Stereospecific functionalization of iodoaziridines via unstabilized aziridinyllithiums generated by iodine-lithium exchange

Article abstract of DOI:10.1021/ol501024y

Lithium-iodine exchange on alkyl- or aryl-substituted N-tosyliodoaziridines afforded unstabilized aziridinyllithiums, which were subsequently trapped at low temperatures with a range of carbon and heteroatom electrophiles affording cis-substituted aziridi

Full text of DOI:10.1021/ol501024y

Letter
pubs.acs.org/OrgLett
Stereospecific Functionalization of Iodoaziridines via Unstabilized
Aziridinyllithiums Generated by Iodine−Lithium Exchange
Tom Boultwood and James A. Bull*
Department of Chemistry, Imperial College London, South Kensington, London SW7 2AZ, U.K.
S
* Supporting Information
ABSTRACT: Lithium−iodine exchange on alkyl- or aryl-
substituted N-tosyliodoaziridines afforded unstabilized azir-
idinyllithiums, which were subsequently trapped at low
temperatures with a range of carbon and heteroatom
electrophiles affording cis-substituted aziridines exclusively.
When using isocyanates as electrophiles, access to aziridine carboxamides or 1,3,5-trisubstituted hydantoins can be selected by
control of reaction temperature.
ziridines are an important class of saturated heterocycles
A
often used as synthetic intermediates.1,2 The strained
three-membered ring is prone to ring-opening with a variety of
nucleophiles affording functionalized amines and other valuable
N-containing compounds.3,4 Consequently, there is continued
interest in developing improved methods for the synthesis of
aziridine derivatives.5 In recent years, there has been significant
interest in the divergent synthesis of aziridine derivatives by
functionalization of preformed, intact aziridine rings. This has
been achieved through the generation of aziridinyl anions and
reaction with electrophiles.6 Unstabilized aziridinyl metal
species have been generated by functional-group exchange
9
(SOR,7 SnBu3,8 SiR3 ) and by direct deprotonation of aziridine
derivatives.10−12 Palladium-catalyzed cross-coupling of meta-
lated aziridine species has also been reported recently by our
group13 and Vedejs14 to afford aryl- and vinylaziridines.
To date, the generation of N-sulfonylaziridinyllithium species
has only been possible through deprotonation, though the
success of the reaction with electrophiles, as well as the
regiochemical outcome, has been dependent on the nature of
the N-group and the inherent substitution of the aziridine.6
Notably, external electrophilic trapping of lithiated N‑tosylazir-
idines has not been successful,11 in part due to rapid
intramolecular nucleophilic attack at the toluene sulfonyl
group (Figure 1A).15,9 Schaumann and Aggarwal observed
that lithiation of phenyl N-tosylaziridine derivatives resulted in
dearomatization by reaction of the added electrophiles adjacent
to the sulfonyl group, yielding a tricyclic product.15,9 More
recently, N-Bus (tert-butyl sulfonyl) aziridines have been
successfully applied in lithiation/trapping sequences (Figure
1B).11 Hodgson reported that monoalkyl N-Bus aziridines
undergo regio- and stereoselective deprotonation with LiTMP
and that trapping with reactive electrophiles gave trans-
substituted aziridines.11a,b On the other hand, Florio and co-
workers observed that aryl substitution on the aziridine ring
results in benzylic deprotonation.11c It is notable that the
anions of these activated aziridines are carbenoid-like16 and
require low temperatures for structural stability. A stabilizing
interaction between the sulfonyl group and the lithium has
Figure 1. Functionalization of N-sulfonylaziridines via aziridinyllithium
intermediates keeping the aziridine intact.
been proposed in these instances to account for stereo-
selectivity and configurational stability.11
We recently reported strategies for the synthesis of a range of
aryl-17 and branched alkyl-substituted cis-iodoaziridines.17b We
envisaged that iodoaziridines could provide suitable precursors
for further derivatization of the intact aziridine. In particular,
the regio- and stereospecific lithiation by Li−I exchange from
N-tosyliodoaziridines would afford cis-N-tosylaziridines (Figure
1C) and provide complementary stereo- and regiochemical
access to N-sulfonylaziridinyllithium species versus deprotona-
tion approaches. The success of this strategy would be reliant
upon several factors: (i) the lithiated aziridine must be
Received: April 8, 2014
Published: May 1, 2014
© 2014 American Chemical Society
2740
dx.doi.org/10.1021/ol501024y | Org. Lett. 2014, 16, 2740−2743

Organic Letters
Letter
sufficiently structurally stable to avoid degradation or other
possible reactions (e.g., carbenoid dimerization, ring-open-
ing);12 (ii) the lithiated aziridine must be formed and react
stereospecifically with retention, and be configurationally stable
to afford the cis product; (iii) the N-tosyl group must remain
trans to C−Li to avoid addition to the tosyl group;15 this is
likely the preferred conformation due to the presence of the R-
group, but precludes the possibility of stabilizing interactions by
coordination of the sulfonyl oxygen with lithium; and (iv) to
ensure regiospecific reaction with aryl-substituted aziridines, the
anion must not equilibrate to the more stabilized benzylic
position.
Here, we report the successful stereospecific lithiation of N-
tosyliodoaziridines and trapping with a range of electrophiles to
afford cis-substituted aziridines in high yields with alkyl- and
aryl-substituted iodoaziridine derivatives. We also report the
selective synthesis of a range of 1,3,5-substituted hydantoins
using aryl and alkyl isocyanates via a lithium−iodine exchange,
trapping, and aziridine ring-opening sequence.
Lithium−halogen exchange is a highly effective and rapid
process for the generation of organolithium species from the
corresponding halides, driven by pKa considerations.18 Knochel
recently reported the generation of stereodefined acyclic
organolithium compounds and also axial and equatorial
cyclohexyllithium derivatives from iodides using t-BuLi.19
High retention of the stereochemical configuration at the
reacting center was achieved on trapping with reactive
electrophiles. We started our studies from iodoaziridine 1
(Scheme 1), intending to submit to conditions for lithium−
Table 1. Optimization of Li−I Exchange Protocol and
Trapping of Aziridinyllithium with 3-Pentanone
b
yield (%)
a
c
entry deviation from standard conditions
4a
5
1
1
2
3
4
5
6
7
8
9
none
83
61
76
11
17
0
14
0
n-BuLi (1.2 equiv)
n-BuLi 91.2 equiv)/30 s lithiation
reaction run at −78 °C
hexane/Et2O (3:2), instead of THF 10
hexane/THF (3:2), instead of THF 46
22
15
36
4
23
54
17
0
29
THF/Et2O (3:2), instead of THF
no 3-pentanone
73
0
17
d
90 (86)
11
0
e
d
concentration = 0.065 M
84 (81)
0
a
Reaction conditions: n-BuLi (1.5 equiv), THF (0.13 M), −100 °C;
then addition of aziridine (0.27 mmol) in THF, 5 s; then 3-pentanone
b
1
(3.0 equiv), THF, −100 °C, 5 min. Yield determined by H NMR
spectroscopy with reference to an internal standard (1,3,5-trimethox-
ybenzene). Unreacted iodoaziridine 1. Isolated yield. n-BuLi
c
d
e
concentration before aziridine addition.
Performing the reaction at −78 °C gave poor results due to
the structural instability of the unstabilized anion at this
increased temperature. Toluene sulfonamide was the major
identifiable product at this temperature.16b Various solvent
combinations were attempted, aiming to reduce the formation
of aziridine 5 (Table 1, entries 5−7), including those
successfully used by Knochel.19 With iodoaziridine 1, THF
alone was found to be superior to being in combination with n-
hexane or diethyl ether, which may be due in some part to poor
solubility of the iodoaziridine in these systems. In the absence
of the addition of 3-pentanone under the optimized reaction
conditions, protonated aziridine 5 was formed in high yield
after the 5 min reaction time (Table 1, entry 8). No significant
degradation of the lithiated aziridine was observed in this time
frame, indicating structural stability at low temperature, and
addition to the N-tosyl group was also not observed, which
suggests configurational stability. Ultimately, we chose to
perform the reaction under the more dilute conditions to
investigate the reaction scope (Table 1, entry 9), to aid
temperature control during addition of the aziridine and
electrophile.
The scope of the reaction was explored varying the
electrophile (Scheme 2), forming exclusively cis-substituted
aziridines in all cases. Under the final conditions, a yield of 81%
was obtained for 4a. Alkyl and aromatic aldehydes both
provided the corresponding cis-aziridinyl alcohols 4b and 4c,
respectively, in excellent yield.21 Reaction with 5 equiv of
MeOD afforded deuterated aziridine 4d with 95%-D
incorporation.
cis-Heteroatom-substituted aziridines, silane 4e and sulfide
4f, were accessed via trapping of the aziridinyllithium species
with Me3SiCl and (PhS)2 respectively. In the case of (PhS)2,
butyl phenyl sulfide was observed in the crude mixture due to
the reaction of n-BuI generated in the I/Li exchange with the
phenyl thiolate leaving group. This may act to protect the
aziridine product from ring-opening with the thiolate
nucleophile. cis-Aziridine aldehyde 4g was accessed by trapping
Scheme 1. Preparation of Iodoaziridine Substrates
iodine exchange and then trap with electrophiles. cis-
Iodoaziridines 1−3 were prepared in gram quantities according
to our previously reported method by the addition of
diiodomethyllithium to N-tosylimines and highly stereo-
selective cyclization.20
Our initial studies used t-BuLi, with temperature control
found to be crucial. Performing the reaction at −100 °C rapidly
generated the aziridinyllithium, which could be trapped keeping
the ring intact. However, from the perspective of cost and
safety, we chose to further develop the reaction using n-BuLi.
The exchange was also rapid with this reagent, and there was no
apparent reaction of the lithiated intermediate with the
generated n-BuI at the low reaction temperature. After
extensive experimentation we established a robust and
reproducible protocol to generate the desired aziridinyllithium
and react with 3-pentanone in high yields (Table 1, entry 1).
The procedure involved the addition of a solution of the
aziridine in THF to a solution of 1.5 equiv of n-BuLi at −100
°C. After 5 s, the lithiation was complete and an excess of
electrophile was added to afford an 83% yield of desired
1
aziridine 4a (measured by H NMR spectroscopy against an
internal standard), along with a small amount of protonated
aziridine 5. Each parameter was varied during optimization, and
selected results are included in Table 1. Reduced quantities of
n-BuLi (1.2 equiv) led to recovered starting iodide, which was
improved using a longer time for the lithiation step 4a (Table 1,
entries 2 and 3).
2741
dx.doi.org/10.1021/ol501024y | Org. Lett. 2014, 16, 2740−2743

Organic Letters
Letter
Scheme 2. Formation of cis-Substituted Aziridines via Li−I
Table 2. Formation of 1,3,5-Trisubstituted Hydantoin via
Intramolecular Aziridine Ring-Opening
a
Exchange/Electrophilic Trapping
a
entry
conditions
4j/8
yield (%)
1
2
3
4
5
−100 °C, 5 min
−100 °C, 10 min
warm to −90 °C, 5 min
warm to −78 °C, 5 min
warm to −0 °C, 5 min
6.8:1
2.4:1
3.8:1
1.5:1
8 only
4j, 65
8, 85
a
1
Ratio from H NMR spectroscopy of crude reaction mixture.
entries 3 and 4). Full conversion to hydantoin 8 was achieved
by warming the reaction mixture to 0 °C directly after addition
of the electrophile, leading to the formation of hydantoin 8 as a
single diastereoisomer in 85% yield.
Mechanistically, we propose that the amide anion generated
by the first addition reacts with the excess phenyl isocyanate
(Scheme 3).23 From this compound, aziridine opening (5-exo-
a
Reaction conditions: n-BuLi (1.5 equiv), THF (0.065 M) −100 °C,
Scheme 3. Proposed Mechanism and Examples of Formation
of Hydantoins Using Isocyanates as Electrophiles
addition of aziridine (0.27 mmol) in THF, 5 s; then electrophile (3.0
equiv), THF, −100 °C, 5 min. dr observed by 1H NMR spectroscopy
in crude reaction mixture. 5.0 equiv of MeOD used. 1.0 equiv of imine
used. Reaction mixture warmed to −90 °C. Contained 5 as an
inseparable impurity (13% yield). Yield for 4i calculated on the basis of
desired product only.
a
the aziridinyllithium with DMF. Reaction with 1 equiv of
phenyl N-tosyl imine gave rise to a mixture of cis-aziridine
amines in excellent yield and modest dr at the newly formed
stereocenter. No reaction occurred between the aziridinyl-
lithium and iodomethane under the optimized conditions.
However, methylation could be promoted by warming the
reaction mixture to −90 °C to afford the cis-aziridine 4i. Aryl-
substituted aziridines 2 and 3 were subjected to the optimized
conditions and trapping with butyraldehyde, and cis-aziridines 6
and 7 were formed exclusively, with no reaction at the benzylic
position. In all cases, only the cis-substituted aziridine was
a
Reaction conditions: n-BuLi (1.5 equiv), THF (0.065 M) −100 °C,
addition of aziridine (0.27 mmol) in THF, 5 s; then isocyanate (3.0
equiv), THF, −100 °C, then 0 °C, 5 min. Aziridine carboxamide 4k
also isolated in 44% yield.
1
observed, supported by coupling constants in the H NMR
spectrum of the crude reaction mixture (e.g., for aziridine 4a, δ
2.88 ppm, J = 7.2 Hz for the aziridine CH(CEt2OH); cf. J = 4−
5 Hz for typical trans-aziridine substitution).11 This stereo-
chemical outcome suggests that the Li−I exchange occurs
without the involvement of radical intermediates, which would
be expected to afford epimerization.18
Initial attempts to trap the lithiated intermediate with phenyl
isocyanate showed interesting further reactivity after the initial
electrophilic trapping. The anticipated product 4j was formed
along with cyclized hydantoin 8 as a single diastereoisomer
(Table 2, entry 1).
Hydantoins are interesting scaffolds in medicinal chemistry
and are found in many biologically active compounds.22 As this
approach afforded a rapid synthesis of substituted hydantoins as
single diastereoisomers, we optimized for the formation of this
product. Prolonged reaction time gave rise to increased
amounts of hydantoin 8 (Table 2, entry 2). Warming of the
reaction mixture after the addition of phenyl isocyanate led
further increases in the formation of the hydantoin (Table 2,
tet) afforded the hydantoin as a single diastereoisomer. A range
of isocyanates were then examined under conditions to the
form the 1,3,5-trisubstituted hydantoins from iodoaziridine 1.
Aryl isocyanates afforded hydantoins 8−11. Monoaddition was
also observed with the more electron-rich isocyanate to afford
4k alongside 10, indicating a slower second addition. Primary
and secondary alkyl isocyanates were also employed to access
N-alkyl 1,3,5-trisubstituted hydantoins (12 and 13).
In summary, we have established an effective lithium−iodine
exchange protocol from alkyl and aryl iodoaziridines, leading to
their stereospecific functionalization with a broad range of
electrophiles in high yields. cis-substituted aziridines are formed
exclusively, providing a complementary stereochemical out-
come compared to methods involving the deprotonation of N-
sulfonylaziridines. The Li−I exchange occurs rapidly even at
low temperature, allowing the unstabilized organolithium to be
generated and trapped cleanly without decomposition or side
reaction. In addition, a route has been developed to interesting
2742
dx.doi.org/10.1021/ol501024y | Org. Lett. 2014, 16, 2740−2743

Organic Letters
Letter
Tetrahedron 2003, 59, 9849. (d) Capriati, V.; Florio, S.; Luisi, R.;
Musio, B. Org. Lett. 2005, 7, 3749. (e) Hodgson, D. M.; Humphreys,
P. G.; Xu, Z.; Ward, J. G. Angew. Chem., Int. Ed. 2007, 46, 2245.
(11) (a) Hodgson, D. M.; Humphreys, P. G.; Ward, J. G. Org. Lett.
2005, 7, 1153. (b) Hodgson, D. M.; Hughes, S. P.; Thompson, A. L.;
Heightman, T. D. Org. Lett. 2008, 10, 3453. (c) Musio, B.; Clarkson,
G. J.; Shipman, M.; Florio, S.; Luisi, R. Org. Lett. 2009, 11, 325. (d)
For use of 1,3,5-triisopropylphenyl sulfonyl derivatives, see: Huang, J.;
Moore, S. P.; O’Brien, P.; Whitwood, A. C.; Gilday, J. Org. Biomol.
Chem. 2009, 7, 335.
1,3,5-trisubstituted hydantoins as single diastereoisomers, using
isocyanates as electrophiles.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures and 1H and 13C NMR spectra for new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
(12) For ring-opening reactions of lithiated aziridine derivatives, see:
(a) Schmidt, F.; Keller, F.; Vedrenne, E.; Aggarwal, V. K. Angew.
Chem., Int. Ed. 2009, 48, 1149. (b) Coote, S. C.; Moore, S. P.; O’Brien,
P.; Whitwood, A. C.; Gilday, J. J. Org. Chem. 2008, 73, 7852.
(c) Hodgson, D. M.; Humphreys, P. G.; Miles, S. M.; Brierley, C. A. J.;
Ward, J. G. J. Org. Chem. 2007, 72, 10009. (d) Hodgson, D. M.; Miles,
S. M. Angew. Chem., Int. Ed. 2006, 45, 935. (e) Moore, S. P.; Coote, S.
C.; O’Brien, P.; Gilday, J. Org. Lett. 2006, 8, 5145. (f) Rosser, C. M.;
Coote, S. C.; Kirby, J. P.; O’Brien, P.; Caine, D. Org. Lett. 2004, 6,
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: j.bull@imperial.ac.uk.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
̌
4817. (g) Hodgson, D. M.; Stefane, B.; Miles, T. J.; Witherington, J.
Chem. Commun. 2004, 3, 2234.
For financial support we gratefully acknowledge the EPSRC
(Career Acceleration Fellowship to J.A.B., EP/J001538/1) and
Imperial College London. We thank Prof. Alan Armstrong for
generous support.
(13) Hughes, M.; Boultwood, T.; Zeppetelli, G.; Bull, J. A. J. Org.
Chem. 2013, 78, 844.
(14) (a) Nelson, J. M.; Vedejs, E. Org. Lett. 2010, 12, 5085.
(b) Theddu, N.; Vedejs, E. J. Org. Chem. 2013, 78, 5061.
(15) Breternitz, H.-J.; Schaumann, E.; Adiwidjaja, G. Tetrahedron Lett.
1991, 32, 1299.
(16) (a) Hodgson, D. M.; Humphreys, P. G.; Ward, J. G. Org. Lett.
2006, 8, 995. (b) O’Brien, P.; Rosser, C. M.; Caine, D. Tetrahedron
2003, 59, 9779.
REFERENCES
■
(1) (a) Sweeney, J. B. Chem. Soc. Rev. 2002, 31, 247. (b) Aziridines
and Epoxides in Organic Synthesis; Yudin, A. K., Ed.; Wiley-VCH:
Weinheim, 2006.
(2) For reactivity of C-heteroatom substituted aziridines, see: Singh,
G. S.; D’hooghe, M.; De Kimpe, N. Chem. Rev. 2007, 107, 2080.
(3) (a) Nielsen, D. K.; Huang, C.-Y.; Doyle, A. G. J. Am. Chem. Soc.
2013, 135, 13605. (b) Huang, C.-Y.; Doyle, A. G. J. Am. Chem. Soc.
2012, 134, 9541. (c) Duda, M. L.; Michael, F. E. J. Am. Chem. Soc.
2013, 135, 18347. (d) Lu, P. Tetrahedron 2010, 66, 2549. (e) Wu, B.;
Parquette, J. R.; RajanBabu, T. V. Science 2009, 326, 1662.
(4) For ring expansion and rearrangements, see: (a) Ilardi, E. A.;
Njardarson, J. T. J. Org. Chem. 2013, 78, 9533. (b) Dauban, P.; Malik,
G. Angew. Chem., Int. Ed. 2009, 48, 9026.
(17) (a) Bull, J. A.; Boultwood, T.; Taylor, T. A. Chem. Commun.
2012, 48, 12246. (b) Boultwood, T.; Affron, D. P.; Trowbridge, A. D.;
Bull, J. A. J. Org. Chem. 2013, 78, 6632. (c) Boultwood, T.; Affron, D.
P.; Bull, J. A. J. Visualized Exp. 2014, DOI: 10.3791/51633.
(18) (a) Clayden, J. Organolithiums: Selectivity for Synthesis;
Pergamon: Oxford, U.K., 2002. (b) Seyferth, D. Organometallics
2006, 25, 2. (c) Bailey, W.; Patricia, J. J. Organomet. Chem. 1988, 352,
1. (d) Barl, N. M.; Werner, V.; Samann, C.; Knochel, P. Heterocycles
̈
2014, 88, 827.
(19) (a) Kuzmina, O. M.; Steib, A. K.; Markiewicz, J. T.; Flubacher,
D.; Knochel, P. Angew. Chem., Int. Ed. 2013, 52, 4945. (b) Dagousset,
G.; Moriya, K.; Mose, R.; Berionni, G.; Karaghiosoff, K.; Knochel, P.
Angew. Chem., Int. Ed. 2014, 53, 1425.
(5) For N-transfer to alkenes, see: (a) Jat, J. L.; Paudyal, M. P.; Gao,
H.; Xu, Q.-L.; Yousufuddin, M.; Devarajan, D.; Ess, D. H.; Kurti, L.;
̈
Falck, J. R. Science 2014, 343, 61. (b) Watson, I. D. G.; Yu, L.; Yudin,
A. K. Acc. Chem. Res. 2006, 39, 194. For aza-Darzens reactions, see:
(c) Sweeney, J. Eur. J. Org. Chem. 2009, 4911. (d) Huang, L.; Wulff,
W. D. J. Am. Chem. Soc. 2011, 133, 8892. For organocatalytic
approaches, see: (e) Pesciaioli, F.; De Vincentiis, F.; Galzerano, P.;
Bencivenni, G.; Bartoli, G.; Mazzanti, A.; Melchiorre, P. Angew. Chem.,
(20) See ref 17b and the Supporting Information for further details.
(21) For recent examples of oxidation of N-sulfonylaziridinyl alcohols
to diastereomerically pure aziridinyl ketones, see ref 11b,d and: Moore,
S.; O’Brien, P.; Whitwood, A.; Gilday, J. Synlett 2008, 237.
(22) (a) Mehta, N. B.; Diuguid, C. A. R.; Soroko, F. E. J. Med. Chem.
1981, 24, 465. (b) Marton, J.; Enisz, J.; Hosztafi, S.; Timar, T. J. Agric.
Food Chem. 1993, 41, 148−152. (c) El-Barbary, A. A.; Khodair, A. I.;
Pedersen, E. B.; Nielsen, C. J. Med. Chem. 1994, 37, 73. (d) Comber,
R. N.; Reynolds, R. C.; Friedrich, J. D.; Manguikian, R. A.; Buckheit, R.
W.; Truss, J. W.; Shannon, W. M.; Secrist, J. A. J. Med. Chem. 1992, 35,
3567.
Int. Ed. 2008, 47, 8703. (f) Jung, N.; Brase, S. Angew. Chem., Int. Ed.
̈
2012, 51, 5538. (g) Deiana, L.; Dziedzic, P.; Zhao, G.-L.; Vesely, J.;
Ibrahem, I.; Rios, R.; Sun, J.; Cordova, A. Chem.Eur. J. 2011, 17,
́
7904.
(6) (a) Florio, S.; Luisi, R. Chem. Rev. 2010, 110, 5128. (b) Satoh, T.
Chem. Rev. 1996, 96, 3303. (c) Hodgson, D. M.; Humphreys, P. G.;
Hughes, S. P. Pure Appl. Chem. 2007, 79, 269.
(7) (a) Satoh, T.; Fukuda, Y. Tetrahedron 2003, 59, 9803. (b) Satoh,
T.; Matsue, R.; Fujii, T.; Morikawa, S. Tetrahedron 2001, 57, 3891.
(c) Satoh, T.; Ozawa, M.; Takano, K.; Chyouma, T.; Okawa, A.
Tetrahedron 2000, 56, 4415. (d) Satoh, T.; Sato, T.; Oohara, T.;
Yamakawa, K. J. Org. Chem. 1989, 54, 3973.
(23) Miura, T.; Mikano, Y.; Murakami, M. Org. Lett. 2011, 13, 3560.
(8) (a) Vedejs, E.; Moss, W. O. J. Am. Chem. Soc. 1993, 115, 1607.
(b) Vedejs, E.; Little, J. J. Am. Chem. Soc. 2002, 124, 748. (c) Vedejs,
E.; Little, J. D.; Seaney, L. M. J. Org. Chem. 2004, 69, 1788.
(d) Wiedner, S. D.; Vedejs, E. Org. Lett. 2010, 12, 4030.
(9) (a) Aggarwal, V. K.; Alonso, E.; Ferrara, M.; Spey, S. E. J. Org.
Chem. 2002, 67, 2335. (b) Aggarwal, V. K.; Ferrara, M. Org. Lett. 2000,
2, 4107.
(10) (a) Beak, P.; Wu, S.; Yum, E. K.; Jun, Y. M. J. Org. Chem. 1994,
59, 276. (b) Vedejs, E.; Kendall, J. T. J. Am. Chem. Soc. 1997, 119,
6941. (c) Vedejs, E.; Bhanu Prasad, A. S.; Kendall, J. T.; Russel, J. S.
2743
dx.doi.org/10.1021/ol501024y | Org. Lett. 2014, 16, 2740−2743