Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1...
Transcript of Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1...
![Page 1: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/1.jpg)
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
![Page 2: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/2.jpg)
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.
![Page 3: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/3.jpg)
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
![Page 4: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/4.jpg)
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.
![Page 5: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/5.jpg)
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
![Page 6: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/6.jpg)
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.
![Page 7: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/7.jpg)
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
![Page 8: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/8.jpg)
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
![Page 9: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/9.jpg)
Overview: Advances in Cyclobutane Synthesis
• [2+2] photocycloadditions
• Lewis acid catalyzed [2+2] cycloadditions
• organocatalyzed [2+2] cycloadditions
• ring closures
![Page 10: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/10.jpg)
[2+2] Photocycloadditons: Mechanistic Considerations
S. Poplata, A. Tröster, Y.‐Q. Zou, T. Bach, Chem. Rev. 2016, 116, 9748‐9815.
![Page 11: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/11.jpg)
[2+2] Photocycloadditons: Mechanistic Considerations
S. Poplata, A. Tröster, Y.‐Q. Zou, T. Bach, Chem. Rev. 2016, 116, 9748‐9815.
![Page 12: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/12.jpg)
[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
![Page 13: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/13.jpg)
[2+2] Photocycloadditons: Mechanistic Considerations
S. Poplata, A. Tröster, Y.‐Q. Zou, T. Bach, Chem. Rev. 2016, 116, 9748‐9815.
![Page 14: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/14.jpg)
[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
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[2+2] Photocycloadditons: Enantioselective Variants
![Page 16: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/16.jpg)
[2+2] Photocycloadditons: Enantioselective Variants
R. Brimioulle, D. Lenhart, M. M. Maturi, T. Bach, Angew. Chem. Int. Ed. 2015, 54, 3872‐3890.
![Page 17: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/17.jpg)
C. Müller, A. Bauer, T. Bach, Angew. Chem. Int. Ed. 2009, 48, 6640‐6642.
[2+2] Photocycloadditons: Enantioselective Variants
![Page 18: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/18.jpg)
C. Müller, A. Bauer, T. Bach, Angew. Chem. Int. Ed. 2009, 48, 6640‐6642.
[2+2] Photocycloadditons: Enantioselective Variants
![Page 19: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/19.jpg)
C. Müller, A. Bauer, T. Bach, Angew. Chem. Int. Ed. 2009, 48, 6640‐6642.
[2+2] Photocycloadditons: Enantioselective Variants
![Page 20: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/20.jpg)
[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.
![Page 21: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/21.jpg)
[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.
![Page 22: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/22.jpg)
[2+2] Photocycloadditons: Enantioselective Variants
R. Alonso, T. Bach, Angew. Chem. Int. Ed. 2014, 53, 4368‐4371.
![Page 23: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/23.jpg)
[2+2] Photocycloadditons: Enantioselective Variants
R. Alonso, T. Bach, Angew. Chem. Int. Ed. 2014, 53, 4368‐4371.
![Page 24: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/24.jpg)
[2+2] Photocycloadditons: Enantioselective Variants
R. Alonso, T. Bach, Angew. Chem. Int. Ed. 2014, 53, 4368‐4371.
![Page 25: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/25.jpg)
[2+2] Photocycloadditons: Enantioselective Variants
![Page 26: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/26.jpg)
[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
![Page 27: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/27.jpg)
[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
![Page 28: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/28.jpg)
[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
![Page 29: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/29.jpg)
[2+2] Photocycloadditons: Enantioselective Variants
R. Brimioulle, H. Guo, T. Bach, Chem. Eur. J. 2012, 18, 7552‐7560.
![Page 30: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/30.jpg)
[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
![Page 31: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/31.jpg)
[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
![Page 32: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/32.jpg)
[2+2] Photocycloadditons: Enantioselective Variants
R. Brimioulle, T. Bach, Science 2013, 342, 840‐843.
N
O
O
M
![Page 33: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/33.jpg)
[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
![Page 34: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/34.jpg)
[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
![Page 35: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/35.jpg)
[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
![Page 36: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/36.jpg)
[2+2] Photocycloadditons: PET Catalysis
![Page 37: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/37.jpg)
[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
![Page 38: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/38.jpg)
[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
![Page 39: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/39.jpg)
[2+2] Photocycloadditons: PET Catalysis
M. A. Ischay, Z. Lu, T. P. Yoon, J. Am. Chem. Soc. 2010, 132, 8572‐8574.
![Page 40: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/40.jpg)
[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
![Page 41: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/41.jpg)
[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
![Page 42: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/42.jpg)
[2+2] Photocycloadditons: PET Catalysis
M. A. Ischay, M. E. Anzovino, J. Du, T. P. Yoon, J. Am. Chem. Soc. 2008, 130, 12886‐12887.
![Page 43: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/43.jpg)
[2+2] Photocycloadditons: PET Catalysis
M. A. Ischay, M. E. Anzovino, J. Du, T. P. Yoon, J. Am. Chem. Soc. 2008, 130, 12886‐12887.
![Page 44: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/44.jpg)
[2+2] Photocycloadditons: PET Catalysis
M. A. Ischay, M. E. Anzovino, J. Du, T. P. Yoon, J. Am. Chem. Soc. 2008, 130, 12886‐12887.
![Page 45: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/45.jpg)
[2+2] Photocycloadditons: PET Catalysis
J. Du, K. L. Skubi, D. M. Schultz, T. P. Yoon, Science 2014, 344, 392‐396.
![Page 46: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/46.jpg)
[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
![Page 47: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/47.jpg)
[2+2] Photocycloadditons: PET Catalysis
J. Du, K. L. Skubi, D. M. Schultz, T. P. Yoon, Science 2014, 344, 392‐396.
![Page 48: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/48.jpg)
[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
![Page 49: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/49.jpg)
[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
![Page 50: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/50.jpg)
[2+2] Cycloadditions: Lewis Acid Catalysis
![Page 51: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/51.jpg)
[2+2] Cycloadditions: Lewis Acid Catalysis
E. Canales, E. J. Corey, J. Am. Chem. Soc. 2007, 129, 12686‐12687.
![Page 52: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/52.jpg)
[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
![Page 53: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/53.jpg)
[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
![Page 54: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/54.jpg)
[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
![Page 55: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/55.jpg)
[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
![Page 56: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/56.jpg)
[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
![Page 57: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/57.jpg)
[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
![Page 58: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/58.jpg)
[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
![Page 59: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/59.jpg)
[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.
![Page 60: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/60.jpg)
[2+2] Cycloadditions: Lewis Acid Catalysis
M. L. Conner, Y. Xu, M. K. Brown, J. Am. Chem. Soc. 2015, 137, 3482‐3485.
![Page 61: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/61.jpg)
[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
![Page 62: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/62.jpg)
[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
![Page 63: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/63.jpg)
[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.
![Page 64: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/64.jpg)
[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.
![Page 65: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/65.jpg)
[2+2] Cycloadditions: Organocatalysis
![Page 66: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/66.jpg)
[2+2] Cycloadditions: Organocatalysis
K. Ishihara, K. Nakano, J. Am. Chem. Soc. 2007, 129, 8930‐8931
![Page 67: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/67.jpg)
[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
![Page 68: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/68.jpg)
[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.
![Page 69: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/69.jpg)
[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
![Page 70: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/70.jpg)
[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
![Page 71: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/71.jpg)
[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
![Page 72: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/72.jpg)
[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.
![Page 73: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/73.jpg)
[2+2] Cycloadditions: Organocatalysis
G. Talavera, E. Reyes, J. L. Vicario, L. Carrillo, Angew. Chem. Int. Ed. 2012, 51, 4104‐4107.
![Page 74: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/74.jpg)
[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
![Page 75: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/75.jpg)
[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.
![Page 76: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/76.jpg)
[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.
![Page 77: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/77.jpg)
Other [2+2] Cycloadditions
I. Colomer, R. Coura Barcelos, T. J. Donohoe, Angew. Chem. Int. Ed. 2016, 55, 4748‐4752.
![Page 78: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/78.jpg)
Other [2+2] Cycloadditions
I. Colomer, R. Coura Barcelos, T. J. Donohoe, Angew. Chem. Int. Ed. 2016, 55, 4748‐4752.
![Page 79: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/79.jpg)
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%
![Page 80: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/80.jpg)
Ring Closures
![Page 81: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/81.jpg)
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
![Page 82: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/82.jpg)
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.
![Page 83: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/83.jpg)
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
![Page 84: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/84.jpg)
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
![Page 85: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/85.jpg)
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
![Page 86: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/86.jpg)
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
![Page 87: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/87.jpg)
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
![Page 88: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/88.jpg)
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
![Page 89: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/89.jpg)
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
![Page 90: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/90.jpg)
Ring Expansions
![Page 91: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/91.jpg)
Ring Expansions
J. P. Markham, S. T. Staben, F. D. Toste, J. Am. Chem. Soc. 2005, 127, 9708‐9709.
![Page 92: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/92.jpg)
Ring Expansions
J. P. Markham, S. T. Staben, F. D. Toste, J. Am. Chem. Soc. 2005, 127, 9708‐9709.
![Page 93: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/93.jpg)
Ring Expansions
J. P. Markham, S. T. Staben, F. D. Toste, J. Am. Chem. Soc. 2005, 127, 9708‐9709.
![Page 94: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/94.jpg)
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
![Page 95: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/95.jpg)
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
![Page 96: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/96.jpg)
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
![Page 97: Modern Approaches to Cyclobutanes · R2 R1 R3 R4 R4 R1 R2 R3 ring expansion ring opening (X) n R1 R2 R3 R4 X = CH 2,O, NH N O H SiMe 3 O BF 3·OEt 2 CH 2Cl 2 N O O N O CH OMe 2N 2](https://reader033.fdocuments.us/reader033/viewer/2022042621/5f64d492607f8f2f0e03f29e/html5/thumbnails/97.jpg)
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.