Construction of Tetrahydrofurans by Pd(II)/Pd(IV) - Catalyzed - - PowerPoint PPT Presentation

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 O PdIV 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

• HX

H R2N 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 Organic Synthesis: 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 TsN O 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 TsN O 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 O O

• [LnPdiiH]
• Hydride Eliminaton

(Pd0/PdII Manifold)

2 equiv PhI(OAc)2

• [LnPdII]

Oxidative Functionalization (PdII/PdIV Manifold)

NPhth AcO C6H13 NPhth C6H13 NPhth PdIV C6H13 AcO via

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)2 2.5 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

Alkene Product Yield

1H 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)2 20 mol% AgBF4 CH3CN, 60oC

O [Pd] H NPhth

3 equiv PhI(OAc)2

O O

+

NPhth OAc

45%

OH AcO NPhth OH NPhth

• r
• -Coordination of the alcoholic oxygen

to 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 OH AcO 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. O Ph PhthN OH Ph LnPdIV NPhth SN2 O Ph PhthN

cis Aminopalladation/oxidation

Only the trans THF products were observed.

O Ph PhthN O Ph 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, O2 OH Ph NPhth + OH NPhth Ph > 10 : 1 From cis aminopalladation

Support from Stahl’s Work:

Ph OMe + PhthNH 10 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

• bserved 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