Radical reactions. Decarboxylative alkenylations and alkynylations

reactions

Radical reactions

Other reactions (metathesis)

one radical

M. A. J. Duncton, Med. Chem. Commun., 2011, 2, 1135-1161

There is a selectivity problem (innate selectivity, dictated by radical acceptor)

Minisci reaction

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

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

cross couplings (RCC)?

The radical binds to a metal ion and then selectively (!!!) reacts with the determined partner

S. Baran, Acc. Chem. Res. 2018, 51, 1807-1817.

as α, β – unsaturated alkenylzinc reagents can be used
Many functional groups are tolerated

Decarboxylative Alkenylations

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

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

2019, 21, 3625−3630

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

Also ArB(OH)2 can be used (sometimes) instead of ArZnCl!

of the sulfones is very simple

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.

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

Summary:

Decarboxylative Alkynylations

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

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

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

It can even happen that alternative cycloaddition reaction doesn’t work due to electronic factors!

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

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