Samarium(II) Iodide Mediated Cyclizations in Natural Product

52 Pages·2004·0.66 MB·English

Samarium(II) Iodide Mediated Cyclizations in Natural Product Synthesis
The Kagan Reagent Part II
An Evans Group Afternoon Seminar
Keith Fandrick
Seminar outline: Primary References
-Introduction and Background Procter, D. J. Chem. Rev. 2004, 3371.
-Intramolecular Barbier Reaction Krief, A. Chem. Rev. 1999, 745.
-Intramolecular Reformatsky Reaction Molander, G. Chem. Rev. 1996, 307.
-Radical Alkene and Alkyne Cyclizations Molander, G. Chem. Rev. 1992, 29.
-Carbonyl-Alkene Reductive Cyclizations Curran, D. R. Synlett 1992, 943.
-Intramolecular Pinacol Couplings Rajapakse, H. Evans Group Seminar 1998
-Intramolecular Reductive Couplings of Carbonyls and Hydrazones
-Total Synthetic endeavors utilizing mutiple SmI cyclizations
2
SmI Discovery and Background
2
Introduction
-Samarium diiodide was first reported by Kagan in 1977. Kagan reported the preliminary deoxygenation of
epoxides and sulfoxides, chemoselective reduction of aldehydes in the presence of ketones, dehalogenations,
and couplings between ketones and alkyl halides. (Kagan, H. B. Nouv. J. Chim. 1977, 5. Kagan, H. B. J. Am. Chem. Soc.
1980, 2693)
-Samarium diiodide is the subject of >20 reviews and >850 publications.
-Samarium diiodide is commercially available as an anhydrous powder (5g, $185) or as a 0.1 M solution in THF
(100mL, $32). (Aldrich catalog 2003-2004)
-Samarium diiodide can be prepared from Sm metal and CH I , ICH CH I, or I
2 2 2 2 2.
-Reactions are generally performed with an excess of samarium diiodide, degassed reagents and solvents, and
in dry THF containing an antioxidant.
-Catalytic amounts of SmI can be used with the addition of mischmetall (alloy of lanthanides [La 33%, Ce 50%,
2
Nd 12%, Pr 4%, Sm and other lanthanides 1%] to regenerate SmI . The use of catalytic amounts of Sm(II) and
2
mischmetall is more cost effective. The alloy is unreactive to carbonyls and simple to use.
-The normal work-up usually requires acidic conditions. However, Rochelle's salt and potassium carbonate
can be used for acid sensitive substrates. (Little D. J. Org. Chem. 1996, 3240)
-THF appears to be the proton source for the termination of radical cascades. If a second reduction with
additional equivalent of SmI occurs the proton source is generally the alcoholic co-solvent. (Curran D. P. J. Am.
2
Chem. Soc. 1988, 5046)
-Samarium diiodide chemoselectively reduces: organic halides, carbonyls, α-hetero-sustituted carbonyls,
cyclopropyl ketones, epoxides, amine oxides, sulfoxides, phosphine oxides, sulfones, sulfonates, nitro, nitroso,
and azo compounds, allyl acetates, and isoxazoles.
Krief, A. Chem. Rev. 1999, 745.
SmI Reduction Potential
2
Effects on the Eo of SmI with HMPA
2
-Samarium diiodide is a polyvalent single
-1
electron reducing agent. 0 1 2 3 4 5 6 7
-1.25
al
-The reduction potential (Eo) of Sm+2/Sm+3 nti
e -1.5
in water is -1.55 V compared to Nao/Na+1 Pot
n
of -2.77 V. atio -1.75
d
xi
O
-2
-The reduction potential of SmI can be
2
increased by the addition of HMPA, and LiBr
-2.25
or LiCl. Equiv of HMPA relative to Samarium Diiodide
UV-vis spectrum of SmI in THF
-The addition of transition metal increases 2
the rate of several SmI reactions.
2
(Kagan, H. B. Synlett 1996, 633)
-Changes in protic solvents can alter
the rates of SmI mediated reactions and
2
in some cases alter the mechanism.
-Visible light increases the reduction potential
of SmI (Ogawa, A. J. Am. Chem. Soc. 1997, 2745)
2.
Krief, A. Chem. Rev. 1999, 745.
SmI Barbier Reaction
2
Basic Mechanism
I
HMPA HMPA
I I + Sm I +
HMPA HMPA Outer Sphere HMPA HMPA HMPA HMPA HMPA HMPA
-
Sm + R-I Sm + R I Sm + R
HMPA HMPA ET HMPA HMPA Outer Sphere ET HMPA HMPA
I I I
O
OH OSmI HMPA
n m
I R
H+ R' R' R HMPA HMPA HMPA
R' R' R' R' Sm or Sm
R R HMPA HMPA HMPA HMPA
I I
-Reduction of the ketone followed by substitution of alkyl-halide with ketyl-radical ruled out by Kagan, because
the use of chiral alkyl-halides leads to racemic products.
-The replacemed of HMPA with LiBr predominately leads to the Pinacol product via inner sphere electron
transport/reduction of the ketone via formation of SmBr .
2
-Replacement of HMPA with HMDS leads to the formation of [Sm(HMDS) ] , which has a redox potential
2 2
inbetween SmI and [Sm(HMPA) ]I [Sm(HMDS) ] reacts faster with alkyl halides and ketones via change in
2 6 2. 2 2
mechanism towards an inner sphere ET process.
Molander, G. J. Am. Chem. Soc. 1987, 6556.
Curran, D. P. Synlett 1992, 943.
Flowers, R. A. Org. Lett. 1999, 2133.
Flowers, R. A. J. Am. Chem. Soc. 2000, 7718.
Flowers, R. A. J. Am. Chem. Soc. 2002, 6895.
Flowers, R. A. J. Am. Chem. Soc. 2002, 14663.
Flowers, R. A. J. Am. Chem. Soc. 2004, 6891.
Intramolecular SmI Barbier Reactions
2
Basic Mechanism
Me Me Me
Me Me Me
K H
C
SmI Me Me Me
2 O O O
C
H+
SmI
2
Me
Me SmI Me Me Me
2
K Me Me Me
I Sm H+
I2Sm OSmI2 OH
Me
O Me O Me Me
B
Me Me Me
Me
Me Me
H+
SmI
2 OSmI OH
2
Me O Me Me
A
Me
SmI (M) A B C D Me
2
0.01 64% 21% 11% 4%
0.03 42% 42% 11% 5%
Me
0.05 27% 55% 13% 5% O
0.07 20% 59% 15% 6% D
Curran, D. P. Tetrahedron 1997, 9023
Krief, A. Chem. Rev. 1999, 745
Reactions performed with 2 equiv of SmI and 20 equiv of HMPA Molander, G. A. J. Org. Chem. 1991, 4112
2
Intramolecular SmI Barbier Reactions
2
Eunicellin and Muscone
CH
O O AcO Me 2
AcO OAc
SmI , THF
2
Me O
I -78 oC to rt Me
Me Me
O Me OAc
OH Me Me
88% Single Diastereomer
Eunicellin
Hoffman, M. R. Tetrahedron 1997, 4331
O
Me 1) HgO, I
Me 2
PhH, hv, O oC
I
Me
SmI , HMPA 59%
2
THF 2) Bu SnH-AIBN
3
O
PhH, hv, 82%
H
H OH
90% Single Diatereomer
(+/-) Muscone
Suginome, H. Tetrahedron 1987, 3963
Intramolecular SmI Barbier Reactions
2
Polyoxypeptin A
Me
HO
Me
Me OH Me O
I Me
OH H
O OH Me
SmI NH HN O
2
OR THF, HMPA OR + OR N H iPr
N N N H H
Ts HO O O
Ts Ts
N O
A B Pr
O OH
Me O H N
R Yield A:B N
HN N
O
H
TBDPS 76% 13:87 Me
OH
Tr 45% 31:69
OH
H 75% 97:3
Polyoxypeptin A
Hamada's Explanation Procter's Explanation
I
I I
Me
I Sm(III)(HMPA)n
O H Me
Me SmI SmI O OP Sm(III)(HMPA)
O 2 N O 2 n
N
H H N Me N O
Ts O O
Ts Ts Ts
H H
H H
Favored Disfavored
-Mechanism might proceed through a bis-radical stucture
Hamada, Y. Tetrahedron Letters 2002, 4695
Procter D. Chem. Rev. 2004, 3371
Me
Intramolecular SmI Barbier Cyclizations Me
2
H
Synthetic Studies Towards Variecolin H
OHC
Me
H
O
OMe
OMe O Me
H
SmI , cat. NiI
2 2 Cl Me
+ OH
THF, 72% Variecolin
I
Cl
1:1 Mixture of diastereomers
due to racemic starting
RuCl , NaIO
materials 3 4
MeCN, CCl , H O
4 2
Model of Intermediate A 65%
O
H
HO
SmI , NiI
2 2 Cl
hv, THF
H O O
63%
H
A
Molander, G. Org. Lett. 2001, 2257
For increased reaction rates with NiI see: Kagan, H. Synlett 1996, 633
2
For increasing reducing ability of SmI with visible light see: Ogawa A. J. Am.
2
Chem. Soc. 1997, 2745
SmI Reformatsky reactions
2
Basic Mechanism
O O
Br 2 equiv SmI O
2
O O Ph O
THF, -78 oC Me
O
SmI THF OH
Ph Me <15min H O n m Ph Me
95%. Single Diastereomer
Molander, G. A. J. Am. Chem. Soc. 1987, 6556
-Due to Sm(III)'s ionic radius, high coordination number, and high oxophilicity: SmI has been used succesfully as
2
a chelation element to bring two reaction centers in proximity for the formation of large ring.
CHO
OH
n Ring Size Yield
(CH ) (CH )
2 n 2 n
Br
6 8 68%
CO Me
2 7 9 70%
CO Me
2
9 11 74%
12 14 82%
O
O 13 15 82%
SmI THF
(CH2)n n m (CH2)n SmInTHFm
O O
OMe
OMe
Inanaga, J. Tetrahedron Lett. 1991, 6371
SmI Intramolecular Reformatsky reactions
2
(+/-) Paeoniflorigenin and Paeoniflorin
O
Me
Slow Addition NC
O
of SmI (7 equiv) O
O 2
H OTIPS
THF, -45 oC HO Me
Cl
O
10h
NC OTIPS
93% Single Diastereomer
H
Chem 3D w/ MM2 energy minimization -Product of the cyclization is base sensitive. Retro-Aldol is
observed upon treatment of product with Et N.
3
HO O HO O
O O
HO Me Me
O O HO
HOHO
OH OH OH
Paeoniflorin Paeoniflorigenin
Corey, E. J. J. Am. Chem. Soc. 1993, 8871