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Construction of Tetrahydrofurans by Pd(II)/Pd(IV) -
Catalyzed Aminooxygenation of Alkenes
Desai, L.; Sanford, M.S. Angew. Chem. Int. Ed., 2007, 46, 5737-5740.
Melissa Sprachman
July 28, 2007
OH
PdII
Ar
O
Ar
NH
O
O
+
PhI(OAc)2
OPdIV
NPhth
Ar
NPhth
Melissa Sprachman @ Wipf Group 1 7/30/2007
Oxidative Functionalization Via PdIV Intermediates
Yoneyama, T.; Crabtree, R.H. J. Mol. Catal. A 1996, 108, 35.
Dick, A.R.; Hull, K.L.; Sanford, M.S. J. Am. Chem. Soc. 2004, 126, 2300.
PhH + Pd(OAc)2-AcOH
PdII(OAc)
PhI(OAc)2
PhH
PdIV(OAc)3
PdII
OAc
+ Pd(OAc)2
+ Pd(0)
Slide info first found in: Gorin, D. ACS Fellowship essay, Univ. California Berkeley, Berkeley, CA 2006.
Melissa Sprachman @ Wipf Group 2 7/30/2007
Studies on Isolable PdIV Complexes
Synthesis of Stable PdIV Complexes:
C-O Bond Forming Reductive Elimination Upon Heating:
Dick, A.R.; Kampf, J. W..; Sanford, M.S. J. Am. Chem. Soc. 2005, 127, 12790.
R = H, Me; X = R, Ar, X, NO2
Melissa Sprachman @ Wipf Group 3 7/30/2007
Aminopalladation Background
Pd
X
X
NH
R
R
-HXHR2N
Pd
-HPdX R2N
--Aliphatic amines often displace the alkene from the palladium center
--Amides are viable alternatives due to their decreased basicity.
(n)
NH
O
+Z
Z = EWG (n)
N
O
Z
5 % PdCl2(MeCN)2
5 % CuCl
1 atm O2, DME
Hegedus, L.S. Tetrahedron, 1984, 40, 2415.
NH2
+ Pd(II)
NH2
Pd
NHTs
+ Pd(II)NTs
Hosokawa, T. In Handbook of Organopalladium Chemistry for OrganicSynthesis: Negishi, E.-I., Ed.; John Wiley and Sons: New York, 2002,
vol 2, pp 2211-2213.
Melissa Sprachman @ Wipf Group 4 7/30/2007
Recent Work in Aminopalladation/Aminoacetoxylation
Chemistry
TsHN O
O
10 mol% Pd(OAc)2
2 eq PhI(OAc)2
1 equiv Bu4NOAc
CH3CN, 25oC, 7 h
TsNO
O
OAc
92%, 9.5:1 dr
TsHN O
O 10 mol% Pd(OAc)2
2 eq PhI(OAc)2
1 equiv Bu4NOAc
CH3CN,60oC, 2.5 h
TsNO
O
OAc
65%, >20:1 dr
Alexanian, E. J.; Chulbom, L.; Sorenson, E.J. J. Am. Chem. Soc. 2005, 127, 7690.
Melissa Sprachman @ Wipf Group 5 7/30/2007
NH
O
O
C6H13
5 mol % Pd(OAc)2
CH2Cl2, 60oC
+
(Aminopalladation) C6H13
[LnPdII]
N OO
-[LnPdiiH]
!-Hydride Eliminaton
(Pd0/PdII Manifold)
2 equiv PhI(OAc)2
-[LnPdII]
Oxidative Functionalization
(PdII/PdIV Manifold)
NPhth
AcOC6H13
NPhth
C6H13
NPhth
PdIV
C6H13AcOvia
Stahl and Sanford’s Approach to Aminoacetoxylation
Melissa Sprachman @ Wipf Group 6 7/30/2007
Intermolecular Pd-Catalyzed Aminoacetoxylation of
Alkenes (Stahl)
C6H13+ NH
O
O
PdCl2(CH3CN)22.5 equiv PhI(OAc)2
C6H13
OAc
NPhth
+C6H13
NPhth+
C6H13
OAc
OAc
60 : 19 : 28
Key Features:
--Excellent Regioselectivity (no phthalimide addn at the terminal carbon observed)
--Substantial yields, even for unactivated alkenes
AlkeneProduct
Yield1H NMR (isolated)
Reactions with PdCl2(CH3CN)2 and PhI(OAc)2
-- Single diastereomers observed by 1HNMR:
--Favorable yields with allylic
Oxygens suggest chelation;
Yields drop with vinyl ethers (45%)
And homoallylic ethers (30%)
Liu, G.; Stahl, S. J. Am. Chem. Soc. 2006, 128, 7179.
Melissa Sprachman @ Wipf Group 7 7/30/2007
Sanford: Suppression of !-Hydride Elimination
Using Tethered Alcohols
OH
+
NH
O
O
10 mol % Pd(OAc)220 mol% AgBF4
CH3CN, 60oC O[Pd]
H
NPhth
3 equiv PhI(OAc)2
O O
+
NPhth OAc45%
OHAcO
NPhth
OH
NPhthor
--Coordination of the alcoholic oxygento Pd slows !-hydride elimination
Possible SN2 Mechanisms for Aminooxygenation:
--Subjection of authentic samples of either substrate did not yield amidated THF products
NH
O
O
+
O
O2CPh
SN2
O
NPhth
SN2
OHAcO
NPhth
Melissa Sprachman @ Wipf Group 8 7/30/2007
Alternative Routes Considered
NH
O
O
+
OH
Ph
[LnPdII]
PhI(OAc)2
O
LnPdIV
Ph
NPhth
Direct Red. Elim. OPh
PhthN
OH
Ph
LnPdIV
NPhthSN2
OPh
PhthN
cis Aminopalladation/oxidation
Only the trans THF products were observed.
OPh
PhthN
OPh
PhthN
OH
Ph
LnPdIV
NPhth
O
LnPdIV
NPhth
Ph
NH
O
O
+
OH
Ph
[LnPdII]
PhI(OAc)2
trans Aminopalladation/oxidation
SN2
Direct Red.Elim.
Melissa Sprachman @ Wipf Group 9 7/30/2007
Determination of the Stereochemistry of Aminopalladation
NH
O
O
+
OH
Ph 5 mol % Pd(OAc)2
10 mol % AgBF4
CH3CN, 60oC, O2OH
Ph
NPhth+
OH
NPhth
Ph
> 10 : 1
From cis aminopalladation
Support from Stahl’s Work:
Ph OMe + PhthNH10 mol% [Pd]
2.5 eq. PhI(OAc)2
DCE, 70oC, 20 h
Ph OMe
OAc
NPhth
+
Ph OMe
NPhth
[Pd] = PdCl2(CH3CN)2 :
Pd(OAc)2 :
52% 5%
44% 0%
Possible routes:
A) trans-aminopalladation followed by oxidative Pd-C cleavage with retention
B) cis-aminopalladation followed by oxidative Pd-C cleavage with inversion
Liu, G.; Stahl, S. J. Am. Chem. Soc. 2006, 128, 7179.
3%
Melissa Sprachman @ Wipf Group 10 7/30/2007
Decreased diastereoselectivities were
observed with substituents in the meta and
para positions
Melissa Sprachman @ Wipf Group 11 7/30/2007
Conclusions
-3 aminotetrahydofurans were unexpectedly synthesized in Sanford and coworkers’
attempts to suppress the beta-hydride elimination pathway of an
aminopalladation/oxidation sequence.
-Evidence from experiments by Stahl and Sanford supports cis-aminopalladation of
alkenes.
-The promising diastereoselectivities and consequent mechanistic elucidation may
lay the framework for the development of enantioselective PdII/PdIV reactions.
Melissa Sprachman @ Wipf Group 12 7/30/2007