Highlighting the Transformation and Formation of Allenes Via Pericyclic Reactions

Grenning Research Lab

July, 06, 2020 Journal Club Allenes and Pericyclic Introduction Reactions

• Earliest method for synthesizing allenes via sigmatropic Recent developments in allene transformations and synthesis via rearrangement found by Black and Landor: pericyclic reactions:

2019 J. Chem. Soc., 1965, 6784-6788 • Earliest approaches using an allene as a starting material to Adv. Synth. Catal. 2019, 361, 1160 undergo sigmatropic rearrangements were recorded in 1972 by Pierre Cresson and Michel Huche where allenes were converted to conjugated diene amides. • Allenes typically act as intermediates, being synthesized via a 2017 traditional method (Claisen variation or Crabbe method). New J. Chem., 2017,41, 1902-1904

• Novel synthetic methods can contribute to development of natural product scaffolds and new functionalities. 2012 Keywords: allene, sigmatropic rearrangement, Claisen rearrangement, Cope rearrangement, [3,3] rearrangement, [2,3] J. Am. Chem. Soc. 2012, 134, 37, 15497–15504 sigmatropic rearrangement

July 06, 2020 Journal Club “Photochemical Doyle–Kirmse Reaction: A Route to Allenes and Pericyclic Allenes” Reactions Gryko Group (Polish Academy of Sciences) Summary Precedent Reaction development

• Precedent for photochemical reaction route • Optimization • Scope of both Aryl Diazocarbonyl compounds and Propargylic Sulfides • Potential Mechanism • Mechanistic Experiments

Organic Letters 2020 22 (3), 1018-1021 Mariana M. Alves July 06, 2020 Journal Club “Photochemical Doyle–Kirmse Reaction: A Route to Allenes and Pericyclic Allenes” Reactions Gryko Group (Polish Academy of Sciences)

Potential Mechanism

TPP(tetraphenyl porphprin) acts as a triplet state sensitizer, encouraging electrons to enter the triplet state. In doing so, electrons enter a non-bonding orbital and can’t react, limiting the yield of the overall reaction.

This mechanistic experiment was done to prove diastereoselectivity under blue LED light irridation. The experiment used both the cis- and trans-stilbene and used NMR experiments to determine the diastereomers formed. The cis-stilbene resulted in the above diastereoselectivity while the trans-stilbene yielded the opposite.

Organic Letters 2020 22 (3), 1018-1021 Mariana M. Alves July 06, 2020 Journal Club “Synthesis of Fully Substituted Pyrroles through a Copper-Catalyzed Allenes and Pericyclic Aza-Michael/Claisen Rearrangement/Cyclization Cascade” Reactions Hao Tan, Xue-Fei Jiang, Lu Jiang, Chang Yuan, Xue Tang, Meng-Fan Li, Si-Wei Liu, Si Liu, Hai-Lei Cui

Catalyst: CuI, CuBr, CuBr2, Cu(Oac)2, CuCl, CuCl2, Cu(Otf)2, CuNO3H2O, Cu2O, Ni(OTf)2, Zn(OTf)2, Pd(OAc)2, ZnBr2, ZnCl2, Fe2(SO4)3, FePO4, Sc(OTf)3, Yb(OTf)3, AgSbF6, AgBF4, AuPPh3Cl

Solvent: DCE, m-xylene, DMF, DMSO, 1,4-dioxane, iPrOH, PhCl, DCE-PhCl

Optimal conditions: Cu2O (20 mol %), DCE (57% yield)

Synlett. 2020, 31, 723–729. Sara E. Kearney July 6, 2020 Journal Club “Synthesis of Fully Substituted Pyrroles through a Copper-Catalyzed Allenes and Pericyclic Aza-Michael/Claisen Rearrangement/Cyclization Cascade” Reactions Hao Tan, Xue-Fei Jiang, Lu Jiang, Chang Yuan, Xue Tang, Meng-Fan Li, Si-Wei Liu, Si Liu, Hai-Lei Cui

Synlett. 2020, 31, 723–729. Sara E. Kearney July 6, 2020 Journal Club “Ketonitrones via Cope-Type Hydroamination of Allenes” Allenes and Pericyclic Joseph Moran, Jennifer Y. Pfeiffer, Serge I. Gorelsky, André M. Beauchemin Reactions (University of Ottawa)

Primary Reaction Mechanism

Precedent Reaction Development

1 eq 2 eq Tested at 110°C, 0.5M in benzene (62%), chloroform (63%), n-PrOH (62%), i-PrOH (65%), t-BuOH (61%) Alkyl-hydroxylamines are sensitive to thermal decomposition. t-BuOH most effectively reduces decomposition. In t-BuOH, temperature increased to 140 °C (87%)

Org. Lett. 2009, 11, 9, 1895–1898 Matthew Albritton July 9, 2020 Journal Club “Ketonitrones via Cope-Type Hydroamination of Allenes” Allenes and Pericyclic Joseph Moran, Jennifer Y. Pfeiffer, Serge I. Gorelsky, André M. Reactions Beauchemin (University of Ottawa)

Varying Allene substitution: Regiospecificity: Transition State Analysis

1 eq 2 eq

R = Cyclohexyl (91%), n-hexyl (81%), BnO(CH2)2 (75%), TBDPSO(CH2)3 (73%), Ph (90°C, 40%) Aryl-allenes have low yield 100% regiospecificity Hydroxylamine Disubstituted allene reactions had very poor yield. prefers central Varying Hydroxylamine Substitution: carbon attack, only one regioisomer formed.

2 eq 1 eq R = Bn (81%), i-Pr (63%), sec-Bu (49%), neopentyl (47%), n-hexyl (51%), cyclopentyl (58%), cycloheptyl (71%), norbornyl (38%). Hydroxylamine and Multi-Substituted Allenes

2 eq 1 eq Reactions with

While R2 = R3 = H, R1 = cyclohexyl (75%), n-hexyl (93%), BnO(CH2)2 (99%), TBDPSO(CH2)3 (88%), Ph disubstituted allenes (71%) require geometry

R1 = n-hexyl and R2 = n-Pr (160°C, 21%) resembling high R1 = n-Pr and R3 = n-Pr (13%) energy transition >1 allene substituent greatly hinders reaction. states. Hydroxylamine stability compared to N-alkylhydroxylamines likely contributes to better yield

Org. Lett. 2009, 11, 9, 1895–1898 Matthew Albritton July 9, 2020