Catalytic Heterocycle Synthesis Group 万伯顺 杂环合成中的 环加成与环化反应

Why Cycloadditon? Advantages:  Two C-C bonds & One C-N bond simultaneously  High atom efficiency Problems:  Regioselectivity  Chemoselectivity D. Siegel et al, J. Am. Chem. Soc. 2010, 132, 5924.

Why Iron? Iron (0.02 US$/mol) US$ per mol 2011 Iron(0) complex Organometallics, 1996, 15, 2713 Organometallics, 2002, 21, 2578 Iron(I) complex Wan

Iron Catalytic System

Holland’s investigation : The binding affinity toward the low-valent iron: Holland, P. L. et al. Inorg. Chem. 2006, 45, Problems and Solutions

EntryIron saltLigandFe%Conv.(%)3a% 1FeCl 3 -20%00 2FeCl 3 dppe20%9997 3FeCl 3 dppp20% FeBr 3 dppp20%9989 5FeBr 2 dppp20% FeI 2 dppp20%100>99 7FeCl 3 dppp10%169 8FeBr 2 dppp10%7568 9FeI 2 dppp10%100>99 10FeI 2 dppp5% FeI 2 dppp2.5%136

Cycloaddition of Diynes and Unactivated Nitriles

(Continued) Cycloaddition of Tetrayne

All-intramolecular Cycloaddition Cycloaddition of Alkynenitrile and Alkyne

Control Experiments

Possible Pathways to Form Pyridines With Wang, C. X. Angew. Chem. Int. Ed. 2011, 50, 7162

a 5 mol% catalyst, 5 equiv nitrile b 10 mol% catalyst, 2 equiv nitrile With Wang, C. X. J. Org. Chem. 2013, 78, 3065

[2+2+2] Cycloaddition in Pure Water

With Xu, F. ChemSusChem. 2012, 5, 854 [2+2+2] Cycloaddition in Pure Water

[2+2+2] Cycloaddition New Cycloaddition of Oximes and Diynes Aldehyde [Ru] Oxime Catalyst H2OH2O

 Reactivity of the C=N double bond  Water generated from cycloadducts  Rearrangement of oximes into amides New Cycloaddition of Oximes and Diynes

Key Point With Xu, F. Chem Eur J 2013, 19, 2252.

Nickel-catalyzed [3 + 2] cycloaddition of diynes with MAs Chem. Commun. 2013, ASAP C3CC41061G C-C bond cleavage N-C bond cleavage

Proposed mechanism

Building blocks What ? Synthesis of Pyrroles via Cyclization 杂原子 叁键 双键 电子 / 空间 调控基团

× × DMF, Ar 140 o C Synthesis of Pyrroles via Cyclization Ts = p-CH 3 PhSO 2 -

Synthesis of Pyrroles via Cyclization With Xin, X. Y. Angew. Chem. Int. Ed. 2012, 51, 1693.

"α" Migration Mechanism Study

"β" Migration Mechanism Study

Crossover Experiment

Competition Experiment

 Cyclization of Aza-enynes EntryCatalystSolvent3a(%) 1-DMF-85 2BPO (20)DMF1526 3AIBN (20)DMF2943 4NHPI (20)DMF4231 5TEMPO (20)DMF-66 6Anthraquinone (20)DMF-93 7DDQ (20)DMF84- 8DDQ (20)CCl DDQ (20)Benzene85- 11DDQ (10)THF89- 12DDQ (10)THF92- Catalyst + 2a(%) J. Org. Chem ASAP jo400387b

EntryCatalystSolventTime(h)2a% 1DDQ-H 2 THF4897 2HydroquinoneTHF4895 3PhenolTHF4874 4H2OH2OTHF4887 5MeOH (50)THF4893 6MeOH (solvent)MeOH4897  Cyclization of Aza-enynes J. Org. Chem ASAP jo400387b

Mechanism Study

Proposed Mechanism J. Org. Chem ASAP jo400387b

With Yu, X. Z. J. Org. Chem. 2013, jo Another example of cyclization with Ts migration

Xingwei Li,* Boshun Wan*, Angew. Chem. Int. Ed. 2013, 52, 2577 Other important finding

环加成与环化反应小结 六元环 : (1) JOC jo400387b (2) Unpublished results 五元环 : ACIE, 2012, 51, 1693 四元环 : Unpublished results 三元环 : Unpublished results