sp 3 C-H Alkylation with Olefins Yan Xu Dec. 3, PDF Free Download

sp 3 C-H Alkylation with Olefins, Yan Xu Dec. 3, 2014

1) sp 3 C-H Alkylation via Directed C-H activation 2) Hydroaminoalkylation (still via C-H activation) 3) Hydrohydroxyalkylation (via radical chemistry) 4) Hydrohydroxyalkylation (via transfer hydrogenation chemistry)

1) sp 3 C-H Alkylation via Directed C-H activation Rare-earch-metal-philic DG Allylic C-H bond alkylation (double bond as DG) Pyridine type DG 2) Hydroaminoalkylation (still via C-H activation) 3) Hydrohydroxyalkylation (via radical chemistry) 4) Hydrohydroxyalkylation (via transfer hydrogenation chemistry)

sp 3 C-H Alkylation with Olefins Through C-H activation, Yan Xu Dec. 3, 2014

1) sp 3 C-H Alkylation via Directed C-H activation Rare-earch-metal-philic DG Allylic C-H bond alkylation (double bond as DG) Pyridine type DG 2) Hydroaminoalkylation (still via C-H activation)

Rare-earth metal: Strong oxophilicity High activity of rare-earth alkyl species toward olefin Zhaomin Hou, ACIE. 2012, 51, 12828 12832

Zhaomin Hou, ACIE. 2012, 51, 12828 12832 Olefin: must be terminal Ethylene: oligomer

Zhaomin Hou, ACIE. 2013, 52, 4418

KIE = 3.7

non-reactive substrates: cis/trans-2-butene, 1-hexene, 1-butene, 2-methylpropene, norbornylene, and 2-butyne T. Don Tilley J. Am. Chem. Soc., 2003, 125, 7971

Zhi-Xiang Yu, JACS. 2010, 132, 4542

Zhi-Xiang Yu, ACIE. 2011, 50, 2144 Bis-allylic Rh complex facilitate the reductive elimination Diene coordination disfavored the double-bond isomerization Zhi-Xiang Yu, Organometallics, 2012, 31, 5185

95% Chul-Ho Jun Chem. Commun., 1998, 1405

Chul-Ho Jun Chem. Commun., 1998, 1405

Shinji Murai J. Am. Chem. Soc., 2001, 123, 10935

Olefin part substrate scope is similar as Jun s Shinji Murai J. Am. Chem. Soc., 2001, 123, 10935

Shinji Murai J. Am. Chem. Soc., 2001, 123, 10935

1) H/D exchange experiment provided good evidence for the reversibility of C-H bonds between substrates and reactants (alkenes), indicating that the cleavage of C-H bonds is not the rate-determining step 2) Shinji Murai J. Am. Chem. Soc., 2001, 123, 10935

Bert U. W. Maes Chem. Eur. J. 2012, 18, 10393

carboxylic acid / alcohol has a significant effect on catalyst initiation Bert U. W. Maes Chem. Eur. J. 2012, 18, 10393

Bert U. W. Maes Chem. Eur. J. 2012, 18, 10393

Bert U. W. Maes Adv. Synth. Catal. 2014, 356, 1610

[Ru] = (PCy 3 ) 2 (CO)RuHCl Chae S. Yi Organometallics 2004, 23, 5392

1 = (PCy 3 ) 2 (CO)RuHCl 1) catalytic active 2) k NH /k ND = 1.9 (consistent with a rate-limiting N-H bond activation step) Chae S. Yi Organometallics 2004, 23, 5392

Takanori Shibata Org. Lett., 2011, 13, 4692

For substrate scope: R = Me, Et Olefin = styrene, diene, ee = 61-90% terminal olefin s yield is low Takanori Shibata Org. Lett., 2011, 13, 4692

Takanori Shibata Tetrahedron 68 (2012) 9009

Reaction condition: Acrylate, Vinylsilane (DME, 85 ) Styrene, vinylboronic ester, 1-hexene (DME, 140 ) better substrate scope 63% 42% 64% Till Opatz Org. Lett., 2014, 16, 4201

60 % 46 % Dalibor Sames J. Am. Chem. Soc., 2004, 126, 6556

Kinetic competent and chemical competent catalyst Dalibor Sames J. Am. Chem. Soc., 2004, 126, 6556

Guangbin Dong, Science 2014, 345, 68

1) sp 3 C-H Alkylation via Directed C-H activation Rare-earch-metal-philic DG Allylic C-H bond alkylation (double bond as DG) Pyridine type DG 2) Hydroaminoalkylation (still via C-H activation)

toluene, 200 o C, 150h * Isolated by distillation Maspero, F. Synthesis 1980, 305.

yield not given The activity of the various metal amides for this reaction roughly parallels their efficacy for H-D exchange Nugent, W. A Organometallics 1983, 2, 161

Nugent, W. A Organometallics 1983, 2, 161 zirconocene-η 2 -imine complexes was formed faster from N-alkyl arylamido complexes than from dialkylamido complexes. Organometallics 1994, 13, 190 John Hartwig J. Am. Chem. Soc., 2007, 129, 6690

Cannot use styrene and 1,2-disubstituted olefin John Hartwig J. Am. Chem. Soc., 2007, 129, 6690

John Hartwig J. Am. Chem. Soc., 2008, 130, 14940

Sven Doye Angew. Chem. Int. Ed. 2009, 48, 1153

Sven Doye Angew. Chem. Int. Ed. 2009, 48, 1153 [Ti(Bn) 4 ] Slightly enhanced activity First addition to styrene: 30% yield, 1:1 branch:linear Sven Doye ChemCatChem 2009, 1, 162

Laurel L. Schafer J. Am. Chem. Soc., 2009, 131, 2116

Zr: larger metal center 2-pyridonate ligand: less sterically demanding

Laurel L. Schafer Angew. Chem. Int. Ed. 2009, 48, 8361

1 Laurel L. Schafer Angew. Chem. Int. Ed. 2009, 48, 8361

Laurel L. Schafer Angew. Chem. Int. Ed. 2009, 48, 8361

Laurel L. Schafer Angew. Chem. Int. Ed. 2009, 48, 8361 60% R = Ph 68% R = Me 43% See: Org. Lett., 2013, 15, 2182

For further improvement, See: Guofu Zi, Chem. Commun., 2010, 46, 6296 Guofu Zi, Dalton. Trans., 2011, 40, 1547 Laurel L. Schafer Angew. Chem. Int. Ed. 2009, 48, 8361

Only 105 o C: is this catalyst able to solve the styrene problem? Sven Doye Angew. Chem. Int. Ed. 2009, 48, 1153 Sven Doye Angew. Chem. Int. Ed. 2010, 49, 2626

Sven Doye Angew. Chem. Int. Ed. 2010, 49, 2626

Sven Doye Chem. Eur. J. 2013, 19, 3833 Sven Doye Angew. Chem. Int. Ed. 2010, 49, 2626

Sven Doye, Angew. Chem. Int. Ed. 2011, 50, 6401

Zero-order rate dependence on aminoalkene Sven Doye, Angew. Chem. Int. Ed. 2011, 50, 6401

k obs (1-H)/k obs (1-D) = 7.3 at 130 o C with 5 mol% and 10 mol% [Ti(NMe 2 ) 4 ] Zero-order rate dependence on aminoalkene Sven Doye, Angew. Chem. Int. Ed. 2011, 50, 6401

Sven Doye, Angew. Chem. Int. Ed. 2011, 50, 6401

59-98% ee 61-95% yield Kai C. Hultzsch J. Am. Chem. Soc., 2012, 134, 3300

Non-dissociative Fast reversible r.d.s: Either by amide exchange Or by alkene insertion Catalyst activity can be enhanced by a more electron deficient ligand

84% 73% 61% 130 o C 36% 145 o C Styrene disubstituted terminal alkenes internal unstrained alkenes dialkylamines. Laurel L. Schafer Chem. Eur. J. 2013, 19, 8751

84% 73% 61% 130 o C 36% 145 o C 16% 145 o C 85% Styrene disubstituted terminal alkenes internal unstrained alkenes dialkylamines. Laurel L. Schafer Chem. Eur. J. 2013, 19, 8751

84% 73% 61% 130 o C 36% 145 o C Styrene disubstituted terminal alkenes internal unstrained alkenes dialkylamines. Laurel L. Schafer Chem. Eur. J. 2013, 19, 8751

Laurel L. Schafer Chem. Eur. J. 2013, 19, 8751 84% 73% 61% 130 o C 36% 145 o C Styrene disubstituted terminal alkenes internal unstrained alkenes dialkylamines. Laurel L. Schafer Tetrahedron 2013, 69, 5737

minimum temperature required to achieve at least three turnovers within 20 h sufficient steric bulk is critical Electron withdrawing ligand is critical Phosphoramidates increased electronwithdrawing properties tunable steric bulk at both phosphorus and nitrogen Laurel L. Schafer Angew. Chem. Int. Ed. 2013, 52, 9144

Laurel L. Schafer Angew. Chem. Int. Ed. 2013, 52, 9144

Laurel L. Schafer Org. Lett., 2013, 15, 6002

e-withdrawing and steric less hindered ligand! Laurel L. Schafer Org. Lett., 2013, 15, 6002 Ta Cl bond [2.4959(8) Å] is significantly longer than Ta NMe2(axial) bond [1.970(3) Å] the bonding the of Ta N amido bond lengths are shorter in 1 than in 2 Improved metal accessibility increased electrophilic nature of the metal center Laurel L. Schafer J. Am. Chem. Soc., 2014, 136 (31), pp 10898

Laurel L. Schafer J. Am. Chem. Soc., 2014, 136 (31), pp 10898

Another unsolved problem: Styrene selectivity w/ [Ti] Branched selectivity: has already been achieved by [Ta] a:b>99:1 Eur. J. Org. Chem. 2014, 2790

Linear selectivity? Schafer s catalyst for intramaleculor HAA reaction By NMR Sven Doye Angew. Chem. Int. Ed. 2013, 52, 1806

Summary sp 3 C-H alkylation has been achieved via many different machanism Metal: d 0 & d 8 Logical development of ligand and catalyst is critical Inspiration of our own work

The predominance of multiply deuterated products, especially from the Zr catalyst, suggests that further metalation of the intermediate metallacycle is fast compared with the reverse reaction.

sp 3 C-H Alkylation with Olefins Yan Xu Dec. 3, 2014