Catalytic asymmetric claisen rearrangement of enolphosphonates: Construction of vicinal tertiary and all-carbon quaternary centers

Article abstract of DOI:10.1002/anie.201203092

A copper-catalyzed enantioselective Claisen rearrangement of easily accessible enolphosphonates using the commercially available PhBOX as the chiral ligand was developed. A wide range of rearrangement products with contiguous tertiary and all-carbon quaternary centers were obtained in excellent yields and stereoselectivities. The α-ketophosphonate substituent in the products could be easily transformed into other functional groups. Copyright

Full text of DOI:10.1002/anie.201203092

Angewandte
Chemie
DOI: 10.1002/anie.201203092
Asymmetric Catalysis
Catalytic Asymmetric Claisen Rearrangement of Enolphosphonates:
Construction of Vicinal Tertiary and All-Carbon Quaternary Centers**
Jiajing Tan, Cheol-Hong Cheon, and Hisashi Yamamoto*
The development of a one-step catalytic method for the
enantioselective construction of contiguous tertiary and all-
carbon quaternary centers is a challenging task but of great
significance.[1,2] Among the limited number of available
approaches for the assembly of such sterically congested
structures by a single transformation, the Claisen rearrange-
rangement reactions (Scheme 1). Importantly, the corre-
sponding products, a-ketophosphonates, are well-known as
one of the most synthetically useful phosphorous motifs and
could undergo various transformations with ease and effi-
ciency.[9] Herein, we are glad to report the first catalytic
enantioselective Claisen rearrangement of enolphosphonates
À
ment, well-known as one of the most effective carbon
carbon bond-formation strategies, has shown promise.
Since its discovery one century ago,[3] the Claisen rear-
rangement has become a powerful method widely used by
synthetic organic chemists.[4] Despite many efforts made in
this field, the development of the catalytic asymmetric
Claisen rearrangement is still in the early stages. Until now,
only Hiersemannꢀs copper[5] and Jacobsenꢀs hydrogen- Scheme 1. Claisen rearrangement of enolphosphonates.
bonding catalysts[6] have been applied to catalytic versions
of asymmetric Claisen rearrangement. Both of these
methods are excellent but rely heavily on ketocarboxylic
acid derivatives as substrates, thus affording products with
limited generality that are in most cases difficult to further
functionalize. Moreover, there are only a few examples of the
use of these catalytic systems for the direct formation of
a quaternary carbon center in the presence of a vicinal tertiary
center, with moderate to good stereoselectivities. In this
regard, the development of a novel catalytic enantioselective
Claisen rearrangement as an alternative efficient method for
the rapid creation of vicinal tertiary and quaternary carbon
center motifs, which are widely present in complex natural
products as well as medicinal and biologically active mole-
cules, remains an important goal.[7]
Recently, many groups including our own have reported
that a phosphonate group on the substrate is able to tightly
coordinate to metal ions and provide excellent enantiocontrol
through chelation with an additional binding site, which is
adjacent to the phosphonate group, to chiral metal catalysts.[8]
We thus envisioned that enolphosphonates would be favor-
able bidentate substrates for metal-catalyzed Claisen rear-
for the synthesis of a wide range of a-ketophosphonate
derivatives with contiguous tertiary and quaternary carbon
centers in excellent yields and selectivities.
Initially, a convenient protocol was developed for sub-
strate preparation. These compounds could be simply
obtained by treating allylic bromides with a-ketophospho-
nates in the presence of DBU.[10] Next, based on our previous
success in the use of metal/TBOx complexes in catalytic
asymmetric reactions of ketophosphonates,[11] we investigated
the use of Al/TBOx complexes in the Claisen rearrangement
of enolphosphonate S1 (Table 1, entry 1).[12] However, no
rearrangement product was detected. When the Cu/TBOx
complex was used, the reaction proceeded slowly to give the
product with 70% yield but in racemic form (Table 1,
entry 2). Bidentate bisoxazoline ligands instead of tetraden-
tate TBOx ligands were then examined. To our delight, when
the (R,R)-PhBOX ligand (L1) was used the product was
obtained with 88% yield and 93% ee in 2 hours (Table 1,
entry 3).[13,14] When the aminoindanol-derived bisoxazoline
ligand L2 was used the rearrangement product was obtained
in 93% ee but with lower yield (Table 1, entry 4). Other metal
triflates and copper sources were also tested but none of them
gave more-satisfying results.[10] A screen of solvents indicated
that several solvents were suitable for this reaction and that
the enantioselectivity could be improved when the reaction
was performed in a dichloromethane/n-hexane (1:5) solvent
mixture (Table 1, entry 5).[10] The best results were achieved
when the catalyst loading was lowered to 5 mol% (Table 1,
entry 6). Unfortunately, the use of this dichloromethane/n-
hexane (1:5) solvent mixture failed to increase the enantio-
selectivity when ligand L2 was used (Table 1, entry 7).
Interestingly, in the presence of L1 the catalyst loading
could even be lowered to 0.1 mol% without significant
detrimental effect on the selectivity and yield, although
[*] J.-J. Tan, Prof. H. Yamamoto
Department of Chemistry, The University of Chicago
5735 South Ellis Avenue, Chicago, IL 60637 (USA)
E-mail: yamamoto@uchicago.edu
Dr. C.-H. Cheon
Department of Chemistry, Korea University
145 Anam-ro, Seongbuk-gu, Seoul 136-701 (Korea)
[**] Support of this research was provided by the NSF (CHE-1049551)
and NIH (P50 GM086 145-01). We thank Dr. Antoni Jurkiewicz for
NMR, Dr. Ian M. Steele for X-ray analysis and Dr. Furong Sun
(UIUC) for MS data. Dr. David Dickson is acknowledged for his
original work for this project.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201203092.
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Table 1: Screening of reaction conditions for the copper-catalyzed
Claisen rearrangement of enolphosphonates.
Entry[a] Metal
S
Ligand Solvent
t
Yield ee
[h] [%][b] [%][c]
1
2
3
4
Me2AlCl S1 TBOx
Cu(OTf)2 S1 TBOx
Cu(OTf)2 S1 L1
Cu(OTf)2 S1 L2
Cu(OTf)2 S1 L1
Cu(OTf)2 S1 L1
Cu(OTf)2 S1 L2
Cu(OTf)2 S1 L1
Cu(OTf)2 S1 L1
Cu(OTf)2 S2 L1
Cu(OTf)2 S3 L1
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
24 N.R. N.D.
16 70
0
2
4
4
4
88
80
90
90
93
93
96
97
83
93
97
95
95
5
CH2Cl2/n-hexane[d]
CH2Cl2/n-hexane[d]
6[e]
7[e]
8[f]
9[e,g]
10[e]
11[e]
CH2Cl2/n-hexane[d] 24 69
CH2Cl2/n-hexane[d] 72 76
CH2Cl2/n-hexane[d] 72 80
CH2Cl2/n-hexane[d]
CH2Cl2/n-hexane[d]
2
2
84
86
[a] All reactions performed at 0.1 mmol scale. [b] Yield of the isolated
product. [c] Determined by HPLC on a chiral staionary phase.
[d] Dichloromethane/n-hexane=1:5. [e] 5 mol% of catalyst.
[f] 0.1 mol% of catalyst. [g] Reaction performed at 08C. N.R.=no
reaction, N.D.=not determined, Tf=trifluoromethanesulfonyl.
a longer reaction time was required (Table 1, entry 8).
Decreasing the reaction temperature to 08C failed to give
rise to further improvement to the enantioselectivity (Table 1,
entry 9). Notably the size of the R group on the phosphonate
motif does not have a significant effect on the reaction.
Substrates S2 and S3, with either a smaller or a larger R group
than that of S1, both gave the desired product with only
slightly lower selectivity (Table 1, entries 10 and 11).
Scheme 2. Substrate scope for CuII/PhBOX catalyzed asymmetric
Claisen rearrangement reaction. All reactions were performed on
a 0.1 mmol scale. The yields are of the isolated products. The
diastereomeric ratio (d.r.) was determined by 1H NMR analysis of the
crude mixture. Enantioselectivity was determined by HPLC on a chiral
stationary phase. The absolute configuration was assigned by X-ray
crystallographic analysis of the hydrolyzed product of 17 and the rest
were assigned by analogy. [a] (S, S)-PhBOX ligand used instead.
[b] Reaction time: 72 h. [c] Reaction time: 10 h. [d] Reaction performed
at 08C. [e] Reaction time: 4 h. [f] Reaction time: 24 h. [g] Reaction
time: 1 week. Bn=benzyl.
With the fully optimized reaction conditions established,
a wide range of substrates were examined and the rearrange-
ment products were obtained with good to excellent yields
and stereoselectivities (Scheme 2). With regard to the R1 and
R2 groups on the enolphosphonates, substrates bearing
a range of cyclic substituents provided the desired products
2–4 with similar levels of enantioselectivity as product 1,
which has a dimethyl substituent. For the R3 group, in
addition to an aryl group, aliphatic R3 groups were also
tolerated and products 5, 6, and (S)-7 were obtained with
similar results but with longer reaction times than for product
1. The steric bulk of the R3 group has no significant effect on
the enantioselectivity. Substrates bearing large naphthyl rings,
in place of the phenyl group, were also examined, and 8 and 9
were generated with high enantioselectivities. For conjugated
substrates, the reaction had to be carried out at 08C to
attenuate the background reactions, thus providing 10 with
90% ee. Notably the existence of R4 substituents, which have
seldom been studied in previous reports, did not prevent the
rearrangement. Enolphosphonates bearing either an alkyl
group or halogen atom as the R4 group all underwent the
rearrangement reaction to give a-ketophosphonates 11–13 in
high efficiency. Unfortunately, under the optimized reaction
conditions, substrates bearing either cis-cinnamyl or a 3, 3-
disubstituted allylic moiety failed to undergo rearrangement
reactions, thus indicating that our method still has its own
limitations at the current stage.[15] The utilization of the
commercially available (S,S)-PhBOX ligand enabled us to
generate the products (R)-1 and (S)-7, which have the
opposite sense of chirality than the products obtained from
the same starting materials but with the (R,R)-PhBOX ligand
(L1).
More importantly, the construction of vicinal chiral
tertiary and all-carbon quaternary centers was successfully
achieved by this rearrangement protocol. With two different
R1 and R2 groups on the double bond of the enolphospho-
nates,[16] the substrate bearing a tetrahydronaphthyl ring
underwent the Claisen rearrangement to give the desired
2
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product 14 in 95% yield, > 97:3 d.r., and 87% ee.[17] Encour-
aged by this result, we also found that substrates bearing
heteroatoms such as oxygen and sulfur were well-tolerated
under the reaction conditions, furnishing the products 15 and
16, respectively, in good yield and stereoselectivity.[17] The
absolute stereochemistry of the Claisen rearrangement prod-
ucts was unambiguously assigned on the basis of the X-ray
structure of the carboxylic acid that was obtained from the
hydrolysis of rearrangement product 17.[10,17]
A plausible transition-state model is proposed as the well-
defined tetrahedral substrate/catalyst complex, in which
bidentate chelation control results in excellent enantioface
differentiation (Scheme 3).[4k,13b,18] As depicted, the substrate,
tightly bound to the catalyst, is assumed to arrange in a chair-
give the carboxylic acid product without any loss of enantio-
selectivity. The amino acid derivative can be accessed
straightforwardly by treating 1 with l-valine methyl ester in
1,2-dichloroethane (DCE), which is heated to reflux. More-
over, the carbonyl group of 1 could be transformed by
a simple reduction. When DIBAL-H was utilized, the a-
ketophosphonate 1 was converted into an a-hydroxy phos-
phonate but with poor diastereoselectivity. When 1 was
treated with LiAlH4, the ketophosphonate group was com-
pletely reduced to give the alcohol product.
In summary, we have successfully developed the first
copper-catalyzed enantioselective Claisen rearrangement of
enolphosphonates. A number of desired a-ketophosphonate
products with diverse substitents were obtained in excellent
yields and stereoselectivities and these products can easily
undergo further functionalization to provide various chiral
building blocks, effectively. Significantly, this method pro-
vides a single-step rapid construction of chiral motifs, with
contiguous tertiary and all-carbon quaternary centers bearing
unfunctionalized substituents, that are otherwise difficult to
access. Since the starting materials as well as the catalysts are
readily available and the highly enantioenriched products can
be easily functionalized, this reaction is expected to be widely
applicable for asymmetric synthesis. Future efforts will be
directed at expanding the substrate scope and synthesis of
complex natural products.
Scheme 3. Proposed transition state.
like configuration so that the enolphosphonate unit
approaches the Si face of the allylic ether moiety, which is
positioned opposite to the bulky phenyl ring on the BOX
ligand.[19] This proposed transition-state model is fully con-
sistent with the observed stereochemical outcome as well as
reaction reactivity[20] and was used for predicting the relative
stereochemistry.
To highlight the synthetic utility of this method, the
Claisen rearrangement product, a-ketophosphonate 1, was
examined for further functionalization. Gratifyingly, we
found that the phosphonate group could be easily trans-
formed into various functional groups under mild reaction
conditions (Scheme 4). First, the a-ketophosphonates 1 acted
as a masked acyl chloride and could readily react with
alcohols and amines to give the corresponding ester and
amide products. Furthermore, these transformations could be
carried out in a simple one-pot procedure. Additionally,
under basic conditions, a-ketophosphonate 1 hydrolyzed to
Received: April 23, 2012
Published online: && &&, &&&&
Keywords: asymmetric catalysis · BOX ligands ·
.
Claisen rearrangement · copper · quaternary carbon centers
[1] For reviews, see: a) K. Fuji, Chem. Rev. 1993, 93, 2037; b) E. J.
Corey, A. GuzmanPerez, Angew. Chem. 1998, 110, 2092; Angew.
Chem. Int. Ed. 1998, 37, 388; c) J. Christoffers, A. Mann, Angew.
Chem. 2001, 113, 4725; Angew. Chem. Int. Ed. 2001, 40, 4591;
d) I. Denissova, L. Barriault, Tetrahedron 2003, 59, 10105;
e) D. J. Ramon, M. Yus, Curr. Org. Chem. 2004, 8, 149; f) J.
Christoffers, A. Baro, Adv. Synth. Catal. 2005, 347, 1473;
g) Quaternary Stereocenters: Challenges and Solutions for
Organic Synthesis (Eds.: J. Christoffers, A. Baro), Wiley-VCH,
Weinheim, 2005; h) B. M. Trost, C. Jiang, Synthesis 2006, 369;
i) P. G. Cozzi, R. Hilgraf, N. Zimmermann, Eur. J. Org. Chem.
2007, 5969; j) M. Bella, T. Gasperi, Synthesis 2009, 1583; k) N.
Kumagai, Chem. Pharm. Bull. 2011, 59, 1; l) J. P. Das, I. Marek,
Chem. Commun. 2011, 47, 4593.
[2] For selected communications, see: a) M. S. Taylor, E. N. Jacob-
sen, J. Am. Chem. Soc. 2003, 125, 11204; b) N. Mase, R.
Thayumanavan, F. Tanaka, C. F. Barbas III, Org. Lett. 2004, 6,
2527; c) J. F. Austin, S.-G. Kim, C. J. Sinz, W.-J. Xiao, D. W. C.
MacMillan, Proc. Natl. Acad. Sci. USA 2004, 101, 5482; d) T.
Okino, Y. Hoashi, T. Furukawa, X. Xu, Y. Takemoto, J. Am.
Chem. Soc. 2005, 127, 119; e) H. Li, Y. Wang, L. Tang, F. Wu, X.
Liu, C. Guo, B. M. Foxman, L. Deng, Angew. Chem. 2005, 117,
107; Angew. Chem. Int. Ed. 2005, 44, 105; f) M. S. Taylor, D. N.
Zalatan, A. M. Lerchner, E. N. Jacobsen, J. Am. Chem. Soc.
2005, 127, 1313; g) T. B. Poulsen, C. Alemparte, S. Saaby, M.
Bella, K. A. Jørgensen, Angew. Chem. 2005, 117, 2956; Angew.
Chem. Int. Ed. 2005, 44, 2896; h) G. Bartoli, M. Bosco, A.
Carlone, A. Cavalli, M. Locatelli, A. Mazzanti, P. Ricci, L.
Sambri, P. Melchiorre, Angew. Chem. 2006, 118, 5088; Angew.
Scheme 4. Synthetic applications of rearrangement product 1.
DBU=1,8-diazabicyclo[5.4.0]undec-7-ene, DIBAL-H=diisobutylalumi-
nium hydride, LAH=lithium aluminium hydride.
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
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These are not the final page numbers!

.
Angewandte
Communications
Chem. Int. Ed. 2006, 45, 4966; i) F. Wu, H. Li, R. Hong, L. Deng,
Angew. Chem. 2006, 118, 961; Angew. Chem. Int. Ed. 2006, 45,
947; j) M. P. Lalonde, Y. Chen, E. N. Jacobsen, Angew. Chem.
2006, 118, 6514; Angew. Chem. Int. Ed. 2006, 45, 6366; k) Y. Qin,
C. E. Stivala, A. Zakarian, Angew. Chem. 2007, 119, 7610;
Angew. Chem. Int. Ed. 2007, 46, 7466; l) Y. Wang, H. M. Li, Y.-Q.
Wang, Y. Liu, B. M. Foxman, L. Deng, J. Am. Chem. Soc. 2007,
129, 6364; m) Z. H. Chen, H. Morimoto, S. Matsunga, M.
Shibasaki, J. Am. Chem. Soc. 2008, 130, 2170; n) G. Bencivenni,
L.-Y. Wu, A. Mazzanti, B. Giannichi, F. Pesciaioli, M.-P. Song, G.
Bartoli, P. Melchiorre, Angew. Chem. 2009, 121, 7336; Angew.
Chem. Int. Ed. 2009, 48, 7200; o) J. Streuff, D. E. White, S. C.
Virgil, B. M. Stoltz, Nat. Chem. 2010, 2, 192; p) R. P. Singh, B. M.
Foxman, L. Deng, J. Am. Chem. Soc. 2010, 132, 9558; q) A.
Quintard, A. Lefranc, A. Alexakis, Org. Lett. 2011, 13, 1540;
r) B. M. Trost, J. R. Miller, C. M. Hoffman, Jr., J. Am. Chem.
Soc. 2011, 133, 8165; s) Y. Fujiwara, G. C. Fu, J. Am. Chem. Soc.
2011, 133, 12293; t) M. Terada, K. Moriya, K. Kanomata, K.
Sorimachi, Angew. Chem. 2011, 123, 12794; Angew. Chem. Int.
Ed. 2011, 50, 12586.
[11] a) N. Takenaka, G. Xia, H. Yamamoto, J. Am. Chem. Soc. 2004,
126, 13198; b) G. Xia, H. Yamamoto, J. Am. Chem. Soc. 2006,
128, 2554; c) G. Xia, H. Yamamoto, J. Am. Chem. Soc. 2007, 129,
496; d) N. Takenaka, J. P. Abell, H. Yamamoto, J. Am. Chem.
Soc. 2007, 129, 742; e) J. P. Abell, H. Yamamoto, J. Am. Chem.
Soc. 2008, 130, 10521; f) J. P. Abell, H. Yamamoto, J. Am. Chem.
Soc. 2009, 131, 15118; g) D. L. Usanov, H. Yamamoto, Angew.
Chem. 2010, 122, 8345; Angew. Chem. Int. Ed. 2010, 49, 8169;
h) D. L. Usanov, H. Yamamoto, J. Am. Chem. Soc. 2011, 133,
1286.
[12] For representative references, see: a) H. Yamamoto, K. Mar-
uoka, Pure Appl. Chem. 1990, 62, 2063; b) K. Nonoshita, H.
Banno, K. Maruoka, H. Yamamoto, J. Am. Chem. Soc. 1990, 112,
316.
[13] For reviews, see: a) D. A. Evans, K. T. Chapman, J. Bisaha, J.
Am. Chem. Soc. 1988, 110, 1238; b) J. S. Johnson, D. A. Evans,
Acc. Chem. Res. 2000, 33, 325; c) G. Desimoni, G. Faita, P.
Quadrelli, Chem. Rev. 2003, 103, 3119; d) G. Desimoni, G. Faita,
K. A. Jørgensen, Chem. Rev. 2006, 106, 3561; e) R. Rasappan, D.
Laventine, O. Reiser, Coord. Chem. Rev. 2008, 252, 702; f) G. C.
Hargaden, P. J. Guiry, Chem. Rev. 2009, 109, 2505.
[3] L. Claisen, Ber. Dtsch. Chem. Ges. 1912, 45, 3157.
[14] For selected communications, see: a) D. A. Evans, S. J. Miller, T.
Lectka, J. Am. Chem. Soc. 1993, 115, 6460; b) D. A. Evans, J. S.
Johnson, E. J. Olhava, J. Am. Chem. Soc. 2000, 122, 1635;
c) D. A. Evans, T. Rovis, M. C. Kozlowski, C. W. Downey, J. S.
Tedrow, J. Am. Chem. Soc. 2000, 122, 9134; d) D. A. Evans, K. A.
Scheidt, J. N. Johnston, M. C. Willis, J. Am. Chem. Soc. 2001, 123,
4480; e) D. A. Evans, D. Seidel, M. Rueping, H. W. Lam, J. T.
Shaw, C. W. Downey, J. Am. Chem. Soc. 2003, 125, 12692; f) C.
Palomo, M. Oiarbide, B. G. Kardak, J. M. Garcꢁa, A. Linden, J.
Am. Chem. Soc. 2005, 127, 4154; g) D. Magdziak, G. Lalic, H. M.
Lee, K. C. Fortner, A. D. Aloise, M. D. Shair, J. Am. Chem. Soc.
2005, 127, 7284; h) M. P. Sibi, L. M. Stanley, X. Nie, L.
Venkatraman, M. Liu, C. P. Jasperse, J. Am. Chem. Soc. 2007,
129, 395; i) Z. Sun, S. Yu, Z. Ding, D. Ma, J. Am. Chem. Soc.
2007, 129, 9300; j) A. Sakakura, R. Kondo, M. Akakura, K.
Ishihara, J. Am. Chem. Soc. 2009, 131, 17762; k) X. Xu, W.-H.
Hu, M. P. Doyle, Angew. Chem. 2011, 123, 6516; Angew. Chem.
Int. Ed. 2011, 50, 6392.
[4] For reviews, see: a) H. Ito, T. Taguchi, Chem. Soc. Rev. 1999, 28,
43; b) M. Hiersemann, L. Abraham, Eur. J. Org. Chem. 2002,
1461; c) Y. Chai, S.-P. Hong, H. A. Lindsay, C. McFarland, M. C.
McIntosh, Tetrahedron 2002, 58, 2905; d) A. M. Martꢁn Castro,
Chem. Rev. 2004, 104, 2939; e) The Claisen Rearrangment (Eds.:
M. Hiersemann, U. Nubbemeyer), Wiley-VCH, Weinheim, 2007;
f) E. A. Ilardi, C. E. Stivala, A. Zakarian, Chem. Soc. Rev. 2009,
38, 3133. For selected communication, see: g) T. P. Yoon,
D. W. C. MacMillan, J. Am. Chem. Soc. 2001, 123, 2911; h) H.
Helmboldt, M. Hiersemann, Tetrahedron 2003, 59, 4031; i) C. E.
Anderson, L. E. Overman, J. Am. Chem. Soc. 2003, 125, 12412;
j) K. Afarinkia, A. J. Twist, H.-W. Yu, J. Org. Chem. 2004, 69,
6500; k) L. Abraham, M. Koerner, P. Schwab, M. Hiersemann,
Adv. Synth. Catal. 2004, 346, 1281; l) K. Afarinkia, A. J. Twist,
H. W. Yu, J. Organomet. Chem. 2005, 690, 2688; m) E. C. Linton,
M. C. Kozlowski, J. Am. Chem. Soc. 2008, 130, 16162; n) M. E.
Geherty, R. D. Dura, S. G. Nelson, J. Am. Chem. Soc. 2010, 132,
11875; o) J. Kaeobamrung, J. Mahatthananchai, P. Zheng, J. W.
Bode, J. Am. Chem. Soc. 2010, 132, 8810.
[15] A detailed explanation of the substrate scope as well as the
limitations of this reaction can be found in the Supporting
Information.
[16] As a result of the relative steric bulk of the phosphonate group,
we were able to synthesize and isolate E-isomers of enolphosph-
onates.
[5] a) L. Abraham, R. Czerwonka, M. Hiersemann, Angew. Chem.
2001, 113, 4835; Angew. Chem. Int. Ed. 2001, 40, 4700; b) L.
Abraham, M. Koerner, M. Hiersemann, Tetrahedron Lett. 2004,
45, 3647.
[6] a) C. Uyeda, E. N. Jacobsen, J. Am. Chem. Soc. 2008, 130, 9228;
b) C. Uyeda, A. R. Rotheli, E. N. Jacobsen, Angew. Chem. 2010,
122, 9947; Angew. Chem. Int. Ed. 2010, 49, 9753; c) C. Uyeda,
E. N. Jacobsen, J. Am. Chem. Soc. 2011, 133, 5062.
[7] C. J. Douglas, L. E. Overman, Proc. Natl. Acad. Sci. USA 2004,
101, 5363.
[17] The relative stereochemistry was determined by the proposed
transition state, as shown in Scheme 3. CCDC 877511 contains
the supplementary crystallographic data for this paper. These
data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_
request/cif.
[8] For representative references, see: a) D. A. Evans, J. S. Johnson,
J. Am. Chem. Soc. 1998, 120, 4895; b) D. A. Evans, K. A. Scheidt,
K. R. Fandrick, H. W. Lam, J. Wu, J. Am. Chem. Soc. 2003, 125,
10780.
[9] a) E. Breuer, The Chemistry of Organophosphorus Compounds,
Vol 4, Wiley, New York, 1996; b) B. Iorga, F. Eymery, V. Mouries,
P. Savignac, Tetrahedron 1998, 54, 14637; c) C. E. McKenna,
B. A. Kashemirov, Top Curr. Chem. 2002, 220, 201.
[18] a) M. Johannsen, K. A. Jørgensen, J. Org. Chem. 1995, 60, 5757;
b) M. Johannsen, S. Yao, A. Graven, K. A. Jørgensen, Pure
Appl. Chem. 1998, 70, 1117; c) D. A. Evans, J. S. Johnson, C. S.
Burgey, K. R. Campos, Tetrahedron Lett. 1999, 40, 2879.
[19] A possible boat-like transition state cannot be excluded.
[20] Substrates bearing either cis-cinnamyl or 3,3’-disubstituted
allylic ether segment might have a severe 1,3-diaxial repulsion
in the chair-like transition state, thus possibly leading to no
reaction activity for Claisen rearrangement.
[10] For details see the Supporting Information.
4
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
These are not the final page numbers!

Angewandte
Chemie
Communications
Asymmetric Catalysis
J.-J. Tan, C.-H. Cheon,
H. Yamamoto*
&&&& — &&&&
Catalytic Asymmetric Claisen
Rearrangement of Enolphosphonates:
Construction of Vicinal Tertiary and All-
Carbon Quaternary Centers
A copper-catalyzed enantioselective
Claisen rearrangement of easily accessi-
ble enolphosphonates using the com-
mercially available PhBOX as the chiral
ligand was developed. A wide range of
rearrangement products with contiguous
tertiary and all-carbon quaternary centers
were obtained in excellent yields and
stereoselectivities. The a-ketophospho-
nate substituent in the products could be
easily transformed into other functional
groups.
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!