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Lewis Base Activation of Lewis Acids: Development of a LewisBase Catalyzed Selenolactonization
Denmark, S.E. and Collins, W.R. Org. Lett. 2007, 9, 3801-3804.
Presented by: Melissa SprachmanOctober 27, 2007
Ph CO2HLewis Base O
CH2Cl2O
Ph
PhSe+ N
O
O
SePh
Melissa Sprachman @ Wipf Group 1 10/29/2007
Lactonization Reactions
Halolactonization:Corey’s Prostaglandin SynthesisJ. Am. Chem. Soc. 1970, 92, 397. OH
O
OH
OCH3
KI3
H2O, 20 h
O
O
I
OH OCH3
1. Ac2O, pyr, 2. Bu3SnH, PhH O
O
OH OCH3
97% (99%, two steps)
O
HOn-C5H11
(CH2)3CO2H
OH
Mechanism-- Markovnikov Addn:
J. Org. Chem. 1975, 40, 2843.
H CO2- H CO2-
Br+
H CO2-
Br
O CH3
O
Br
H3C
major
Selenolactonization:
Nicolaou’s Prostaglandin SynthesisJ. Am. Chem. Soc. 1981, 103, 3480.
COOCH3
HO
OH
HO
O
HO
SePh
COOCH3
HO
PhSeCl, CH2Cl2
Melissa Sprachman @ Wipf Group 2 10/29/2007
Development of Organoselenium Chemistry
Sharpless: Preparation of Allylic Alcohols:
+ PhSeXSePh
X
ROH SePh
OR
H2O2
THF OR
J. Org. Chem. 1974, 39, 429.
Campos, Clive: Cyclofunctionalization:
OSePh
OH+ PhSeCl
J. Chem. Soc. Chem. Commun. 1977, 725.
Clive, Nicolaou: Selenolactonization:
CO2H PhSeCl, Et3N
CH2Cl2, -78oC, quant.
OO
SePh
H2O2, THFO
O
Raney Ni, THF
OO
J. Am. Chem. 1977, 99, 3185.
Melissa Sprachman @ Wipf Group 3 10/29/2007
Recent Developments in Selenium Chemistry
Selenium catalyzed halolactonization:
HOPh
O+ N O
O
Br cat, PhSeSePh
CH3CNO
O
Br Ph
PhSeSePh
N OO
PhSeSePhBr
RO
OH
NH
OO
O
Br
OR
SePhSePh
O
O
Br R
J. Org. Chem. 2004, 69, 8979.
Melissa Sprachman @ Wipf Group 4 10/29/2007
Developments in Selenium Chemistry
Ph CO2H
Se+
O
O
OTf-
OO
PhSeAr*
99 % de, 62% yield
Use of EnantiopureSelenium Reagents:
Catalytic Use of Selenium Electrophiles:
Ph CO2H
5 mol % PhSeSePhPhI(OCOCF3)2
CH3CN, rt
O OPh(70%)
O OR
R CO2H
Org. Lett. 2007, 9, 3169.
Tetrahedron Lett. 1997, 38, 4753.
Melissa Sprachman @ Wipf Group 5 10/29/2007
Initial Studies on the Mechanism of Selenolactonization
Denmark et al. J. Org. Chem. 2006, 71, 7293
--Based on initial observation of stereospecific
anti-addition of benzenesleneyl halides to alkenes
--Both the episelenurane and the seleniranium ion
have been isolated and characterized
Proposed Mechanism of Selenocyclization:
R2R1
R1 R2Se
X Ph
R1 R2SePh
X-
SePhR2
XR1
+
PhSeX
Melissa Sprachman @ Wipf Group 6 10/29/2007
Lewis Base Activation of Lewis Acids
SiCl4 + P
O
NMe2Me2N NMe2
Cl SiCl
Cl
OP(NMe2)3
OP(NMe2)3
Cl
PhSe X
DL
LL SeD
LLL
XPh
δ+δ- δ-δ+
SeDL
LL
XPh
+ X-
SnBu3 + PhCHO
N
NP
Me
Me
O
NMe
CH2
2
SiCl4 (1.1 equiv), CH2Cl2, -78oC
(5 mol %)
Ph
OH SiLB
LB O
Cl
Cl
Cl
Ph
H
Cl
Via
Activation of a Selenium Electrophile?
Denmark, S. E. in Modern Aldol Reactions; Marhwalk, R., Ed.: Wiley-VCH: Weinheim, 2004
Melissa Sprachman @ Wipf Group 7 10/29/2007
Development of a Lewis Base Promoted Selenolactonization
--Benzeneselenyl chloride reacts witholefins spontaneously at cryogenictemperatures
--Competitive pathways of seleniraniumion trapping and reversible formation ofseleniranium ion exist
---> Choice of Leaving Group is Critical
Ph
Selenamide Yield of Selenolactone (%)
NN
NN
SePh 87
NN
N
SePh79
N
O
O
SePh 18
N
O
O
SePh 8
CO2HR2N-SePh
CH2Cl2, 23oC, 3h
OO
Ph
PhSePh CO2HPhSeCl O
CH2Cl2O
Ph
PhSe
Initially studied reaction:
Melissa Sprachman @ Wipf Group 8 10/29/2007
Finding a Feasible Lewis Base Activator
**Use of softer chalcogens enhanced reaction efficiency: Reaction times ranged from3 h with HMPA to 10 min with thiophosphoramide to < 5 min with selenophosphoramide!
Melissa Sprachman @ Wipf Group 9 10/29/2007
Survey of Lewis Bases
--> Isolated ~10% Selenol ester
PhO
SePh
Melissa Sprachman @ Wipf Group 10 10/29/2007
Mechanistic Insight: Observation of an HMPT-Selenium Adduct
N
O
O
SePh + PMe2N NMe2NMe2
CD2Cl223oC, 30s
N
O
O
SePMe2N
Me2NMe2N
Prior to Olefin Coordination Either…
1.) Ionization of the N-Se bond to form a contact ion pair or
2) Activation of the succinimide LG to form a selenium cation
Role of the Carboxylate Proton:
Melissa Sprachman @ Wipf Group 11 10/29/2007
Postulated Catalytic Cycle Based on Collective Data
Melissa Sprachman @ Wipf Group 12 10/29/2007
Recent Developments in Electrophile-Promoted Cyclizations
N N
O O t-Bu
t-But-Bu
t-Bu Co
I2, CH2Cl2-78oC
1.
2. HOPh
OPh
I
J. Am. Chem. Soc. 2003, 125, 15748.
Nature, 2007, 445, 900.
SiPh3
OO P N
H
Ph
SiPh3
Nu* =
Melissa Sprachman @ Wipf Group 13 10/29/2007
Summary and Outlook
-- Lewis base catalyzed selenolactonization was performed, and viable proof for reactionintermediates was established.
--The successful suppression of the background reaction and rapid turnover rate make asymmetricmodifications a possibility.
-- The inherent toxicity of selenium may prove a barrier in the overall utility of these transformations;however, the concept of Lewis base activation of electrophiles is worthwhile.
Melissa Sprachman @ Wipf Group 14 10/29/2007
Development of a Lewis Base Promoted Selenolactonization
Ph CO2H
PhSeCl O
CH2Cl2O
Ph
PhSe
--Benzeneselenyl chloride reacts with olefins spontaneously at cryogenic temperatures
--Competitive pathways of seleniranium ion trapping and reversible formation ofseleniranium ion exist
---> Choice of Leaving Group is Critical
Melissa Sprachman @ Wipf Group 15 10/29/2007