Modern Approaches to Cyclobutanes
Ru(bipy)3+
Ru(bipy)32+
Ru(bipy)32+*
i-Pr2NEt
i-Pr2NEt+
h
Ph
O
R
LnEu
Ph
O
R
LnEu
Ph
O
REuLn
O
OO
Ph
S0
S1T1
ISC
T1
sensitizerE
h
R2 R1
R4R3
R4
R1
R2
R3
ring openingring expansion(X)n
R1
R2
R3 R4
X = CH2, O, NH
N
OH
SiMe3
O
BF3·OEt2
CH2Cl2N
O
O
N
OOMeCH2N2
THF
O
N
O
O
OMe
Cyclobutanes as Useful Synthetic Precursors
J. C. Namyslo, D. E. Kaufmann, Chem. Rev. 2003, 103, 1485‐1537.
R2 R1
R4R3
R4
R1
R2
R3
ring openingring expansion(X)n
R1
R2
R3 R4
X = CH2, O, NH
N
OH
SiMe3
O
BF3·OEt2
CH2Cl2N
O
O
N
OOMeCH2N2
THF
O
N
O
O
OMe
E. V. Anslyn, D. A. Dougherty, Modern Physical Organic Chemistry, University Science Books, Sausalito, 2006, pp. 100‐109.
Cyclobutanes as Useful Synthetic Precursors
Cyclobutanes as Useful Synthetic Precursors
R2 R1
R4R3
R4
R1
R2
R3
ring openingring expansion(X)n
R1
R2
R3 R4
X = CH2, O, NH
N
OH
SiMe3
O
BF3·OEt2
CH2Cl2N
O
O
N
OOMeCH2N2
THF
O
N
O
O
OMe
S. Faure, S. Piva‐Le Blanc, O. Piva, Tetrahedron Lett. 1999, 40, 6001‐6004.J. C. Namyslo, D. E. Kaufmann, Chem. Rev. 2003, 103, 1485‐1537.
R2 R1
R4R3
R4
R1
R2
R3
ring openingring expansion(X)n
R1
R2
R3 R4
X = CH2, O, NH
N
OH
SiMe3
O
BF3·OEt2
CH2Cl2N
O
O
N
OOMeCH2N2
THF
O
N
O
O
OMe
L. M. Reeder, L. S. Hegedus, J. Org. Chem. 1999, 64, 3306‐3311.J. C. Namyslo, D. E. Kaufmann, Chem. Rev. 2003, 103, 1485‐1537.
Cyclobutanes as Useful Synthetic Precursors
Cyclobutanes in Natural Products
O
OH H
H
O
Rhodonoid A
OH
H
H
O
HO
Wallichanol B
H
H
OHHO
O
HO
H
Tsugicoline M
HN
O OH
OH
OH
HH
H
H
OO
TripartilactamO CO2Me
H
H
Hippolachnin A
O
O
OMe
H
OO
H
Elysiapyrone A
O
O
O
OHO
HO
Katsumadain C
HO
OH
OH
Dendrowardol C
O
OH
O
GlcO
BzO
Paeoniflorin
CO2H7
HH H H
HHHH
Pentacycloanammoxic acid
Y.‐Y. Fan, X.‐H. Gao, J.‐M. Yue, Sci. China Chem. 2016, 59, 1126‐1141.
Cyclobutanes in Drug Discovery
E. M. Carreira, T. C. Fessard, Chem. Rev. 2014, 114, 8257‐8322.D. C. Blakemore et al., Bioorg. Med. Chem. 2010, 20, 461‐464.
• defined spatial arrangement
• rigid scaffold
• well-defined exit vectors
NH
N
O
MeO
MeO
MeO
MeO
H
H
NH2
CO2H
Lyrica analog
Procoralan
Cyclobutanes in Drug Discovery
E. M. Carreira, T. C. Fessard, Chem. Rev. 2014, 114, 8257‐8322.D. C. Blakemore et al., Bioorg. Med. Chem. 2010, 20, 461‐464.
• defined spatial arrangement
• rigid scaffold
• well-defined exit vectors
NH
N
O
MeO
MeO
MeO
MeO
H
H
NH2
CO2H
Lyrica analog
Procoralan
Overview: Advances in Cyclobutane Synthesis
• [2+2] photocycloadditions
• Lewis acid catalyzed [2+2] cycloadditions
• organocatalyzed [2+2] cycloadditions
• ring closures
[2+2] Photocycloadditons: Mechanistic Considerations
S. Poplata, A. Tröster, Y.‐Q. Zou, T. Bach, Chem. Rev. 2016, 116, 9748‐9815.
[2+2] Photocycloadditons: Mechanistic Considerations
S. Poplata, A. Tröster, Y.‐Q. Zou, T. Bach, Chem. Rev. 2016, 116, 9748‐9815.
[2+2] Photocycloadditons: Mechanistic Considerations
S. Poplata, A. Tröster, Y.‐Q. Zou, T. Bach, Chem. Rev. 2016, 116, 9748‐9815.
via first excited triplet state:h
*
S0 S1
ISC
with sensitizer:
S0
S1T1
ISC
T1
sensitizerE
h
T1
[2+2] Photocycloadditons: Mechanistic Considerations
S. Poplata, A. Tröster, Y.‐Q. Zou, T. Bach, Chem. Rev. 2016, 116, 9748‐9815.
[2+2] Photocycloadditons: Mechanistic Considerations
S. Poplata, A. Tröster, Y.‐Q. Zou, T. Bach, Chem. Rev. 2016, 116, 9748‐9815.
PET mechanism: catalyst catalyst * catalyst
+e
-eh
[2+2] Photocycloadditons: Enantioselective Variants
[2+2] Photocycloadditons: Enantioselective Variants
R. Brimioulle, D. Lenhart, M. M. Maturi, T. Bach, Angew. Chem. Int. Ed. 2015, 54, 3872‐3890.
C. Müller, A. Bauer, T. Bach, Angew. Chem. Int. Ed. 2009, 48, 6640‐6642.
[2+2] Photocycloadditons: Enantioselective Variants
C. Müller, A. Bauer, T. Bach, Angew. Chem. Int. Ed. 2009, 48, 6640‐6642.
[2+2] Photocycloadditons: Enantioselective Variants
C. Müller, A. Bauer, T. Bach, Angew. Chem. Int. Ed. 2009, 48, 6640‐6642.
[2+2] Photocycloadditons: Enantioselective Variants
[2+2] Photocycloadditons: Enantioselective Variants
M. M. Maturi, M. Wenninger, R. Alonso, A. Bauer, A. Pöthig, E. Riedle, T. Bach, Chem. Eur. J. 2013, 19, 7461‐7472.
[2+2] Photocycloadditons: Enantioselective Variants
M. M. Maturi, M. Wenninger, R. Alonso, A. Bauer, A. Pöthig, E. Riedle, T. Bach, Chem. Eur. J. 2013, 19, 7461‐7472.
[2+2] Photocycloadditons: Enantioselective Variants
R. Alonso, T. Bach, Angew. Chem. Int. Ed. 2014, 53, 4368‐4371.
[2+2] Photocycloadditons: Enantioselective Variants
R. Alonso, T. Bach, Angew. Chem. Int. Ed. 2014, 53, 4368‐4371.
[2+2] Photocycloadditons: Enantioselective Variants
R. Alonso, T. Bach, Angew. Chem. Int. Ed. 2014, 53, 4368‐4371.
[2+2] Photocycloadditons: Enantioselective Variants
[2+2] Photocycloadditons: Enantioselective Variants
R. Brimioulle, H. Guo, T. Bach, Chem. Eur. J. 2012, 18, 7552‐7560.
O O
C (50 mol%)h ( = 366 nm)
CH2Cl2–75 °C, 5 h O O
H
84% yield82% ee
WITHOUT SENSITIZER
NB
OBr3Al
XylXylH
CF3
C
[2+2] Photocycloadditons: Enantioselective Variants
R. Brimioulle, H. Guo, T. Bach, Chem. Eur. J. 2012, 18, 7552‐7560.
O O
C (50 mol%)h ( = 366 nm)
CH2Cl2–75 °C, 5 h O O
H
84% yield82% ee
WITHOUT SENSITIZER
NB
OBr3Al
XylXylH
CF3
C
[2+2] Photocycloadditons: Enantioselective Variants
R. Brimioulle, H. Guo, T. Bach, Chem. Eur. J. 2012, 18, 7552‐7560.
O O
C (50 mol%)h ( = 366 nm)
CH2Cl2–75 °C, 5 h O O
H
84% yield82% ee
WITHOUT SENSITIZER
NB
OBr3Al
XylXylH
CF3
C
[2+2] Photocycloadditons: Enantioselective Variants
R. Brimioulle, H. Guo, T. Bach, Chem. Eur. J. 2012, 18, 7552‐7560.
[2+2] Photocycloadditons: Enantioselective Variants
R. Brimioulle, H. Guo, T. Bach, Chem. Eur. J. 2012, 18, 7552‐7560.
O O
C (50 mol%)h ( = 366 nm)
CH2Cl2–75 °C, 5 h O O
H
84% yield82% ee
WITHOUT SENSITIZER
NB
OBr3Al
XylXylH
CF3
C
[2+2] Photocycloadditons: Enantioselective Variants
R. Brimioulle, T. Bach, Science 2013, 342, 840‐843.
C (50 mol%)h ( = 366 nm)
CH2Cl2–70 °C, 5 h
84% yield88% ee
WITHOUT SENSITIZER
NB
OBr3Al
XylXylH
CF3
C
N
O
O
N
H
HH
O
O
[2+2] Photocycloadditons: Enantioselective Variants
R. Brimioulle, T. Bach, Science 2013, 342, 840‐843.
N
O
O
M
[2+2] Photocycloadditons: Enantioselective Variants
N. Vallavoju, S. Selvakumar, S. Jockusch, M. P. Sibi, J. Sivaguru, Angew. Chem. Int. Ed. 2014, 53, 5604‐5608.
O O
D (10 mol%)h ( = 350 nm)
PhMe/xylene–78 °C, 2 h O O
H
77% yield92% ee
NH
S
NH
F
F
F
FOH
F3C
F3CD
WITHOUT SENSITIZER
[2+2] Photocycloadditons: Enantioselective Variants
N. Vallavoju, S. Selvakumar, S. Jockusch, M. P. Sibi, J. Sivaguru, Angew. Chem. Int. Ed. 2014, 53, 5604‐5608.
O O
D (10 mol%)h ( = 350 nm)
PhMe/xylene–78 °C, 2 h O O
H
77% yield92% ee
NH
S
NH
F
F
F
FOH
F3C
F3CD
WITHOUT SENSITIZER
[2+2] Photocycloadditons: Enantioselective Variants
N. Vallavoju, S. Selvakumar, S. Jockusch, M. P. Sibi, J. Sivaguru, Angew. Chem. Int. Ed. 2014, 53, 5604‐5608.
O O
D (10 mol%)h ( = 350 nm)
PhMe/xylene–78 °C, 2 h O O
H
77% yield92% ee
NH
S
NH
F
F
F
FOH
F3C
F3CD
WITHOUT SENSITIZER
F3C
O
H
N
S
N
H H
F3C
O
O
F
F
F
F
[2+2] Photocycloadditons: PET Catalysis
[2+2] Photocycloadditons: PET Catalysis
M. A. Ischay, Z. Lu, T. P. Yoon, J. Am. Chem. Soc. 2010, 132, 8572‐8574.
O
E (5 mol%)MV(PF6)2 (15 mol%)h ( = 400–700 nm)
MgSO4
MeNO2RT, 3.5 h
O
Ph
HH
MeOMeO
Ph
89% yieldd.r. > 10:1
Ru
N
N
N
NN
N
2
2 PF6
E
[2+2] Photocycloadditons: PET Catalysis
M. A. Ischay, Z. Lu, T. P. Yoon, J. Am. Chem. Soc. 2010, 132, 8572‐8574.
O
Ru(bpy)3(PF6)2 (5 mol%)MV(PF6)2 (15 mol%)h ( = 400–700 nm)
MgSO4
MeNO2RT, 3.5 h
O
Ph
HH
MeOMeO
Ph
89% yieldd.r. > 10:1
[2+2] Photocycloadditons: PET Catalysis
M. A. Ischay, Z. Lu, T. P. Yoon, J. Am. Chem. Soc. 2010, 132, 8572‐8574.
[2+2] Photocycloadditons: PET Catalysis
M. A. Ischay, Z. Lu, T. P. Yoon, J. Am. Chem. Soc. 2010, 132, 8572‐8574.
O
Ru(bpy)3(PF6)2 (5 mol%)MV(PF6)2 (15 mol%)h ( = 400–700 nm)
MgSO4
MeNO2RT, 3.5 h
O
Ph
HH
MeOMeO
Ph
89% yieldd.r. > 10:1
[2+2] Photocycloadditons: PET Catalysis
M. A. Ischay, M. E. Anzovino, J. Du, T. P. Yoon, J. Am. Chem. Soc. 2008, 130, 12886‐12887.
O
Ph
O
Ph
F (5 mol%)h ( = 400–700 nm)
LiBF2, i-Pr2NEt
MeCNRT, 50 min
89% yieldd.r. > 10:1
OO
PhPhHH
Ru
N
N
N
NN
N
2
2 Cl
F
[2+2] Photocycloadditons: PET Catalysis
M. A. Ischay, M. E. Anzovino, J. Du, T. P. Yoon, J. Am. Chem. Soc. 2008, 130, 12886‐12887.
[2+2] Photocycloadditons: PET Catalysis
M. A. Ischay, M. E. Anzovino, J. Du, T. P. Yoon, J. Am. Chem. Soc. 2008, 130, 12886‐12887.
[2+2] Photocycloadditons: PET Catalysis
M. A. Ischay, M. E. Anzovino, J. Du, T. P. Yoon, J. Am. Chem. Soc. 2008, 130, 12886‐12887.
[2+2] Photocycloadditons: PET Catalysis
J. Du, K. L. Skubi, D. M. Schultz, T. P. Yoon, Science 2014, 344, 392‐396.
[2+2] Photocycloadditons: PET Catalysis
J. Du, K. L. Skubi, D. M. Schultz, T. P. Yoon, Science 2014, 344, 392‐396.
Ru(bipy)3+
Ru(bipy)32+
Ru(bipy)32+*
i-Pr2NEt
i-Pr2NEt+
h
Ph
O
R
LnEu
Ph
O
R
LnEu
Ph
O
REuLn
O
OO
Ph
DUAL CATALYSIS
–e
[2+2] Photocycloadditons: PET Catalysis
J. Du, K. L. Skubi, D. M. Schultz, T. P. Yoon, Science 2014, 344, 392‐396.
[2+2] Photocycloadditons: PET Catalysis
M. Riener, D. A. Nicewicz, Chem. Sci. 2013, 4, 2625‐2629.
H (3 mol%)anthracene (50 mol%)
h ( = 450 nm)
MeCN, RT, 24 h
54% yield
MeO
2
MeO OMe
O
PMP
PMPPh
BF4-
H
[2+2] Photocycloadditons: PET Catalysis
M. Riener, D. A. Nicewicz, Chem. Sci. 2013, 4, 2625‐2629.
h
ORGANIC ELECTRON RELAY SYSTEM
O
PMP
PMPPh
O
PMP
PMPPh
O
PMP
PMPPh
anthracene
anthracene
+
+Ar
R
ArR product
*
–e +e
[2+2] Cycloadditions: Lewis Acid Catalysis
[2+2] Cycloadditions: Lewis Acid Catalysis
E. Canales, E. J. Corey, J. Am. Chem. Soc. 2007, 129, 12686‐12687.
[2+2] Cycloadditions: Lewis Acid Catalysis
E. Canales, E. J. Corey, J. Am. Chem. Soc. 2007, 129, 12686‐12687.
A (10 mol%)
CH2Cl2–78 °C, 3 h
87% yield99% ee
NB
OBr3Al
PhPhH
A
OO
OCH2CF3+
O
O
OCH2CF3H
H
[2+2] Cycloadditions: Lewis Acid Catalysis
E. Canales, E. J. Corey, J. Am. Chem. Soc. 2007, 129, 12686‐12687.
A (10 mol%)
CH2Cl2–78 °C, 12 h
97% yieldd.r. = 97:3
92% ee
O
OCH2CF3+
O
OCH2CF3TIPSO
H
OTIPS
[2+2] Cycloadditions: Lewis Acid Catalysis
M. R. Luzung, P. Mauleón, F. D. Toste, J. Am. Chem. Soc. 2007, 129, 12402‐12403.
C
Ph
MeO2C
MeO2C
B (3 mol%)AgBF4 (6 mol%)
CH2Cl2, RT
MeO2C
MeO2CPh
H
H
O
O
O
O
Ar2P AuCl
AuClPAr2
B
92% yield95% ee
[2+2] Cycloadditions: Lewis Acid Catalysis
M. R. Luzung, P. Mauleón, F. D. Toste, J. Am. Chem. Soc. 2007, 129, 12402‐12403.
C
Ph
MeO2C
MeO2C
B (3 mol%)AgBF4 (6 mol%)
CH2Cl2, RT
MeO2C
MeO2CPh
H
H
O
O
O
O
Ar2P AuCl
AuClPAr2
B
92% yield95% ee
LAu+
C
Ph
MeO2C
MeO2C
C
Ph
MeO2C
MeO2C
LAu+
MeO2C
MeO2CPh
HH
AuL
MeO2C
MeO2CPh
H
H
[2+2] Cycloadditions: Lewis Acid Catalysis
H. Teller, S. Flügge, R. Goddard, A. Fürstner, Angew. Chem. Int. Ed. 2010, 49, 1949‐1953.
C
Ph
MeO2C
MeO2C
C (5.5 mol%)AgBF4 (5 mol%)
CH2Cl2, 0 °C
MeO2C
MeO2CPh
H
H
91% yield99% ee
O
O
ArAr
Ar Ar
MeO
MeO
P
Au
Cl
N
Ph
Ph
C
TsN
C
Ph
D (5 mol%)AgBF4 (5 mol%)
CH2Cl2, RT24 h
TsN
Ph
H
H
86% yield94% ee
O
OP
Au
Cl
N
Ph
Ph
D
[2+2] Cycloadditions: Lewis Acid Catalysis
H. Teller, S. Flügge, R. Goddard, A. Fürstner, Angew. Chem. Int. Ed. 2010, 49, 1949‐1953.A. Z. González, D. Benitez , E. Tkatchouk, W. A. Goddard, III, F. D. Toste, J. Am. Chem. Soc. 2011, 133, 5500‐5507.
C
Ph
MeO2C
MeO2C
C (5.5 mol%)AgBF4 (5 mol%)
CH2Cl2, 0 °C
MeO2C
MeO2CPh
H
H
91% yield99% ee
O
O
ArAr
Ar Ar
MeO
MeO
P
Au
Cl
N
Ph
Ph
C
TsN
C
Ph
D (5 mol%)AgBF4 (5 mol%)
CH2Cl2, RT24 h
TsN
Ph
H
H
86% yield94% ee
O
OP
Au
Cl
N
Ph
Ph
D
[2+2] Cycloadditions: Lewis Acid Catalysis
S. Suárez‐Pantiga, C. Hernández‐Díaz, E. Rubio, J. M. González, Angew. Chem. Int. Ed. 2012, 51, 11552‐11555.M. Jia, M. Monari, Q.‐Q. Yang, M. Bandini, Chem. Commun. 2015, 51, 2320‐2323.
C
N
Ts
Ph +
LAuCl (5 mol%)AgNTf2 (4.5 mol%)
CH2Cl2, –70 °C2 h
NTsPh
86% yield92% ee
NBoc
+
C
N
OO
LAuCl (2.5 mol%)AgOTf (5 mol%)
CH2Cl2, –60 °C16 h
NBoc
N
O
O
95% yield93% ee
[2+2] Cycloadditions: Lewis Acid Catalysis
S. Suárez‐Pantiga, C. Hernández‐Díaz, E. Rubio, J. M. González, Angew. Chem. Int. Ed. 2012, 51, 11552‐11555.M. Jia, M. Monari, Q.‐Q. Yang, M. Bandini, Chem. Commun. 2015, 51, 2320‐2323.
[2+2] Cycloadditions: Lewis Acid Catalysis
M. L. Conner, Y. Xu, M. K. Brown, J. Am. Chem. Soc. 2015, 137, 3482‐3485.
[2+2] Cycloadditions: Lewis Acid Catalysis
M. L. Conner, Y. Xu, M. K. Brown, J. Am. Chem. Soc. 2015, 137, 3482‐3485.
n-Pr
+C
CO2CH2CF3 E (20 mol%)
CH2Cl2, RT16 h n-Pr
CO2CH2CF3
42% yieldd.r. > 20:1
86% ee
n-Pr n-Pr
+C
CO2CH2CF3 E (20 mol%)
CH2Cl2, RT16 h n-Pr
CO2CH2CF3
41% yieldd.r. > 20:1
84% ee
n-Pr n-Pr
n-Pr
[2+2] Cycloadditions: Lewis Acid Catalysis
M. L. Conner, Y. Xu, M. K. Brown, J. Am. Chem. Soc. 2015, 137, 3482‐3485.
SiMe3
+C
CO2Bn E (20 mol%)
CH2Cl2, RT16 h
CO2Bn
Me3Si
85% yield86% ee
NB
OH
PhPhH
E
CF3
Cl
NTf2
[2+2] Cycloadditions: Lewis Acid Catalysis
C. M. Rasik, M. K. Brown, J. Am. Chem. Soc. 2013, 135, 1673‐1676.E. M. Rigsbee, C. Zhou, C. M. Rasik, A. Z. Spitz, J. J. Nichols, M. K. Brown, Org. Biomol. Chem. 2016, 14, 5477‐5480.
[2+2] Cycloadditions: Lewis Acid Catalysis
J.‐L. Hu, L.‐W. Feng, L. Wang, Z. Xie, Y. Tang, X. Li, J. Am. Chem. Soc. 2016, 138, 13151‐13154.
[2+2] Cycloadditions: Organocatalysis
[2+2] Cycloadditions: Organocatalysis
K. Ishihara, K. Nakano, J. Am. Chem. Soc. 2007, 129, 8930‐8931
[2+2] Cycloadditions: Organocatalysis
K. Ishihara, K. Nakano, J. Am. Chem. Soc. 2007, 129, 8930‐8931
i-Pr+
BzO CHO A (10 mol%)
EtNO2, –20 °C48 h
CHOOBz
i-Pr
NH
i-BuN
Bn NH2
·2.6 Tf2NH
A
64% yieldd.r. = 92:8
85% ee
[2+2] Cycloadditions: Organocatalysis
G.‐J. Duan, J.‐B. Ling, W.‐P. Wang, Y.‐C. Luo, P.‐F. Xu, Chem. Commun. 2013, 49, 4625‐4627.
[2+2] Cycloadditions: Organocatalysis
G.‐J. Duan, J.‐B. Ling, W.‐P. Wang, Y.‐C. Luo, P.‐F. Xu, Chem. Commun. 2013, 49, 4625‐4627.
N
Ph
Ph
OTMSPh NR
NR
Ph
N
PhTMSO Ph
PhH
NPh
TMSO Ph
NR
NH
Ph
OTMSPh
H2O
Ph
NR
H
O
Ph
CHO
H2O
[2+2] Cycloadditions: Organocatalysis
L. Albrecht, G. Dickmeiss, F. Cruz Acosta, C. Rodríguez‐Escrich, R. L. Davis, K. A. Jørgensen, J. Am. Chem. Soc. 2012, 134, 2543‐2546.
O
+NO2
Ph
C (20 mol%)N,N-diethyacetamide
H2O, CH2Cl2, RT, 24 h
NO2
Ph Ph
OHC
86% yield99% ee
NH
NH
NH
CF3
CF3
O O
C
Ph
[2+2] Cycloadditions: Organocatalysis
L. Albrecht, G. Dickmeiss, F. Cruz Acosta, C. Rodríguez‐Escrich, R. L. Davis, K. A. Jørgensen, J. Am. Chem. Soc. 2012, 134, 2543‐2546.
NN
NO
O
O
OHN
Ar
H
[2+2] Cycloadditions: Organocatalysis
L. Albrecht, G. Dickmeiss, F. Cruz Acosta, C. Rodríguez‐Escrich, R. L. Davis, K. A. Jørgensen, J. Am. Chem. Soc. 2012, 134, 2543‐2546.
[2+2] Cycloadditions: Organocatalysis
G. Talavera, E. Reyes, J. L. Vicario, L. Carrillo, Angew. Chem. Int. Ed. 2012, 51, 4104‐4107.
[2+2] Cycloadditions: Organocatalysis
G. Talavera, E. Reyes, J. L. Vicario, L. Carrillo, Angew. Chem. Int. Ed. 2012, 51, 4104‐4107.
O
+NO2
Ph
B (20 mol%)D (20 mol%)
PhMe, –20 °C, 72 h
Ph
Ph
86% yield91% ee
Ph
OH
OO2N
HOH
NH
Ph
OTMSPh
B NH
S
NH
CF3
F3C
CF3
CF3
D
[2+2] Cycloadditions: Organocatalysis
K. S. Halskov, F. Kniep, V. H. Lauridsen, E. H. Iversen, B. S. Donslund, K. A. Jørgensen, J. Am. Chem. Soc. 2015, 137, 1685‐1691.
[2+2] Cycloadditions: Organocatalysis
K. S. Halskov, F. Kniep, V. H. Lauridsen, E. H. Iversen, B. S. Donslund, K. A. Jørgensen, J. Am. Chem. Soc. 2015, 137, 1685‐1691.
Other [2+2] Cycloadditions
I. Colomer, R. Coura Barcelos, T. J. Donohoe, Angew. Chem. Int. Ed. 2016, 55, 4748‐4752.
Other [2+2] Cycloadditions
I. Colomer, R. Coura Barcelos, T. J. Donohoe, Angew. Chem. Int. Ed. 2016, 55, 4748‐4752.
Other [2+2] Cycloadditions
I. Colomer, R. Coura Barcelos, T. J. Donohoe, Angew. Chem. Int. Ed. 2016, 55, 4748‐4752.
MeO75%
OAc MeO70%
Br
MeO73%
CO2H MeO60%
Ring Closures
Ring Closures
M. Chaumontet, R. Piccardi, N. Audic, J. Itce, J.‐L. Peglion, E. Clot, O. Baudoin, J. Am. Chem. Soc. 2008, 130, 15157‐15166.
CO2Me
Br
CO2Me
78% yield
Pd(OAc)2 (10 mol%)(t-Bu3PH)BF4 (20 mol%
K2CO3, DMF140 °C, 1 h
Ring Closures
M. Chaumontet, R. Piccardi, N. Audic, J. Itce, J.‐L. Peglion, E. Clot, O. Baudoin, J. Am. Chem. Soc. 2008, 130, 15157‐15166.
Pd0
CO2Me
Br
CO2Me
PdII
Br L
CO2Me
PdII
O L
CO32-
Br-
O-O
H
PdIIL
OOH
-O
CO2Me
CO2Me
ox. ad.
ligandexchange
protonabstraction
red. elim.
Ring Closures
M. Chaumontet, R. Piccardi, N. Audic, J. Itce, J.‐L. Peglion, E. Clot, O. Baudoin, J. Am. Chem. Soc. 2008, 130, 15157‐15166.
CO2Me
Br
CO2Me
78% yield
Pd(OAc)2 (10 mol%)(t-Bu3PH)BF4 (20 mol%
K2CO3, DMF140 °C, 1 h
Ring Closures
H. Ito, T. Toyoda, M. Sawamura, J. Am. Chem. Soc. 2010, 132, 5990‐5992.
PhMe2SiOMs
CuCl (5 mol%), dppp (5 mol%)B2pin2, KOt-Bu
THF, RT, 20 h
PhMe2Si Bpin
93% yieldd.r. > 99:1
SiX "Cu–B"
Cu
Si
B
X
Cu
X
Si B
–CuX
Si B
Ring Closures
H. Ito, T. Toyoda, M. Sawamura, J. Am. Chem. Soc. 2010, 132, 5990‐5992.
PhMe2SiOMs
CuCl (5 mol%), dppp (5 mol%)B2pin2, KOt-Bu
THF, RT, 20 h
PhMe2Si Bpin
93% yieldd.r. > 99:1
SiX "Cu–B"
Cu
Si
B
X
Cu
X
Si B
–CuX
Si B
Ring Closures
H. Ito, T. Toyoda, M. Sawamura, J. Am. Chem. Soc. 2010, 132, 5990‐5992.
CuCl (5 mol%), dppp (5 mol%)B2pin2, KOt-Bu
THF, RT, 20 h
PhMe2Si Bpin
76% yieldd.r. = 95:5
PhMe2SiOMs
Me3SiOMs
CuCl (5 mol%), dppp (5 mol%)B2pin2, KOt-Bu
THF, RT, 20 h
Me3Si Bpin
74% yieldd.r. = 99:1
OMs
Bpin
CuCl (5 mol%), dppp (5 mol%)B2pin2, KOt-Bu
THF, RT, 20 h
89% yieldd.r. = 95:5
Ring Closures
Y.‐M. Wang, N. C. Bruno, Á. L. Placeres, S. Zhu, S. L. Buchwald, J. Am. Chem. Soc. 2015, 137, 10524‐10527.
Ph
Br
Cu(OAc)2 (5 mol%)A (5.5 mol%)
LiOMe, (EtO)2MeSiHTHF, 50 °C, 36 h
Ph
O
O
O
O
PAr2
PAr2
A
83% yield99% ee
Ring Closures
Y.‐M. Wang, N. C. Bruno, Á. L. Placeres, S. Zhu, S. L. Buchwald, J. Am. Chem. Soc. 2015, 137, 10524‐10527.
LCuH
Ar
Br
ArX
H CuL
H
LCuXAr
H
LiOMe
LiBr
LCuOMe
HSiR3
MeOSiR3
syn-hydrocupration
Ring Closures
Y.‐M. Wang, N. C. Bruno, Á. L. Placeres, S. Zhu, S. L. Buchwald, J. Am. Chem. Soc. 2015, 137, 10524‐10527.
Ph
Br
Cu(OAc)2 (5 mol%)A (5.5 mol%)
LiOMe, (EtO)2MeSiHTHF, 50 °C, 36 h
Ph
O
O
O
O
PAr2
PAr2
A
83% yield99% ee
Ph
87% yield99% ee
MeO
47% yield97% ee
OMe
MeO
MeO2C
59% yield98% ee
F
79% yield99% ee
S
Ring Expansions
Ring Expansions
J. P. Markham, S. T. Staben, F. D. Toste, J. Am. Chem. Soc. 2005, 127, 9708‐9709.
Ring Expansions
J. P. Markham, S. T. Staben, F. D. Toste, J. Am. Chem. Soc. 2005, 127, 9708‐9709.
Ring Expansions
J. P. Markham, S. T. Staben, F. D. Toste, J. Am. Chem. Soc. 2005, 127, 9708‐9709.
Ring Expansions
F. Kleinbeck, F. D. Toste, J. Am. Chem. Soc. 2009, 131, 9178‐9179.
OH
Ph
C
O
Ph
A (2.5 mol%)NaBARF (5 mol%)
DCE, –30 °C, 24 h
76% yield91% ee
MeO
MeO
P
P
AuCl
AuCl
(xyl)2
(xyl)2
A
O
Cy
O
n-hex
O
OBz
O
NPhth
O
Ph
O
CO2Me
85% yield86% ee
89% yield92% ee
99% yield92% ee
97% yield93% ee
95% yield85% ee
99% yield84% ee
Ring Expansions
F. Kleinbeck, F. D. Toste, J. Am. Chem. Soc. 2009, 131, 9178‐9179.
OH
Ph
C
O
Ph
A (2.5 mol%)NaBARF (5 mol%)
DCE, –30 °C, 24 h
76% yield91% ee
MeO
MeO
P
P
AuCl
AuCl
(xyl)2
(xyl)2
A
O
Cy
O
n-hex
O
OBz
O
NPhth
O
Ph
O
CO2Me
85% yield86% ee
89% yield92% ee
99% yield92% ee
97% yield93% ee
95% yield85% ee
99% yield84% ee
Ring Expansions
F. Kleinbeck, F. D. Toste, J. Am. Chem. Soc. 2009, 131, 9178‐9179.
OH
Ph
C
O
Ph
A (2.5 mol%)NaBARF (5 mol%)
DCE, –30 °C, 24 h
76% yield91% ee
MeO
MeO
P
P
AuCl
AuCl
(xyl)2
(xyl)2
A
O
Cy
O
n-hex
O
OBz
O
NPhth
O
Ph
O
CO2Me
85% yield86% ee
89% yield92% ee
99% yield92% ee
97% yield93% ee
95% yield85% ee
99% yield84% ee
Another Approach
R. Panish, S. R. Chintala, D. T. Boruta, Y. Fang, M. T. Taylor, J. M. Fox, J. Am. Chem. Soc. 2013, 135, 9283‐9286.