Lewis Base Activation of Lewis Acids: Development of a Lewis Base Catalyzed Selenolactonization Denmark, S.E. and Collins, W.R. Org. Lett. 2007, 9, 3801-3804. Presented by: Melissa Sprachman October 27, 2007 Ph CO 2 H Lewis Base O CH 2 Cl 2 O Ph PhSe + N O O SePh Melissa Sprachman @ Wipf Group 1 10/29/2007
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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.
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