日本东京大学Fukuyama组10年组会2012有机反应机理习题(适合研究生)

日本东京大学Fukuyama组10年组会2012有机反应机理习题(适合研究生)

Fukuyama Group - Group Meeting Problems 1/17/20121O OH

O

O O H1O 2,

*TPP

1) FeSO4, I2 MeOH, rt 2) DBU, toluene 80°C 69% (2 steps)

1) NiCl2·6H2O, NaBH4 THF/MeOH (2:3) 0°C to rt, 92% 2) LAH, THF, 45°C 66% TBDPSO H

H

H TBDPSO H

O

H

CH2Cl2, hν 0°C quant

H

OH

*TPP= tetraphenylporphyrin

W. Tian et al., Angew. Chem. Int. Ed., 50, 7093 (2011)

2OPh

Me

Me O Bicyclic compound hν, Pyrex MeCN, rt 99% 82% MeMgBr THF 0°C to rt H Me Ph OMe O

CSA, H2O MeO MeO MeCN, rt OMe 52%

J. A. Porco Jr. et al., J. Org. Chem., 76, 9792 (2011) J. A. Porco Jr. et al., Synthesis, 2254 (2010)

3i-PrS CO2Me

OH

SO2Cl2 CH2Cl2,–40°C; Et3N–35°C to rt 77%

K2CO3 acetone re ux 77%

O

O

K. Sato et al., J. Org. Chem., 52, 5495 (1987)

4OMe Ph OMe

TESOTf Ph3P CH2Cl2, 0°C; *PhMgBr (5.0 eq.) dry air (containing O2) 0°C 81% *theoretically 3.0 eq. Ph

OH Ph

H. Fujioka et al., Chem. Commun., 47, 9894 (2011)

日本东京大学Fukuyama组10年组会2012有机反应机理习题(适合研究生)

Fukuyama Group - Group Meeting Problems 2/15/20121Me N TfOH MeO MeO O CH2Cl2, 0ºC 97% 1) TBHP, Triton B, THF, rt 2) SiO2, rt, 76% (2 steps) MeN HO O S. E. Reisman et al., Angew. Chem. Int. Ed., 50, 9447 (2011) MeO OMe

2Et3Si

D SiEt3 O

t-BuLi (3.0 eq.)* THF-HMPA–78°C 80%

Et3Si SiEt3 OH E:Z= 1:1

D

* theoretically 1 eq.Z. Song et al., Org. Lett., 14, 1094 (2012)

3O N OMe OMe K, NH3 t-BuOH (1 eq) THF,–78°C; piperylene; MeI 95% S.-K. Khim et al., J. Org. Chem., 69, 7728 (2004) 1) 6 N HCl MeOH, rt 95% 2) I2, THF-H2O rt, 90% LiOMe THF,–78°C 87% O O Me CO2Me

4OH i-Pr Me Me

Me Si

Me

H

H

1) Rh(acac)(CO)2 (1 mol%) CO (1000 psi) benzene, 60°C 2) H2O2, KF THF-MeOH, 40°C 62% (2 steps) d.r.= 15:1 i-Pr

OH O

OH

NaH (20 mol%) hexane, re ux 87%

Me

Me

Me

J. L. Leighton et al., Org. Lett., 10, 5593 (2008)

日本东京大学Fukuyama组10年组会2012有机反应机理习题(适合研究生)

Fukuyama Group - Group Meeting Problems 04/04/20121TMSO ( )3 N3 TiCl4 CH2Cl2,–78 to 10°C MeO OMe 82%, dr=1:0.84 1) AlCl3, EtSH, rt 2) DMP CH2Cl2, 0°C to rt 87%(2 steps) O N O H

S. Zhang et al., Org. Lett., 13, 724 (2011)

2O NIS DBU OH CH2Cl2–40°C to rt 73% Bu3SnH AIBN t-BuOH/benzene re ux; NIS, CH2Cl2–20°C 60% P. Renaud et al., Angew. Chem. Int. Ed., 41, 4321 (2002) O H O Ot-Bu H I

31) mCPBA (1.0 eq) CH2Cl2, 0°C 2) NaOMe MeOH, re ux (isomerization) 72% (2 steps) M. E. Jung et al., J. Org. Chem., 62, 4601 (1997)MgBr

PCC CH2Cl2, rt 81%

BuSSBu benzene, hν 66% H

H H

O

THF, rt to 60°C 70%

H

4I N Ph R. C. Larock et al., J. Am. Chem. Soc., 125, 11506 (2003) Pd(OAc)2 (5 mol%) dppm (5 mol%) CsO2CCMe3 (2 eq.) DMF, 100°C 65% Ph N

日本东京大学Fukuyama组10年组会2012有机反应机理习题(适合研究生)

Fukuyama Group - Group Meeting Problems 04/14/20121Ph S O Ph3PAuCl (5 mol%) AgSbF6 (5 mol%) CH2Cl2, rt 56% F. D. Toste et al., J. Am. Chem. Soc., 129, 4160 (2007) O

S

2O Br BrMe Li Me

Et3N TFE/Et2O–78°C to rt 70%

5 mol% Grubbs 1st generation cat. ethylene CH2Cl2, rt 50%

H

O

THF,–78°C 90%

H

M. Harmata et al., Org. Lett., 7, 2563 (2005)

3Ph N O 1,4-dioxane, re ux 72% TFE, rt 73% SeO2 HCO2H, t-BuNC O t-Bu N H O H

N O O Ph

X. Chen et al., J. Org. Chem., 77, 1386 (2012) T. F. Molinski et al., J. Org. Chem., 61, 2044 (1996)

4

CN

CO2Et CHO+ NO2+ NH2

CO2Me

MeO2C MeOH, rt; toluene reflux 89% N

OEt O

J. Zhu et al., Eur. J. Org. Chem., 475 (2012)

日本东京大学Fukuyama组10年组会2012有机反应机理习题(适合研究生)

Fukuyama Group - Group Meeting Problems 04/16/20121I EtO Ms N S SNHBoc

O

(C11H23COO)2 (10 mol%) EtOAc re ux 86%

(t-BuCOO)2 PhCl re ux 73%

TFA CH2Cl2, rt; evap; I Et3N toluene, 90°C 55%

NH2

N H

O

S. Z. Zard et al., Org. Lett., 7, 1653 (2005) S. Z. Zard et al., Org. Lett., ASAP (DOI: 10.1021/ol3005276)

2O O PhCH2NH2 dichloroethane 0 to 5°C 89%

Br

Br

NHBn NBS HCO2H, 80°C 93% O O OCHO

K2CO3 DMF, rt 92%

C.-H. Oh et al., Arch. Pharm. Chem., 340, 530 (2007) F. Liang et al., Org. Lett., 14, 712 (2012)

3OTMS Me NaNH2 bromobenzene THF 45°C to re ux 42% 1) Br2, AlCl3, 80°C 81% 2) trisyl azide, n-Bu4NBr 18-crown-6, KOH benzene-H2O, rt 77%

i-Pr

OTIPS

hν (254 nm) 1,2-dichloroethane; re ux 62%

HO Br

OTIPS

Me

R. L. Danheiser et al., J. Am. Chem. Soc., 116, 9471 (1994)

41) EtMgBr, Ti(Oi-Pr)4 (cat.) Et2O, 20°C, 99% CO2Me 2) Ph3P, Br2, pyridine CH2Cl2, 20°C, 78% 3) t-BuOK, DMSO, 20°C, 81%

CO2Me CO2Me,

CO2MeI

MeO2C

Pd(OAc)2, Ph3P, Et3N DMF, 75°C 49% (diastereomeric mixture) MeO2C CO2Me

A. de Meijere et al., J. Org. Chem., 58, 502 (1993) A. de Meijere et al., Angew. Chem. Int. Ed., 34, 2545 (1995)

5NHBoc

Cl Me SCl Me H

N2 CO2Et

CO2Et TFA CH2Cl2 rt 95% Cl NH N

[Rh2((S)-tbsp)4] (5 mol%) CH2Cl2 rt 89%

N H

CH2Cl2 rt 74%

J. D. Rainier et al., Angew. Chem. Int. Ed., 47, 5374 (2008)

日本东京大学Fukuyama组10年组会2012有机反应机理习题(适合研究生)

Fukuyama Group - Group Meeting Problems 05/09/20121O NaN3, MsOH, rt; aq. KOH 68% DPPA, Et3N toluene, rt; BnOH, re ux 87%

TfOH CH2Cl2, 0°C 79%

NH

Y. Iwabuchi et al., Synthesis, 3418 (2011)

2

MeO

Cr(CO)5

MeO MeO

OMe OMe

t-BuNC THF, rt 85%

1) TFA THF-H2O, rt 85% 2) MeOH, 100ºC 92%

O O MeO

OMe NHt-Bu

neat, rt 98%

J. Barluenga et al., Chem. Eur. J., 8, 4149 (2002)

31) Co2(CO)8 CH2Cl2 rt, 92% BzO TMS 2) furan, EtAlCl2 CH2Cl2–20 to 0°C, 77% 1) I2, MeOH, rt 52% 2) n-BuLi THF,–78°C 90% H OH

MeO

K. Tanino et al., Tetrahedron Lett., 52, 910 (2011)

4NaH N-methylaniline Adiponitrile THF, re ux 98% C6H7NO 4-chlorobutyronitrile K2CO3 DMF, 80°C 65% NaH DME, re ux 25% N NH2 O

H.-J. Liu et al., Tetrahedron, 59, 1209 (2003) K. Sasaki et al., Tetrahedron Lett., 51, 903 (2010)

日本东京大学Fukuyama组10年组会2012有机反应机理习题(适合研究生)

Fukuyama Group - Group Meeting Problems 05/23/20121Cl O DMAD, i-Pr2NEt 1-Me-imidazole CH2Cl2,–10°C to rt; H2O, rt 58%, Z/E= 79:21 Y. Wang et al., Org. Lett., 7, 2125 (2005)

CO2Me CO2Me

2

1)Ph O

O OEt

re ux N H 2) TsNHNH2 DME 0ºC to re ux 80% (2 steps)

KOt-Bu toluene, re ux 60% dr= 3.5:1

HCl (gas) MeOH, rt 100%

Ph H

CO2Me NH HCl

J. D. Winkler et al., J. Org. Chem., 63, 9628 (1998)

3O Me Me O O H Me hν DIBAL MeCN/acetone (9/1) Et2O,–60°C; Me 0 to 15°C AcOEt, H2O 98% monocyclic compound p-TsOH benzene re ux 50% (2 steps) dr= 3:2 H. Takeshita et al.

, Bull. Chem. Soc. Jpn., 66, 2694 (1993) O O Me Me

4O O O H Me3NO 2H2O 0°C to rt 69% Co2(CO)8, MS4A toluene, rt; O K2CO3 MeOH 0°C to rt 55% J. D. Winkler et al., Org. Lett., 7, 1489 (2005) O H

CO2Me

日本东京大学Fukuyama组10年组会2012有机反应机理习题(适合研究生)

Fukuyama Group - Group Meeting Problems 06/05/20121Me MeO MeO OMe O OMe O3, CH2Cl2,–78°C; Me2S,–78°C to rt hν C6D6, 30°C 52% (2 steps) HO MeO O MeO OMe Me O H OMe

E. I. Léon, E. Suárez et al., Angew. Chem. Int. Ed., 47, 8917 (2008)

2OH+ Ph N2 CO2Me Rh2(S-DOSP)4 (1 mol%) heptane, rt to re ux; Sc(OTf)3 (20 mol%) re ux 95%, 82% ee H. M. L. Davies et al., Chem. Sci., 2, 2378 (2011) MeO2C OH

Ph

3TBSO CO2Et N O N Bn OBzTfO SO2Ph

MeCN, rt; BnMe3NCN MeCN 66%

1) NaOEt EtOH, rt 86% 2) NaH, DMF 0°C, 70%

OTBS CO Et 2 NBn O N H HO

E. Vedejs et al., J. Org. Chem., 65, 5498 (2000)

4NH2 Me CO2H Ac2O (2.2 eq.) Et3N, DMAP AcOH, 50°C; evap; malononitrile NaOH H2O, rt 83% R. W. Fischer et al., Org. Process Res. Dev., 5, 581 (2001) Me Me N H CN NH2

日本东京大学Fukuyama组10年组会2012有机反应机理习题(适合研究生)

Fukuyama Group - Group Meeting Problems 06/13/20121CO2Bn

NCS 1,4-dimethylpiperazine CH2Cl2, 0°C; Cl3CCO2HTIPS HO

(binap)Pd(SbF6)2 (20 mol%) H2O (5 mol%) C6H5Cl, 40°C 95%, 92% ee

O O

Me TIPS O

N H

N H

59%

M. C. Kozlowski et al., Angew. Chem. Int. Ed., 51, 2448 (2012)

2O Br Ph

CO2Me NHBoc

+

CO2Me

KOt-Bu THF, rt 90%

K2CO3 acetone, 40ºC 73%

MeNH2 THF, 100ºC 61%

O MeN Ph

Boc N CO2Me

J. Christoffers et al., Eur. J. Org. Chem., 1809 (2012)

3O O OEt LDA (2.6 eq) THF, 0°C;O N3

PBu3 THF 45°C 64%

H N O O

OEt

–78°C to rt 57%

P. Langer et al., Chem. Commun., 3044 (2003)

4O t-BuO O TBS CH2Cl2-TFA-H2O rtPh Br

Et3N, Bu4NI CH2Cl2-Et2O re ux 50% (2 steps)

MeMgBr Et2O, 0°C to rt; TMSOTf, rt; 1 M HCl aq. 55%

HO2C

OH Ph

J. S. Johnson et al., Org. Lett., 12, 944 (2010)

日本东京大学Fukuyama组10年组会2012有机反应机理习题(适合研究生)

Fukuyama Group - Group Meeting Problems 06/20/20121NO2 BrMgCl EtO2C CO2Et

O CO2Et N Br G. Bartoli et al., J. Org. Chem., 55, 4456 (1990) J. Yang et al., Angew. Chem. Int. Ed., 51, 5110 (2012) CO2Et

THF,–70°C; sat. NH4Cl aq 65% (E:Z= 98:2)

toluene, 80°C 74%

2N2 O O O N Ph 1) Rh2(pfb)4 (cat.) benzene, rt, 94% 2) xylene, 145ºC 68% O O N Ph O

A. Padwa et al., J. Org. Chem., 68, 227 (2003)

3O Me Me

O S

p-tol CCl4, re ux 96%

n-BuLi (1.1 eq) THF,–78°C; TMSCl,–78°C quant.

MeLi THF,–78°C; SO2, THF–78 to–70°C 75% Me

S

SO2p-tol Me

S. E. Denmark et al., J. Org. Chem., 52, 4031 (1987) B. Zwanenburg et al., Tetrahedron Lett., 32, 3867 (1991)

4Ph H2N OH p-NsCl (3.0 eq.*) CH2Cl2-pyridine, rt; C14H12N2O4S KOH, rt 97% ( theoretically 2 eq.)

EtO2C

CO2Et

Ph EtO2C

Ph3P

NH

NO2

CH2Cl2, rt 73%

CO2Et (trans:cis= 90:10)

J. Farrás et al., Tetrahedron, 57, 7665 (2001) O. Kwon et al., J. Am. Chem. Soc., 131, 6318 (2009)

5SO2Ph+ SO2Ph CO2Et toluene, re ux 95% (diastereomeric mixture) 2) n-Bu3SnH (5.0 eq) AIBN (2.0 eq) benzene, re ux 83% NOH 1) 5% Na/Hg THF, rt, 75%

O

N H O

A. Padwa et al., J. Org. Chem., 75, 1992 (2010)

日本东京大学Fukuyama组10年组会2012有机反应机理习题(适合研究生)

Fukuyama Group - Group Meeting Problems 07/07/20121Cl NO2

KCN Cl EtOH-H2O re ux 10% (73% SM recover) von Richter, V. et al., Ber., 4, 459 (1871) von Richter, V. et al., Ber., 4, 553 (1871) J. F. Bunnett et al., J. Org. Chem., 21, 944 (1956) CO2H

21) hν, acetone, rt 75% O HO2C 2) DPPA, Et3N 1,4-dioxane, re ux 89% C13H17NO2 3) RuO2, NaIO4 CCl4, H2O, MeCN, rt; 2 M aq. H2SO4; aq. NaHCO3 55% O H

O H H H O

J. K. Cowell et al., Tetrahedron Lett., 37, 2177 (1996)

31) TBSOTf, Et3N Et2O, 0°C, quant O 2) CH2I2, Et2Zn CH2Cl2, 25°C, 86% 1) CO (0.2 atm)[Rh(CO)2Cl]2 (cat.) dioxane, 80°C 2) HCl, EtOH-H2O, rt 62% (2 steps) H OH

H

O

Z. Yu et al., J. Am. Chem. Soc., 130, 4421 (2008)

4R (pin)B MeCl

O

SnBu3

n-BuLi, THF,–105°C to rt; RNMe2

R Me

R

(Ghosez rgt)

re ux R= 48% V. K. Aggarwal et al., J. Am. Chem. Soc., 134, 7570 (2012)

日本东京大学Fukuyama组10年组会2012有机反应机理习题(适合研究生)

Fukuyama Group - Group Meeting Problems 07/11/20121N OH AgOTf (10 mol%) p-BrC6H4 Ph DMF, 75°C 83% N

C6H4p-Br O Ph J. Wu et al., Org. Lett., 14, 3430 (2012)

2CO2H 1) conc HCl, re ux 82% 2) ClCO2Et, Et3N THF, 0ºC; Zn(BH4)2 0ºC, 85% Cl NaOAc, H2O2 aq AcOH, 60ºC 63% HO O O

O

G. Helmchen et al., Eur. J. Org. Chem., 2551 (2008)

3O Me OHC O O N Me H Me Me O NH2OH·HCl pyridine MeOH, 45°C 94% 65% NCS DMF, rt; A, NEt3 THF, 0°CMeN P O Ph

O Me CN O O N Me H Me Me O A S HN NH

toluene 110°C 54%

V. H. Rawal et al., J. Am. Chem. Soc., 133, 5798 (2011)

4

HO N O O

(HCHO)n CuI, i-Pr2NH 1,4-dioxane re ux 76% Me Me O O N O

(COCl)2, DMSO, Et3N CH2Cl2,–78 to–20°C; B, DMAP CH2Cl2,–20°C to rt 62%

MeLi, ZnCl2 Ni(cod)2 (10 mol%) Ti(Oi-Pr)4 THF–20°C to rt 57% dr= 98:2

Me Me O O N O H N O O

Me

PPh3Br B

J. Montgomery et al., J. Am. Chem. Soc., 121, 11139 (1999)

日本东京大学Fukuyama组10年组会2012有机反应机理习题(适合研究生)

Fukuyama Group - Group Meeting Problems 07/18/20121O CHN2 1) Rh2(OAc)4 benzene, re ux N S 2) Raney Ni acetone, rt 66% (2 steps) 1) Me3OBF4, CH2Cl2, 0°C; evap.; NaBH4, MeOH, rt 2) ClCO2R, benzene, rt 38% (2 steps) R= p-MeOBn S. J. Danishefsky et al., J. Am. Chem. Soc., 115, 30 (1993) N RO2C

O

21) NaH, Cl3CCN Et2O, 0°C to rt OH 2) xylenes, re ux 50% (2 steps) Grubbs' cat (5 mol%) xylenes, 140°C; styrene 52% Cl

H H N O H Cl Cl Ph dr= 1:1

M. L. Snapper et al., J. Am. Chem. Soc., 127, 16329 (2005)

3I+ O2N Ph Ph Ph O Ph cat. PdCl2(PPh3)2 cat. CuI, Et3N butyronitrile,Δ 91% Ph O Ph

NO2

Ph

T. J. J. Muller et al., Chem. Commun., 4096 (2006)

4CO2Et O O hν styrene benzene, rt 78% 3:2 mixture of two isomers S. Ohta et al., Org. Biomol. Chem., 3, 2296 (2005) Me3S(O)I (2.0 eq) NaH (2.0 eq) DMF, rt 76% O H Ph

H

CO2Et OH

日本东京大学Fukuyama组10年组会2012有机反应机理习题(适合研究生)

Fukuyama Group - Group Meeting Problems 08/01/20121O Me CONHBn Me CO2Me hυ THF, rt; evap. conc. H2SO4 THF-MeOH rt 50% Me Me O O

O

O NHBn OMe

P. S. Baran et al., Angew. Chem. Int. Ed., 45, 249 (2006)

2O Me OBn H

Me

OTES

S (E/Z=4/1)

N

ZnCl2 CH2Cl2, 23ºC 83% (dr> 19:1)

O3 CH2Cl2,–78ºC; PPh3 89%

IR 1827, 1714 cm–1

TESOTf Et3SiH CH2Cl2–78 to 0ºC 66%

Me

H

O

H Me OH O OBn

3Cl Cl OMe

D. Romo et al., J. Org. Chem., 72, 9053 (2007)

TMS

Br Ph

(1.2 eq.) n-BuLi (2.5 eq.) THF,–80°C 81%

H2SO4 MeOH, 30°C

O

TMS

Ph 83% M. Segi et al., Tetrahedron Lett., 51, 1294 (2010)

4Me AuCl3 (6 mol%) O O CH3CN, rt 90% OH Me O

A. S. K. Hashmi et al., Chem. Eur. J., 3703 (2008)

日本东京大学Fukuyama组10年组会2012有机反应机理习题(适合研究生)

Fukuyama Group - Group Meeting Problems 08/08/20121NO2 O2N Cl

90°C; Me2NH (2.2 eq), 0°C to rt; N cyclopentadiene, NaOMe, 125°C 51-59% K-P. Meinhardt et al., Org. Synth., 62, 134 (1984)

2

O N O

1) NH2NH2 CH2Cl2, rt 2)O P O O Cl

CuSO4·5H2O (15 mol%) 1,10-phenanthroline (30 mol%) K3PO4Br Ph

O O P N O toluene, 135°C 84% Ph

toluene, 60°C 47%

Et3N, CH2Cl2 0°C to rt 92% (2 steps)

K.A. DeKorver et al., Org. Lett., 14, 1768 (2012)

3H EtO2C O N OHCO2H 1) PMBO PPh3, DEAD THF, 0ºC, 82%

2) o-dichlorobenzene 150ºC, 73%

tricyclic compound (except for PMB group)

1) TFA CH2Cl2, rt 70% 2) MsCl, Et3N CH2Cl2, 0ºC; evap.; H2, Pd/C MeOH, rt, 20%

O HO H N O

A. Brandi et al., Org. Lett., 2, 2475 (2000)

4EtO2C NO2 (2.0 eq) Ph N Ph BnNH2 re ux 86% O O BnHN O N NHBn

S. Umezawa et al., Bull. Chem. Soc. Jpn., 36, 1150 (1963)

日本东京大学Fukuyama组10年组会2012有机反应机理习题(适合研究生)

Fukuyama Group - Group Meeting Problems 08/22/20121Ph TsN

TsN3, CuI, TBAI, K2CO3 CH2Cl2, rt; neutral Al2O3 77% TsN

O

Ph

Y.-Q. Tu et al., Chem. Sci., 3, 1975 (2012)

2Me Me O H2N O NBoc OTBDPS 1) PhSH, Et3N THF, 70ºC 95% 2) TMSOTf, 2,6-lutidine CH2Cl2,–78 to 0ºC 98%

3)Cl

O

Me

tricyclic compound (except Ph) 4)

i-Pr2NEt CH2Cl2, rt 92%O t-amyl O O Ph

Me Me O N N

OTBDPS

t-BuPh, 120ºC 62%

H O

A. G. Myers et al., J. Am. Chem. Soc., 127, 5342 (2005)

3HO O Br2 (theoretically 3 eq.) Sodium tetraborate THF-NaOH aq. 0°C 13% O O O

O

T. Rosenau et al., Eur. J. Org. Chem., 2011, 3036 (2011)

4Me Me2Si OH[Rh(OH)(cod)2] (2.5 mol%) Ligand (6 mol%) mesitylene, 100°C 75%, 99%ee, dr=19:1 1) TsOH (5 mol%) CH2Cl2, 23°C 2) toluene, 80°C 71% (2 steps) Me H H SiMe2F F F F O O O O PPh2 PPh2

Ligand

N. Cramer et al., Angew. Chem. Int. Ed., 49, 10163 (2010)

日本东京大学Fukuyama组10年组会2012有机反应机理习题(适合研究生)

Fukuyama Group - Group Meeting Problems 09/05/20121O O O BnNH2, PhH re ux (Dean-Stark); evap.; maleic anhydride THF, 0°C 2,2-dimethoxypropane p-TsOH (cat.) MeOH re ux 91% (2 steps) C19H21NO4 POCl3 pyridine MeCN 60°C 82% G. Revial et al., J. Org. Chem., 67, 2252 (2002) CO2Me MeO N Bn

2ClO4 S

CHO O OMe+ Cl

N Mes

CHO

(5 mol%) DBU (20 mol%) THF, 80°C 60% OMe

O O O Cl

F. Glorius et al., Org. Lett., 13, 5624 (2011)

3S Et NHCl

O

O Cl

Br Br

Zn dust–78 to 25ºC 72%

toluene 120ºC 66%

Pd/C, H2, rt lt., evap.; LiAlH4, THF re ux, 83% (dr= 1: 0.73)

NH

H

NO2

Et

N

A. Padwa et al., J. Org. Chem., 74, 7389 (2009)

4O Br H2N SH Me CO2Et K2CO3 EtOH, re ux 60% B. Zhao et al., Synthesis, 3133 (2011) N CO2Et S

日本东京大学Fukuyama组10年组会2012有机反应机理习题(适合研究生)

Fukuyama Group - Group Meeting Problems 09/26/20121HO MsOH microwave O H HO NMe 90°C 75% A. E. Arppe, Justus Liebigs Annalen der Chemie, 55, 96 (1845) J. L. Neumeyer et al.

, Synth. Commun., 38, 866 (2008) HO HO NMe

2O O Me O Me+ O H N Ts cat. ZnCl2 ClCH2CH2Cl, 60°C 70% L. A. Lopez et al., Angew. Chem. Int. Ed., 51, 8063 (2012) Me Me O NTs

3O S8 (0.25 eq.) morpholine (3 eq.) p-TsOH (cat.) 120-130°C; NaOH aq. Et3BnNCl 100°C; OH Br O

C12H14BrNOS

Br

HCl aq. 78%

S. R. Adapa et al., Synth. Commun., 33, 59 (2003)

4N2 Ph O OMe+ PhS Rh2(OAc)4 (1 mol%) toluene, 60°C;[RuCl2(p-cymene)]2 (5 mol%) 80°C 81% J. Wang et al., Angew. Chem. Int. Ed., 46, 1905 (2007) Ph MeO SPh O

日本东京大学Fukuyama组10年组会2012有机反应机理习题(适合研究生)

Fukuyama Group - Group Meeting Problems 10/06/20121N2 O O+ Ph O microwave+ BnNH2 toluene, 140ºC 73% O NBn O Ph

J. Rodriguez et al., Org. Lett., 12, 4212 (2010)

2HO O Si O MeO OH OMe 1) PhI(OAc)2 (1.2 eq.) HFIP, 0°C 2) TBAF, THF, rt 40% (2 steps) S. Canesi et al., J. Org. Chem., 77, 7588 (2012) H O O OMe

3O TBS I p-TolSO2Na DMF, rt 80% PhCH2Br NaHMDS, THF–80 to–60°C 93% TBAF THF–80 to–70°C 86% O Ph

4MeO OTES PhCH2N3, BF3·OEt2–78°C to rt CH2Cl2 47%

K. Takeda et al., Org. Lett., 6, 4849 (2004)

Rh2(OAc)4 CH2Cl2, 0°C to rt 90% N Ph

O

J. Aube et al., Org. Lett., 2, 1657 (2000)

日本东京大学Fukuyama组10年组会2012有机反应机理习题(适合研究生)

Fukuyama Group - Group Meeting Problems 10/13/20121MeO OMe (pin)B–B(pin) (3 eq) Cu(OAc)2 (2 mol%) P(t-Bu)3 (7 mol%) toluene, 80°C 62%1H

PhCHO (3 eq) C28H52O8B4NMR (CDCl)3δ 1.12 (s, 24 H) 1.26 (s, 24 H) 1.85 (s, 4 H)

OH Ph

Ph OH Ph

toluene, 100°C 86%

H. Yoshida et al., Angew. Chem. Int. Ed., 51, 235 (2012) T. Hiyama et al., Chem. Asian. J., 2, 1142 (2007)

2

1) MeOLi OMe

Et t-BuO

O O

THF,–78°C 52% 2) toluene, re ux; Ag2O, K2CO3, rt 92% 3) TFA, toluene, 0°C quant.

H2O2, Na2CO3 dioxane-H2O 60°C; HCl aq. H2SO3 aq. 0°C;

The intermediate contains 5-membered ring. H2O, 70°C 72%

NaOH CuSO4

O HO Me O OMe OMe

H. W. Moore et al., J. Org. Chem., 60, 461 (1995)

3Me N Ph O COCF3 O Me3S I, n-BuLi THF,–20°C to rt; AcOH, 80°C 70% (2 steps) MeS Ph N Me CF3

4O

M. Kawase et al., Tetrahedron Lett., 53, 2782 (2012)

N

1) MeO Cl Et3N, CH2Cl2, rt 2) p-TsOH H2O THF-H2O, re ux O 3) NaIO4, NaHCO3 aq CH2Cl2, rt 53% (3 steps)

Br

Monocyclic Compound

1) Me In (powder) THF-NH4Cl aq, 0ºC 77% 2) MsCl, Et3N hydroquinone toluene 190ºC (sealed tube) 47% MeO

OMs Me H H N O H H

O

B. Alcaide et al., Eur. J. Org. Chem., 98 (2005)

日本东京大学Fukuyama组10年组会2012有机反应机理习题(适合研究生)

Fukuyama Group - Group Meeting Problems 10/31/20121

O

SPh2 BF4 KOH N3 DMSO 0°C to rt TiCl4 CH2Cl2–78°C to rt 78% (2 steps) N

O

S. Baskaran et al., Chem. Commun., 48, 5778 (2012)

2Me O O Me O Ph Ph 1) BF3·OEt2 CDCl3, rt quant. 2) TfOH (20 eq.) CDCl3, 30°C 98% O Me Ph

O

Me

T. Oshima et al., Eur. J. Org. Chem., 3917 (2012)

3O N2 O TMS Rh2(esp)2 (0.5 mol%) CH2Cl2, rt O 71% TBAF THF, 45ºC 63% J. A. May et al., J. Am. Chem. Soc., 134, 17877 (2012) O O O

4Ph OMe (OC)5Cr Ph n-BuLi, THF,–78°C; TMSOTf;, CH3CN 73% spiro compound[(JohnPhos)Au(CH3CN)][SbF6] (5 mol%) DCE, 100°C,μ W Ph 41% J. Barluenga et al., Angew. Chem., 124, 10523 (2012) Ph

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