Lewis base activation of lewis acids: Development of a lewis base catalyzed selenolactonization

Article abstract of DOI:10.1021/ol701617d

The concept of Lewis base activation of Lewis acids has been applied to the selenolactonization reaction. Through the use of substoichiometric amounts of Lewis bases with "soft" donor atoms (S, Se, P) significant rate enhancements over the background reac

Full text of DOI:10.1021/ol701617d

ORGANIC
LETTERS
2007
Vol. 9, No. 19
3801-3804
Lewis Base Activation of Lewis Acids:
Development of a Lewis Base Catalyzed
Selenolactonization
Scott E. Denmark* and William R. Collins
Roger Adams Laboratory, Department of Chemistry, UniVersity of Illinois,
600 South Mathews AVenue, Urbana, Illinois 61801
denmark@scs.uiuc.edu
Received July 10, 2007
ABSTRACT
The concept of Lewis base activation of Lewis acids has been applied to the selenolactonization reaction. Through the use of substoichiometric
amounts of Lewis bases with “soft” donor atoms (S, Se, P) significant rate enhancements over the background reaction are seen. Preliminary
mechanistic investigations have revealed the resting state of the catalyst as well as the significance of a weak Brønsted acid promoter.
The asymmetric functionalization of prochiral olefins is one
of the most powerful transformations in organic chemistry.
From large-scale generation of bulk chemicals to the late
stages of a complex molecule synthesis, asymmetric epoxi-
dations,1 dihydroxylations,2 aminohydroxylations,3 and hy-
droborations4 are invaluable methods for the chemo-, regio-,
and stereoselective introduction of functional groups. In
addition to redox chemistry, stereoselective, electrophile-pro-
moted, nucleophilic addition reactions to olefins are efficient
methods for the preparation of a multitude of stereodefined,
synthetically relevant acyclic and heterocyclic structures.5
Despite the significance of these transformations, catalytic,
enantioselective variants are, with few exceptions, outside
of transition-metal-initiated processes, limited to the above-
mentioned redox-based reactions.6 Stereoselective, electro-
philically initiated olefin additions have primarily relied on
substrate- or reagent-controlled diastereoselectivity.
is known. This is particularly surprising, as selenium electro-
philes efficiently promote intramolecular cyclization for the
construction of functionalized rings.7 Moreover, the resultant
arylselenide is a versatile group that can undergo oxidative
elimination as well as radical homologation reactions.7 Thus
far, efforts at stereocontrol in the selenofunctionalization of
olefins have relied on the stoichiometric preparation and use
of chiral selenium derivatives.8 Although synthetically useful
diastereoselectivities have been achieved for several sele-
nylation reactions, the multistep preparation of the chiral
selenide detracts from the utility of these methods.
(4) Burgess, K.; van der Donk, W. A. In AdVanced Asymmetric Synthesis;
Stephenson, G. R., Ed.; Chapman & Hall: London, 1996.
(5) Schmid, G. H.; Garratt, D. G. In The Chemistry of Double Bonded
Functional Groups; Patai, S., Ed.; Wiley: New York, 1977.
(6) (a) Sakakura, A.; Ukai, A.; Ishihara, K. Nature 2007, 445, 900-
903. (b) Kang, S. H.; Kim, M.; Kang, S. Y. Angew. Chem., Int. Ed. 2004,
43, 6177-6180. (c) Kang, S. H.; Lee. S. B.; Park, C. M. J. Am. Chem.
Soc. 2003, 125, 15748-15749. (d) Browne, D. M.; Niyomura, O.; Wirth,
T. Org. Lett. 2007, 9, 3169-3171.
(7) (a) Nicolaou, K. C.; Petasis, N. A. In Selenium in Natural Product
Synthesis; CIS: Philadelphia, 1984. (b) Paulmier, C. Selenium Reagents
and Intermediates in Organic Synthesis; Pergamon Press: Oxford, 1986.
(c) Liotta, D. Organoselenium Chemistry; John Wiley: New York, 1986.
(d) Organoselenium ChemistrysA Practical Approach; Back, T. G., Ed.;
Oxford University Press: Oxford, 1999. (e) Ranganathan, S.; Muraleedharan,
K. M.; Vaish, N. K.; Jayaraman, N. Tetrahedron 2004, 60, 5273-5308. (f)
Petragnani, N.; Stefani, H. A.; Valduga, C. J. Tetrahedron 2001, 57, 1411-
1448. (g) Tiecco, M. Electrophilic Selenium, Selenocyclization, in Topics
in Current Chemistry: Organoselenium Chemistry; Wirth, T., Ed.;
Springer: Heidelberg, 2000; pp 7-54. (h) Back, T. G. In The Chemistry of
Organic Selenium and Tellurium Compounds; Patai, S., Ed.; Wiley: New
York, 1987; Vol. 2, pp 94-215.
A case in point is the selenofunctionalization of olefins.
To date, no catalytic, enantioselective variant of this reaction
(1) (a) Katsuki, T. In ComprehensiVe Asymmetric Catalysis; Jacobsen,
E. N., Pfaltz, A., Yammamoto, H., Eds.; Springer: Heidelberg, 1999; Vol.
2, Chapter 18.1. (b) Jacobsen, E. N.; Wu, M. In ComprehensiVe Asymmetric
Catalysis; Jacobsen, E. N., Pfaltz, A., Yammamoto, H., Eds.; Springer:
Heidelberg, 1999; Vol. 2; Chapter 18.2.
(2) Marko, I. E.; Svendson, J. S. In ComprehensiVe Asymmetric Catalysis;
Jacobsen, E. N., Pfaltz, A., Yammamoto, H., Eds.; Springer: Heidelberg,
1999; Vol. 2, Chapter 20.
(3) (a) Li, G.; Chang, H. T.; Sharpless, K. B. Angew. Chem., Int. Ed.
Engl. 1996, 35, 451-454. (b) Li, G.; Angert, H. H.; Sharpless, K. B. Angew.
Chem., Int. Ed. Engl. 1996, 35, 2813-2817.
10.1021/ol701617d CCC: $37.00
© 2007 American Chemical Society
Published on Web 08/17/2007

Recently, we have undertaken a broadly based program
to investigate opportunities for catalysis within the Main
Group.9 In particular, we are interested in expanding the
concept of Lewis base activation of Lewis acids10 to include
selenium-induced reactions (Scheme 1). By analogy to
previous work from this laboratory,11 coordination of a strong
Lewis base donor to an arylselenium electrophile could
enhance the electrophilicity at the selenium atom through a
net polarization of the electron density of the resultant Lewis
acid-base adduct.12 In the limit of this polarization, ioniza-
tion of a ligand on the arylselenium moiety could occur,
resulting in a highly electrophilic selenium cation. After the
Lewis base-selenium adduct has undergone successful
reaction with an olefin, fission of the dative bond between
the Lewis base and the selenium atom would allow for
turnover. Finally, if the Lewis base is chiral, the catalyzed
reaction pathway could occur in a chiral environment and
thus might allow for enantiotopic face selection. Herein we
report the first examples of Lewis base catalyzed selenolac-
tonization and identify key features of the catalysts and
reactive intermediates.
bined with 1 at a rate and yield on par with that observed
with benzeneselenyl chloride (Scheme 2). Modifying the
selenium electrophile to incorporate a benzotriazole instead
of the tetrazole qualitatively (as monitored by NMR) slowed
the reaction slightly. Nonetheless, the N-phenylselenylben-
zotriazole 4 still afforded 2 in 79% yield in 3 h. Only by
changing to N-phenylselenylphthalimide 5 was a significant
decrease in the background reaction seen, as 2 was isolated
in only 18% yield. Finally, N-phenylselenylsuccinimide
(NPSS) 6, which lacks the electronically stabilizing arene
ring of the phthalimide, afforded 2 in only 8% yield after 3
h at room temperature. Thus, near complete suppression of
the background reaction could be achieved with the use
of 6.
Scheme 2. Selenenamide Background Reaction Survey with 1
Scheme 1. Lewis Base Activation of a Selenium Electrophile
The key proof of principle experiment involved identifying
a viable Lewis base activator for the NPSS-promoted
reaction. Gratifyingly, using only 10 mol % of HMPA (7)
brought about a considerable rate enhancement.16 After 3 h,
2 was isolated in 55% yield (Table 1). To our knowledge,
this is the first example of a Lewis base catalyzed seleno-
functionalization reaction.
The selenolactonization of (E)-4-phenyl-3-butenoic acid
1 was chosen as the test reaction for the development of a
Lewis base catalyzed process. Earlier mechanistic investiga-
tions13 had shown that the most common selenylating agent,
benzeneselenyl chloride, reacted with olefins spontaneously
even at cryogenic temperatures. Additionally, the lactoniza-
tion reaction was complicated by competitive trapping of
the putative seleniranium species14 with chloride ion as well
as by reversible seleniranium ion formation. Thus, the study
began by investigating whether judicious choice of the
leaving group (X) could suppress both the background and
side reactions.
Selenenamides were particularly appealing choices at the
outset of this study because of the ease of synthesis, the
ability to tune the electronic character of the selenium elec-
trophile, and the non-nucleophilicity of the amide counter-
ion.15 In the first experiment, N-phenylselenyltetrazole 3 com-
Table 1. Lewis Base Catalyzed Selenolactonization of 1
entry
Lewis base catalyst
yield,a %
1
2
3
(Me2N)3PdO (7)
(Me2N)3PdS (8)
(Me2N)3PdSe (9)
55
89
95
a Isolated yield of chromatographically homogeneous material
Kinetic analysis of the interactions of a variety of Lewis
bases with o-nitrobenzeneselenyl halides shows that sulfur-
(8) For recent reviews on the subject, see: (a) Browne, D. M.; Wirth,
T. Curr. Org. Chem. 2006, 10, 1893-1903. (b) Wirth, T. Angew. Chem.,
Int. Ed. Engl. 2000, 39, 3740-3749.
(9) Denmark, S. E.; Fujimori, S. In Modern Aldol Reactions; Marhwald,
R., Ed.; Wiley-VCH: Weinheim, 2004; Vol. 2, Chapter 7. (b) Denmark,
S. E.; Stavenger, R. A. Acc. Chem. Res. 2000, 33, 432-440.
(10) Denmark, S. E.; Beutner, G. L. Angew. Chem., Int. Ed. 2007, in
press.
(11) (a) Denmark, S. E.; Beutner, G. L.; Wynn, T.; Eastgate, M. D. J.
Am. Chem. Soc. 2005, 127, 3774-3789. (b) Denmark, S. E.; Wynn, T.;
Beutner, G. L. J. Am. Chem. Soc. 2002, 124, 13405-13407.
(12) (a) Gutmann, V. The Donor-Acceptor Approach to Molecular
Interactions; Plenum Press: New York, 1978. (b) Jensen, W. B. The Lewis
Acid-Base Concept; Wiley-Interscience: New York, 1980.
(13) Denmark, S. E.; Edwards, M. G. J. Org. Chem. 2006, 71, 7293-
7306.
(14) Schmid, G. H.; Garratt, D. G. Tetrahedron Lett. 1975, 16, 3991-
3994.
(15) (a) Kirsch, G.; Christiaens, L. In The Chemistry of Organic Selenium
and Tellurium Compounds; Patai, S., Ed.; Wiley: New York, 1987; Vol.
2; pp 421-461. (b) Nicolaou, K. C.; Petasis, N. A.; Claremon, D. A.
Tetrahedron 1985, 41, 4835-4841.
(16) The reactions were monitored by in situ ReactIR spectroscopy. The
increase in the selenolactone signal allowed for qualitative rate comparisons
of these reactions. See the Supporting Information.
3802
Org. Lett., Vol. 9, No. 19, 2007

based donors generally have a stronger interaction than the
corresponding oxygen-based donors. These studies suggest
that the highly polarizable selenium center might bind more
strongly to soft, polarizable chalcogen donors.17 Thus, the
thio- (8) and selenophosphoramide (9) analogues were pre-
pared and tested (Table 1). The increased efficacy of these
catalysts was immediately apparent. Whereas with HMPA
the selenolactonization reaction went to ∼60% conversion
in 3 h, with 10 mol % of the HMPA(S) (8) the reaction went
nearly to completion in 10 min. After workup, an 89% yield
of the lactone 2 was isolated. Utilizing HMPA(Se) (9) had
an even more dramatic effect as the reaction went rapidly
to completion in under 5 min, providing a 95% yield of
lactone 2!
these reagents underwent oxidation to the phosphorus(V)
compounds with concomitant formation (ca. 10%) of the
corresponding selenol ester. These reactions most likely
proceed via a mechanism similar to that invoked by Grieco.18
The stereospecificity of the selenolactonization was in-
vestigated next with the stereoisomeric (Z)-4-phenyl-3-
butenoic acid 11 (Scheme 3). Previous mechanistic studies
by Schmid and Garratt as well as by Luh and co-workers
showed that the nucleophilic trapping of the seleniranium
ion is a stereospecific anti ring opening.14,19 Thus, (E)-olefins
should generate trans lactones, and (Z)-olefins should give
the cis isomers.
An expanded set of structurally diverse Lewis base donors
were next tested under the selenolactonization reaction
conditions (Table 2). With 10 mol % of either triphenylphos-
phine oxide or tricyclohexylphosphine oxide as the donor
the selenolactonization reaction did not proceed much further
than the background reaction. Employing a substoichiometric
amount of the cyclic urea DMPU gave slightly better results
(Table 2, entry 3), comparable to those with HMPA (Table
1, entry 1). On the other hand, the sulfide derivatives of these
Lewis bases gave much better results. Thus, employing 10
mol % of either triphenylphosphine sulfide, tricyclohexyl-
phosphine sulfide, or the sulfur analogue of DMPU, lactone
2 could be isolated in excellent yield.
Scheme 3. Stereospecific Selenolactonization
The synthesis of geometrically homogeneous 11 proceeded
according to the procedure developed by Sullivan.20 The se-
quence consisted of a stereoselective nickel-catalyzed addi-
tion of phenylmagnesium bromide to 2,3-dihydrofuran fol-
lowed by a Jones oxidation of the primary alcohol. With
the acid in hand, treatment of 11 with 1.2 equiv of NPSS
and 10 mol % of HMPA(Se) provided a 94% yield of the
cis-lactone 12 exclusively. This result implies that the reac-
tion proceeds via a mechanism similar to the uncatalyzed
process.
Table 2. Extended Survey of Lewis Bases
The divergence of pathways in the phosphorus(III)-
catalyzed reactions stimulated an investigation aimed at
identifying the nature of the reactive intermediates to obtain
a clearer mechanistic picture of the catalytic cycle. Many
phosphorus(III)-selenium(II) adducts have been spectro-
scopically characterized and thus provided good reference
points for a multinuclear, solution NMR study (Scheme 4).
Combining HMPT in a 1:1 stoichiometry with NPSS (6) in
CDCl3 led to an instantaneous disappearance of the 31P NMR
resonance of HMPT (δ 31P, 122 ppm). The parent signal
was replaced with a new doublet at 60.2 ppm with 1JSe-P of
488 Hz. Additionally, the 77Se NMR spectrum revealed the
absence of the signal for 6 at 1181 ppm21 and the appearance
a Isolated yield of chromatographically homogeneous material. b Isolation
of ∼10% of the selenol ester, with oxidation of the P(III) catalyst to the
P(V) species.
1
of a doublet at 290.4 ppm with a JSe-P of 488 Hz. These
(17) (a) Austad, T. Acta Chem. Scand. 1977, 31, 227-231. (b) Austad,
T. Acta Chem. Scand. 1977, 31, 93-103. (c) Austad, T. Acta Chem. Scand.
1976, 30, 579. (d) Austad, T. Acta Chem. Scand. 1975, 29, 895-906.
(18) (a) Grieco, P. A.; Jaw, J. Y. J. Org. Chem. 1981, 46, 1215-1217.
(b) Grieco, P.; Yokoyama, Y.; Williams, E. J. Org. Chem. 1978, 43, 1283-
1285.
(19) (a) Schmid, G. H.; Garratt, D. G. Tetrahedron 1978, 34, 2869-
2872. (b) Luh, T. Y.; So, W. H.; Cheung, K. S.; Tam, S. W. J. Org. Chem.
1985, 50, 3051-3053.
(20) Baumgartner, H.; Sullivan, A. C.; Schneider, J. Heterocycles 1997,
45, 1537-1549.
The superior behavior of the “soft” sulfur and selenium
Lewis base derivatives could be extended also to phosphorus-
(III) species (Table 2, entries 7-9). Hexamethylphosphorous
triamide (HMPT) proved to be a very effective catalyst
affording lactone 2 in a 92% yield. Interestingly, both N,N′-
dimethyl diphenylphosphoramidite and triphenyl phosphite
afforded no lactone product. Closer inspection of the 31P
NMR spectra of the crude reaction mixtures showed that
Org. Lett., Vol. 9, No. 19, 2007
3803

data are nearly identical to the spectroscopic data given
for the phenylselenyl iodide-HMPT adduct prepared by
Godfrey and co-workers.22,23 It is therefore reasonable to
assume that the HMPT‚6 complex 13 exists as a hypervalent
10-Se-3 charge-transfer species. Importantly, the same
spectroscopic change occurs when the HMPT was used in a
substoichiometric quantity during the course of a selenolac-
tonization reaction. The new 31P NMR peak at ca. 61 ppm
persists throughout the time course of the reaction and is
currently believed to be the resting state of the catalyst.
Taken together, all of this data reveals a consistent
mechanistic picture of the Lewis base catalyzed selenolac-
tonization reaction (Figure 1). The Lewis base catalyst
coordinates to the selenium electrophile producing a hyper-
valent Lewis base-selenium complex. Subsequent protona-
tion of the succinimide by a carboxylic acid forms the fully
ionized phenylselenyl cation. Nucleophilic attack on the
selenium by the olefin forms the putative seleniranium
species with concomitant ejection of the Lewis base. The
seleniranium is then trapped by the pendant carboxylate to
afford the selenolactone product.
Scheme 4. HMPT-Selenium Adduct
If the resting state of the catalyst is the putative hypervalent
10-Se-3 species, the selenium atom is coordinatively satu-
rated. Therefore, one of two events must occur prior to olefin
coordination: (1) ionization of the nitrogen selenium bond
directly to form a contact ion pair or (2) activation of the
succinimide leaving group to form a selenium cation. That
activation could come from the weak Brønsted acidity of
the carboxylic acid.
Figure 1. Proposed catalytic cycle.
This possibility was tested by sequestering the proton with
a stoichiometric amount of the bulky base 2,6-di(tert-butyl)-
4-methylpyridine (DTBMP) 14 (Table 3). Under standard
reaction conditions (10 mol % of 9, 3 h, rt), the salt afforded
no lactone product. Similarly, by employing the trimethylsilyl
(E)-4-phenyl-3-butenoate ester 15 instead of a carboxylic
acid, the catalyzed reaction did not proceed. Further support
for a critical role of the carboxylic acid proton was secured
from a reaction of ester 15 in the presence of 1.0 equiv of
acetic acid.24 Without a Lewis base catalyst, the lactone could
be isolated in only 13% yield, similar to the background
reaction of 10. However, with 10 mol % of 9, the reaction
went to completion in 3 h.
Current efforts are focused on the expansion of this
concept to other reactions with selenium as an electrophile
as well other Main Group elements. Through structural
modification of these catalysts we are also in the process of
developing asymmetric variants of these reactions.
Acknowledgment. We are grateful to the National
Science Foundation for generous financial support (CHE
0414440). W.R.C. thanks Lilly Research Laboratories for a
graduate fellowship. We also thank Dr. Michael G. Edwards
for preliminary experiments and helpful discussions.
Supporting Information Available: Detailed procedures
for the preparation and characterization of all new com-
pounds along with ReactIR data. This material is available
free of charge via the Internet at http://pubs.acs.org.
Table 3. Effect of the Carboxylate Proton on Reactivity
OL701617D
(21) Hosay, T.; Christiaens, L. Tetrahedron. Lett. 1990, 31, 873-874.
(22) The spectroscopic data reported for the complex is 31P NMR δ 61.6
(JP-Se 494.2 Hz): Godfrey, S.; Ollerenshaw, R. T.; Pritchard, R. G.;
Richards, C. L. J. Chem. Soc., Dalton Trans. 2001, 508-509.
(23) For additional relevant phosphorus-selenium complexes, see: (a)
Barnes, N. A.; Godfrey, S. M.; Halton, R. T.; Mustaq, I.; Pritchard, R. G.
J. Chem. Soc., Dalton Trans. 2006, 4795-4804. (b) Barnes, N. A.; Godfrey,
S. M.; Halton, R. T.; Mushtaq, I.; Pritchard, R. G.; Sarwar, S. J. Chem.
Soc., Dalton Trans. 2006, 1517-1523. (c) Boyle, P. D.; Godfrey, S. M.;
McAuliffe, C. A.; Pritchard, R. G.; Sheffield, J. M. Chem. Commun. 1999,
2159-2160.
entry
1
R
conditions
yield,a %
0
H (1)
1.0 equiv of DTBMP,
0.1 equiv of (Me2N)3PdSe
0.1 equiv of (Me2N)3PdSe
1.0 equiv of AcOH
1.0 equiv of AcOH,
0.1 equiv of (Me2N)3PdSe
2
3
4
SiMe3 (15)
SiMe3 (15)
SiMe3 (15)
0
13
91
(24) NMR experiments confirmed that the metathetical reaction between
the TMS ester and acetic acid is slow and does not reach equilibrium within
8 h.
a Isolated yield of chromatographically homogeneous material.
3804
Org. Lett., Vol. 9, No. 19, 2007