Asymmetric induction during Yang cyclization of α-oxoamides: The power of a covalently linked chiral auxiliary is enhanced in the crystalline state

Article abstract of DOI:10.1021/ja043999p

γ-Hydrogen abstraction has been revealed to be the primary photoprocess in the crystalline state of α-oxoamides through photochemical and X-ray structural studies. The outstanding ability of a covalent chiral auxiliary in generating asymmetric induction i

Full text of DOI:10.1021/ja043999p

Published on Web 02/19/2005
Asymmetric Induction during Yang Cyclization of
r-Oxoamides: The Power of a Covalently Linked Chiral
Auxiliary Is Enhanced in the Crystalline State
Arunkumar Natarajan,† Joel T. Mague, and V. Ramamurthy*,†
Contribution from the Department of Chemistry, Tulane UniVersity,
New Orleans, Louisiana 70118
Received October 1, 2004; E-mail: murthy1@miami.edu
Abstract: γ-Hydrogen abstraction has been revealed to be the primary photoprocess in the crystalline
state of R-oxoamides through photochemical and X-ray structural studies. The outstanding ability of a
covalent chiral auxiliary in generating asymmetric induction in the photoproduct â-lactam has been
established with 10 examples. We have shown that the crystal lattice preorganizes the reactant molecules
toward a single diastereomer of the â-lactam and prevents large motions of the 1,4-diradical intermediate
that would result in the loss of stereochemical memory. A rare single-crystal-to-single-crystal transformation
path of one of the examples investigated establishes the direct correlation between the stereochemistries
of the reactant and the product.
Introduction
method due to a lack of understanding of the factors controlling
crystallization of achiral molecules in a chiral space group has
Traditionally, chirality control of a photochemical reaction
is a challenging task.1 Asymmetric induction in a photochemical
reaction in solution with a maximum enantiomeric excess (ee)
of 2% has been achieved with circularly polarized light in a
limited number of examples.2 Following the benchmark report
on geometric photoisomerization of 1,2-diphenylcyclopropane
by Cole and Hammond,3 studies on photosensitization with
chiral sensitizers in solution have led to moderate success.4
While most photoreactions with chiral sensitizers have had ee
< 15%, the best result of 49% ee under ambient conditions has
been achieved during the sensitized photoisomerization of
achiral cis-cyclooctene to chiral trans-cyclooctene.5 Rationally
designed chiral templates yield respectable chiral induction (98%
ee) during photocycloaddition reactions of lactams.6,7 This
promising approach has so far been limited to a few systems.
In contrast to studies in solution, those in the crystalline state
have been more rewarding. For example, irradiation of a few
pure chiral crystals resulting from achiral molecules leads to a
quantitative ee.8-10 The limited general applicability of this
been overcome through the use of ionic chiral auxiliaries. The
latter strategy of an achiral reactant ionically bonded to a chiral
amine ensures crystallization of the reactant salt in a chiral space
group and thus affords photoproducts in >90% diastereomeric
excess (de).11,12 Yet another successful approach relying on
organic hosts containing chiral centers (e.g., deoxycholic acid,
cyclodextrin, 1,6-bis(o-chlorophenyl)-1,6-diphenyl-2,4-diyne-
1,6-diol, tartaric acid derivatives, etc.) is limited in its
success to guests that can form a crystalline host-guest
complex.13,14 Identifying the correct host in a given case could
lead to a rewarding chiral induction of 100% ee.15 Recently,
we have established the use of achiral zeolites as hosts in
bringing about asymmetric induction in photoreactions.16,17
Diastereomeric excesses as high as 90% and enantiomeric
excesses up to 78% have been obtained with selected systems
within zeolites.
One of the best methods of asymmetric induction in solution
making use of a “removable covalent chiral auxiliary” works
best during cycloaddition of enones to olefins.18,19 To our
† Present address: Department of Chemistry, University of Miami, Coral
Gables, FL 33124.
(1) Chiral Photochemistry; Inoue, Y., Ramamurthy, V., Eds.; Marcell Dek-
ker: New York, 2004; Vol. 11.
(2) Rau, H. In Chiral Photochemistry; Ramamurthy, V., Ed.; Marcell Dekker:
New York, 2004; Vol. 11, p 1.
(3) Hammond, G. S.; Cole, R. S. J. Am. Chem. Soc. 1965, 87, 3256-3257.
(4) Inoue, Y. In Chiral Photochemistry; Ramamurthy, V., Ed.; Marcell
Dekker: New York, 2004; Vol. 11, p 129.
(5) Inoue, Y.; Wada, T.; Asaoka, S.; Sato, H.; Pete, J.-P. Chem. Commun.
2000, 251.
(6) Grosch, B.; Orlebar, C. N.; Herdtweck, E.; Massa, W.; Bach, T. Angew.
Chem., Int. Ed. 2003, 42, 3693.
(10) Green, B. S.; Lahav, M.; Rabinovich, D. Acc. Chem. Res. 1979, 12, 191.
(11) Scheffer, J. R. Can. J. Chem. 2001, 79, 349.
(12) Scheffer, J. R. In Chiral Photochemistry; Ramamurthy, V., Ed.; Marcell
Dekker: New York, 2004; Vol. 11, p 463.
(13) Toda, F.; Tanaka, K.; Miyamoto, H. In Understanding and Manipulating
Excited-State Processes; Schanze, K. S., Ed.; Marcel Dekker: New York,
2001; Vol. 8, p 385.
(14) Toda, F. Acc. Chem. Res. 1995, 28, 480.
(15) Zimmerman, H. E.; Alabugin, I. V.; Smolenskaya, V. N. Tetrahedron 2000,
56, 6821.
(16) Sivaguru, J.; Natarajan, A.; Kaanumalle, L. S.; Shailaja, J.; Uppili, S.; Joy,
A.; Ramamurthy, V. Acc. Chem. Res. 2003, 36, 509.
(7) Grosch, B.; Bach, T. In Chiral Photochemistry; Inoue, Y., Ramamurthy,
V., Eds.; Marcel Dekker: New York, 2004; Vol. 11, p 315.
(8) Elgavi, A.; Green, B. S.; Schmidt, G. M. J. J. Am. Chem. Soc. 1973, 95,
2058.
(17) Joy, A.; Ramamurthy, V. Chem.-Eur. J. 2000, 6, 1287.
(18) Pete, J.-P. In AdVances in Photochemistry; Von Bunan, G., Ed.; John Wiley
& Sons: New York, 1996; Vol. 21, p 135.
(19) Pete, J.-P.; Hoffmann, N. In Chiral Photochemistry; Ramamurthy, V., Ed.;
Marcell Dekker: New York, 2004; Vol. 11, p 179.
(9) Sakamoto, M. Chem.-Eur. J. 1997, 3, 684.
9
3568
J. AM. CHEM. SOC. 2005, 127, 3568-3576
10.1021/ja043999p CCC: $30.25 © 2005 American Chemical Society

Yang Cyclization of
R-Oxoamides
A R T I C L E S
Scheme 1
Scheme 2
Results and Discussion
knowledge there are only two reports of the use of a covalent
chiral auxiliary in providing asymmetric induction in the
crystalline state.20,21 In fact both reports imply that this method
is less general. The less general nature of this method is clear
from the good asymmetric induction of 87% during photo-
cyclization of 2,4,6-triisopropylbenzophenones in the crystalline
state with only one of the four chiral auxiliaries examined and
likewise in the case of 2-benzoyladamantane-2-carboxylic acid
derivative the de of 98% with one of the two chiral auxiliaries,
with the other leading to the Yang cyclization product in low
de (18%).20,21 These reports prompted us to examine the general
value of the covalent chiral auxiliary during solid-state photo-
reactions. We have investigated 10 R-oxoamides covalently
linked with chiral auxiliaries to study the influence of a remote
chiral auxiliary on asymmetric induction in the Yang cyclization
product â-lactam.
We have undertaken photochemical and X-ray structural
investigations of R-oxoamides 1-10 (Scheme 1) that undergo
γ-hydrogen (with respect to the benzylic carbonyl) abstraction
in the crystalline state. As shown in Scheme 2 abstraction of
the γ-hydrogen leads to â-lactams in which a new chiral center
is generated at the benzylic carbon. Earlier reports on mecha-
nistic and asymmetric induction studies on R-oxoamide22-26 and
available literature on the use of ionic chiral auxiliaries on these
systems27 allowed us to evaluate the effectiveness of covalent
chiral auxiliaries in R-oxoamides in the crystalline state. Further,
(22) Aoyama, H.; Hasegawa, M.; Watabe, M.; Shiraishi, H.; Omote, Y. J. Org.
Chem. 1978, 43, 419.
(23) Aoyama, H.; Sakamoto, M.; Omote, Y. J. Chem. Soc., Perkins Trans. 1
1981, 1357.
(24) Aoyama, H.; Sakamoto, M.; Kuwabara, K.; Yoshida, K.; Omote, Y. J. Am.
Chem. Soc. 1983, 105, 1958.
(25) Wang, R.; Chen, C.; Duesler, E.; Mariano, P. S. J. Org. Chem. 2004, 69,
1215.
(20) Cheung, E.; Netherton, M. R.; Scheffer, J. R.; Trotter, J.; Zenova, A.
Tetrahedron Lett. 2000, 41, 9673.
(21) Ito, Y.; Kano, G.; Nakamura, N. J. Org. Chem. 1998, 63, 5643.
(26) Chesta, C. A.; Whitten, D. G. J. Am. Chem. Soc. 1992, 114, 2188.
(27) Natarajan, A.; Wang, K.; Ramamurthy, V.; Scheffer, J. R.; Patrick, B. Org.
Lett. 2002, 4, 1443.
9
J. AM. CHEM. SOC. VOL. 127, NO. 10, 2005 3569

A R T I C L E S
Scheme 3
Natarajan et al.
Table 1. Asymmetric Induction in the â-Lactam Product Formed
during Solution and Solid-State Irradiations of Oxoamides 1-10
we believed that geometrical data based on X-ray crystal
structure studies would help resolve the controversy concerning
the nature of the primary photoreaction (hydrogen abstraction
vs electron transfer, Scheme 3) during the conversion of
R-oxoamides to â-lactams.28-37
time of irradiation
(min)
conversion
(%)
% de in
solid stateb
% de in
solutiona
oxoamide
1
2
50
10
45
7
25
10
30
5
15
60
120
10
30
30
10
60
1200
98
22
100
7
>99A
96B
79B
82A
70A
>99B
87B
85B
78B
91B
87B
93B
87B
95B
80A
48A
>99B
2B
2A
A mixture of â-lactam and oxazolidinone was obtained from
all 10 R-oxoamides following irradiation in solution, and
asymmetric induction in the â-lactam product was negligible
(Table 1, Scheme 1). Remarkably, the â-lactam was the
exclusive product of irradiation of 1-10 as crystals, and in
several cases the reaction could be carried out to total conver-
sion. Despite the slow photoreaction of 10 due to absorption
by the chiral auxiliary (naphthyl unit), the asymmetric induction
was excellent (de ) 99%). With all 10 R-oxoamide crystals at
<20% conversion â-lactams with >80% de were obtained. Our
observation of decreased de in several cases with progressive
conversion has been witnessed earlier in solid-state reactions
and therefore is not unusual. In solid-state reactions this is
3
4
5
6
7
2B
3B
5A
3B
5B
37
14
70
15
60
70
100
60
80
75
17
74
4
8
9
10B
0
10
2A
a Solution irradiation was done in CH3CN for compounds 1 and 3-10;
that for 2 was done in benzene. b A refers to the first peak eluted in HPLC;
B refers to the second peak eluted in HPLC.
(28) Aoyama, H.; Hasegawa, T.; Omote, Y. J. Am. Chem. Soc. 1979, 101, 5343.
(29) Asahi, T.; Nakamura, M.; Kobayashi, J.; Toda, F.; Miyamoto, H. J. Am.
Chem. Soc. 1997, 119, 3665.
(30) Toda, F.; Tanaka, K.; Yagi, M. Tetrahedron 1987, 43, 1495.
(31) Hashizume, D.; Kogo, H.; Sekine, A.; Ohashi, Y.; Miyamoto, H.; Toda, F.
J. Chem. Soc., Perkin Trans. 2 1996, 61.
(32) Toda, F.; Miyamoto, H. J. Chem. Soc., Perkins Trans. 1 1993, 1129.
(33) Sekine, A.; Hori, K.; Ohashi, Y.; Yagi, M.; Toda, F. J. Am. Chem. Soc.
1989, 111, 697.
(34) Toda, F.; Miyamoto, H.; Matsukawa, R. J. Chem. Soc., Perkin Trans. 1
1992, 1461.
(35) Toda, F.; Miyamoto, H.; Kanemoto, K. Chem. Commun. 1995, 1719.
(36) Toda, F.; Miyamoto, H.; Koshima, H.; Urbanczyk-Lipkowska, Z. J. Org.
Chem. 1997, 62, 9261.
(37) Aoyama, H.; Miyazaki, K.-I.; Sakamoto, M.; Omote, Y. Tetrahedron 1987,
43, 1513.
believed to be due to the disruption of the reactant’s long-range
order in the crystalline state by accumulation of products.38
Recently, solid-state reactions have been established to proceed
in stages, and it is suggested that products from original crystals
and the crystals that contain the product molecules adjacent to
(38) Keating, A. E.; Garcia-Garibay, M. A. In Molecular and Supramolecular
Photochemistry; Schanze, K. S., Ed.; Marcel Dekker: New York, 1998; p
195.
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Yang Cyclization of
R-Oxoamides
A R T I C L E S
Table 2. Crystallographically Derived γ-Hydrogen Abstraction Parameters for Oxoamidesa 1-10
oxoamide
space group
d (Å)
ω
(deg)
∆
(deg)
θ
(deg)
torsion angle (deg)
1
2
3
4
5
6
7
P21
2.814
50.89
20.95
51.35
19.94
56.08
21.31
53.34
17.88
50.76
19.67
51.51
20.21
52.71
17.19
53.66
15.92
55.02
18.45
52.99
20.66
52.9 ( 1.7
53.7 ( 9.7
0
52.90
54.00
53.97
54.57
60.18
51.75
59.04
53.00
53.31
56.10
55.94
54.07
58.57
56.99
61.66
64.63
61.23
59.74
55.30
46.75
117.87
50.08
118.28
49.99
128.03
50.44
122.58
51.32
116.77
50.01
114.85
49.93
119.44
51.27
113.32
52.30
117.46
52.01
127.39
48.20
119.6 ( 4.95
115.52 ( 2.8c
180
90.36
5.077
2.776
5.066
2.618
5.130
2.562
5.091
2.766
5.025
2.804
5.030
2.662
5.034
2.713
4.850
2.686
4.956
2.737
5.214
2.71 ( 0.08
2.64 ( 0.08
2.72
P212121
P21
89.55
-89.51
-86.99
81.83
P21
P212121
P21
86.48
P21
88.12
9b
P21
-69.12
-75.90
10
P21
-100.00
av 1-10b
av lit. value
ideal value
57.2 ( 3.3
81.96 ( 8.14
90-120
a See Figure 1 for definitions of the parameters. b Two independent molecules in the asymmetric unit; average based on Scheffer’s 57 examples. c Average
based on Scheffer’s 40 examples (θ not calculated for 17 examples): Leibovitch, M.; Olovsson, G.; Scheffer, J. R.; Trotter, J. J. Am. Chem. Soc. 1998, 120,
12755. Scheffer, J. R.; Scott, C. In CRC Handbook of Photochemistry and Photobiology, 2nd ed.; Horspool, W., Lenci, F., Eds.; CRC Press: Boca Raton,
FL, 2004; Vol. 54, pp1-25. Ihmels, H.; Scheffer, J. R. Tetrahedron 1999, 55, 885.
the reactant molecules may not yield the same products.39,40
Given this literature knowledge, the noteworthy photobehavior
of p-(R)-phenylethylamide 1 was that the de in the â-lactam
product remained constant (100%) even at 100% conversion.
As expected the p-(S)-phenylethylamide as the chiral auxiliary
gave the opposite diastereomer in 100% excess. The importance
of the crystalline medium is obvious in recognizing that the
same chiral auxiliaries have a negligible effect in solution (de
< 5%).
To gain insight into the factors that control the photobehavior
of R-oxoamides 1-10 in the crystalline state, X-ray crystal
structures of nine of the compounds were determined. Single
crystals of R-oxoamide 8 suitable for X-ray studies could not
be obtained. In Table 2 the geometrical parameters12,41-43
derived from X-ray data for hydrogen abstraction (Figure 1) in
R-oxoamides are provided. Also included are the average values
based on 54 ketones undergoing γ-hydrogen abstraction reported
by Scheffer’s group.12,41-43 In R-oxoamides 1-10 one of the
two abstractable γ-hydrogens is closer to the reactive carbonyl
group, and we believe that the closer hydrogen is the one that
is being abstracted in the crystalline state. Except for the CO---H
Figure 1. Definition of geometrical parameters d, ∆, ω, and θ for
distance, all other parameters are slightly far from ideal
values.12,41-43 Such deviations could be due to differences in
structure between the ground state (X-ray data that are used to
correlate the reactivity) and the excited state (from which the
reaction occurs). Closeness in hydrogen abstraction parameters
for R-oxoamides with numerous ketones12,41-43 reported in the
literature (Table 2) prompts us to suggest that the primary
process during cyclization of R-oxoamides to â-lactams is the
γ-hydrogen abstraction (Scheme 3). Mariano and co-workers
intramolecular γ-hydrogen abstraction.
have reached a similar conclusion for photoreactions of N,N-
dialkyl-R-oxoamides.25
In general, the chirality of the â-lactam product is decided at
the stage of the ring closure of the 1,4-diradical intermediate
(Scheme 3), i.e., to which face of the prochiral benzylic radical
center the γ-carbon radical adds. In media where the equilibrium
between the two rotomers of the diradical (diradicals A and B
in Scheme 3) is not reached, the chirality would be decided at
the hydrogen abstraction stage itself. Note that, as illustrated in
Figure 1, the torsion angle OdCsCRsNâ in R-oxoamide could
be positive or negative, and such a possibility leads to abstraction
of the isopropyl hydrogen from the top or bottom phase of the
(39) Zimmerman, H. E.; Nesterov, E. E. Acc. Chem. Res. 2002, 35, 77.
(40) Zimmerman, H. E.; Nesterov, E. E. J. Am. Chem. Soc. 2002, 124, 2818.
(41) Ihmels, H.; Scheffer, J. R. Tetrahedron 1999, 55, 885.
(42) Gudmundsdottir, A. D.; Lewis, T. J.; Randall, L. H.; Scheffer, J. R.; Rettig,
S.; Trotter, J.; Wu, C.-H. J. Am. Chem. Soc. 1996, 118, 6167.
(43) Leibovitch, M.; Olovsson, G.; Scheffer, J. R.; Trotter, J. J. Am. Chem.
Soc. 1998, 120, 12755.
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A R T I C L E S
Natarajan et al.
Câ-Cγ) for the two independent molecules, reveals that the
reactive carbonyl is tilted toward the same abstractable isopropyl
hydrogen in both molecules. Note that the above dihedral angles
for molecule 1, -75.9° and -7.9°, and molecule 2, -69.1° and
-15.9°, are fairly close and more importantly in the same
direction. The geometrical parameters listed in Table 2 (Figure
1) for γ-hydrogen abstraction for compounds 1-7, 9, and 10
clearly bring out the preference for abstraction of one of the
two hydrogens.
The covalent chiral auxiliary method reported here compares
well with the established ionic chiral auxiliary approach.11,12
Excellent de’s (>85%) in the â-lactam product have been
reported with five R-oxoamides linked with ionic chiral
auxiliaries.27 Four crystal structures reported by Scheffer’s group
are clearly suggestive of the chiral auxiliary’s role in ensuring
crystallization of each molecule in a chiral space group. In the
current study the covalent chiral auxiliary assumes a similar
role to result in asymmetric induction in all nine systems
investigated. As revealed by X-ray structural data for nine
crystals, the remote chiral auxiliary orients the molecules to
crystallize in a chiral space group (Table 2, P21 or P212121)
that forces them to adopt a homochiral conformation which
predisposes them to react diastereoselectively. The absence of
direct interaction between the chiral auxiliary and the photo-
reactive carbonyl chromophore in all of the structures is
indicative of the chiral auxiliary passively preorganizing the
reactive R-oxoamides toward a single diasteromer of the
â-lactam product.
Figure 2. Oxoamide 1 showing one independent molecule in the asym-
metric unit. Note the two abstractable γ-hydrogens are at different distances
from the carbonyl chromophore.
During irradiation of the p-(R)-(+)-phenylethylamide of N,N-
diisopropyl-R-oxoamide-4-carboxylic acid 1, the crystal re-
mained intact throughout the course of the reaction and the de
obtained in the â-lactam product was 100%, suggesting that
the photoreaction might belong to the rare single-crystal-to-
single-crystal category.43,45-60 To explore this possibility, the
structure of the reactant crystal was determined prior to
irradiation and at 20%, 50%, 80%, and 100% conversions.61
To monitor the integrity of the crystal with respect to conversion,
several single crystals were irradiated for various times and the
conversion was monitored by analyzing the product by HPLC
after the crystal was dissolved in a suitable solvent while yet
another single crystal from this batch was chosen for X-ray
structural analysis. Crystallinity was maintained at all stages of
the reaction. The structures at various stages of irradiation are
Figure 3. Oxoamide 9 showing two independent molecules in the
asymmetric unit which are not related by a plane of symmetry.
carbonyl, leading to two diradical rotomers, A and B. Under
ideal conditions both rotomers of the reactant R-oxoamide would
be present in equal amounts, leading to the â-lactam with 0%
ee (Scheme 2). Clearly, in the crystalline state this is not the
case, and exclusive formation of a single diastereomer suggests
that the hydrogen abstraction occurs preferentially from one
rotomer of the reactant R-oxoamide. This is possible only when
all molecules in the reactant crystal are frozen in a homochiral
conformation; i.e., all have the same OdCsCRsNâ torsion
angle. In the crystals of eight of the systems there is a single
independent molecule in the asymmetric unit, indicating that
all molecules in the crystal adopt the same conformation. As a
representative, the structure of p-(R)-phenylglycinol amide 7 is
shown in Figure 2.44 On the basis of the distance between the
carbonyl oxygen and the two abstractable isopropyl hydrogens
(see also Table 1), it is clear that only one would be
preferentially abstracted. Further, every molecule in the reactant
crystal has the same OdCsCRsNâ torsion angle (Table 2),
suggesting that the geometry of the reactive CdO with respect
to the γ-hydrogen is fixed, prompting the photoreaction in the
crystal to be diastereoselective. Despite having two independent
molecules per asymmetric unit, R-oxoamide 9 gave the â-lactam
product in 80% de. Careful analysis of the structure (Figure 3),
especially the dihedral angles (OdC-CR-Nâ and OC-CR-
(45) Ohasi, Y.; Sakai, Y.; Sekine, A.; Arai, Y.; Ohgo, Y.; Kamiya, N.; Iwasaki,
H. Bull. Chem. Soc. Jpn. 1995, 68, 2517.
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Soc. 1997, 119, 1462.
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Watanabe, S. J. Am. Chem. Soc. 1996, 118, 10664.
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1818.
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1636.
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Irie, M. Chem. Lett. 2002, 1224.
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9
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Yang Cyclization of
R-Oxoamides
A R T I C L E S
Figure 4. Molecular structure of oxoamide 1 and product â-lactam at (a) 0%, (b) 20%, (c) 50%, (d) 80%, and (e) 100% conversion. Structures are shown
with thermal ellipsoids at the 50% probability level.
provided in Figure 4. The structure at 50% conversion is
particularly revealing (Figure 4c). It is clear that there are modest
changes in the positions of all atoms except those of C5 and
C8 carbons (the ones that are involved in the reaction) and the
phenyl carbons. The photoproduct seems to fit quite well in
the lattice site of the reactant. The packing arrangements and
the cell parameters for the reactant, the product (as formed),
and the product following recrystallization are provided in Figure
5. In the crystals the reactant molecules are held by two
hydrogen bonds. Upon transformation to the product the two
hydrogen bonds are retained. Most importantly, the packing
arrangements of the product as formed and as recrystallized are
not the same. In the latter case the molecules in the crystal are
held by four hydrogen bonds (indicated in Figure 5) whereas
in the former they are held by two hydrogen bonds. The unit
cell dimensions and packing arrangement of the product as
formed in the crystal are much closer to those of the reactant
than to those of the recrystallized product. The adaptability of
the structure of the product within the reactant structure leads
to 100% de even at complete conversion. The different packing
arrangements of the product as formed on recrystallization
suggest that during the photoreaction the product formed is in
a metastable state. The product can accommodate itself without
disrupting the lattice of the reactant molecules even though the
reactant lattice may not be the most favorable for it.
The final discussion concerns the direct correlation of the
structure of the reactant with that of the product. With the known
absolute configuration of the chiral auxiliary the absolute
configuration of the newly formed chiral center in the â-lactam
can be assigned. On the basis of X-ray data the product â-lactam
from p-(R)-(+)-phenylethylamide of N,N-diisopropyl-R-oxo-
amide-4-carboxylic acid 1 is assigned to have the R configu-
ration. Formation of this isomer as the exclusive product
suggesting that (a) the nearest hydrogen (2.81 vs 5.08Å) is
abstracted by the excited carbonyl and (b) the intermediate 1,4-
diradical collapses to the â-lactam without any large motions
around any bond is easily visualized with the structure shown
in Figure 4c containing reactant and product in a 1:1 ratio. In
this structure following hydrogen abstraction by C(8A)dO(2),
the radical center at C(5A) bonds (from the bottom face) simply
by moving closer to the radical center at C(8A). Any motion
that takes the radical center at C(5A) to the top face would have
9
J. AM. CHEM. SOC. VOL. 127, NO. 10, 2005 3573

A R T I C L E S
Natarajan et al.
spectra were recorded using deuterated samples ordered from Aldrich
on a 400 MHz (Varian Inova) instrument. Irradiations were performed
using a 450 W medium-pressure mercury arc lamp in a water-cooled
immersion well. Light emitted from a Hanovia lamp was filtered
through Pyrex (transmits λ g 290 nm). Gas chromatographic analyses
were performed on a Hewlett-Packard 5890 fitted with a flame
ionization detector, capillary column RTX5, 15 m × 0.25 mm. High-
pressure liquid chromatography was performed on a Rainin instrument
with an HPXL solvent delivery system and connected to a tunable
Dynamax absorbance detector. For determinations of diastereomeric
excesses, chiral columns (chiralcel-OD, OC, OJ; chiralpak-AD, ADRH),
250 mm × 4.6 mm, from Chiral Technologies, Inc. were used.
Synthesis of Oxoamides 1-10. p-(R)-(+)-Phenylethylamide of
N,N-Diisopropylglyoxylamides (1). The carboxylic acid containing
N,N-diisopropylglyoxylamide (N,N-bis(1-methylethyl)-R-oxobenzene-
acetamide-4-carboxylic acid) synthesized following the procedure
adopted by Scheffer et al.62 (∼150 mg) was dissolved in 25 mL of
dichloromethane taken in a 100 mL round-bottom flask. 1-[3-(Di-
methylamino)propyl]-3-ethylcarbodiimide hydrochloride (EDC; 1.1
equiv) was added with stirring followed by the addition of 1.1 equiv
of the (R)-(+)-phenylethylamine. The mixture was stirred for 3-4 h.
The amide product 1 was purified using column chromatography (silica
gel) using hexane/ethyl acetate as eluent in the ratio 8:2. After
rotovapping and drying amide 1 was obtained as a white powder (150
mg, 70%). The same procedure was adopted for the synthesis of
compounds 2, 9, and 10 using (R)-(-)3-methyl-2-butylamine for 2 and
(R)-(+)-phenylethylamine and (S)-naphthylethylamine for coupling with
the m-carboxylic acid of N,N-diisopropylglyoxylamide to obtain 9 and
10, respectively.
For the synthesis of the amino acid derivative p-(S)-phenylalanine
methyl ester amide of N,N-diisopropylglyoxylamides (3), 1.1 equiv of
the ester of the amino acid ((S)-phenylalanine methyl ester) was
dissolved in dichloromethane in a 100 mL round-bottom flask cooled
to 0 °C. Triethylamine (1.1 equiv) was added, and the solution was
stirred for 5 min. The free amino acid obtained was added to the solution
of the carboxylic acid containing N,N-diisopropylglyoxylamide (∼150
mg) and 1.1 equiv of EDC dissolved in dichloromethane. The amino
acid coupled product 3 was purified using hexane/ethyl acetate as eluent
in the ratio 8:2. After rotovapping and drying amino acid derivative 3
was obtained as a white powder (180 mg, 75%). The same procedure
was adopted for the synthesis of compound 4 using (S)-tyrosine methyl
ester as the amino acid derivative.
Figure 5. Packing diagram of (a) oxoamide 1 before irradiation, (b) the
product â-lactam from 1 formed upon irradiation (100% conversion), and
(c) the recrystallized â-lactam from 1.
yielded the S isomer. Clearly the transformation from reactant
to product is topochemically controlled, and any large motion
is resisted by the crystal lattice.
Three independent steps are required for coupling of amino alcohols
to the carboxylic acid unit of substituted N,N-diisopropylglyoxylamides.
a. Preparation of Silyl Derivatives of the Amino Alcohols. The
chiral amino alcohol (1S,2S)-2-amido-3-methoxy-1-phenyl-1-propanol
(0.275 mg, 1.0 equiv) was taken in a 100 mL round-bottom flask, 25
mL of dichloromethane was added to it, and the flask was flushed with
nitrogen. The mixture was then cooled in an ice bath, and 2,6-lutidine
(1.2 equiv) was added while the solution was stirred. TBDMS triflate
(1.2 equiv) was then added to the solution. After 1 h, the reaction was
quenched by addition of water, extracted with dichloromethane, and
dried over MgSO4. The silyl derivative was then purified using column
chromatography with hexane and ethyl acetate in the ratio 8:2. The
silylated product was obtained as a yellow gel (350 mg, 80%). Similarly,
silylation of other amino alcohols, (-)-ephedrine, (R)-phenylglycinol,
and (S)-phenylalaninol, was done.
b. Coupling of Silyl Derivatives of Amino Alcohols as Amides
to the p-Carboxylic Acid Unit of N,N-Diisopropylglyoxylamides.
The carboxylic acid containing N,N-diisopropylglyoxylamide (∼150
mg, 1 equiv) was dissolved in 25 mL of dichloromethane in a 100 mL
round-bottom flask. A 1.1 equiv sample of EDC (3-(dimethylamino)-
propyl]-3-ethylcarbodiimide hydrochloride) was added to it, and the
solution was allowed to stir for 10 min followed by the addition of 1
Conclusions
We have shown in this paper that a covalent chiral auxiliary
functions as effectively as an ionic chiral auxiliary during
photocyclization of R-oxoamides to â-lactams. All 10 examples
investigated gave excellent de’s in the product â-lactam. The
crystal lattice preorganizes the reactant molecules toward a
single diasteromer of the â-lactam and forbids large motions
of the 1,4-diradical intermediate that would lose the stereo-
chemical memory. One of the 10 examples investigated proceeds
via a rare single-crystal-to-single-crystal transformation, and
X-ray structural information of the reaction at various stages
of conversion has allowed us to establish a direct correlation
between the sterochemistries of the reactant and the product.
We are in the process of establishing the synthetic usefulness
of the covalent chiral auxiliary approach in solid-state photo-
chemistry.
Experimental Section
General Information. Commercial spectral grade solvents were used
for photochemical reactions. Melting points were determined using a
Mel-Temp apparatus and are uncorrected. Nuclear magnetic resonance
(62) Scheffer, J. R.; Wang, K. Synthesis 2001, 1253.
9
3574 J. AM. CHEM. SOC. VOL. 127, NO. 10, 2005

Yang Cyclization of
R-Oxoamides
A R T I C L E S
equiv of chiral amino alcohol. After the reaction mixture was stirred
at room temperature for 2 h, the reaction was quenched by adding water,
and the organic layer was separated and dried over MgSO4. Later the
silyl-protected amino alcohol coupled R-oxoamide was purifed using
column chromatography with hexane and ethyl acetate as the eluent in
the ratio 8:2. The purified product was obtained in 75% yield, 115
mg.
c. Conversion of Silyl Derivatives to Free Amino Alcohols. The
purified silyl derivative (100 mg) was dissolved in dry THF in a flame-
dried round-bottom flask and was kept under a N2 atmosphere. To this
solution was added 1.2 equiv of tetrabutylammonium fluoride solution
(1 M solution in THF), and the reaction mixture was allowed to stir
for 30 min. Purification of the product was done using column
chromatography with hexane and ethyl acetate as the eluent in the ratio
7:3. After rotovapping and drying amide 5 was obtained as a white
powder (65 mg, 82%). Similar synthetic procedures (a-c) were adopted
for the synthesis of compounds 6-8.
Spectral Data for Compounds 1-10. 4-(Aminoformyl-N,N-
diisopropylformyl)-N-((R)-1-phenylethyl)benzamide (1). 1H NMR
(CDCl3, 400 MHz, δ, ppm): 1.15 (d, 6H, J ) 6.8 Hz), 1.56 (d, 6H, J
) 6.8 Hz), 1.62(d, 3H), 3.6 (m, 2H), 5.3 (q, 1H), 6.45 (d, 1H), 7.25-
7.4 (m, 5H), 7.87 (d, 2H), 7.93 (d, 2H). 13C NMR (CDCl3, 100 MHz,
δ, ppm): 20.4, 20.5, 21, 46.2, 50.0, 51.0, 52, 66.2, 126.5, 127.8, 127.9,
129.1, 129.95, 132, 134.2, 134.6, 135.5, 138, 143, 166, 167, 190.1.
GC-MS (EI): m/e 380 (M+), 252 (20), 225 (3), 148 (3), 128 (81),
105 (19), 86 (100), 43 (56).
4-(Aminoformyl-N,N-diisopropylformyl)-N-(1-hydroxy-3-phenyl-
propan-2-ylbenzamide (8). 1H NMR (CDCl3, 400 MHz, δ, ppm):
1.1-1.18 (m, 6H), 1.56-1.6 (d, 6H, J ) 6.8 Hz), 2.96-3.02 (d, 2H,
J ) 2.4 Hz), 3.54-3.64 (m, 2H), 3.64-3.84 (m, 2H), 4.3-4.4 (m,
1H), 5.2-5.25 (m, 1H), 7.25-7.4 (m, 5H), 7.42 (d, 1H), 7.808-7.88
(m, 4H). 13C NMR (CDCl3, 100 MHz, δ, ppm): 20.4, 20.5, 20.6, 20.8,
46.2, 50.6, 56.5, 66.2, 127, 128.1, 128.3, 129.1, 129.8, 135.2, 139.1,
139.9, 167, 190.1.
3-(Aminoformyl-N,N-diisopropylformyl)-N-((R)-1-phenylethyl)-
benzamide (9). 1H NMR (CDCl3, 400 MHz, δ, ppm): 1.0 (d, 6H, J )
6.8 Hz), 1.2 (d, 3H), 1.4 (d, 6H, J ) 6.8 Hz), 3.3-3.5 (2H, m), 5.06
(m, 1H), 6.3 (d, 1H), 7.25-7.36 (m, 5H), 7.4 (m, 1H), 7.82 (m, 1H),
7.9 (m, 1H), 8.1 (m, 1H). 13C NMR (CDCl3, 100 MHz, δ, ppm): 20.5,
20.6, 21, 46.2, 50.0, 51.0, 52, 66.2, 127, 128.1, 129.1, 129.8, 132, 134,
135.5, 138, 143, 166, 167, 190.1. GC-MS (EI): m/e 380 (M+), 252
(20), 225 (3), 148 (3), 128 (81), 105 (19), 86 (100), 43 (56).
3-(Aminoformyl-N,N-diisopropylformyl)-N-((S)-1-naphthalen-1-
1
ylethyl)benzamide (10). H NMR (CDCl3, 400 MHz, δ, ppm): 1.06
(d, 3H, J ) 8.0), 1.12 (d, 3H, J ) 8.0 Hz), 1.4 (d, 3H, J ) 8.0 Hz),
1.51 (d, 3H, J ) 8.0 Hz), 1.77 (d, 3H, J ) 8.0 Hz), 3.46-3.62 (m,
2H), 6.12 (m, 1H), 6.54 (d, 1H), 7.4-7.6 (m, 5H), 7.8-8.1 (m, 6H).
13C NMR (CDCl3, 100 MHz, δ, ppm): 20.3, 20.4, 20.6, 45, 46, 50,
123, 123.5, 126, 126.2, 127, 127.3, 129, 129.3, 130, 132, 133, 134,
134.5, 135, 138, 165, 166.5, 190. GC-MS (EI): m/e 430 (M+), 302
(7), 275 (3), 260 (3), 231 (2), 155 (30), 128 (100), 104 (9), 86 (94), 76
(8).
4-(Aminoformyl-N,N-diisopropylformyl)-N-((R)-3-methylbutan-
2-yl)benzamide (2). H NMR (CDCl3, 400 MHz, δ, ppm): 0.945-
Irradiation Procedures. a. Solution. Reaction solutions (with <4
mg of ketone) were purged by bubbling nitrogen through the solution
for at least 15 min prior to irradiation. During the irradiations the
reaction vessel was sealed. Photoproducts were monitored using GC,
GC-MS, and TLC. The percent conversion was kept within 50-60%
to avoid the formation of secondary products. For HPLC analysis the
solution-irradiated sample was dissolved in appropriate solvents (iPrOH)
and used for analyses.
b. Solid State. The ketones (∼2-3 mg), either as ground single
crystals or in polycrystalline form (powder), were sandwiched between
two Pyrex plates and spread out to cover a surface area of 2-3 cm2.
The plates were sealed with Parafilm on all sides before the irradiation
process. After irradiation the solid was dissolved in appropriate solvents,
and the products were analyzed using GC, GC-MS, and TLC. For
HPLC analysis the solution-irradiated sample was dissolved in ap-
propriate solvents (iPrOH) and used for analyses. For studies on the
single-crystal-single-crystal reaction after the X-ray crystal structure
of the reactant crystal was obtained, the mounted crystal was placed
between Pyrex plates, the corners were completely sealed with Parafilm,
and the crystal was irradiated in the UV chamber. The same crystal
was irradiated for different intervals of time and the X-ray crystal
structure determined after each interval.
1
0.973 (dd, 6H, J ) 6.8, 4.4 Hz), 1.146-1.167 (dd, 6H, J ) 6.8, 2 Hz),
1.18-1.152 (d, 3H, J ) 6.8 Hz), 1.56 (d, 6H, J ) 6.8 Hz), 1.9 (m,
1H), 3.56-3.68 (m, 2H), 4.04-4.12 (m, 1H), 6.02 (d, 1H), 7.84 (d,
2H), 7.96 (d, 2H). 13C NMR (CDCl3, 100 MHz, δ, ppm): 17.79, 18.74,
18.89, 20.48, 20.5, 20.78, 21.78, 33.3, 46.39, 50.46, 51.03, 127.68,
129.94, 135.4, 140.5, 166, 166.6, 190.32. Mass spectral data: m/e
(relative intensity) 346 (M+, 1), 303 (1), 260 (4), 218 (11), 191 (3),
148 (2), 128 (60), 104 (33), 86 (100), 43 (97).
2-(4-Diisopropylaminooxalylbenzoylamino)-(S)-3-phenylpro-
1
pionic Acid Methyl Ester (3). H NMR (CDCl3, 400 MHz, δ, ppm):
1.14-1.18 (dd, 6H, J ) 6.8, 2.0 Hz), 1.55 (d, 6H), 3.2-3.34 (m, 2H),
3.56-3.68 (2H, m), 3.78 (3H, s), 5.08 (m, 1H), 6.67 (d, 1H), 7.0-7.3
(m, 5H), 7.8 (d, 2H), 7.9 (d, 2H).
2-(4-Diisopropylaminooxalylbenzoylamino)-3-((S)-4-hydroxy-
phenyl)propionic Acid Methyl Ester (4). 1H NMR (CDCl3, 400 MHz,
δ, ppm): 1.16-1.2 (dd, 6H, J ) 6.8, 2.0 Hz), 1.56 (d, 6H, J ) 6.8
Hz), 3.085-3.223 (m, 2H), 3.577-3.653 (2H, m), 3.76 (3H, s), 4.98-
5.2 (m, 1H), 6.75 (d, 1H), 6.86 (d, 2H), 7.8 (d, 2H), 7.94 (d, 2H).
4-Diisopropylaminooxalyl-N-((1S,2S)-2-hydroxy-1-methoxymethyl-
1
2-phenylethyl)benzamide (5). H NMR (CDCl3, 400 MHz, δ, ppm):
1.07-1.12 (dd, 6H, J ) 6.8, 2.0 Hz), 1.48-1.52 (d, 6H, J ) 6.8),
3.48-3.65 (m, 4H), 3.9 (s, 3H), 4.32-4.38 (m, 1H), 5.04 (d, 1H, J )
3.6 Hz), 6.85(d, 1H), 7.16-7.36 (m, 5H), 7.72 (d, 2H), 7.88 (d, 2H).
4-(Aminoformyl-N,N-diisopropylformyl)-N-((1R,2S)-1-hydroxy-
1-phenylpropan-2-yl)-N-methylbenzamide (6). 1H NMR (CDCl3, 400
MHz, δ, ppm): 1.1 (d, 6H, J ) 6.8 Hz), 1.34 (d, 3H, J ) 6.8 Hz),
1.52 (d, 6H, J ) 6.8 Hz), 2.58-2.98 (two s, 3H), 3.48-3.8 (3H, m),
4.6-4.92 (two m, 1H), 6.86-7.0 (two d, 1H), 7.25-7.42 (m, 6H),
7.76-7.88 (two d, 2H). Mass spectral data: m/e (relative intensity)
424 (M+, 1), 317 (42), 296 (5), 260 (100), 251 (3), 233 (5), 190 (3),
161 (5), 132 (17), 128 (25), 104 (33), 86 (55).
2-(4-(1-(2-Hydroxy-1-phenylethylamino)vinylphenyl)-N,N-diiso-
propyl-2-oxoacetamide (7). 1H NMR (CDCl3, 400 MHz, δ, ppm): 1.15
(dd, 6H, J ) 6.8, 2.0 Hz), 1.57 (d, 6H, J ) 6.8 Hz), 3.54-3.64 (m,
2H), 3.88-3.96 (m, 2H), 5.2-5.25 (m, 1H), 7.25-7.4 (m, 5H), 7.42
(d, 1H), 7.808-7.88 (m, 4H). 13C NMR (CDCl3, 100 MHz, δ, ppm):
20.5, 20.6, 20.7, 46.2, 50.6, 56.5, 66.2, 127, 128.1, 129.1, 129.8, 135.2,
139.1, 139.9, 167, 190.1.
Reaction Conversion Determinations. Conversions were deter-
mined on the basis of the results of GC analysis. The difference in the
GC detector response for starting material and its reaction products
was found to be negligible (all are structural isomers in most cases).
Thus, no correction was made to the integration data.
Analysis Conditions. HPLC and GC conditions for â-lactam
photoproducts of substrates are given below. All the samples were
monitored at 254 nm. The solvent composition of the eluent and the
retention times for individual diastereomers are as follows: (oxoamide
1) HPLC-chiralcel-OD, mobile phase 90:10 hexane to 2-propanol; flow
rate 0.7 mL/min; retention time of diastereomers, 48.5 and 55.4 min;
(oxoamide 2) HPLC-chiralcel-OJ, mobile phase 95:5 hexane to
2-propanol; flow rate 0.7 mL/min; retention time of diastereomers, 28.3
and 37 min; (oxoamide 3) HPLC-chiralcel-OD, mobile phase 80:20
hexane to 2-propanol; flow rate 0.5 mL/min; retention time of
diastereomers, 24.3 and 30.0 min; (oxoamide 4) HPLC-chiralpak-AD,
mobile phase 80:20 hexane to 2-propanol; flow rate 0.6 mL/min;
retention time of diastereomers, 34.0 and 56.0 min; (oxoamide 5)
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A R T I C L E S
Natarajan et al.
HPLC-chiralpak-ADRH, mobile phase 78:22 hexane to 2-propanol;
flow rate 0.3 mL/min; retention time of diastereomers, 20.7 and 24.7
min; (oxoamide 6) HPLC-chiralpak-AD, mobile phase 90:10 hexane
to 2-propanol; flow rate 0.5 mL/min; retention time of diastereomers,
95.0 and 110.0 min; (oxoamide 7) HPLC-chiralcel-OJ, mobile phase
90:10 hexane to 2-propanol; flow rate 0.7 mL/min; retention time of
diastereomers, 18.0 and 24.0 min; (oxoamide 8) HPLC-chiralcel-OJ,
mobile phase 96:4 hexane to 2-propanol; flow rate 0.9 mL/min;
retention time of diastereomers, 100.0 and 115.0 min; (oxoamide 10)
HPLC-chiralpak-AD, mobile phase 85:15 hexane to 2-propanol; flow
rate 0.6 mL/min; retention time of diastereomers, 25.0 and 29.8 min;
(oxoamide 9) GC-SE-30; initial temperature 100 °C; initial time 1.0;
rate 20 deg/min; final temperature 240 °C; final time 60 min; retention
time of diastereomers, 51.5 and 52.5 min.
Characterization of â-Lactam Products. â-Lactam Photoproduct
from Oxoamide 1. 1H NMR (CDCl3, 400 MHz, δ, ppm): 0.7 (s, 3H),
1.3 (dd, 6H, J ) 6.8 Hz, 4.8 Hz), 1.47 (s, 3H), 1.66 (d, 3H, 7.2 Hz),
3.58 (m, 1H), 5.30-5.38 (m, 1H), 7.1 (d, 1H), 7.20-7.32 (m, 5H),
7.35-7.42 (m, 2H), 7.52 (d, 2H). GC-MS (EI): m/e 380 (M+), 360
(2), 295 (60), 280 (11), 252 (13), 191 (15), 175 (100), 148 (5), 147(5),
105 (29), 77 (10).
â-Lactam Photoproduct from Oxoamide 2. 1H NMR (CDCl3, 400
MHz, δ, ppm): 0.81 (s, 3H), 0.945-0.973 (dd, 6H, J ) 6.8 Hz), 1.18
(d, 3H, J ) 6.8 Hz), 1.335-1.359 (dd, 6H, J ) 6.8 Hz, 4H), 1.49 (s,
3H), 1.82 (m, 1H), 3.56-3.58 (m, 1H), 4.0-4.12 (m, 1H), 6.2 (s, 1H),
7.34 (d, 2H), 7.64 (d, 2H). GC-MS (EI): m/e 346 (M+), 303 (7), 261
(60), 219 (11), 218 (42), 192 (21), 191 (22), 175 (100), 147(6), 105
(7), 100 (32), 43 (73).
â-Lactam Photoproduct from Oxoamide 3. 1H NMR (CDCl3, 400
MHz, δ, ppm): 0.8 (s, 3H), 1.3 (d, 6H, J ) 6.8 Hz), 1.47 (s, 3H),
3.2-3.34 (m, 2H), 3.58 (m, 1H), 3.78 (s, 3H), 5.10 (m, 1H), 6.67 (d,
1H), 7.1-7.3 (m, 5H), 7.42 (d, 2H), 7.64 (d, 2H). GC-MS (EI): m/e
438 (M+), 381(2), 312 (4), 260 (100), 202 (5), 191 (38), 162 (48), 133
(62), 119(38), 91(78), 77 (20).
â-Lactam Photoproduct from Oxoamide 8. 1H NMR (CDCl3, 400
MHz, δ, ppm): 0.75 (s, 3H), 1.32-1.34 (dd, 6H, J ) 6.8 Hz), 1.48 (s,
3H), 3.01 (d, 2H, J ) 7.2 Hz), 3.4-3.48 (m, 1H), 3.6-3.82 (m, 2H),
4.3-4.4 (m, 1H), 6.75 (s, 1H), 7.29-7.40 (m, 5H), 7.5-7.53 (m, 4H).
â-Lactam Photoproduct from Oxoamide 9. GC-MS (EI): m/e
380 (M+, 50), 345 (5), 295 (39), 260 (34), 233 (22), 191 (30), 175
(49), 133 (77), 119 (54), 105 (100), 77 (48).
Crystal Structure Determination. Crystals of 1-7 and 10 were
mounted in Cryoloops with Paratone oil and placed in the cold nitrogen
stream of the Kryoflex attachment of the Bruker APEX CCD diffrac-
tometer. Full spheres of data were collected using 606 scans in ω (0.3°
per scan) at æ ) 0°, 120°, and 240°. The raw data were reduced to F2
values using the SAINT+ software,63 and global refinements of unit
cell parameters employing approximately 2000-5000 reflections chosen
from the full data sets were performed. Multiple measurements of
equivalent reflections provided the basis for empirical absorption
corrections as well as corrections for any crystal deterioration during
the data collection (SADABS64). The structures were solved by direct
methods and completed by successive cycles of full-matrix, least-
squares refinement followed by the calculation of difference maps. Most
hydrogen atoms could be located in these maps, and those attached to
nitrogen or oxygen were placed in these locations. All hydrogen atoms
attached to carbon were placed in calculated positions with isotropic
displacement parameters 20% larger than those of the attached atoms
and allowed to ride. In the case of 2, the isopropyl group in the chiral
auxiliary is disordered over two alternate sites. These two locations
were refined with restraints making corresponding distances in the two
equal. All computations associated with structure solution, refinement,
and presentation were performed with the SHELXTL65 package.
Acknowledgment. V.R. thanks the NSF for financial support
(Grants CHE-9904187 and CHE-0212042), J. R. Scheffer for
insightful discussions, and J. R. Scheffer, Keyan Wang, and
Brian Patrick for providing crystallographic help at the early
stages of the project. J.T.M. thanks the Louisiana Board of
Regents through the Louisiana Educational Quality Support
Fund (Grant LEQSF (2003-2003)-ENH-TR-67) for the purchase
of the Bruker APEX diffractometer.
â-Lactam Photoproduct from Oxoamide 4. 1H NMR (CDCl3, 400
MHz, δ, ppm): 0.8 (s, 3H), 1.3-1.36 (d, 6H), 1.45 (s, 3H), 3.2-3.34
(m, 2H), 3.52-3.54 (m, 1H), 3.7 (s, 3H), 4.9-5.0 (m, 1H), 6.52-6.8
(m, 4H), 7.5-7.8 (m, 4H).
â-Lactam Photoproduct from Oxoamide 5. 1H NMR (CDCl3, 400
MHz, δ, ppm): 0.8 (s, 3H), 1.34-1.39 (dd, 6H, J ) 6.8 Hz), 1.5 (s,
3H), 3.55-3.72 (m, 3H), 3.92 (s, 3H), 4.36-4.45 (s, 1H), 5.10 (m,
1H), 6.68 (d, 1H), 7.28-7.42 (m, 5H), 7.6 (d, 2H), 7.8 (d, 2H).
â-Lactam Photoproduct from Oxoamide 6. 1H NMR (CDCl3, 400
MHz, δ, ppm): 0.854 (s, 3H), 1.23-1.25 (m, 3H), 1.34-1.39 (dd,
6H, J ) 6.8 Hz), 1.49 (s, 3H), 2.62-3.0 (two s, 3H), 3.62-3.89 (m,
2H), 4.58-4.95 (two m, 1H), 7.0-7.5 (m, 9H).
Supporting Information Available: Crystallographic reports
and tables of positional and thermal parameters and bond lengths
and angles provided as 15 CIF files. The material is available
free of charge via the Internet at http:// pubs.acs.org.
JA043999P
â-Lactam Photoproduct from Oxoamide 7. 1H NMR (CDCl3, 400
MHz, δ, ppm): 0.76 (s, 3H), 1.3-1.35 (dd, 6H, J ) 6.8 Hz), 1.54 (s,
3H), 3.4-3.48 (m, 1H), 3.92-4.04 (m, 2H), 5.2-5.3 (m, 1H), 6.8 (s,
1H), 7.25-7.42 (m, 5H), 7.6 (d, 2H), 7.8 (d, 2H).
(63) SAINT+, Version 6.22, Bruker-AXS, Madison, WI, 2001.
(64) SADABS, Version 2.05, Bruker-AXS, Madison, WI, 2000.
(65) SHELXTL, Version 6.10, Bruker-AXS, Madison, WI, 2000.
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3576 J. AM. CHEM. SOC. VOL. 127, NO. 10, 2005