Radical reactions. Decarboxylative alkenylations and alkynylations

1. Radical reactions. Decarboxylative alkenylations and alkynylations

Dr. Vadim Korotkov, St.-Petersburg, 03.01.2020

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Methods of C–C – Bond Formation
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Reactions of nucleophiles with electrophiles
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Pericyclic reactions
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Radical reactions
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Other reactions (metathesis)

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Radical Reactions
The best results if A = B
Also possible if only one radical
Minisci reaction
There is a selectivity problem (innate selectivity, dictated by radical acceptor)
M. A. J. Duncton, Med. Chem. Commun., 2011, 2, 1135-1161

4.

Radical Reactions
Giese Reaction
N. P. Ramirez,J. C. Gonzalez-Gomez, Eur. J. Org. Chem. 2017, 2154–2163
I. Ryu, S. Uehara, H. Hirao, T. Fukuyama, Org. Lett., 2008, 10, 1005-1008.
Barton Decarboxylation
K. Okada, K. Okamoto, M. Oda, J. Am. Chem. Soc., 1988, 110 (26), pp 8736–8738

5.

Radical Reactions
Modification of Giese reaction
T. Qin, L. R. Malins, J. T. Edwards, R. R. Merchant, A. J. E. Novak, J. Z. Zhong, R. B. Mills, M. Yan, C. Yuan, M. D. Eastgate, and P. S. Baran, Angew.
Chem. Int. Ed. 2017, 56, 260 –265

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7.

Radical Reactions
Is there an alternative for innate radical cross couplings (RCC)?
Programmed radical cross-coupling (RCC)!
The radical binds to a metal ion and then selectively (!!!) reacts with the determined partner

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Radical Reactions
Key steps of RCC
J. M. Smith, S. J. Harwood, P. S. Baran, Acc. Chem. Res. 2018, 51, 1807-1817.

9.

Decarboxylative Alkenylations
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Primary, secondary and tertiary acids can be used
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Usual as well as α, β – unsaturated alkenylzinc reagents can be used
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Many functional groups are tolerated
J. T. Edwards, R. R. Merchant, K. S. McClymont, K. W. Knouse, T. Qin, L. R. Malins, B. Vokits, S. A. Shaw, D.-H.Bao, F.-L. Wei, T. Zhou, M. D.
Eastgate, P. S. Baran, Nature, 545, 213–218
X.-G. Liu, C.-J. Zhou, E. Lin, X.-L. Han, S.-S. Zhang, Q. Li, H. Wang, , Angew. Chem. Int. Ed. 2018, 57, 13096-13100

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Decarboxylative Alkenylations (Another possibility)
H. Chen, S. Sun, X. Liao, Org. Lett. 2019, 21, 3625−3630

12.

Decarboxylative (Hetero)Arylations
Also ArB(OH)2 can be used (sometimes) instead of ArZnCl!
F. Sandfort, M. J. O’Neill, J.Cornella, L. Wimmer, P. S. Baran, Angew. Chem. Int. Ed. 2017, 56, 3319 –3323
T.-G. Chen, H. Zhang, P. K. Mykhailiuk, R. R. Merchant, C. A. Smith, T. Qin, P. S. Baran, 2Angew. Chem. Int. Ed. 2019, 58, 2454 –2458
X.-G. Liu, C.-J. Zhou, E. Lin, X.-L. Han, S.-S. Zhang, Q. Li, H. Wang, , Angew. Chem. Int. Ed. 2018, 57, 13096-13100

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Another Possibility of (Hetero)Arylations
Synthesis of the sulfones is very simple
Particiularly interesting for the synthesis of fluorinated compounds
Merchant, R. R.; Edwards, J. T.; Qin, T.; Kruszyk, M. M.; Bi, C.; Che, G.; Bao D-H.; Qiao, W.; Sun, L.; Collins, M. R.; Gallego, G. M.; Mousseau, J. J.; Nuhant, P.; Baran, P. S., Science,
2018, 360, 75-80.

15.

Decarboxylative Alkynylations
Summary:
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two variants of decarboxylative alkynylation (Ni and Fe): one for
monosubstituted alkynes (Ni), one for disubstituted alkynes (Fe)
terminal alkynes can be synthesized using BOTH variants
nearly all functional groups in acids are tolerated
very mild conditions
there are some limitations
Smith, J. M.; Qin, T.; Merchant, R. R.; Edwards, J. T.; Malins, L. R.; Liu, Z.; Che, G.; Shen, Z.; Shaw, S. A.; Eastgate, M. D.; Baran, P. S., Angew. Chem. Int. Ed. 2017, 56, 11906-11910

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Sequences of Radical Reactions. The Real Power of This Approach
1.
Giese Reaction and Desulfonylative Coupling
Merchant, R. R.; Edwards, J. T.; Qin, T.; Kruszyk, M. M.; Bi, C.; Che, G.; Bao D-H.; Qiao, W.; Sun, L.; Collins, M. R.; Gallego, G. M.; Mousseau, J. J.; Nuhant, P.;
Baran, P. S., Science, 2018, 360, 75-80.
2. Cycloaddition and Cross-Coupling Reaction
It can even happen that alternative cycloaddition reaction doesn’t work due to electronic factors!
Chen, T. –G.; Barton, L. M.; Lin, Y.; Tsien, J.; Kossler, D.; Bastida, I.; Asai, S.; Bi, C.; Chen, J. S.; Shan, M.; Fang, H.; Fang, F. G.; Choi, H. –W.; Hawkins, L.; Qin, T.;
Baran, P. S., Nature, 2018, 560, 350-354

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Synthesis of Amino Acids
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Sulfinimines are chiral. They can be used as chiral auxiliaries
Products are enantiomerically pure
The reaction works also without protecting gas
For Bn-Substituents doesn’t work
Ni, S.; Garrido-Castro, A. F.; Merchant, R. R.; deGruyter, J. N.; Schmitt, D. C.; Mousseau, J. J.; Gallego, G. M.; Yang, S.; Collins, M. R.; Qiao, J. X.; Yeung, K.; Langley, D. R.;
Poss, M. A.; Scola, P. M.; Qin, T.; Baran, P. S., Angew. Chem. Int. Ed. 2018, 57, 14560

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Thank you for attention!!!