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sp3 C-H Alkylation with Olefins
,
Yan Xu
Dec. 3, 2014
1) sp3 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) sp3 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)
Rare-earch-metal-philic DG
Allylic C-H bond alkylation (double bond as DG)
Pyridine type DG
1) sp3 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)
Rare-earch-metal-philic DG
Allylic C-H bond alkylation (double bond as DG)
Pyridine type DG
Yong-Qiang Tu, Angew. Chem. Int. Ed. 2009, 48, 8761
1) sp3 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)
Rare-earch-metal-philic DG
Allylic C-H bond alkylation (double bond as DG)
Pyridine type DG
Michael J. Krische, Science. 2012, 336, 324
sp3 C-H Alkylation with Olefins
Through C-H activation,
Yan Xu
Dec. 3, 2014
1) sp3 C-H Alkylation via Directed C-H activation
2) Hydroaminoalkylation (still via C-H activation)
Rare-earch-metal-philic DG
Allylic C-H bond alkylation (double bond as DG)
Pyridine type DG
Zhaomin Hou, ACIE. 2012, 51, 12828 –12832
Rare-earth metal:
Strong oxophilicity
High activity of rare-earth alkyl species toward olefin
Zhaomin Hou, ACIE. 2012, 51, 12828 –12832
Rare-earth metal:
Strong oxophilicity
High activity of rare-earth alkyl species toward olefin
Olefin: must be terminal
Ethylene: oligomer
Zhaomin Hou, ACIE. 2012, 51, 12828 –12832
Olefin: must be terminal
Ethylene: oligomer
Zhaomin Hou, ACIE. 2012, 51, 12828 –12832
Olefin: must be terminal
Ethylene: oligomer
Zhaomin Hou, ACIE. 2012, 51, 12828 –12832
Zhaomin Hou, ACIE. 2013, 52, 4418
Zhaomin Hou, ACIE. 2013, 52, 4418
Zhaomin Hou, ACIE. 2013, 52, 4418
Zhaomin Hou, ACIE. 2013, 52, 4418
KIE = 3.7
KIE = 3.7
KIE = 3.7
T. Don Tilley J. Am. Chem. Soc., 2003, 125, 7971
non-reactive substrates:cis/trans-2-butene, 1-hexene,1-butene, 2-methylpropene, norbornylene, and 2-butyne
Zhi-Xiang Yu, JACS. 2010, 132, 4542
Zhi-Xiang Yu, JACS. 2010, 132, 4542
Zhi-Xiang Yu, JACS. 2010, 132, 4542
Zhi-Xiang Yu, ACIE. 2011, 50, 2144
Zhi-Xiang Yu, Organometallics, 2012, 31, 5185
Diene coordinationdisfavored the double-bond isomerization
Bis-allylic Rh complex facilitate the reductive elimination
Zhi-Xiang Yu, ACIE. 2011, 50, 2144
Zhi-Xiang Yu, Organometallics, 2012, 31, 5185
Diene coordinationdisfavored the double-bond isomerization
Bis-allylic Rh complex facilitate the reductive elimination
Zhi-Xiang Yu, ACIE. 2011, 50, 2144
Zhi-Xiang Yu, Organometallics, 2012, 31, 5185
Diene coordinationdisfavored the double-bond isomerization
Bis-allylic Rh complex facilitate the reductive elimination
Chul-Ho Jun Chem. Commun., 1998, 1405
95%
Chul-Ho Jun Chem. Commun., 1998, 1405
95%
Chul-Ho Jun Chem. Commun., 1998, 1405
Shinji Murai J. Am. Chem. Soc., 2001, 123, 10935
Shinji Murai J. Am. Chem. Soc., 2001, 123, 10935
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
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
Bert U. W. Maes Chem. Eur. J. 2012, 18, 10393
Bert U. W. Maes Chem. Eur. J. 2012, 18, 10393
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] = (PCy3)2(CO)RuHCl
Chae S. Yi Organometallics 2004, 23, 5392
catalytic active
1)
2) kNH /kND = 1.9
(consistent with a rate-limiting
N-H bond activation step)
1 = (PCy3)2(CO)RuHCl
Chae S. Yi Organometallics 2004, 23, 5392
Takanori Shibata Org. Lett., 2011, 13, 4692
For substrate scope:R = Me, EtOlefin = styrene, diene,
ee = 61-90%terminal olefin’s yield is low
Takanori Shibata Org. Lett., 2011, 13, 4692
For substrate scope:R = Me, EtOlefin = styrene, diene,
ee = 61-90%terminal olefin’s yield is low
Takanori Shibata Org. Lett., 2011, 13, 4692
Takanori Shibata Tetrahedron 68 (2012) 9009
Till Opatz Org. Lett., 2014, 16, 4201
Reaction condition:Acrylate, Vinylsilane (DME, 85 ℃)Styrene, vinylboronic ester, 1-hexene (DME, 140 ℃)
42% 64%
better substrate scope
63%
Till Opatz Org. Lett., 2014, 16, 4201
Reaction condition:Acrylate, Vinylsilane (DME, 85 ℃)Styrene, vinylboronic ester, 1-hexene (DME, 140 ℃)
42% 64%
better substrate scope
63%
60 %
46 %
Dalibor Sames J. Am. Chem. Soc., 2004, 126, 6556
60 %
46 %
Dalibor Sames J. Am. Chem. Soc., 2004, 126, 6556
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) sp3 C-H Alkylation via Directed C-H activation
2) Hydroaminoalkylation (still via C-H activation)
Rare-earch-metal-philic DG
Allylic C-H bond alkylation (double bond as DG)
Pyridine type DG
1) sp3 C-H Alkylation via Directed C-H activation
2) Hydroaminoalkylation (still via C-H activation)
Rare-earch-metal-philic DG
Allylic C-H bond alkylation (double bond as DG)
Pyridine type DG
toluene, 200 oC, 150h
Maspero, F. Synthesis 1980, 305.
* Isolated by distillation
Nugent, W. A Organometallics 1983, 2, 161
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
yield not given“ The activity of the various metal amides for this reaction roughly parallels their efficacy for H-D exchange”
John Hartwig J. Am. Chem. Soc., 2007, 129, 6690
zirconocene-η2-imine complexes was formed faster from N-alkyl arylamido complexes than from dialkylamido complexes.
Nugent, W. A Organometallics 1983, 2, 161
Organometallics 1994, 13, 190
John Hartwig J. Am. Chem. Soc., 2007, 129, 6690
Nugent, W. A Organometallics 1983, 2, 161
Organometallics 1994, 13, 190zirconocene-η2-imine complexes was formed faster from N-alkyl arylamido complexes than from dialkylamido complexes.
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
John Hartwig J. Am. Chem. Soc., 2008, 130, 14940
John Hartwig J. Am. Chem. Soc., 2008, 130, 14940
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
Sven Doye Angew. Chem. Int. Ed. 2009, 48, 1153
Sven Doye Angew. Chem. Int. Ed. 2009, 48, 1153
Sven Doye Angew. Chem. Int. Ed. 2009, 48, 1153
Sven Doye ChemCatChem 2009, 1, 162
[Ti(Bn)4]
Sven Doye Angew. Chem. Int. Ed. 2009, 48, 1153
Slightly enhanced activity First addition to styrene: 30% yield, 1:1 branch:linear
Sven Doye ChemCatChem 2009, 1, 162
[Ti(Bn)4]
Sven Doye Angew. Chem. Int. Ed. 2009, 48, 1153
Slightly enhanced activity First addition to styrene: 30% yield, 1:1 branch:linear
Laurel L. Schafer J. Am. Chem. Soc., 2009, 131, 2116
Laurel L. Schafer J. Am. Chem. Soc., 2009, 131, 2116
Zr: larger metal center 2-pyridonate ligand: less sterically demanding
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
60%R = Ph 68%R = Me 43% See: Org. Lett., 2013, 15, 2182
Laurel L. Schafer Angew. Chem. Int. Ed. 2009, 48, 8361
For further improvement, See: Guofu Zi, Chem. Commun., 2010, 46, 6296Guofu Zi, Dalton. Trans., 2011, 40, 1547
Laurel L. Schafer Angew. Chem. Int. Ed. 2009, 48, 8361
Only 105 oC: is this catalyst able to solve the styrene problem?
Sven Doye Angew. Chem. Int. Ed. 2010, 49, 2626
Sven Doye Angew. Chem. Int. Ed. 2009, 48, 1153
Only 105 oC: is this catalyst able to solve the styrene problem?
Sven Doye Angew. Chem. Int. Ed. 2010, 49, 2626
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. 2011, 50, 6401
Sven Doye, Angew. Chem. Int. Ed. 2011, 50, 6401
Zero-order rate dependence on aminoalkene
Sven Doye, Angew. Chem. Int. Ed. 2011, 50, 6401
Zero-order rate dependence on aminoalkene
Sven Doye, Angew. Chem. Int. Ed. 2011, 50, 6401
kobs(1-H)/kobs (1-D) = 7.3 at 130oC
with 5 mol% and 10 mol% [Ti(NMe2)4]
Zero-order rate dependence on aminoalkene
Sven Doye, Angew. Chem. Int. Ed. 2011, 50, 6401
kobs(1-H)/kobs (1-D) = 7.3 at 130oC
with 5 mol% and 10 mol% [Ti(NMe2)4]
Zero-order rate dependence on aminoalkene
Sven Doye, Angew. Chem. Int. Ed. 2011, 50, 6401
Kai C. Hultzsch J. Am. Chem. Soc., 2012, 134, 3300
59-98% ee
61-95% yield
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
Laurel L. Schafer Chem. Eur. J. 2013, 19, 8751
84% 73% 61%130 oC
36%145 oC
Styrene disubstituted terminal alkenes internal unstrained alkenes dialkylamines.
Laurel L. Schafer Chem. Eur. J. 2013, 19, 8751
84% 73% 61%130 oC
36%145 oC
16%145 oC
85%
Styrene disubstituted terminal alkenes internal unstrained alkenes dialkylamines.
Laurel L. Schafer Chem. Eur. J. 2013, 19, 8751
84% 73% 61%130 oC
36%145 oC
Styrene disubstituted terminal alkenes internal unstrained alkenes dialkylamines.
84% 73% 61%130 oC
36%145 oC
Styrene disubstituted terminal alkenes internal unstrained alkenes dialkylamines.
Laurel L. Schafer Chem. Eur. J. 2013, 19, 8751
Laurel L. Schafer Tetrahedron 2013, 69, 5737
Laurel L. Schafer Angew. Chem. Int. Ed. 2013, 52, 9144
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
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
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
e-withdrawing and steric less hindered ligand!
Laurel L. Schafer J. Am. Chem. Soc., 2014, 136 (31), pp 10898
Laurel L. Schafer Org. Lett., 2013, 15, 6002
Laurel L. Schafer J. Am. Chem. Soc., 2014, 136 (31), pp 10898
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]
Eur. J. Org. Chem. 2014, 2790
a:b>99:1
Linear selectivity?
Schafer’s catalyst for intramaleculor HAA reaction
By NMR
Sven Doye Angew. Chem. Int. Ed. 2013, 52, 1806
Summary
sp3 C-H alkylation has been achieved via many different machanism
Metal: d0 & d8
Logical development of ligand and catalyst is critical
Inspiration of our own work
Summary
sp3 C-H alkylation has been achieved via many different machanism
Metal: d0 & d8
Logical development of ligand and catalyst is critical
Inspiration of our own work
“The predominance of multiply deuterated products, especially from the Zrcatalyst, suggests that further metalation of the intermediate metallacycle is fast compared with the reverse reaction.”
