Fukuyama Group - Group Meeting Problems

01/06/2018

1
CuBr•Me2S (5 mol%)
ligand (10 mol%)
O (t-BuO)2 (3 eq.)
+ N N
O O N N
Ph H t-BuOH/DCE, 120 °C
Me Ph O
83% ligand

J. F. Soule et al., Org. Lett., 19, 6720 (2017)

1) [(C2H4)PtCl2]2 (3 mol%)
2 1-octene (10 mol%)
base (10 mol%)
Ph
Ph
toluene, 40 °C OH MeO2C
O CO2Me 98% Ph
+
O
2) neat, 200 °C
n-Pr H CO2Me
n-Pr
Me Et
34% 59%

t-Bu N t-Bu
base
E. M. Ferreira et al., J. Am. Chem. Soc., 138, 108 (2016)

TMS Ti(Oi-Pr)4, n-BuLi Me Ph Me Ph

toluene, −78 to 50 °C; TMS TMS
OH + OH
A, −78 °C to rt; Ph Ph
Ph MeOH, −78 °C H
Me

67% 17%
Ph dr = 10:1
A: Me
OPh
OLi
G. C. Micalizio et al., J. Am. Chem. Soc., 136, 8209 (2014)
 Fukuyama Group - Group Meeting Problems
02/21/2018

1
O O
Tf2O, 2-iodopyridine
Ph Ph
N N
CH2Cl2, 0 °C;
2,6-lutidine N-oxide, 0 °C; BnO2C CO2Bn
dibenzyl malonate, NaH
0 °C to rt

89%

N. Maulide et al., J. Am. Chem. Soc., 139, 16040 (2017)

2
Tol Cu(OAc)2 (1.1 eq) NH
O BOP (1.1 eq) Me
O S O DMAP (1.0 eq) Ph NH2 • HCl O
OH + N
MeNO2, reflux DMSO, reflux
N
OH Ph
Me 80% 85%
N
N PF6
N
O P(NMe2)3 M.-Y. Chang et al., J. Org. Chem., 83, 2361 (2018)
BOP

3
OMe
Me MeO
N TBHP, Triton B
TfOH THF, rt;
MeO CH2Cl2, 0 °C SiO2, rt

97% 76% N
MeO Me
O
HO
O

S. E. Reisman et al., Angew. Chem. Int. Ed., 50, 9447 (2011)

4
OMe [RhCl(CO)2]2
OH OMe
(5 mol%)
CO (1 atm)
CHO
MeO
CO2Me DCE, 85 °C
CO2Me
OMe 86%

Z. Yang et al., Nat. Commun., 5, 5707 (2014)

 Fukuyama Group - Group Meeting Problems
03/10/2018

1
N2 O
OH (C6F5)3B
O CH2Cl2, −15 °C

88%

M. Brewer et al., Chem. Sci., 8, 6810 (2017)

2
Ot-Bu
Me
Me Ot-Bu Pb(OAc)4 (3.0 eq.) K2CO3 (5.6 eq.) Me O
HO Ot-Bu
O
MeCN, rt O MeOH-H2O, rt
HO OH
82% OAc OAc 92%

S. Arseniyadis et al., Tetrahedron, 52, 12443 (1996)

3
O Tf2O (2.0 eq) Me
pyridine (5.0 eq)
N N
CH2Cl2 toluene O
OH
−78 °C to rt O S
Me 130 °C CF3
75% 96%

A. Padwa et al., Org. Lett., 5, 189 (2003)

4
O
O O O
fac-Ir(ppy)3 (0.2 mol%)
+ N
O DMSO, rt
O O 5W blue LEDs

67%
K. Ueda
F. Glorius et al., Org. Lett., 20, 1546 (2018)
 Yokoshima Group - Group Meeting Problems
04/07/2018
1 HN
O
O
N
MeO2C NH N
H LHMDS (3.0 eq.), THF, –78 to 0 °C;
O H
OTBS BocHN
Boc N AcOH (1.0 eq.), –78 °C to rt H H
N F3C N OTBS
OTBS 74%
F3C O OTBS
O (without AcOH : 27-50%)

K. Namba et al., Nat. Commun., 6, 8731 (2015)

2 NC
m-CPBA (1.5 eq.)
I AcOH, 40 °C;
OH
NC I
(2 eq.)
OH
rt

55%
H. Yorimitsu et al., Angew. Chem. Int. Ed., 57, 4663 (2018)

Cl
3 N Mes
Mes N
OCOMe
(20 mol%) Me
O
Cs2CO3 (20 mol%)
Me O
Ph
THF, rt
O O Ph
H
92% (dr > 20:1) Ph

X. Fang et al., Org. Lett., 20, 64 (2018)

4 Me Me
O
O O
O OMe
Me K2CO3 Me HO
OBz
MeOH, 65 °C H
O
O O Me
Me 60%
Me Me Me
Me
H. Ding et al., Angew. Chem. Int. Ed., 54, 6905 (2015)

5 O Me
Me
O O O
O2, hν
H H
CO2Me benzene, 0 °C N CO2Me
N
71%
OTBS O OTBS
O
A. Li et al., Nat. Chem., 5, 679 (2013)
 Yokoshima Group - Group Meeting Problems
04/28/2018
1
NTs NTs
N [Rh2(Adc)2] (0.01 eq.)
O Ph
N
CHCl3, 60 °C
O Ph H
92%

R. Sarpong et al., Angew. Chem. Int. Ed., 53, 9904 (2013)

2 1) A (1.4 eq.) O
SmI2 (3 eq.)
PhMe2Si OEt
H2O (8 eq.) B (4 eq.)
BnO LiBr (12 eq.) BnO O A
KH (5 eq.)
O THF, −78 to −30 °C TBAF (2 eq.)
N N
BnO BnO
2) Zn DMF, rt
Ph OOH
BnO AcOH. 80 °C BnO H OH
57% B
49% (2 steps)

P. Gilles and S. Py, Org. Lett., 14, 1042 (2012)

3
O O
OMe OH
hν O
Me Me
O
Me hexane, rt
Me Me
Me H O Me H
OH 90% Me O OMe

G. Majetich and J. Yu, Org. Lett., 10, 89 (2008)

4 OtBu

AdO ZnCl (1.5 eq.) OAd

Pd(OAc)2 (0.05 eq.) N
Bs
I dpph (0.1 eq.) OBn OMe

THF, rt toluene, 50 °C
MeO N OH
Bs
80% 60% OBn

J. M. Ready et al., J. Am. Chem. Soc., 138, 10684 (2016)

 Yokoshima Group - Group Meeting Problems
05/12/2018
1 Ph
N O
Ph
O
HO BF3•Et2O (4.0 eq.) PPh3 (3.0 eq.)
N
O CH2Cl2, rt m-xylene, 130 °C
N N O Ph
Me 57% 74%
Me
The product was also obtained in refluxing 1,2-dichlorobenzene for 6 h even in the absence of PPh3
in the seond step. Different mechanisms were proposed. Please answer each mechanisms.

J. N. Kim et al., Tetrahedron Lett., 59, 1484 (2018)

2 H
H Br2 H
OMe hν CH2Cl2, 0 ºC;
H + H O
pentane evaporation;
MeO
OMe nBu3SnH
65%
59%

P. A. Wender and J. J. Howbert, J. Am. Chem. Soc., 103, 688 (1981)

3 O
Rh2(OAc)4 (cat.) O
Ph N3 Ph
+ N
EtO2C CH2Cl2, rt CO2Et
N2 (2.0 eq.) 71%

S. Katukojvala and V. Kanchupalli, Angew. Chem. Int. Ed., 57, 1 (2018)

4 N
Ph
10% KOH aq., rt; Ph
N
4 M HCl aq.
rt to 90 °C O
O
NO2
83%

H. E. Zimmerman et al., Helv. Chim. Acta, 84, 1342 (2001)

5 CO2H
O3, CH2Cl2, –78 ºC;
OH +
Me2S, –78 ºC to rt;
O
water (quench) OH
O
74% (ca. 4/1)

A. G. Martinez et al., Tetrahedron Lett., 46, 5157 (2005)

 Yokoshima Group - Group Meeting Problems
05/19/2018
1) m-CPBA (2.5 eq.)
1 N3
CHCl3, rt
O
2) Pd/C, H2, Ac2O NAc
O Et EtOAc, rt
N Et
3) TFA
CH2Cl2, rt
30% (3 steps) O
N
H
M. Dai et al., Org. Lett., 16, 6216 (2014)

LDA
2 THF, –78 to 0 °C;
OH
B Ph
OH
ZnCl2•TMEDA
N
rt; Me

Br S Br PdCl2(dppf)•CH2Cl2
Pd(PPh3)4 (5.0 mol%) S
I (5.0 mol%)
t-Bu3P•HBF4 Me
NHPh (20 mol%)
60 °C NaOt-Bu, K3PO4
1,4-dioxane, 125 °C
69%
57% A. Mori et al., Org. Lett., 20, 958 (2018)

Ph
3 AcO Ph3PAuCl (5 mol%) O
AgSbF6 (10 mol%)
H Ph O
BnO
O CH2Cl2, rt
OBn
BnO 80%

X.-W. Liu et al., Chem. Sci., 8, 6656 (2017)

4 1) TsCl, Et3N
CH2Cl2, rt
83%
2) 4-ethyl-4-pentenoic acid O
O EDCI, DMAP
H
N CO2Me CH2Cl2, rt N
N N 87%
H H
O Me
3) o-dichlorobenzene O
N reflux N
Me 74% Me
CO2Me

D. L. Boger et al., Org. Lett., 7, 741 (2005)

OH
5
I H
Pd(OAc)2 O
DEAD K2CO3, Bu4NCl

CH2Cl2, 0 ºC DMF, 80 ºC H
N N CO2Et
quant. 63% EtO2C H

K. V. Radhakrishnan et al., J. Am. Chem. Soc., 131, 5042 (2009)

 Yokoshima Group - Group Meeting Problems
05/26/2018
1 Me
IrCl(CO)(PPh3)2 (1 mol%)
TMDS (2 eq.) N N
O toluene, rt;
N Me Me
+
SiO2
−78 °C to rt N CO2Me N CO2Me
Me Me
N CO2Me
Me major minor
52% 31%
*TMDS = 1,1,3,3-Tetramethyldisiloxane

D. J. Dixon et al., Angew. Chem. Int. Ed., 55, 13436 (2016)

Br
NH2OH•HCl (1.2 eq.) Me A H
O H2O, rt; KHCO3 N Me
A Me O
O
HO NaHCO3 (2.5 eq.), rt; EtOAc, rt
Me
Br2 (1.7 eq.)∗, CH2Cl2, 0 ºC O Me
91% O Me
∗theoretically 2.0 eq.

D. Y.-K. Chen et al., Angew. Chem. Int. Ed., 56, 12277 (2017)
E. M. Carreira et al., Angew. Chem. Int. Ed., 54, 11227 (2015)

3 CF3
Me
OH
AgSbF6 (50 mol%) Me
A (10 mol%) CF3
H2O (1.1 eq.) O O O O
O P
O DCE, rt O O OH
Me O Me O
CF3
92%
Me
Me O A
CF3

T. Wang and D. Z. Wang et al., Org. Lett., 15, 2362 (2013)

4
SiMe2Ph Et3N (3 eq.)
Me nBu
nBu (5 eq.) H
Cl
TFE/Et2O Cl
Cl
−78 ºC to rt O
O
42%

P. R. Schreiner et al., Angew. Chem. Int. Ed., 47, 8696 (2008)

 Yokoshima Group - Group Meeting Problems
06/02/2018
1 H OH
1) VO(acac)2, t-BuOOH H OH
CH2Cl2, MS4A, 0 °C to rt K2CO3 (15 eq.)
OO
H 2) Et3N, SiO2 DMF, MS4A
O O 75 °C H
O CH2Cl2, rt
OH
O
93% (2 steps) 68%

J. D. Winkler et al., Org. Lett., 5, 1805 (2003)

2
OH
O2N MeO2C CO2Me N
Zn powder (20 eq.)
NC +
n-Pr NH4Cl aq., MeOH, rt
n-Pr n-Pr
MeO2C CO2Me MeO2C CO2Me
pH A (%) B (%)
4.5 45 18
5.7 18 27

A. Kamimura et al., Tetrahedron Lett., 54, 1842 (2013)

3
H H Pd(OAc)2 (10 mol%)
N N HN
PhI(OAc)2 (3 eq.) O
O N
EtOAc, 25 °C OAc

71%
H

L. Tao and M. Shi, Org. Lett., 20, 3017 (2018)

4
PBu3 (10 mol%)
(9-BBN-H)2 (0.48 eq) EtO2C Ph (0.95 eq)
O
EtO B
Ph
THF, 60 °C; 80 °C
Ph
95% Ph

M. Sawamura et al., J. Am. Chem. Soc., 136, 10605 (2014)

5
Ph Ph 1) NIS (2.5 eq) 3) NaClO2, 2-methyl-2-butene
MeCN-H2O NaH2PO4, t-BuOH-H2O
0 °C, 62% rt, 92% O O
O O I
2) DDQ 4) CAN, MeCN-H2O, rt;
MeCN-H2O K2CO3, rt, 80% O
60 °C, 58%

Y. Kita et al., Angew. Chem. Int. Ed., 44, 734 (2005)

 Yokoshima Group - Group Meeting Problems
06/09/2018
1
HO O HO O
Boc LHMDS TESOTf (0.3 eq.) H Boc H Boc
O
N THF, −78 °C; CH2Cl2, −78 °C;
N N
O TESCl, rt Et3N•3HF, rt
TBDPSO
76% 51% TBDPSO TBDPSO
1 : 5

P. Chiu et al., Angew. Chem. Int. Ed., 57, 5253 (2018)

2 1) Br2HC
O Me3Si
Br2HC
OH
Et2Zn F3CCOMe Me3SiOTf HO
O O Na
O
toluene, rt Oxone 2,6-lutidine N
NCO2Me MeO2CN N
HO
2) Zn/Cu, NH4Cl Na2EDTA aq. CH2Cl2, rt O O Na
MeOH, 0 °C MeCN, 0 °C O
80% O Na2EDTA
36% (2 steps) 87%

M. Dekhane et al., Org. Lett., 12, 2834 (2010)

3 [IrCp*Cl2]2 (2.0 mol%)

N2 AgNTf2 (8.0 mol%)
O O O NaOAc (1.0 eq.) K2CO3
+ O
N O O 1,2-DCE, 70 °C MeOH, rt N
H H
90%
91%

P. Patel and G. Borah, Chem. Commun., 53, 443 (2017)

4
O Et3N OH
OH microwave O
toluene, 220 °C
in sealed tube

87%

J. M. Warrington and L. Barriauly, Org. Lett., 7, 4589 (2005)

5 Me
O
Boc2O Boc
H O HN N
Me N O 70% HClO4 Et3N
+
O H2O/1,4-dioxane THF, 60 °C
105 °C H
H
65% (2 steps) Me
NH2

R. Sarpong et al., J. Am. Chem. Soc., 132, 5926 (2010)

 Yokoshima Group - Group Meeting Problems
06/16/2018

OH Me 1) Pb(OAc)4 H O
AcOH K2CO3 NaIO4, HCl aq.

2) xylenes EtOH THF, (pH 4)

HO2C
reflux Me
22% (2 steps)

P. Yates and T. S. Macas, Can. J. Chem., 66, 1 (1988)

2
1) t-BuOK (0.1 eq.)
THF, 70 °C
t-BuLi (2.4 eq.) 2) t-BuOK, TBSCl, LDA
LaCl3•2LiCl (1.3 eq.) NH2
THF, rt to –50 °C
Boc C20H30N2O5
N Et2O, –40 to –70 °C; 3) TFA/DCM = 1/10
H N
O 0 °C H
68% (3 steps)
NBoc
, –70 °C to rt

75%

K. C. Nicolaou et al., Angew. Chem. Int. Ed., 47, 4217 (2008)

H Dy(OTf)3 (5.0 mol%)

N
O MeCN, 80 °C N
OH
96%

L. Palmer and J. Read de Alaniz, Angew. Chem. Int. Ed., 50, 7167 (2011)
 Yokoshima Group - Group Meeting Problems
06/23/2018
Me
1
TMS O
TMS Me
Me Me Me
Me Me

O
1,2-DCE, 100 °C
N sealed tube N
Ts Ts Me
89%

Y. R. Hoye and T. Wang, J. Am. Chem. Soc., 138, 13870 (2016)

2
1) nBu3SnH (1.2 eq.), AIBN (cat.) OH Me
Br Tl(ONO2)3 (2 eq.) benzene, 80 °C
S S
TMS MeOH, Celite, −15 °C 2) TBAF
H
THF
66%
81% (2 steps)

Y.-M. Tsai et al., Tetrahedron Lett., 34, 1303 (1993)

3 O
O CO2H
CuBr2 (20 mol%), O2
NaOMe (2 eq.) O

NH DMF, MS3A, 150 °C O

N
Me 84% Me

F. Zhang et al., Org. Lett., 19, 3418 (2017)

4
[Ru(bpy)3]Cl2·6H2O (1 mol%) Me O
KH2PO4 (1 eq.), hν (14 W CFL) Me
NH O OMe
N
O2, MeOH, rt H
Me Me O
69%

bpy:2,2'-bipyridine, CFL:Compact Fluorescent Light

Mechanistic studies suggest generation of 1O2 in situ.
W. Fan and P. Li, Angew. Chem. Int. Ed., 53, 12201 (2014)

5
1) NaOH, RMe3NCl
nC CHCl3-H2O, 80 °C, 58%
11H23 2) conc.HCl-MeOH, rt, 89% nC
O 11H23
HO
O 3) K2CO3, MeOH, rt, 77% O
4) NaBH4, MeOH, rt, 84%

(R = C16H33)

Y. Masaki et al., Chem. Pharm. Bull., 52, 848 (2004)

 Yokoshima Group - Group Meeting Problems
06/30/2018
1
CO2Et [RhCp*Cl2]2 (2.5 mol%) O
KF (2.0 eq.)
+
O
OMe DME, 100 °C
O N OH O N
H 87% H

X. Fan et al., Adv. Synth. Catal., 360, 1 (2018)

2
BocN N
Grubbs 2nd
DCM, rt; NaBH4
O A and B MeO
TFA, rt; Et2O/DCM/H2O H
O
O H aq. Na2CO3, rt rt
HCl H
Et2O/DCM, rt; OH
OMe 65% (2 steps)
aq. NaOH, rt;

M. D. Smith et al., Angew. Chem. Int. Ed., 55, 14306 (2016)

3
NHTs Me
N
NaH H
OTBDPS Me
Me
• toluene
Me reflux
Me Me
Me OTBDPS
Me 87%

H.-Y. Lee et al., J. Am. Chem. Soc., 136, 10274 (2014)

4
TBDPSO O O 1) Rh2(OAc)4 O
benzene, reflux
MPMO 90% TBDPSO
OMe
N2 2) DBU
toluene, 70 °C O OMPM
OTBDPS 89% OMe
3) diphenyl ether, 180 °C
58%
K. Iguchi et al., Org. Lett., 8, 4883 (2006)

5
OMe H H H H H
PtCl2 (5 mol%) H
H + H
H toluene, 80 °C H
MeO
OMe
56% (Z/E = 2 : 1) 15%

C. D. Vanderwal et al., Angew. Chem. Int. Ed., 51, 7572 (2012)

 Yokoshima Group - Group Meeting Problems
07/07/2018
1
1) Cl3CCN (excess) 3) mCPBA (1.05 eq.) O
DBU (1 eq.) CH2Cl2, −20 °C
OH HN CCl3
CH2Cl2, −20 °C to rt 97%
PhS
2) Na2CO3 (2 eq.) 4) P(OMe)3 (excess)
OH o-xylene, 140 °C OH HN CCl3
MeOH, reflux
in a sealed tube O
58% (2 steps)
(crude, dr = 1:1)

N. Chida et al., Org. Lett., 11, 2687 (2009)

2
(TMS)3SiH
O AIBN
O HO O O
O benzene, reflux;
Si MeLi, 0 °C TMS
Br
92%

L. Fensterbank et al., Tetrahedron, 52, 11405 (1996)

3
Ph
Ph O
C
CO2Et toluene, reflux
N + + O
• 61% O N
EtO

J. Li et al., Org. Lett., 16, 5604 (2014)

4
1) PhNCO Cl2Ce
NO2 Et3N O
HO
OTMS benzene, rt BF3⋅Et2O CF3CO2H
O
2) HCl in MeOH THF, −78 °C MeCN, 80 °C
O DCM, rt N
H
68% 67%
75% (2 steps)
(dr = 4:1)

S. Diethelm and E. M. Carreira, J. Am. Chem. Soc., 137, 6084 (2015)

 Yokoshima Group - Group Meeting Problems
07/14/2018
1 O
(EtO)2P CN
Hex
O 1) Br2
CH2Cl2, 0 °C N-O acetal t-BuOK
CN
Hex (C19H24BrNO3)
Br N 2) DMF O
Ac HO −78 °C to rt Br N
MS4A H
MeCN-DMF, rt 70% (98%ee)

50% (2 steps)

T. Kawasaki et al., Chem. Commun., 420 (2006)

2 N
S
N
O O 1) TMP, n-BuLi 3) N N
, DMAP
t-BuOMe, 0 °C to rt DCM, 0 °C to rt
90% 84% O
Me H
2) 6.0 M HCl 4) P(OMe)3, reflux
O THF, 50 °C 88% H
77%
OMOM

B. Liu et al., Org. Lett., 13, 5406 (2011)

3
CO2Et
CO2Et Cs2CO3
N
Br DMF, 80 °C Me
N
77%

J. Chang et al., J. Org. Chem., 82, 7045 (2017)

4
O O
I2 (50 mol%) S
+ NaNO2 Me
Me (1.2 eq)
DMSO, 90 °C N
Br Br OH
76%
Radical quenchers almost inhibit this reaction.

S. Batra et al., Org. Lett., 18, 4190 (2016)

5 O
CuCN Me3Al (2 eq)
Me BF3•OEt2 OH
THF, 0 °C; CH2I2 (2 eq)
Ph Si Li
allene, –40 °C; –40 to 0 °C CH2Cl2
Me
–60 °C to rt

58% (2 steps)

F. J. Pulido et al., J. Am. Chem. Soc., 127, 8022 (2005)

 Yokoshima Group - Group Meeting Problems
07/28/2018
1
O 1) Zn
N CO2i-Pr O
AcOH-H2O (4:1) i-PrO2C N
O 15 °C PPh3 O
N H
H 2) NH3 aq. THF
O CHCl3, rt 0 °C to rt
O N
Cl3C 51% (2 steps)
87%

S. Jiang et al., Chem. Commun., 50, 9284 (2014)

2 O
N
Me

NHBoc
N OH
O TBA
H
(15 mol%)
+ NBoc
SMe Et2O, –50 °C; N
N NaBH4, CeCl3·7H2O SMe
PMB
PMB MeOH, –50 °C

87% (96% ee)

D. W. C. MacMillan et al., J. Am. Chem. Soc., 131, 13606 (2009)

3 Me
O O O
Me CO2Me hv (310 nm) BBr3
Me
Me solid state, 0 °C CH2Cl2, 0 °C Me
OMe Me
76%

M. A. Garcia-Garibay et al., Org. Lett., 6, 645 (2004)

4
Me Me
1) t-BuOOH
VO(acac)2 OH
benzene, rt TiCl4
OH
N3 2) TMSCl CH2Cl2
imidazole N
–78 °C to 0 °C
DMF, rt
66% (2 steps) O
68%
C. Fan et al., Org. Lett., 10, 1763 (2008)

5 OMe

HO Me Ph OMe OH
TsOH H3PO4
two tricyclic compounds
(one is an eimer of the other.) Ph Me
CH2Cl2, rt CH2Cl2, rt
H O
OH
Me 86% 93%

R. Sarpong et al., J. Am. Chem. Soc., 140, 9291(2018)

 Yokoshima Group - Group Meeting Problems
08/04/2018
1 Me Me
H
N

N LDA (1.05 eq.) Me

THF, rt

50% O
Br O O
O
L. Mark et al., J. Am. Chem. Soc., 134, 15572 (2012)

2
1) NH2OH•HCl
BnO NaHCO3 Ti(Oi-Pr)4 (1.1 eq.) BnO H
O 91% EtMgBr (2.2 eq.) N
OH
2) MsCl (2 eq.) −78 °C to rt;
BnO OBn pyridine BF3•OEt2, rt BnO OBn
76%
42%

P. Bertus and J. Szymoniak, Synlett, 9, 1346 (2007)

3
O
O Tf2O (1.5 eq.) n-Bu
pyridine (3.0 eq.) N
BocHN n-Bu HN
N
H DCM O
Ph 4 to 25 °C
Ph
83%
Z. Pan et al., Org. Lett., 16, 5902 (2014)

OBn OBn PhSeSePh OBn OBn

SPh2•BF4 mCPBA
KOH NaBH4 pyridine
N3 DMSO, rt EtOH, rt n-hexane-DCM N3
OMe OMe
−30 °C to rt O
O
57% (3 steps)

Y. Q. Tu et al., Org. Lett., 14, 3604 (2012)

 Yokoshima Group - Group Meeting Problems
08/18/2018
1 Ph
OEt OH
[RuCl2(p-cymene)]2 (0.5 mol%) p-TsOH (cat.) O
t-BuCO2H Ph
toluene, 0 to 40 ºC CH2Cl2, rt O t-Bu

80% 80%

Y. Kita et al., J. Chem. Soc., Perkin Trans. 1, 2999 (1993)

2 TBSO OTBS

OAc TBSO OTBS

(1.5 eq.) t-Bu SbF6
t-Bu
A solution (cat.) P Au NCMe
H
CH2Cl2

48-55% A solution
OAc

A. M. Echavarren et al., Angew. Chem. Int. Ed., 52, 6396 (2013)

3 Me
OH O
N TMS CsF (3.0 eq.)
+ Me
Me N
OTf MeCN, 80 °C
Me 96%
2.2 eq.

T. Yao et al., Org. Lett., 19, 3135 (2017)

4 Ph Ph
HO MeO
MeO (1.0 eq.) O
BF3·OEt2 (3.0 eq.) H
MeO
MeO CHO H
CH2Cl2, rt
3.0 eq.
86% OMe
MeO

S. Nagumo et al., J. Org. Ch., 83, 9103 (2018)

5 MeO B
O
O i-Pr
N N
i-Pr

i-Pr i-Pr
[RhCl(C2H4)2]2 (3.0 mol%)
dppf (6.0 mol%) (10 mol%)
Et3N, H2O Ni(cod)2 (5.0 mol%)
OBn dioxane, 100 ºC toluene, 70 ºC OBn
OBn OBn
81% 90%
M. Murakami et al., J. Am. Chem. Soc., 128, 2516 (2006)
 Yokoshima Group - Group Meeting Problems
08/25/2018
1 Li•(+)sp
O
CbO PMP Cb =
SePh MeOTf Ni-Pr2
Et2O, –78 °C; CH2Cl2, rt; Ph
Ph • PMP
B(pin) H
MgBr2 NaHCO3 H (+)sp =
H MeOH, 40 °C MeOH, rt N N

91% (99:1 e.r.) 83% (98:2 e.r.)

V. K. Aggarwal et al., Angew. Chem. Int. Ed., 57, 8203 (2018)

2 O
Me

P CO2Me
OTBDMS CF3CH2O
CF3CH2O tBu N tBu CHO
OHC
KHMDS, 18-crown-6 Tf2O
MeO2C
THF, –78 °C to rt CD2Cl2, rt; N
iPr2NEt, rt NC
OHC N CN >39%
44%
G. Bélanger et al., Org. Lett., 13, 6204 (2011)

3 NH2
O O3 O
CO2Me AcOH-H3PO4 (1:1) CH2Cl2, –78 °C; KOH
O
toluene, reflux Me2S, –78 °C to rt CH2Cl2, rt
N
85% 84% 90%
Y. Kadokawa
X. She et al., Org. Lett., 18, 4682 (2016)

4 O
H Me
Me Cp2TiCl O
NBS
A+B + O
(A:B = 3:2) CDCl3, rt O
O THF, rt
H Me Me O Me
Me diastereomers
68%
86% from A 90% from B

R. Sarpong et al., J. Am. Chem. Soc., 137, 6327 (2015)

5 1)
1) TFA, CH2Cl, 0 ºC
O CN CO2Bn 2) cyclopentadiene O
BocHN CHCl3, rt HCHO, H2O, rt MeHN
SH protected dipeptide N CO2Bn
2) n-Bu3SnH (2.5 eq.) 3) Et3SiH, TFA Me
AIBN (1.0 eq.) CHCl3, rt
toluene, 100 ºC
52% (3 steps)
62% (2 steps)
S. J. Danishefsky et al., J. Am. Chem. Soc., 132, 4098 (2010)
 Yokoshima Group - Group Meeting Problems
09/01/2018
1 MgBr
BnO
C6H13 HCO2H K2CO3 N
BnO Boc H
N O
Boc THF, 0 ºC toluene-THF MeOH-H2O HO
0 ºC rt
79% C6H13
88% 98%

C. Kibayashi et al., Angew. Chem. Int. Ed., 41, 3017 (2002)

2 O
Ph (1.2 eq.) Ph
Ph
I2 (1.5 eq.)

THF, rt
O
94% Ph O

N. T. Patil et al., Eur. J. Org. Chem., 5178 (2009)

3 1) Tf2O
BrMg
CH2Cl2, −50 ºC
CeCl3 65% CH2OH

O Br THF 2) LAH
OMe 98%
76%

M. Harmata et al., Tetrahedron Lett., 43, 2347 (2002)

4 O2 (1 atm)
CuBr2 (25 mol%)
OMe
Cy TMEDA (50 mol%)
N
MeO
Cy MeOH-MeCN (1:4)
NCy2
40 °C

66%

J.-S. Tian and T.-P. Loh, Angew. Chem. Int. Ed., 49, 8417 (2010)

5 OCO2Me (2.0 eq.)

TMSN3 (2.0 eq.)

TMS Pd2(dba)3•CHCl3 (2.5 mol%)
P(2-furyl)3 (10 mol%) MeMgBr (4.0 eq.)

toluene THF N TMS

NC 100 ºC 0 °C to rt H

59% 93%

Y. Yamamoto et al., J. Am. Chem. Soc., 124, 11940 (2002)

 Yokoshima Group - Group Meeting Problems
09/08/2018
1)
1 NH

Me2N NMe2
OH CO2H O MeOH, −7 °C; O
O O PhI(OAc)2 (2.4 eq.)
O
Me (EtCO)2O Me −7 °C, 65% O
Me OMe
180 °C 2) ethylene (70 bar) O
toluene, 140 °C
82% 90% (dr = 6:1) Me Me OMe
Me Me

R. Sarpong et al., J. Am. Chem. Soc., 139, 11349 (2017)

2 BF4
Boc
Cl N O BocNHOH N Boc
(1.2 eq.) n-Bu4NIO4 O N
OBz
+ O
OBz MeCN, rt; CH2Cl2, rt OBz
DBU, rt OBz OBz
60% OBz
79% A:B = 9:1 A B
Y. Iwabuchi et al., Angew. Chem. Int. Ed., 55, 13189 (2016)
3
S
O
H
HBF4 MeO2C
MeO2C
DCM, 0 °C MeO2C
MeO2C OMe S
H
77%
OMe
C. Saa et al., Angew. Chem. Int. Ed., 51, 12316 (2012)

4 O

HO OH BF3•Et2O H Me
O O
MsCl Ca(OH)2
Me
Me
DMF MeOH, rt
OH O rt to 90 ºC OH O
40%
90%
Z. W. Shen et al., Eur. J. Org. Chem., 1356 (2013)

5 Cl Me O
N Cu(OAc)2 (cat.), (O2)
N Cl N N Me
N O AcOH/H2O/DMF
H N
Et 80 °C H Et O

71%

L. El Kaim and L. Grimaud et al., Eur. J. Org. Chem., 3117 (2011)

 Yokoshima Group - Group Meeting Problems
09/15/2018
1 CN

N
Hg(NO3)2, H
CH2Cl2
–40 ºC to rt; HCl aq. NH

NaBH4 reflux H
N
MeOH, rt
53%
39%
D. Stoermer and H. Heathcock, J. Org. Chem., 58, 564 (1993)
2
1) (COCl)2, DMSO
O Et3N O
Me O Bu3SnH CH2Cl2, –78 °C
AIBN O
OH 80% O
IR: 1782, 1732 H
TBDPSO OH Me O
O benzene 2) NaBH4
80 °C MeOH, –78 °C Me OH
Me O SePh 3) TsOH TBDPSO
40% toluene, 80 °C
83% (2 steps)

G. C. Micalizio et al., J. Am. Chem. Soc., 138, 1150 (2016)

3 O
HO H
H
H O
I2 (cat.) O N
O H H
TBSO H N MeOH, rt

84% HO
OH

P. D. Brown and A. L. Lawrence, Org. Biomol. Chem., Advance Article

DOI: 10.1039/c8ob00702k
4 1) bromoform
LDA
Br THF
A
Me 2) n-BuLi (2 eq.)
Et2O
−78 to −20 ºC

1) Me2C=C(NMe2)Cl
CH2Cl2, rt;
O MeONHMe•HCl Me O
Me HO H
2 ºC to rt
85% Me
Me O
O
2) A Me Me
O Me H O
Et2O
Me −75 ºC to rt Me
68%
B. Wickberg et al., J. Chem. Soc., Chem. Commun., 865 (1990)
 Yokoshima Group - Group Meeting Problems
09/29/2018

1 1) LHMDS TIPSO TIPSO

O CF3CO2CH2CF3 OTBS
OTBS
THF, –78 °C hν

2) MsN3, Et3N benzene, rt OH

MeCN/H2O, 25 °C
64%
82% (2 steps)

R. L. Danheiser et al., J. Org. Chem., 60, 8341 (1995)

2 1) BF3•OEt2
CH2Cl2, −20 °C formalin
O NBn 97% Et3N O
O O H
H MeOH, 23 °C;
O 2) H2, Pd/C
HCl-MeOH HCl-MeOH, 23 °C O
96% N H
67%

L. E. Overman et al., J. Org. Chem., 56, 5005 (1991)

3 Ph
CO2Me

CO2allyl 1) Pd2(dba)3 (0.06 eq.)

Yb(OTf)3 (0.1 eq.) MeCN, reflux Ph
O MS4A 66% Ph N
+ PhNHOH Ph
Ph toluene, rt 2) DBU (3 eq.)
MeCN, rt MeO2C
91% 88%

M. A. Kerr et al., Angew. Chem. Int. Ed., 51, 11088 (2012)

4
NO2

(EtO)2(O)P

Ot-Bu O2N
Ot-Bu H
mCPBA Al2O3 LHMDS
H
THF, −10 °C

71%

S. J. Danishefsky et al., J. Am. Chem. Soc., 124, 9812 (2002)

 Yokoshima Group - Group Meeting Problems
10/06/2018
1
1) LHMDS, hexane, –10 °C;
CH2=C(Me)CO2Me 1) K2CO3
MeOH, rt, 90% O
O –10 °C to rt, 70%
C15H22O5
2) O3, CH2Cl2-MeOH, –70 °C; 2) p-TsOH·H2O
Ac2O, Et3N, DMAP benzene, reflux, 65% CO2Me
benzene, reflux, 60%

Y. Seno
A. Srikrishna et al., Tetrahedron Lett., 47, 363 (2006)

2
MeO2C Me BF4
S Me
MeO2C
Me S (1.0eq.)
O H
CH3CN, −40 °C;
OAc O O
MeS Et3N, −40 °C MeS N
N O
MeS 80%
dr = 1:1
T. Nakamura
J. D. Ginn and A. Padwa, Org. Lett., 4, 1515 (2002)

3
∗IPrAuNTf2 (5 mol%)
CH2Cl2, rt; O *IPr =
Ph O concentration; i-Pr i-Pr
+ OEt Ph
Me N N
TsOH (20 mol%) HO Me
acetone-H2O (2mM), rt
i-Pr i-Pr
93%

K. Yoshinaga
L. Zhang et al., J. Am. Chem. Soc., 130, 6944 (2008)

4
O O O
SeO2 (2.2 eq.)
Me
N 1,4-dioxane, reflux N

75%

K. Kobayashi
C. M. Shafer and T. F. Molinski, J. Org. Chem., 61, 2044 (1996)
 Yokoshima Group - Group Meeting Problems
10/20/2018

1
MeO2C
CO2Me Ts EtO2C Ts
N microwave microwave N
O N O
PhCF3, 250 °C PhCF3, 200 °C
N
Me in sealed tube in sealed tube Me
EtO2C
99% 99%

C. Meyer and J. Cossy et al., Angew. Chem. Int. Ed., 53, 8705 (2014)

2
LDA (4.0 eq.)
THF, −78 °C to rt; O
O TMSCl (1.2 eq.) 0 °C to rt;
Ph
O NEt2 MeI (1.2 eq.) (scavenger for LDA)
PhCHO (1.3 eq.), rt OH
57%

R. J. Chein et al., Org. Lett., 20, 5362 (2018)

3
S O
hυ NMe
Et2N S NMe PhLi
hexane, reflux Ph2O, reflux O
THF, 0 °C;
NaOH aq., rt Ph
74%* 89%
66%
*mixture of two stereoisomers

R. S. Grainger et al., J. Org. Chem., 73, 8116 (2008)

4
3) TsCl, Et3N Ts
1) NaN3, NH4Cl 51% (3 steps) N
O
2) PPh3 4) BF3•OEt2
SO2Ph SO2Ph
76%

C. M. G. Löfström and J-E. Bäckvall, Tetrahedron Lett., 37, 3371 (1996)

 Yokoshima Group - Group Meeting Problems
10/27/2018
1 O OTf

EtO2C N2 O O
TMS PdCl2 COMe
O SnCl2 CsF CuCl, O2 O NBoc
N
Boc CH2Cl2, rt MeCN, reflux DMF/H2O O
rt
72% CO2Et
80%
70%

S. Chandrasekhar et al., Org. Lett., 18, 2044 (2016)

2
O O O
hν
TMS + B O B OTMS
O
MS4A
MeO CF3 hexane, rt
MeO CF3
quant.

H. Kusama et al., J. Am. Chem. Soc., 133, 3716 (2011)

Mes
N
3 N
Cl

Mes
O (0.15 eq.) O
Ph
Et3N (0.2 eq.)
CHO +
Ph
O THF, 66 °C O
O Ph
68%

V. Nair et al., Org. Lett., 16, 6374 (2014)

4 OMe
OMe
MeO
MeO (CH2OH)2
H
p-TsOH (cat.) NCO2Me
CO2Me
O NH toluene, reflux
O H
OMOM 77%
O

K. Ogasawara et al., Org. Lett., 4, 4515 (2002)

 Yokoshima Group - Group Meeting Problems
11/10/2018
1
O Br
SmI2 (2.5 eq.)
BnO t-BuLi NaH thiophenol

Et2O, −78 to 18 °C THF, reflux THF-HMPA, 0 °C

HO
89% 86% 74% BnO

M. G. Banwell et al., New J. Chem., 27, 50 (2003)

2 O CO2Me
O

Bu3SnH
H S AIBN
CO2Me
O N benzene, 80 °C
N
OH 92%
HO

M. T. Crimmins et al, J. Am. Chem. Soc., 120, 1747 (1998)

3
OAc
(C6F5)3PAuCl (10 mol%)
OAc AgSbF6 (10 mol%)
H
CH2Cl2, MS4A, rt
O Ph O H
78% H

H. N. C. Wong and X. S. Peng et al., Angew. Chem. Int. Ed., 57, 11365 (2018)

4
HO Me O HO Me
O2N Ru(bpy)3Cl2·6H2O (5 mol%)
i-Pr2NEt (10 eq.) N
H H
MeCN, 50 °C
H blue LED (λ=465-467.5 nm) H
O O O O
84%
Mechanistic studies suggested the hydroxyamine
was formed as the reaction intermediate.
B-.C. Hong et al., Org. Lett., 17, 2314 (2015)
 Yokoshima Group - Group Meeting Problems
11/17/2018
1
O TFA
CH2Cl2, 0 °C to rt; O
H
CHCl3, 40 °C;
H H
O NaBH(OAc)3
BocN CH2Cl2, rt N
H
72% HO
TBSO H H

M. D. Smith et al., Angew. Chem. Int. Ed., 53, 13826 (2014)

2 CO2Me
(HCHO)n (5 eq.), CO2Me (4 eq.)
toluene, 100 °C;
CO2H N
N
H Bu2SnCl2 (0.1 eq.), 100 °C

78% MeO2C

H. Ardill et al., Tetrahedron, 50, 5067 (1994)

3
HO
O O
1) Ni(COD)2, Mg(OTf)2 O
H
MeCN, rt
two diastereomers O
OH (dr = 2:1) 2) 3M HCl aq.
O
THF, rt
Br OTBS key structure 59% (2 steps)
•THF ring OH
•aldehyde

4
O hν A (ketone)
MeO OMe CH2=CH2 1) LiAlH4
+ THF, reflux Me
benzene 90% MeO
Me O B (tertiary alcohol) O
62% 2) BF3•OEt2
(A:B = 4.5:1) benzene, rt Me O H
85%
* Starting material is compound B.

S. K. Sabui and R. V. Venkateswaran, Tetrahedron Lett., 45, 983 (2004)

5
1) TsNClNa, cat. NBS Ts
MeCN, 20 ºC, 61% SnCl4 (2 eq.) N
O
pyrrolidine analogues
O OMe 2) Ph C20H21NO3S CH2Cl2, rt
MgBr MW : 355.45 Ph
Et2O, −30 ºC to rt

A. Armstrong et al., Org. Lett., 7, 1335 (2005)

 Yokoshima Group - Group Meeting Problems
11/24/2018
1
O 1) N2=C(COMe)PO(OMe)2 H O
K2CO3
MeOH, 0 °C to rt, 90%
OPh OPh +
2) (t-Bu)2P(o-biphenyl)AuCl O OPh
AgSbF6, i-PrOH OTBDPS
OTES OTBDPS CH2Cl2 OTBDPS

78% 6%

L. E. Overman et al., J. Am. Chem. Soc., 132, 7876 (2010)

2 Me
O
Cu(OAc)2, O2 Me
O
Me 2,2-bipyridine Me
H DABCO
Me H Me H
DMF, 40 °C
H H
90% O
O

V. V. Rheenen, Tetrahedron Lett., 10, 985 (1969)

H
3 H
CHO
Bn
N
1) LDA N
ClCH2SOPh H H H
H THF, –78 °C;
O KOH (aq), rt BrBa KH, 18-crown-6 A
Bn
N
N 2) LiClO4 THF, –78 °C dioxane, 100 °C H
H dioxane, reflux H
H CHO
87% (2 steps) 90% 85% Bn
N
N
Formula: Formula: H H H
C22H20N2O C27H30N2O
B
A:B = 4:1

J. M. Cook et al., Org. Lett., 3, 345 (2001)

4
Ph
CO
Pd(TFA)2 (5 mol%)
tetrafluoro-1,4-benzoquinone

• MeCN, 80 °C Ph

60%
O
J.-E. Bäckvall et al., J. Am. Chem. Soc., 138, 13846 (2016)
 Yokoshima Group - Group Meeting Problems
12/01/2018
1 1) LAH TBSO
THF, rt
NaH 93% CHO
O O toluene, 110 °C 2) DMP
PMBO CO2Et CH2Cl2, rt O
85% 92% PMBO
TBSO CO2Et

R. K. Boeckman, Jr. et al., Org. Lett., 4, 3891 (2002)

2
Ph A (20 mol%) Ph
AcO Cs2CO3 (1.2 eq.) CN
CN O TsN
+ O
toluene, rt Ph P
BnO2C
Ph BnO2C Ph
74%, 93% ee A

T. Nakamura
X. Tong et al, J. Am. Chem. Soc., 137, 6400 (2015)

3
Ph C6F5
TMS (2 eq.)
Li
TMS B B
pentane, −65 °C; pentane, rt, 24 h;1
C6F5
PhBCl2 IR: 2118
B(C6F5)3 (1 eq.) filtration; C6F5
1.4 eq.
rt, 10 min phenylacetylene, 60 °C
Ph TMS
66% 87%

G. Erker et al., Angew. Chem. Int. Ed., 57, 14570 (2018)

O
4 N
MOMO

(2 eq.) Li (1.7 eq.) O

Li
O HO
Br Br THF, –78 °C; THF, –78 °C;
N
Br O HCl, EtOH Br
Br O –78 to 0 °C
H (1.3 eq.)
75%
THF, reflux

71% M. A. Tius et al., Org. Lett., 4, 3363 (2002)

 Yokoshima Group - Group Meeting Problems
12/08/2018
1
1) BrMg
THF, reflux Rh(CO)2acac (0.5 mol%)
92% 6-DPPon (10 mol%)
O N PPh2
2) AlCl3, LiAlH4 CO/H2 (1:1, 30 bar) H
O THF toluene, 80 °C 6-DPPon
0 °C to reflux CHO
72% 56%
(E:Z = 1:9)
A. Köpfer and B. Breit et al., Angew. Chem. Int. Ed., 54, 6913 (2015)

2 1) KOt-Bu
DMF, 80 °C
OMIP 70% OMIP
O OMe 2) Ac2O, pyridine, rt
95% O OMe

O O 3) mCPBA OH
O CH2Cl2, 0 °C;
Et3N, 0 °C OAc
75%
MIP =
OMe
F. D' Andrea et al, Tetrahedron, 46, 5365 (1990)

3
Me (cat.)
Pd(OAc)2, P(2-furyl)3 Me
I Cs2CO3
+ Br Me
DMF, 90 °C
Me
86%
OH O

X. Luan et al., Org. Lett., 20, 7731 (2018)

4 O
1) mCPBA (3 eq.) ∗
K2CO3 (3 eq.) O
CH2Cl2, rt
70% N
O OH
N
Me 2) Zn
O THF-H2O, rt Me
O
H 62% (dr = 1:19) OH
∗ theoretically 2 equivalents
Y.-J. Li et al., Eur. J. Org. Chem., 1932 (2011)

5
Et [Pd(neoc)(OAc)]2(OTf)2 Et
H TiCl(OiPr)3, EtMgBr 1,4-benzoquinone, CO (1 atm) H
N O O N
O THF, 0 °C to rt 1,2-DCE, rt
O O
H 63% 60% (dr = 2.3 : 1) H

M. Dai et al., Angew. Chem. Int. Ed., 57, 15209 (2018)

 Yokoshima Group - Group Meeting Problems
12/22/2018
1
1) I
HO C6H13 , t-BuLi
Boc N ether, −78 °C
80% H
O * N
HO H O
2) DMP
CH2Cl2/TFA, 0 °C H
C6H13
58% (*dr = 10:1)
3) NaBH(OAc)3
AcOH/THF, rt
75%

G. Pandey and V. Janakiram, Chem. Eur. J., 21, 13120 (2015)

2
TfO

Pd(OAc)2 (1.0 mol%) aq. H2O2 OH

B(pin) Li ligand (1.2 mol%) aq. NaOH
D

Et2O THF, 60 °C THF, 0 °C to rt D H

0 °C to rt
Ph 57% (3 steps)
Ar2P Fe
NMe2 er = 82:18, dr > 20:1
ligand : Ph
PAr2
NMe2
Ar = 4-methoxy-3,5-dimethylphenyl J. P. Morken et al., Science, 351, 70 (2016)

3
OBn OBn
BnO OH
BnO OH aq. n-Bu4NOH
hν
TMS
toluene, 100 °C THF DMF, −20 °C BnO
BnO N
N3 80% (2 steps) 77% 49% H

R. Ducray and M. A. Ciufolini, Angew. Chem. Int. Ed., 41, 4688 (2003)

4
Ph Me Ph
Ph
O Ph HO
O
PhCl, 150 °C HO
O Me 63% CHO

S. Zhu et al., Angew. Chem. Int. Ed., 57, 8702 (2018)