyl sulfoxide in different solvent

SMe Et₃SiH (3.1 equiv) catalyst (3 mol%)

THF, rt

H O

4a 2a

Entry Pd catalyst Time Yield^a (%)

1 PdCl2 80 min 94

2 Pd(OAc)₂ 50 min 97

3 Pd₂(dba)₃ 100 min 86

4 Pd/C^b 24 h 67

5 PdCl₂(PPh₃)₂ 24 h 10

6 Pd(PPh3)4 24 h 57

7 - 24 h 0

a Isolated yields.

b 10 % wt of Pd/C including 3 mol% of palladium was used.

SMe Et₃SiH (3.1 equiv) Pd(OAc)₂ (3 mol%)

solvent, rt

H O

4a 2a

Entry Solvent Time Yield^a (%)

1 THF 50 min 97

2 Et2O 21 h trace

3 CH₂Cl₂ 2 h 98

4 toluene 21 h 93

5 MeCN 2 h 92

a Isolated yields.

9:;methyl 2-naphthyl sulfoxideWĖʀ=.;ǯIJǐŸTHFǔĦ¤<Bʝʟ

”l\WɢĦ=.5ʙÇöş@PRʙÇÞ=.;k”™BƫɥWɒ85ˏTable 3-3ːy

•^ybkk”™Wǯ;öşWɒ85Ęý@Cm–‹bkzBʙÇCʑɒ.5$Ǯ/

Sm–…Zz1a#Q{…s—™FBʙÇCH=X>ʑɒ21methyl 2-naphthyl sulfide$ 98ˎ=ˊ÷ǩ<ŚQT5ˏentry 2ːy•…]|–k”™Wǯ5Ęý@Cöşƒʪ25 ƒʪ<{…s—™"PEmethyl 2-naphthyl sulfide$3T4T÷ǩ13ˎ86ˎ<ŚQT;%

5ˏentries 2 and 3ː*TQBȭƥ#Qk”™WʘŮ0S«@PRm–‹bkzBʙÇW

Üś<%S«$ɝÔ,T5

Table 3-3. Reduction of methyl 2-naphthyl sulfoxide with silane

ÉBƫɥ<m–‹bkz#Qm–…ZzFBʙÇ$ʑɒ.5«#Qmethyl 2-naphthyl

sulfoxideWĖʀ=.;ǯIJǐŸʝʟ”l\ɢĦ@PSy•^ybkk”™Wǯ

5ʙÇöş<ȑBǔĦWƫɥ.5ˏTable 3-4ːl^u–^›w–WǔĦ=.;ǯ5 Ęý@CöşCĭȭ2124ƒʪřBǺǸǤB÷ǩC46ˎ=?85ˏentry 2ːld˜˜

‘s™WǔĦ=.;ǯ5Ęý@Möşƒʪ24ƒʪ<CñƇCljĢ21methyl

2-naphthyl sulfideB÷ǩC62ˎ<85ˏentry 3ːy–^™Wǯ5ĘýC,Q@öşB

ʑɒ$ʒ'ǺǸǤB÷ǩC21ˎ<85Yoy|y•–WǔĦ=.;ǯ5Ęý@C 7ƒʪ<ñƇCljĢ.ǺǸǤW95ˎB÷ǩ<¡!5ˏentry 5ː*TQBƫɥ#Qm–…

ZzFBʙÇöş@";MTHFǔĦ$ʖ.;S«$ɝÔ,T5

SMe R₃SiH (3.1 equiv) Pd(OAc)₂ (3 mol%)

THF, rt

H O

SMe or

4a 2a 1a

Entry R₃SiH Time Yield^a (%) of 2a

Yield^a (%) of 1a

1 Et3SiH 50 min 97 0

2 (EtO)3SiH 25 h 1 98

3 Ph3SiH 25 h 13 86

a Isolated yields.

Table 3-4. Reduction of methyl 2-naphthylsulfoxide with different solvent

SMe (EtO)₃SiH (3.1 equiv) SMe Pd(OAc)₂ (3 mol%)

solvent, rt O

4a 1a

Entry Solvent Time (h) Yield^a (%)

1 THF 4 99

2 Et₂O 24 46

3 CH₂Cl₂ 24 62

4 toluene 24 21

5 MeCN 7 95

a Isolated yields.

ș˔Ȝ ĖʀʖǯŢBƫɥ

ƞöşBĖʀʖǯŢWɱGS5LƖʖé,T5ơ³@;ƫɥWɒ «=.5ˏTable

3-5ːIJǐŸTHFǔĦ¤3 molˎBʝʟ”l\ĨēŸȑBm–‹bkzWǯ

;TESH"PEy•^ybkk”™3T4TWǯ;öşWɒ85

3-methylsulfinyl-1,1'-biphenylWĖʀ=.;ǯ5Ęý@Cķş0Sƒ…]|–õEm–…

ZzC3T4T÷ǩ91ˎ88ˎ<ŚQT;%5ˏentry 1ː

4-methyl-3'-methylsulfinyl-1,1'-biphenylWĖʀ=.;ǯ5Ęý@Cķş0Sƒ…]|–

=m–…Zz3T4TW97ˎ97ˎB÷ǩ<¡!5ˏentry 2ːʻħ½¡Ė<S‘yb kĖ$ȵŸ.54-methoxy-3'-methylsulfinyl-1,1'-biphenyl<CöşBʑɒCNNʒ'?Rķ ş0Sƒ…]|–Cöşƒʪ140Õ<97ˎB÷ǩķş0Sm–…ZzCöşƒʪ100Õ

<91ˎB÷ǩ<85ˏentry 3ː˜g™$ȵŸ.54-fluoro-3'-methylsulfinyl-1,1'-biphenyl N3-chloro-3'-methylsulfinyl-1,1'-biphenylWĖʀ=.;ǯ5Ęý@MöşCĊ˃?'ʑɒ .ķş0Sƒ…]|–W3T4T91ˎ98ˎķş0Sm–…ZzW3T4T84ˎ84ˎ B÷ǩ<¡!5ˏentries 4 and 5ːMethy-3’-methylsulfinyl-1,1’-biphenyl-4-carboxylateWǯ5 Ęý@";Cƒ…]|–FBĝŸCåʎ,Töşƒʪ Õ<ǺǸǤW ˎB÷ǩ<¡

!5$m–…ZzFBĝŸCʒ'?Röşƒʪ ƒʪ<ķş0Sm–…ZzW ˎB÷

ǩ<¡!5ˏentry 6ː1-Ethylsulfinyl-4-methylsulfonyl-benzeneBĘýMþư<Rķş 0S‘u–…]|–m–‹™FBĝŸCåʎ,Töşƒʪ Õ<ǺǸǤW÷ǩ ˎ<¡

!m–…ZzFBĝŸCy•^ybkk”™W Œʢǯ;,!öşƒʪ ƒʪWŞ ɜ=.ǺǸǤB÷ǩC ˎ<85ˏentry 7ːˆw˜ǭ@";MöşCʑɒ.

2-ethylsulfinyl-4-methylquinolineWǯ5Ęý@ķş0Sb~•™ɭĺ¹W ˎB÷ǩ<

¡!ķş0Sm–…ZzW ˎB÷ǩ<¡!5ˏentry 8ː

(E)-1-methylsulfinyl-4-styrylbenzeneWǯ5Ęý@C_—…Z™BʙÇ@PSßǮŨǤ$

ɠǑ,TTESHWǯ5ʙÇ<Cmu–‰™B÷ǩC ˎ=?Ry•^ybkk”™

Wǯ5ʙÇ<Cķş0Sm–…ZzC÷ǩ ˎ<85ˏentry 9ːœƊʻħƽōŢ Ė<S^mw–=BÎŖ_—…Z™WƘ0S(E)-ethyl 3-(4-methylsulfinylphenyl)acrylateB öş<CTESHWǯ5Ęý@_—…Z™BʙÇCœʛʑɒ.5MBBǺǸǤW B

÷ǩ<¡!I5y•^ybkk”™Wǯ5ʙÇ<ǺǸǤW ˎB÷ǩ<Ś5ˏentry 10ː

*B¬9BĖʀWǯ5ƫɥȭƥBƹʅ#QʻħĵŊB¸_—…Z™@";Cƞơ

³<BʙÇʎŊ$ʒ'3B5L>7QBơ³=M BĘý@ƹG; @"(Sm–

‹bkzĖBʙÇBʘŮŢ$ˊI85=ȹ!QTSI5 @";y•^ybkk”

™Wǯ5Ęý@ǺǸǤ$ŚQT?#85ǫDZ=.;ƴBP @ȹĶ.5ƞöşơ³@

PRm–‹bkz$ʙÇ,Tm–…Zz@ĝŸ,TS=_—…Z™BʻħĵŊC,Q@

ˊIS=ȹ!QTS3B5LñƇBm–‹bkz@ƹGǮŨǤBm–…Zz@";

ßöş$PRʁ*RN0'?S=ȹ!QTS*B*=#QĖʀ <Cy•^ybk

k”™Wǯ5Ęý@÷ǩ$¸Ÿ.5MB=šVTS.#.?$QéýǤ BĘý@

";C^mw–Ė=ÎŖ.5ʻħĵŊB¸_—…Z™<S5L_—…Z™Bʙ ÇFBöşŢ$¸«@å!y•^ybkk”™Wǯ5ĘýBdžŢȑBʙÇã$ŏ 5LʙÇ$H=X>ʑɒ.?#85=ȹ!QTS

4-methylsulfinyl-1,1'-biphenyl Wǯ5Ęý<Cķş0Sƒ…]|–W95ˎB÷ǩ<¡

!ķş0Sm–…ZzC95ˎB÷ǩ<ŚQT5ˏentry 11ː

²žBƫɥȭƥ#Qk”™WʘŮ0S«@PRm–‹bkz#Qķş0SY—›™I 5Cm–…ZzF=ʘŮǸ@ĝŸúȾ?«$ÙƏ.5

Table 3-5. Reduction of sulfoxide with organosilane and Pd(OAc)2 in THF

aryl S alkyl aryl H

R₃SiH (3.1 equiv) Pd(OAc)₂ (3 mol%)

THF, rt

aryl S alkyl or

O

4 2 1

Time (min) Yield^c (%) of 2 Time Yield^c (%) of 1

1 4b 90 91 50 min 88

2 4c 65 97 100 min 97

3 4d 140 97 100 min 91

4 4e 70 91 210 min 84

5 4f 110 98 70 min 84

6 4g 40 92 2 h 80

7 4h 60 95 21 h 83^d

Reaction conditions B^b Reaction conditions A^a

Sulfoxide Entry

Me S O

F Me S

O

Cl Me S

O

CO₂Me Me S

O

OMe Me S

O

Me Me S

O

EtS

SO₂Me O

Time (min) Yield^c (%) of 2 Time Yield^c (%) of 1

8 160 91 11 h 88

9 4j 140 42 3 h 0

10 4k 140 72 3 h 92

11 4l 120 95 130 min 95

4i

Entry Sulfoxide Reaction conditions A^a Reaction conditions B^b

MeS

CO2Et O

MeS O

N Me

SEt O MeS

O

MeS

CO2Et O

a Reaction condition A: Et3SiH (3.1 equiv).

b Reaction condition B: (EtO)3SiH (3.1 equiv).

c Isolated yields.

d 6.2 equiv of (EtO)3SiH was used.

ș˕Ȝ öşƲƯBȹĶ

I5TESHWǯ5ʙÇ<C1TBĖʀ@";Mķş0Sm–…Zz$¤ʪ¹

=.;ɠǑ,T53B5Lƞöşơ³@"(Sm–‹bkz#QY—›™FBʙÇC m–…ZzWȬDZ.;SMB=ŵĶ,Ty•^ybkk”™Wǯ5Ęý@Cm–…

Zz#QY—›™FBʙÇ$ʼŅ@ʒM.'Cʑɒ.?5L@m–…Zz$÷ǩ P'ŚQT;'SMB=ȹ!QTSm–‹bkz#Qm–…ZzFBĝŸ@";C ʻħƽōŢĖWƘ0SĖʀ@";PRʨöşƒʪWŞɜ=0S*=#QɇˆǭBʻ ħĵŊ=öşŢ=$Ǽʫ0S=ȹ!QTSˏTable 3-5ːI5˓ȗBƫɥȭƥˏTable 2-5ː PRm–…Zz#Qķş0SY—›™FBʙÇBöşʎŊ$ɇˆǭBʻħĵŊ=ʌǼ ʫ0S*=#QTESHWǯ5m–‹bkz#QY—›™FBʙÇBöşʎŊC3TQ Wȯý.5MB@?S=ȹ!QTS.#.?$QʻħƽōŢĖ$ȵŸ.5Ėʀ@"

;öşƒʪ$Ȁȱ0S«#Qm–…Zz#Qķş0SY—›™FBʙÇ$Řʎ<R 3B5Lɇˆǭ"PEm–‹bkzBʻħĵŊ$¸H>öşʎŊ$åʎ0S=ȹ!Q TS

²ž#QƞöşBöşƲƯW²ŸBP @ŵį.;SˏFigure 3-1ːm–‹bkz BS-OȭýCĠ%'Õƭ.;S3B5LʟȨñħžBʻħĵŊ$ˊI8;"R

”l\‚z•zȑBf[Ȩñħ=ƖØ@öş0S=šVTSƴ@Si-Pdȭý$Öƈ, TS==M@‚z•z$ʟȨñħž@ȏRS-OȭýBʻħ$Ȃˍñħ@LJTm–…Zz

$ǮŨ0S

Figure 3-1. Proposed mechanism of reduction of alkyl aryl sulfoxide

I5k”™Bȑ˅@PSöşŢBʕ@9;CƴBP @ȹĶ.5ˏFigure 3-2ː ș˓ȗ@"(SŵįöşƲƯ<B-‘sokm@";f[ȨñħžBʻħĵŊ$k”

™BȵŸĖ@P8;ĝé0S«$ªţ,TS^u–Ė@ƹG^ybkĖ<CRèƥ@

PSʟȨñħžBĪȖʻħķBŕʿ<f[ȨñħžBʻħĵŊ$ˊIS5LSi-Pdȭý$

őIS==M@Si-SȭýWœŨ.@'=ȹ!QTS3B5L-‘sokmBʑɒ

$ŭÜ,Tm–…ZzBʙÇöş$ʑɒ.?MB=ȹ!QTS

aryl S alkyl aryl H

O R₃SiH

cat. Pd(OAc)₂ THF

aryl S alkyl

aryl S alkyl O

SiR₃ Pd H

Figure 3-2. Electron density of silicon atom in σ-metathesis intermediate Si

S Ar Pd alkyl

R H R

R ^R

Et OEt

electron density of silicon atom

low high

ș˕ȗ u_\—Y#Q[tr•|\ęFBĝŸöş@ʫ0Sȁȓ

ș˒Ȝ ʼnɳ

NHC•a™zC1991Ň@ArdiuengoQBȁȓe–›‡@P8;ØL;Ĭį?NHC$ ìʹ³⁶⁾,T;²ƢȣãǸ@ȁȓ,T;%5NHC•a™zC-z{›Ţ$ʼŅ@ő' ȑBʗȏʣĽ=Ĭį?ʣĽʧ¹WœŨ.ˊdžŢ?ɢĦ=.;Å'5L•a™z³⁷⁾=.

;ǯQT;SI5NHC3BMBMƘƲɢĦ³⁸⁾=.;ƲȾ0S«MėĂ,T;S NHCBýŨǂ=.;Cķş0S[tr•\ęN[tr•|\ę#QBĝŸ$H

=X>WîL;"R3B*=#Q[tr•\ęN[tr•|\ęBýŨǂ$ʠ ɜ?MB=?8;S

[tr•\ęN[tr•|\ęBýŨǂC*TI<@ğƄėĂ,T;S ˏScheme 4-1ː³⁶ⁿ⁾ () [tr›–N[tr•™BN-Y–b–é(method A)³⁹⁾() ķş0SlY™=_–ycʟ^mw–Wǯ5ķş0SY|_™q›mWƘ0SʟĨ ēŸ<Böş(method B)⁴⁰⁾()‹–Yl™=^u–l`u_™ț¾¹=Böş(method C)⁴¹⁾ț$Ų)QTS

Scheme 4-1. Synthetic approach to imidazolium and imidazolinium salts

Scheme 4-1@ȇ.5ýŨǂB 7'9#BýŨǂC[tr•\ęN[tr•

|\ęWýŨ0SB@Ƙǯ<CS$ĖʀʖǯŢ$Üʭ,TSĘý$R3TO!

ĖʀʖǯȝĐBň[tr•\ęN[tr•|\ęBƉ5?ýŨǂBȃȖ$ƚI T;S

I5u_\—Y#QʣĽ`•\Wǯ;ķş0SNHCWǻŴǮŨ,2SūǂMė Ă<sup>42)</sup>,T;S$(Scheme 4-1)ʣĽ`•\BéīǸöşŢBˊ,#QƳǝMğ¼!

N N

S R¹

R²

N N

R¹

R² X N

N

R¹X R²

NH NH R¹

R²

N N R¹

R² + HC(OR)₃

(this work) A

B

C

D

N N

R¹

R² K (metal)

base

DʣĽ`•\BʙÇãBˊ,#QʖǯúȾ?Ėʀ$ʭį,TI5`•\Ɂ¹BǷ ǚŢBˊ,#QİˈŽº@ȩŝBǃŤWŞɜ=0S?>Bǝ$Ų)QTS

3*<ș˓ȗ"PEș˔ȗ@"(SǿɝWM=@u_\—Y=ƽʻħÞ=Böş$

ȕȨñħBʻħ½¡ŢBŕʿ@PRȂˍñħž<ʁ*S«#Qu_\—Y=k•–éÞ

=Böş@PRȭƥ=.;Ǯ/S*TQBˆw˜ǭBsp²ǜȨžBy•Y–b–k•–u _Ė$”l\ɢĦĨēŸy•Y–b–k”™@PRʯò<%SB<C?#=ȹ!

5*TQBǿɝ@PSöş$İǪ<%TDʜ·ħWnjå0S«?'öş$ʑɒ0S«

@PRǐą?ơ³İˈŽºBȟǵéˊĮȾĖʘŮŢ?>$İǪ.ˊƘǯŢWƘ 0Söş@?S«$ƛŗ,TS²žB«#Q”l\ɢĦ=ƘƲk”™@PSǭǦ u_\—Y#Q[tr•|\ęFBĝŸWƫɥ.5²Ÿ@ɪȩWʋGS

ș˓Ȝ öşơ³BƖʖé

ș˓ȗ<ʋG5P @Y–b–Y•›–m–…ZzBʙÇơ³<TMSCl$åʎèƥ Wȇ.5«#Q⁴³⁾Ɩʖé,T5ơ³@ķş.5ơ³<STHFǔĦ¤5 mol%B”

l\ɢĦĨēŸTESH (3.0Œʢ)TMSCl(1.2Œʢ)Wǯ;u_\—Y5a⁴⁴⁾WĖʀ=.

;öşWɒ85ˏScheme 4-2ː.#.?$QöşCʑɒ.?ȭƥ=?853*<

PRőã?k•–éÞ<STMSOTfˏ1.2ŒʢːWǯy–^™ǔĦ¤80<öşWɒ 85=*U35ˎB÷ǩ<ǺǸǤ<S[tr•|\ę6a⁴⁵⁾$ŚQT;%5

Scheme 4-2. Preliminary experimental results of Pd-catalyzed transformation of 5a to 6a

3*<ǔĦWy–^™@đį.5.0ŒʢBTESH0.6ŒʢB(TfOSiMe2CH2)2

46)Wǯ;

”l\ɢĦBƫɥWɒ85ˏTable 4-1ː

ʝʟ”l\Wǯ;öşWɒ85=*U90Õ<ǺǸǤ6aW97ˎB÷ǩ<¡!5 ˏentry 1ːę達l\WɢĦ=.;ǯ5Ęý@CöşBʑɒCʒ'?R23ƒ ʪřMöşCĭȭ21ǺǸǤB÷ǩC31ˎ<85Pd2(dba)3Wǯ5Ęý@C90 Õ<ñƇCljĢ.90ˎB÷ǩ<ǺǸǤW¡!5ˏentry 3ːPd/CWǯ5Ęý@Cö şCʑɒ.5$23ƒʪřMñƇ$ƵĨ.ǺǸǤB÷ǩC32ˎ=¸MB<85‹

m…Z™•a™zWƘ0Sˑ¾B”l\ɢĦ<SPd(PPh3)4N˓¾B”l\ɢ Ħ<SPd(PPh3)2Cl2Wǯ5Ęý@CöşCÍ'ʑɒ.?ȭƥ=?R‹m…Z™

•a™zBnjå@PRöş$ʬij,TS«$ȇĈ,T5ˏentries 5 and 6ː”l\ɢĦ Wnjå.?Ęý@CöşCʑɒ21ƞöş@C”l\ɢĦ$Şˁ<S«$Ñȃ ɬ,T5ˏentry 7ː*TQBƫɥBȭƥ#Qƞöş@ǯS”l\ɢĦCʝʟ”

l\$Ɩʖ<S«$ÙƏ.5

N N

S

N N Et₃SiH (3.0 equiv)

PdCl₂ (5 mol%)

conditions X

TMSCl (1.2 equiv) in THF, rt, 0%

TMSOTf (1.2 equiv) in toluene, 80 ºC, 35%

H

5a 6a

Table 4-1. Reaction of thiourea with TESH and various palladium catalysts

ƴ@ʝʟ”l\WɢĦ=.;ǯ;k”™õEnjåÞBƫɥWɒ85ˏTable 4-2ː

Table 4-1, entry1=entry 2BȭƥBƹʅ#QęéǤ[_™$öşWŭÜ0SúȾŢWȹ!

55L<S

TMSClWk•–éÞ=.;ǯ5Ęý@CNCRöşCʑɒ.?#85ˏentry 1ːȮ

;TMSOTfWǯ5Ęý@C÷ǩ95%<ǺǸǤB[tr•|\ęW¡!5ˏentry 2ː

(TfOSiMe2CH2)2 (0.6Œʢ)Wk•–éÞ=.;ǯ5Ęý@Mentry 2=þ/1.5ƒʪBö şƒʪ<ñƇ$ljĢ.ǺǸǤWˊ÷ǩ<¡!5ˏentry 3ːk•–éÞWnjå.?Ęý

@Cę達l\WɢĦ=.;ǯ5Ęý=þư@öşCʑɒ.?ȭƥ=?85

ˏentry 4ːy•…]|–k”™Wǯ5Ęý@CöşBʑɒCʼŅ@ʒ'23ƒʪřM

ñƇ$ƵĨ.5ˏentry 5ːy•^ybkk”™Wǯ5Ęý@CöşCÍ'ʑɒ.?

ȭƥ=?85ˏentry 6ːI5k”™Wnjå.?Ęý@CöşCÍ'ʑɒ.?ȭƥ=

?85ˏentry 7ː²žPRƞöş@Ck•–y•…”›y"PEk”™$Şˁ<R

I5TESH$Ɩʖ<S«$V#85

N N

S

N N TfO Et₃SiH (5.0 equiv)

(TfOSiMe₂CH₂)₂ (0.6 equiv) Pd cat.

toluene, 80 ºC

H

5a 6a

Entry Pd catalyst (mol%) Time Yield^a (%)

1 Pd(OAc)2 (10) 90 min 97

2 PdCl2 (10) 23 h 31^b

3 Pd2(dba)3 (5) 90 min 90

4 Pd/C (10) 23 h 32^b

5 Pd(PPh3)4 (10) 23 h 0^b

6 Pd(PPh3)2Cl2 (10) 23 h 0^b

7 - 23 h 0^b

a Isolated yields.

b Starting material remained.

Table 4-2. Reaction of thiourea with various silane and additive

5 mol%Bʝʟ”l\WɢĦ=.3.0ŒʢBTESH"PE1.2ŒʢBTMSOTfWǯ

;ȑBǔĦˏtoluene, THF, 1,2-dichloroethane, 1,4-dioxane, benzeneːWƫɥ.5ˏTable 4-3ːy–^™WǔĦ=.;ǯ5Ęý@C96ˎB÷ǩ<ǺǸB[tr•|\ę6a W¡!5ˏentry 1ːI5THFN1,4-dioxaneWǯ5Ęý@CTMSOTf@PRǔĦ$

džŢéWù(;ǔĦ=5a$öş.5ßǮŨǤ$ɠǑ,T5ˏentries 2 and 3ːI5

1,2-dichloroethaneN‰™p™WǔĦ=.;ǯ5Ęý@CöşBʑɒCʒȭƥ<8

5ˏentries 4 and 5ː²žBƫɥ@PRƞöşBǔĦ=.;Cy–^™$Ɩʖ<S«$

ɝÔ,T5

Table 4-3. Reaction of thiourea with TESH and Pd(OAc)2 in various solvent

N N

S

N N R₃SiH (5.0 equiv)

additive Pd(OAc)₂ (10 mol%)

toluene, 80 ºC X H

5a 6a

Entry R3SiH Additive (equiv) Time (h) Yield^a (%)

1 Et3SiH TMSCl (1.2) 23 0^b

2 Et₃SiH TMSOTf (1.2) 1.5 95

3 Et3SiH (TfOSiMe2CH2)2 (0.6) 1.5 97

4 Et₃SiH - 23 0^b

5 Ph3SiH (TfOSiMe2CH2)2 (0.6) 23 80^b 6 (EtO)₃SiH (TfOSiMe₂CH₂)₂ (0.6) 23 0^b

7 - (TfOSiMe2CH2)2 (0.6) 23 0^b

a Isolated yields.

b Starting material remained.

N N

S

N N TfO Et₃SiH (3.0 equiv)

TMSOTf (1.2 equiv) Pd(OAc)₂ (5 mol%)

solvent, 80 ºC

H

5a 6a

Entry Solvent Time (h) Yield^a (%)

1 toluene 24 96

2 THF 2 78^b

3 1,4-dioxane 23 76^b

4 1,2-dichloroethane 24 49^c

5 benzene 24 65^c

a Isolated yields.

b Starting material disappeared.

c Starting material remained.

Table 4-6@öşơ³BŒʢƫɥBȭƥWȇ0ɢĦ=.;ʝʟ”l\W10 mol%ǯ 5Ęý@öşƒʪC˓ƒʪ@Ȁȱ.÷ǩC99ˎ@Āž.5ˏentry 2ː$3 molˎ@Ǐ Q0=24ƒʪřMñƇCljĢ21÷ǩC69ˎ=?85ˏentry 3ːʓàʢBTESHˏ5.0Œ ʢːWǯS=÷ǩCĀž.98ˎ=?Rˏentry 4ːI5TESHBʢWǏQ.5Ęýˏ2.2 Œʢː@C÷ǩC¸Ÿ.80ˎ=?85ˏentry 5ːTMSOTfBʢWǏQ.5Ęýˏ0.6Œʢː

@C÷ǩC56ˎ@¸Ÿ.ñƇ$ƵĨ.5ˏentry 6ː*B*=#QMTMSOTf$u_\

—YWdžŢé.;S«$ȇĈ,TS

TMSOTfB#[email protected]ŒʢB(TfOSiMe2CH2)2Wǯ5Ęý@CöşCþư@ʑɒ.

83%B÷ǩ<ǺǸǤW¡!5ˏentry 7ː (TfOSiMe2CH2)2=5 mol%Bʝʟ”l\"P E˖.0ŒʢBTESHWǯ5Ęý@C˓ƒʪ<öşCĭȭ.92%B÷ǩ<ǺǸǤW¡!

5ˏentry 8ː10 mol%Bʝʟ”l\"PE˖ŒʢBTESHWǯ5Ęý@C1.5ƒʪ

<öşCĭȭ.97ˎB÷ǩ<ǺǸǤW¡!5$ˏentry 9ːʝʟ”l\BʢW3 mol%

F=ǏQ0=18ƒʪřMñƇCljĢ21ǺǸǤ6aB÷ǩC77%=?85ˏentry 10ː

Table 4-6. Preparation of imidazolinium salt 6a

Et3SiH, R3SiOTf, Pd(OAc)2

toluene, 80 ºC N

N S

N N TfO

H

5a 6a

Entry Pd(OAc)2 (mol%) Et3SiH (equiv) R3SiX (equiv) Time (h) Yield^a (%)

1 5 3.0 TMSOTf (1.2) 24 96

2 10 3.0 TMSOTf (1.2) 2 99

3 3 3.0 TMSOTf (1.2) 24 69^b

4 5 5.0 TMSOTf (1.2) 24 98

5 5 2.2 TMSOTf (1.2) 24 80^b

6 5 5.0 TMSOTf (0.6) 24 56^b

7 10 3.0 (TfOSiMe2CH2)2 (0.6) 3.5 83^b

8 5 5.0 (TfOSiMe2CH2)2 (0.6) 2 92

9 10 5.0 (TfOSiMe2CH2)2 (0.6) 1.5 97

10 3 5.0 (TfOSiMe2CH2)2 (0.6) 18 77^b

a Isolated yields.

b Starting material remained.

ș˔Ȝ ĖʀʖǯŢBƫɥ

ĖʀʖǯŢWɱGS5L*TI<Bƫɥ@PRƖʖé,T5ơ³A"PEB@;u_

\—Y5b-kWǯ5ƫɥWɒ85ˏTable 4-7ː1-adamantylɭĺ¹5bWǯ5Ęý@C ơ³A<C˔ƒʪ<öş$ĭȭ.ǺǸǤ6b⁴⁵⁾W98ˎB÷ǩ<¡!ˏentry 1, reaction condition Aːơ³B<C97ˎB÷ǩ<ǺǸǤW¡!5ˏentry 1, reaction condition Bː 2-methylphenylɭĺ¹5c<Cơ³A@";öşCʎN#@ʑɒ.92ˎB÷ǩ<ǺǸǤ 6c⁴⁵⁾W¡!5ˏentry 2, reaction condition Aːơ³B@";CʓʙÇ$ʑɒ.Yl|

\Ưʏ$ʩɕ.5‹–Yzɭĺ¹$ɠǑ,T52,6-dimethylphenylɭĺ¹5d"P E2,6-diethylphenylɭĺ¹5e⁴⁴⁾Wǯ5Ęý@C3T4T@ķş0SǺǸǤ6d"PE6e W3T4T99ˎ÷ǩˏentry 3, reaction condition Bː"PE96ˎ÷ǩˏentry 4, reaction condition Aː<¡!5

2,6-diisoprpylpenylɭĺ¹5f⁴⁷⁾<CȖ¹ʵijB5Löş$ʼŅ@ʒ'6f⁴⁶⁾B÷ǩC58ˎ

=?85ˏentry 5, reaction condition Bː6ćǭBǭǦu_\—Y<S2,4,6-trimethylphenyl ɭĺ¹5g"PE4-methoxy-2,6-dimethylphenylyɭĺ¹5hCķş0S[tr•|\ę 6g6hW3T4T94ˎˏentry 6, reaction condition Bː96%ˏentry 7, reaction condition AːB

÷ǩ<¡!5.#.?$Q4-methoxycarbonyl-2,6-dimethylphenylɭĺ¹5iC>7QBö şơ³@";Mķş0S[tr•|\ę6iC¸÷ǩ=?85ˏentry 8ː*TCö şBʑɒ@µ^mw–B”·@ʻħƽōŢB[tr•|\ę$œŨ,T¶Ő .5ÎŖȤ@PS^mw–BdžŢé$ʁ*R‘u–^mw–BåƼÕɡ$ʑɒ.55L

=ȹ!;S4-carboxy-2,6-dimethylphenylɭĺ¹5jWǯ5öş@";CĖʀBƘ 0S`–Œbk–Ė@TESHNTMSOTf$ljɽ,TS5LʓàʢBTESHNTMSOTfW Şɜ=.53TO!ǺǸǤ6jB÷ǩC38%=¸MB<85.#.?$Q10Œʢ BTESH"PE10 molˎBʝʟ”l\4ŒʢBTMSOTfWǯS«<÷ǩC73ˎI

<ſċ,T5ˏentry 9ː4-fluoro-2,6-dimethylphenylɭĺ¹5kCǺǸǤ6kW98ˎB÷ǩ

<¡!5ˏentry 10, reaction condition Bː*TQBƫɥȭƥ#Qȇ,TSP @TMSOTf Wǯ5Ęý@Cńɻ,T;SɩɐBJ<öşWɒ «$<%S= ǝ$Ûǝ<

R(TfOSiMe2CH2)2Wǯ5Ęý@CTMSOTfWǯ5ĘýPRMöş$ʼŅ@Ǝ'÷

ǩMĘý@P8;CĀž0S= Ûǝ$Ų)QTS

Table 4-7. Reaction of thiourea with TESH and Pd(OAc)2 under reaction conditions A and B

N N

S

R N N

TfO

R R

R

H

n n

5 6

Et₃SiH, R'₃SiOTf, Pd(OAc)₂ toluene, 80 ºC

Entry Thiourea (R)

Time (h) Yield^c (%) Time (h) Yield^c (%)

1 1-adamantyl- (n = 1) (5b) 3 98 2 97

2 2-methylphenyl- (n = 1) (5c) 1 92 1 0^d

3 2,6-dimethylphenyl- (n = 1) (5d) 37 85 3 99

4 2,6-diethylphenyl- (n = 1) (5e) 24 96 2 94

5 2,6-diisopropylphenyl- (n = 1) (5f) 35 44 24 58

6 2,4,6trimethylphenyl- (n = 2) (5g) 24 92 3 94

7 4-methoxy-2,6-dimethylphenyl- (n = 1) (5h) 22 96 3 93

8 4-methoxycarbonyl-2,6-dimethylphenyl- (n = 1) (5i) 24 28 10 32 9 4-carboxyl-2,6-dimethylphenyl- (n = 1) (5j) 24 38 (73)^e 2 19

10 4-fluoro-2,6-dimehylphenyl- (n = 1) (5k) 12 91 1 98

a Reaction condition A: Et3SiH (3.0 equiv), TMSOTf (1.2 equiv), Pd(OAc)2 (5 mol%).

b Reaction condition B: Et₃SiH (5.0 equiv), (TfOSiMe₂CH₂)₂ (0.6 equiv), Pd(OAc)₂ (10 mol%).

c Isolated yields.

d No desired products were obtained owning to overreduction.

e Et₃SiH (10.0 equiv), TMSOTf (4.0 equiv), Pd(OAc)₂ (10 mol%) were used.

Reaction conditions B^b Reaction conditions A^a

I5Ėʀ5l⁴⁸⁾@";Mþư@ƫɥWɒ85=*U3.0ŒʢBTESH10 Bęé

”l\"PE1.2ŒʢBTMSOTfWǯ;öşWɒ «<ˊ÷ǩ<ǺǸǤ6l⁴⁹⁾W¡!

5«#Q[tr•\ęMþưBūǂ@PRýŨúȾ<S«WɝÔ.5ˏScheme 4-3ːʼǭǦ\—Y5mBöş<C99ˎ=ˊ÷ǩ<ǺǸBYl|\ę6mW¡!

ʼǭǦ\—Y5n⁵⁰⁾Böş@";MßǮŨǤ=.;Yl|\ęBåƼÕɡ¹$œʛ ɠǑ,T5MBBǺǸǤ6n⁵¹⁾C÷ǩ70ˎ<ŚQT5²žBȭƥ#QYl|\ęB ýŨFMʖǯúȾ<S«$ȇ,T5

Scheme 4-3. Preparation of 6l, 6m and 6n

Et₃SiH (3.0 equiv) TMSOTf (1.2 equiv) Pd(OAc)₂, (10 mol%)

toluene, 80 ºC, 24 h 85%

N N

S

R N N

TfO

R R

R

H

5l

R = 2,4,6-trimethylphenyl

6l

N N

TfO H

N N

S

Reaction conditions A 60 ºC, 2 h, 99%

5m 6m

N R' R'

N R' R'

TfO H N

R' R' N R' R'

S

Reaction conditions A rt, 21 h, 70%

5n

R' = isopropyl 6n

ș4Ȝ öşƲƯBȹĶ

u_\—Y5a=TMSOTfBCDCl3¤@"(S¹H NMRmŠdy–BɠǑ#Q¤ʪ¹ 7aBǮŨ$ȇĈ,T5ˏFigure 4-1ː3TO!öşơ³AB>7Q@";Mu_\

—Y5a=TESH=B”l\WɢĦ=.5öşC[tr•|\y•…”›yę7 WȬDZ.;ʑɒ0S=ŵĶ,TS7a#QBʙÇöşCș˓ȗ<ŵį.5öşƲƯ=þ ư@‘sokmWȬDZ.;ʑɒ.;SMB=ȹ!;S

Figure 4-1. Proposed intermediate 7a from ¹H NMR analysis

I5ɄăNj«@[tr•|\ę8aWĖʀ=.;ǯ5öş<Cu_\—Y 5a$ŚQT5BJ<85ˏScheme 4-4ː"3Q'öş¤@8aB‘u–ĖWęB`\™

s›Y|_™<S“\Ȩ$ƀŻ.S-Cȭý$ʩɕ.55L=ȹ!QTS

Scheme 4-4. Reaction of 8a

N N

S TMS

N N

S

TfO

5a 7a

4.55 ppm

0.25 ppm 7.14 ppm

3.94 ppm 6.91 ppm

2.43 ppm

2.46 ppm 2.24 ppm

2.26 ppm N N

H

TfO 6a

4.47 ppm 6.95 ppm 2.33 ppm

2.30 ppm

N N

S Me

N N

S MeI (excess)

toluene rt, 2.5 h

y. 98 % I

N N

H

TfO Et₃SiH (3 equiv.)

Pd(OAc)₂ (10 mol%) toluene 80 ºC, 24 h

5a 8a 6a

0%

u_\—Y5a=MeOTf=Wöş,2;ýŨ.59aBöş<Cªţ,TSP @[

tr•|\ę6a$83ˎB÷ǩ<ŚQT;%5ˏScheme 4-5ː.#.?$Q÷ǩC

TMSOTfWǯ5ĘýBƊ$ˊ'å!;MeOTfC3BˊöşŢ@PRˆw˜ñħW

Y–b–é.;.I «?>#QTMSOTfWǯSƊ$ʖ.;S=ȹ!QTS

Scheme 4-5. Reaction of 9a

?"u_\—Y5lCéýǤ10⁵²⁾WÔǷñƇ=.;²ŸBƊǂ@PRýŨ.5ˏScheme 4-6ː

Scheme 4-6. Preparation of 5l

ƞȗWI=LS=[tr•|\ęWķş0Su_\—Y#Q”l\ɢĦWǯ

;ĝŸ0SöşWȃȖ.3Bơ³$[r•\ęNYl|\ęBýŨ@Mʖǯ

<%S«WɝÔ.5I5ƞöş@";ǺǸǤB°@ǮŨ0SéýǤCŹǷŢB

TES-S-TMS=ȹ!QTS3B5LöşȪ©ř@ŹǷŢÕWʯò.”l\ɢĦWǙ

ʓ.;ʯ'6(<ǺǸB[tr•|\ę[tr•\ęYl|\ęWɱ ə0S*=$úȾ<Rȟ¿?ūǂ<SǯSɩɐCńɻĆ<RI5ǐą?ơ

³#9ñƇBu_\—Y$øRŬĴƐ<S5LƞöşCNHCݡ¹BęBýŨ@

";Ƙǯ?ūǂ=ɣ!S

N N

S Me

TfO N

N

S MeOTf (1.0)

toluene rt, 1 h y. 75 %

N N

H

TfO Et₃SiH (3 equiv.)

Pd(OAc)₂ (10 mol%) toluene 80 ºC, 24 h

y. 83 %

5a 9a 6a

Mes HN

O

I Mes

HN

O N H

Mes MesNH₂ (excess)

DMAP (cat.) neat, rt y. 44 %

HI N N

S Mes Mes

N N 1) NaBH₄ (excess) S

EtOH, rt 2) HCl aq. rt y. 98 % O

SCCl₂ (1.2 equiv) Cs₂CO₃ (3.0 equiv)

MeCN, rt y. 60 %

10 11 12 5l