The synthesis and stereospecific solid-state photodecarbonylation of hexasubstituted meso- and d,l-ketones

Article abstract of DOI:10.1039/c1pp05080j

Tertiary carbanions were trapped with half an equivalent of diphosgene to give meso- and d,l-hexasubstituted ketones in moderate yields and modest diastereoselectivities. The ketones were also synthesized by a step-wise synthesis in which the carbonyl group was first installed as an acid before activation and the second nucleophilic attack. This second method gave lower yields but similar diastereoselectivites. Steric limits of both methods were also determined. The photolysis of the resulting crystalline ketones gave a mixture of products in solution, but took place chemoselectively and diastereospecifically in the solid-state. The Royal Society of Chemistry and Owner Societies.

Full text of DOI:10.1039/c1pp05080j

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MacGillivray, Photochem. Photobiol. Sci., 2011, 10, 1384
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Hydroxy-group effect on the regioselectivity in a
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PAPER
The synthesis and stereospecific solid-state photodecarbonylation of
hexasubstituted meso- and d,l-ketones†‡
Saori Shiraki, Arunkumar Natarajan and Miguel A. Garcia-Garibay*
Received 23rd February 2011, Accepted 16th April 2011
DOI: 10.1039/c1pp05080j
Tertiary carbanions were trapped with half an equivalent of diphosgene to give meso- and
d,l-hexasubstituted ketones in moderate yields and modest diastereoselectivities. The ketones were also
synthesized by a step-wise synthesis in which the carbonyl group was first installed as an acid before
activation and the second nucleophilic attack. This second method gave lower yields but similar
diastereoselectivites. Steric limits of both methods were also determined. The photolysis of the resulting
crystalline ketones gave a mixture of products in solution, but took place chemoselectively and
diastereospecifically in the solid-state.
scrambling, disproportionate, or react with solvent or with other
reagents. In contrast, radical pairs formed within close-packed
crystalline solids (Fig. 1) are unable to diffuse or rotate, such that
bond formation occurs with stereochemical retention. The ability
of the crystal environment to control the intrinsic bond-breaking
and bond-making events while limiting the reaction possibilities
and giving high product yields is related to their relatively low
statistical entropy and is reminiscent of the remarkable control
observed in nature with photoenzymes.10 By a similar analogy, the
favorable effects of the crystal can only be observed in the absence
of melting.7
Introduction
Compounds with all-carbon adjacent quaternary stereogenic
centers constitute one the most challenging structural motifs
in organic synthesis, and remain an active topic of research.1
Regardless of the nature of the final disconnections (additions,
couplings, rearrangements, C–H insertions, etc.), most synthetic
methods face the challenge of forming one or more C–C sigma
bonds within highly substituted substrates. As the site of attack is
severely hindered, reactions tend to be slow and with no selectivity
when alternative trajectories are available. Their formation tends
to occur with low selectivities and chemical yields.
It is known that photochemical reactions may offer solutions
to challenging problems in synthetic chemistry. Recent advances
in the use of organizing media to control the behavior of excited
states and reactive intermediates suggest a promising future for the
field.2 Strategies span the use of supramolecular hosts,3 porous
materials,4 polymer matrices5 and crystalline solids.6 As far as
the synthesis of compounds with all-carbon adjacent quaternary
stereogenic centers is concerned, we have shown that the solid-
state photodecarbonylation of hexasubstituted ketones7 offers
a promising and general strategy with additional advantages
from a green chemistry perspective.8 The reaction occurs by
photoinduced a-cleavage and decarbonylation reactions that
generate a radical pair, and is followed by the chemoselective
and stereospecific combination of the two radical centers to form
the coveted C–C bond.7,9 If photolysis is carried out in solution,
the two radicals in the pair diffuse apart. It is well known that
free radicals can recombine indiscriminately with stereochemical
Fig. 1 Photoinduced decarbonylation of hexasubstituted ketones and
stereospecific radical recombination for the synthesis of compounds
with all carbon adjacent stereogenic quaternary centers. The dashed line
represents the enclosure formed by close neighbors in the crystal.
Although the potential of the method in Fig.
1 has
been demonstrated by solid-state photodecarbonylation of sev-
eral cycloalkanones,11 dicumyl ketones,12 trans-a,a¢-dialkenoyl-
cyclohexanone,8b and in the synthesis of the natural products
herebertenolide13 and a-cuparenone,14 in this article we explore
a simple but general strategy for the synthesis of hexasub-
stituted ketones and analyze their solid-state photochemistry.
We recognized that one of the simplest approaches to prepare
hexasubstituted ketones would be the direct coupling of two
trisubstituted carbanions with a carbonyl equivalent to form
ketones with symmetries belonging to the CS (meso-) and C2
(d,l-) point groups (Scheme 1). The method was explored with
the cyclic lithium enolate of 3-phenyl-2-pyrrolidinone to form the
corresponding meso- and d,l-ketones with diastereoselectivities
Department of Chemistry and Biochemistry, University of California, Los
Angeles, CA, 90095-1569, USA. E-mail: mgg@chem.ucla.edu
† This article is published as part of a themed issue in honour of Yoshihisa
Inoue’s research accomplishments on the occasion of his 60th birthday.
‡ CCDC reference numbers 814323 & 814324. For crystallographic data
in CIF or other electronic format see DOI: 10.1039/c1pp05080j
1480 | Photochem. Photobiol. Sci., 2011, 10, 1480–1487 This journal is
The Royal Society of Chemistry and Owner Societies 2011
©

single product with retention of configuration is obtained in good
yields in the crystalline state.
Results and discussion
Preparation of hexasubstituted ketones
The preparation of hexasubstituted ketones was explored by the
two different methods shown in Scheme 2. Method A is a one-pot
reaction of the starting enolate with 0.5 equivalent of the carbonyl
equivalent. Method B is the stepwise installation of the carbonyl
group by the reaction of one equivalent of enolate with CO2 to
form an isolatable carboxylic acid, followed by the activation
into the acyl chloride and addition of the second enolate. While
method B requires two more steps, it offers an opportunity to put
in a different nucleophile in the second step or to carry out an
enantiomeric purification of the acid to prepare enantiomerically
pure ketones.15
Scheme 1
that could be controlled by changing the size of the leaving
group (X), which helps control the face selectivity of the second
nucleophilic attack on the lithium-chelated “acyl” intermediate
in Scheme 1a.15 The meso-isomer was obtained with the larger
carbonyl diimidazole (CDI) and the d,l-pair when the leaving
group was a smaller Cl- anion from phosgene or diphosgene.
In order to explore the scope of this reaction with acyclic
enolates, we report here a study on the synthesis of acyclic ketones
2a–2e shown in Scheme 2 with phenyl, alkyl (R1 = Me, Et, iPr) and
a few functional groups R2 that could be amenable to subsequent
functionalization, including cyano (2a–2c), carbomethoxy (2d),
and amide substituents (2e, Scheme 2). In addition to determining
the reaction efficiency and diastereoselectivity as a function of
the various substituents, we analyzed the crystallization and solid
state photochemistry of all the crystalline ketones. As described
below, we found that complex reaction mixtures are obtained by
the irradiation of the ketones in solution or melted solids, but a
Method A was first explored with the synthesis 2,4-dimethyl-
3-oxo-2,4-diphenylpentanedinitrile 2a by the addition of half
an equivalent of
a carbonyl source to the anion of 2-
phenylpropionitrile 1a, generated by refluxing the nitrile with 2–3
eq. of NaH in THF for 2–3 h or by stirring 1a with 1.2 eq. of
LiHMDS in THF at -78 ◦C for 2 h. Commercially available sam-
ples of trichloromethyl chloroformate (diphosgene) and carbonyl
diimidazole (CDI) were investigated as the carbonyl sources. After
the addition of half an equivalent of the carbonyl source to the
enolate at various temperatures, the solution was stirred for 2 h.
Following an aqueous workup the product was purified by column
chromatography and the formation of ketone 2a established by 1H
and 13C NMR and FTIR. The 1H NMR spectrum of the isolated
product was characterized by the disappearance of the benzylic
quartet (3.8 ppm) and the methyl group doublet (1.7 ppm) of 1a.
The latter had transformed into two singlets at 1.85 and 1.95 ppm
in a 2 : 1 ratio, indicating the formation of the expected d,l- and
meso-diastereomers of ketone 2a. The expected doubling of signals
was observed in the 13C NMR spectrum, including two carbonyls
at 193.6 and 194.3 ppm, which appeared in the IR spectrum as a
single stretching band at 1729 cm-1. Having confirmed the desired
products we explored different reactions conditions in order to
establish the most effective one. As indicated in Table 1, the
reaction efficiency was explored with enolates formed by reaction
of 1a with NaH or LiHMDS and at temperatures varying from
-78 ◦C to 25 ◦C (r.t.). The yields of hexasubstituted ketone 2a were
Table 1 Yields and diastereoselectivities of carbonylation via Method A
using diphosgene as a carbonyl source in THF
S.M.a R1
R2
base
T/◦C
yield (%)b d,l : meso
1a
1a
1a
1a
1b
1c
1d
1e
CN
CN
CN
CN
CN
CN
Me NaH
Me NaH
Me LiHMDS
Me LiHMDS
-78
0
-78
0
-78
-78, rt
rt
46
56
50
73
56
0
2 : 1
3 : 1
3 : 1
2 : 1
2 : 1
—
Et
iPr
LiHMDS
LiHMDS
CO2Me
Me LiHMDS
44
0
2 : 1
—
CONMe2 Me LiHMDSc rt
a Starting material. b Isolated yields. c Full deprotonation was only ob-
tained with sBuLi, but no ketone formation was observed.
Scheme 2
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©

moderate to good when diphosgene was used (46–73%), and the
best yields were obtained with LiHMDS (Table 1). Given that the
same major product was obtained in a ca. 2 : 1 ratio with either Na
or Li enolates, we conclude that chelation is probably not involved
in the second nucleophilic substitution. While the reaction was
also analyzed with CDI, no product was observed under similar
reaction conditions.
As expected, the results in Table 1 clearly show that increasing
the size of the nucleophile led to lower product yields. The smallest
nucleophile, 2-phenylpropionitrile 1a, gave the best yields (73%)
while 2-phenylbutyronitrile 1b and methyl 2-phenylpriopionate 1d
gave moderate yields (56 and 44% respectively). In each successful
reaction, one isomer is preferred in a ca. 3 : 1 to 2 : 1 ratio. The
larger nucleophiles, 3-methyl-2-phenylbutyronitrile 1d and N,N-
dimethyl-2-phenylpropanamide 1e, did not form the ketones due
to their high steric hindrance. Interestingly, anions of the cyclic
1-methyl-3-phenyl-2-pyrrolidinone (Scheme 1) had been shown to
react well with both phosgene and with CDI. The difference in
reactivity between the two carbanion nucleophiles is most likely
due to the cyclic and more compact nature of the lactam, which
significantly reduces the steric hindrance.
Given our initial observations with propionitrile 1a, we explored
the reaction efficiency as a function of an increase in the size of
the alkyl group from methyl to ethyl to isopropyl. With LiHMDS
◦
as the base in experiments carried out at -78 C, we found that
the ethyl-substituted ketone 2b formed in a 2 : 1 diastereomeric
ratio in a moderate yield of 56%. In contrast, the reaction of the
bulkier isopropyl derivative failed to give the desired ketone with
reactions carried out at -78 ◦C and 25 ◦C. We confirmed that
anion formation with LiHMDS had occurred by quenching it
with D2O (95% deuteration), and we noticed that analysis of the
reaction showed the formation of the acyl chloride, which, upon
work-up, had been hydrolyzed to the acid. We conclude that the
steric hindrance of the isopropyl group prevents the addition of
the second anion to the acyl chloride intermediate.
Subsequently, reactions with the enolates derived from methyl
ester 1d and N,N-dimethylamide 1e were also explored. As
indicated in Table 1, while the reaction of 1d proceeded in 44% yield
and a modest diastereoselectvity of 2 : 1, the reaction of amide 1e
failed to give the desired product under the same conditions. It
is important to point out that the deprotonation of 1d failed at
-78 ◦C, as indicated by a D2O quench, but it proceeded smoothly
by stirring over two hours at 25 ◦C. As we also found that
deprotonation of 1e with LiHDMS was not complete even at room
temperature we changed the base to sec-butyl lithium,16 which was
shown to work well at -78 ◦C. Unfortunately, the corresponding
carbanion failed to give the desired ketones 1e when reacted with
diphosgene, suggesting that the N,N-dimethylamino group is also
too hindered to react with the electrophile. To prove that the acyl
chloride had indeed formed and that main problems was due to
sterics we added the smaller anion of propionitrile 1a, to see the
formation of asymmetric ketone 4 (Scheme 3). While the yield of
the reaction was very low (7%), this result supports the likelihood
that the amide is simply too sterically hindered for an efficient
second nucleophilic attack (see below).
Diastereoselectivity of the hexasubstituted ketones
While separation of the two ketone diastereomers by silica gel
chromatography was not possible, we noticed that the major
diastereomer of 2a could be isolated in its pure form by fractional
crystallization from ether. It is important to note here that the
ketones need to be crystalline so that the photodecarbonylation
can take place in the solid-state. The minor diastereomer did not
crystallize and was not obtained in pure form. However, good
quality single crystals of the major isomer of 2a (m.p. 142–143 ◦C)
were analyzed by X-ray diffraction.§ A structure solved in the
chiral space group P21 showed that the relative configuration of
the major product corresponds to the chiral diastereomer d,l-
2a (Fig. 2). Notably, d,l-2a undergoes a spontaneous resolution
crystallizing as a conglomerate with only one enantiomer in
any given single crystal, as was confirmed by circular dichroism
measurements from single crystalline specimens (Fig. 3). The
Fig. 2 Molecular structures of the chiral diastereomers (d,l) of com-
pounds 2a (left) and 2b (right). The view is approximately down the O
C
bond vector with the two methyl and ethyl groups projecting to the front
of the plane of the page.
§ Crystal data for d,l-2a at 100(2) K: C19H16N2O, M = 288.34, monoclini◦c,
˚
space group P21, a = 8.154(2), b = 7.971(2), c = 12.393(3) A, b = 104.930(3) ,
3
-3
˚
˚
V = 778.3(4) A , Z = 2, Dc = 1.230 Mg m , F(000) = 304, l = 0.71073 A,
m(Mo-Ka) = 0.077 m-1, crystal size = 0.50 ¥ 0.30 ¥ 0.20 mm; of the 6915
reflections collected, 2050 (Rint = 0.0213) were independent reflections;
3
˚
max./min. residual electron density 0.288/-0.173 e A , R1 = 0.0325 (I >
2s(I)) and wR2 = 0.0803. Crystal data for d,l-2b at 296(2) K: C21H20N2O,
M = 316.39, monoclinic, spac◦e group Cc, a = 7.3178(14), b = 14.158(3),
3
˚
˚
c = 17.191(3) A, b = 96.227(2) , V = 1770.6(6) A , Z = 4, Dc = 1.187 Mg
-3
-1
˚
m , F(000) = 672, l = 0.71073 A, m(Mo-Ka) = 0.074 m , crystal size =
0.50 ¥ 0.20 ¥ 0.10 mm; of the 8678 reflections collected, 2606 (Rint
=
0.0199) were independent reflections; max./min. residual electron density
3
˚
Scheme 3
0.168/-0.145 e A , R1 = 0.0482 (I > 2s(I)) and wR2 = 0.1013.
1482 | Photochem. Photobiol. Sci., 2011, 10, 1480–1487 This journal is
The Royal Society of Chemistry and Owner Societies 2011
©

Fig. 3 Circular dichroism spectra of solutions prepared with single
crystals of d,l-2a dissolved in chloroform.
Fig. 4 The relative stereochemistry of the major diastereomer of 2d
was determined by titrating with chiral shift reagent europium(III)
tris-[3-(heptafluoropropylhydroxymethelene)-d-camphorate].
molecular structure of d,l-2a is characterized by a conformation
that roughly eclipses the two methyl groups with the carbonyl
C
O bond, placing the two phenyl groups towards the opposite
Table 2 The yields and diastereoselectivities of carboxylation and nucle-
sides of the plane of the carbonyl. The two cyano groups make
dihedral angels of 146.6 and 136.7◦, respectively with the vector of
the carbonyl group. The structure is close to the ideal C2 symmetry
with an approximate two-fold axis along the C O bond vector.
The purification and crystallization properties of the ethyl
ketone 2b mirrored those of the methyl analog. Fractional
crystallization from diethyl ether gave the major isomer in pure
form (m.p. 153–156 ◦C) and single crystal X-ray diffraction
confirmed that it corresponds to the d,l-pair. The structure of
2b was solved in the space group Cc, which unlike the space group
of 2a, makes the composition of the crystal racemic. Also shown
in Fig. 2, the molecular structure of 2b is very similar to that of 2a
with the phenyl and cyano groups projecting up and down from
the plane of the carbonyl.
In remarkable agreement with the previous two ketones,
the major diastereomer of 2d was also isolated by fractional
recrystallization. However, its relative configuration could not
be determined by single crystal X-ray diffraction analysis as
the crystals formed as very thin needles (m.p. 117–119 ◦C).
However, we were able to confirm the relative configura-
tion of the major diastereomer by 1H NMR analysis in
the presence of the chiral shift reagent europium(III) tris-[3-
(heptafluoropropylhydroxymethelene)-d-camphorate], which re-
sulted in the 1 : 1 splitting of the aromatic, quaternary methyl,
and methyl ester signals, indicating that the sample is chiral and
racemic (Fig. 4).
ophilic addition (Method B)
Nucleophilea
Yield (%) of 3b
Yield (%) of 2
d,l : meso 2c
1a
1b
1d
1e
75
50
70
90
55
40
41
0
3 : 1
2 : 1
2 : 1
—
a Carbanions were prepared by reaction with LiHMDS or sBuLi in THF.
b Isolated yield of carboxylic acid. c Determined by 1H NMR.
procedure was applied to compounds 1b, 1d and 1e, which yielded
acids for 3b, 3d and 3e in reasonably good yields that range from
50–90% (Table 2). However, the carboxylation of 1b had to be
carried out -78 ◦C as reactions carried out at 25 ◦C gave the
desired acid in only 20% yield.
Once the carboxylic acids 3 had been synthesized, they were
converted into the corresponding acyl chlorides by reaction with 3
eq. of oxalyl chloride and catalytic DMF in DCM. Following
removal of excess oxalyl chloride, and after addition of THF,
samples of the acyl chloride were exposed to one equivalent
of the corresponding carbanion which was cannulated into the
reaction mixture. After stirring for 1 h, the solvent was removed
and the product was purified by column chromatography. The
yields for hexasubstituted ketones 2a, 2b and 2d were moderate
(40–55%) and the reaction diastereoselectivities were the same as
that in the one pot procedure: 3 : 1 to 2 : 1. Reaction of the amide-
substituted carboxylic acid 3e with amide-substituted enolate 1e
was unsuccessful, as expected from the results of Method A. While
comparison of the results in Tables 1 and 2 indicate that the yields
of 2a, 2b and 2d are 17–36% lower by the stepwise procedure,
the diastereoselectivities of the two procedures are essentially
identical.
Stepwise formation of hexasubstituted ketones
The generation of ketone 2a–2e was also analyzed by method
B. The method involves reaction of the tertiary anions with CO2
to give carboxylic acid 3, which can be isolated and subsequently
treated with oxalyl chloride, to react with one equivalent of the
same carbanion. For example, in the case of propionitrile 1a the
anion was generated as indicated before and exposed to carbon
dioxide, which bubbled through the solution for 45–60 min to
form the carboxylate anion. After protonation with aqueous
HCl, the resulting acid was extracted with ether and purified
as required by liquid–liquid extractions. Pure samples of acid 3a
were characterized by NMR and FTIR spectra, which matched
well with those previously described in the literature.24a The same
Photoinduced generation of all-carbon adjacent stereogenic centers
in solution and in the crystalline state
It is well known that the photodecarbonylation of aliphatic
ketones tends to occur in the triplet excited state by successive
a-cleavage and decarbonylation of the acyl radical intermediate.17
Non-cyclic ketones give triplet radical pairs that diffuse apart to
become free radicals, such that radical-radical combination and
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©

disproportionation reactions occur after random encounters and
with limited stereochemical control (Scheme 4). Recent evidence
shows that the reaction in the solid-state involves the same
intermediates,18 except that radical pairs are unable to diffuse
or to rotate, such that geminate radicals can recombine without
stereochemical loss.
experiments with crystalline d,l-2a, which was shown to give a
single product assigned to d,l-5a in quantitative yield. To verify
these assignments more definitively, we determined the powder
X-ray diffraction (PXRD) pattern of the solid-state photoproduct
and compared it to the PXRD calculated from the reported X-ray
crystal structures of d,l- and meso-5a (Fig. 5).21 It is known that
PXRD patterns depend on the molecular structure and packing
arrangement and can be used to establish the polymorphic nature
of unknown samples, or to establish their structural identity if a
standard is available or can be calculated. We showed that the
experimental PXRD of the solid state photoproduct pattern does
1
indeed match the one of d,l-5a, indicating that the previous H
NMR assignments were correct and that the solid state reaction
proceeds in a completely chemoselective and stereospecific manner
with retention of configuration.
Scheme 4
Ultraviolet irradiation of ketones d,l-2 was studied in benzene
and in the crystalline solid state at ambient temperature. The
results are summarized in Table 3.
Photoinduced reactions carried out with l > 290 nm showed
that radicals from a,a¢-dicyanoketones 2a and 2b have no
tendency to disproportionate in solution or in the solid-state,
such that only radical recombination products d,l-5 and meso-
1
Fig. 5 Comparison of the experimental PXRD pattern of the product
from the solid-state photoreaction of d,l-2a (blue) with the calculated
PXRD patterns of d,l-5a (green) and meso-5a (red).
5 were observed. H NMR analysis of the solution mixture in
benzene-d6 showed that the methyl signal of 2a at 1.48 ppm
had cleanly transformed into two new ones at 1.61 ppm and
1.36 ppm, which matched the reported spectra for diastereomers
d,l-5a and meso-5a, respectively.19 However, we noted that the
stereochemical assignment originally suggested in 1954 for d,l-5a
and meso-5a was based on melting points and solubilities with
the meso designation proposed for the higher melting and lower
solubility diastereomer.20 Supportive evidence for this assignment
was obtained from the results of solid-state UV irradiation
The solution and solid state photochemical reactions of d,l-2b
gave similar results to those of d,l-2a with no disproportionation
products observed from low to high conversion values. The solid-
state photoreaction of d,l-2b gave only one product in quantitative
yield, which in analogy to 2a we assign to the stereospecific
recombination product d,l-5b. The chromatographic and NMR
properties of this compound, are indeed analogous and consistent
with those of d,l-5a, especially when compared to the meso-isomer,
which was obtained as a mixture from the solution irradiation.
Indeed, photoinduced irradiation of d,l-2b in solution led to
both recombination products in a diastereomeric ratio that favors
diastereomer d,l-5b with a modest selectivity that varies as a
function of conversion.
The solution photolysis of the keto diester d,l-2d gave a
larger number of products including diesters d,l-5d and meso-
5d,22 and disproportionation products 1d and 6d. Interestingly,
acrylate 6d was observed in the 1H NMR at low conversions but
disappeared over time, presumably due to in situ polymerization.
Unfortunately, ultraviolet irradiation of d,l-2d in the solid-state
was also expected to give a mixture of product since the predicted
recombination product d,l-5d is known to be an oil.22 Indeed, the
sample of d,l-2d began melting almost as soon as the photolysis
started. Quite notably, the reaction was more selective towards
radical disproportionation while the formation of recombination
products was inefficient and with low stereoselectivity (Table 3).
Table 3 Conversion and product ratio upon excitation of ketones 2a
Medium
Conversion
d,l-5 : meso-5 : Disprop.
d,l-2a
d,l-2b
d,l-2d
C6D6
C6D6
C6D6
54
79
99
100
37 : 17 : 0
52 : 27 : 0
64 : 35 : 0
100 : 0 : 0
Crystal
C6D6
C6D6
C6D6
52
75
100
100
31 : 21 : 0
49 : 26 : 0
53 : 47 : 0
100 : 0 : 0
Crystal
C6D6
C6D6
14
5 : 6 : 3
74
33 : 27 : 14
6c:0 : 21
6c:2 : 35
Crystal
Crystal
27b
32b
a Determined by 1H NMR. b Crystals of d,l-2d begun to melt shortly after
the beginning of the reaction. c Samples of d,l-5d are known to exist as a
viscouos oil at room temperature.
1484 | Photochem. Photobiol. Sci., 2011, 10, 1480–1487 This journal is
The Royal Society of Chemistry and Owner Societies 2011
©

aq. HCl, the aq layer was extracted with ether. Then the org. layer
was extracted with aq. NaHCO3 and the aq. layer was washed
with ether. The aq. layer was then acidified with 1 M aq. HCl and
extracted with ether. The org. layer was dried with brine followed
by MgSO4, and the solvent was removed. The crude product was
used without further purification.
Conclusions
We report the diastereospecific synthesis of compounds con-
taining adjacent quaternary stereogenic centers by the solid-
state photodecarbonylation of hexasubstituted ketones. The ke-
tones were prepared by the one-pot trapping (Method A) of
trisubstituted carbanions with diphosgene, and by a stepwise
procedure (Method B) where the anions were trapped with
CO2, converted to the acyl chloride, and subsequently reacted
with a second carbanion. The preparation of hexasubstituted
ketones worked reasonably well with the smaller anions when
the latter were generated using LiHMDS. The yields of the
reaction decreased as the size of the substituents increased, and
the steric limits were reached with 3-methyl-2-phenylbutyronitrile
1c and N,N-dimethyl-2-phenylpropanamide 1e. Method B gave
the same products 2 in yields that are lower but with the same
diastereoselectivity (2 : 1 to 3 : 1) as compared with Method A.
Having isolated the major d,l-diastereomers by fractional
crystallization, we showed that the photoinduced decarbonylation
reaction in benzene-d6 leads to mixtures of products. While the
dicyano ketones d,l-2a and d,l-2b gave a mixture of recombination
products, solution samples of d,l-2d also gave substantial amounts
of products arising from radical-radical disproportionation. While
low melting samples of d,l-2d gave a mixture of recombination
and disproportionation products at ambient temperature, pho-
todecarbonylation reactions that occurred exclusively in the solid-
state led to the chemoselective and diastereospecific formation of
the corresponding recombination products in quantitative yields.
We continue to extend these methods to the syntheses of natural
products containing adjacent quaternary stereogenic centers.
Acyl chlorides. Acid (0.5 mmol) was dissolved in dry DCM
(10 mL). Following the addition of 1 drop of catalytic DMF,
oxalyl chloride (1.5 mmol) was added and stirred for 1 h.
The acyl chloride was isolated upon evaporation of the DCM
and excess oxalyl chloride. It was used without purification or
characterization.
Synthesis of hexasubstituted ketone 2. To the acyl chloride,
a solution containing 0.6 mmol anion of 1 was cannulated.
Following 1 h of stirring and the evaporation of the solution,
the solid crude was purified on silica gel by flash chromatography.
The major diastereomer was isolated by fractional crystallization
of the diastereomeric mixture from ether.
Separation of d,l-2 from the diastereomeric mixture
The diastereomeric ketone 2 was dissolved in ether, which was
slowly evaporated overnight at r.t. The remaining solution was
decanted and the crystals were rinsed with minimal amount of
ether, leaving pure d,l-2. More d,l-2 was isolated by repeating
the recrystallization from the decanted solution containing the
diastereomeric mixture, yielding up to 54% d,l-2.
2-Cyano-2-phenylpropanoic acid (3a)
1
White solid. H NMR (CDCl3, 300 MHz): d 2.00 (3 H, s, CH3),
Materials and methods
7.42–7.44 (3 H, m, Ph), 7.55–7.59 (2 H, m, Ph), 10.09 (1 H, s,
CO2H) ppm. 13C NMR (CDCl3, 75.5 MHz): d 24.3, 48.4, 118.9,
126.1, 129.4, 129.4, 134.7, 173.4 ppm. The spectral data matches
the previously reported data.24a
Methyl
2-phenylpropanoate
1d
and
N,N-dimethyl-2-
phenylpropionamide 1e are known compounds and were
prepared by the procedure of ref. 14 and,23a respectively. Spectral
data match the previously reported data (ref. 14 and 23a,
respectively).
2-Cyano-2-phenylbutanoic acid (3b)
Colorless oil. 1H NMR (CDCl3, 300 MHz): d 1.09 (3 H, t, J = 7 Hz,
CH3), 2.21 (1 H, dq, J = 14, 7 Hz, CHCH3), 2.46 (1 H, dq, J = 14,
7 Hz, CHCH3), 7.38–7.46 (3 H, m, Ph), 7.57–7.60 (2 H, m, Ph),
9.69 (1 H, s, CO2H) ppm. 13C NMR (CDCl3, 75.5 MHz): d 9.8,
31.0, 55.2, 117.8, 126.3, 129.2, 129.3, 133.5, 172.4 ppm. IR (neat):
n 3066.0, 2980.2, 1722.1, 1494.5, 1450.3, 1220.4, 712.9, 694.2 cm-1.
General synthesis of anion
To a solution of LiHMDS (2.5 mL, 1 M, 2.5 mmol) in dry THF
(40 mL), corresponding 1 (2.25 mmol) was added and the solution
was stirred for 15 min to 2 h.
Synthesis of hexasubstituted ketones: Method A
3-Methoxy-2-methyl-3-oxo-2-phenylpropanoic acid (3d)
To a solution of corresponding anion of 1 (1.5 mmol), diphosgene
(0.09 mL, 148 mg, 0.75 mmol) was added dropwise and the
solution was stirred for 2 h. Quenching with 1 M aq. HCl was
followed by extraction with ether and washing with brine. After
drying with anhydrous MgSO4, the solvent was removed by rotary
evaporator. The solid crude was purified by flash chromatography
on silica gel.
1
White solid. H NMR (CDCl3, 300 MHz): d 1.93 (3 H, s, CH3),
3.79 (3 H, s, OCH3), 7.30–7.43 (5 H, m, Ph), 9.54 (1 H, s, CO2H)
ppm. 13C NMR (CDCl3, 75.5 MHz): d 22.1, 53.2, 58.7, 127.4,
128.1, 128.5, 137.6, 172.3, 177.0 ppm. The spectral data matches
the previously reported data.24b
3-(Dimethylamino)-2-methyl-3-oxo-2-phenylpropanoic acid (3e)
Synthesis of hexasubstituted ketones: Method B
1
White solid. H NMR (CDCl3, 300 MHz): d 1.91 (3 H, s, CH3),
Carboxylic acid 3. Carbon dioxide from dry ice (passed
through drierite) was passed through a solution containing anion
of 1 for 45 min to 1 h. Once the reaction was quenched with 1 M
2.54 (3 H, s, NCH3), 3.00 (3 H, s, NCH3), 7.26–7.34 (5 H, m,
Ph), 12.95 (1 H, s, CO2H) ppm. 13C NMR (CDCl3, 75.5 MHz): d
23.4, 37.5, 38.6, 55.7, 126.2, 127.7, 129.0, 139.1, 174.4, 174.9 ppm.
This journal is
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©

IR (solid-state): n 3023.4, 2937.1, 1732.3, 1712.8, 1609.8, 1496.7,
d,l-Dimethyl 2,4-dimethyl-3-oxo-2,4-diphenylpentanedioate
(d,l-2d)
1401.3, 1238.1, 1189.8, 696.6 cm-1.
1
White solid. H NMR (CDCl3, 300 MHz): d 1.74 (6 H, s, 2 ¥
2,4-Dimethyl-3-oxo-2,4-diphenylpentanedinitrile (2a)
CH3), 3.65 (6 H, s, 2 ¥ OCH3), 7.21–7.36 (10 H, m, 2 ¥ Ph) ppm.
13C NMR (CDCl3, 75.5 MHz): d 24.6, 52.4, 64.6, 127.5, 127.6,
128.3, 138.6, 172.3, 203.3 ppm. IR (solid-state): n 3011.4, 2958.9,
1721.6, 1703.7, 1598.7, 1264.4, 1111.6, 692.1 cm-1. mp 117–119◦.
White solid. Major diastereomer (74%): 1H NMR (CDCl3,
300 MHz): d 1.85 (6 H, s, 2 ¥ CH3), 7.40–7.55 (10 H, m, 2 ¥ Ph)
1
ppm. Minor diastereomer (26%): H NMR (CDCl3, 300 MHz):
d 1.95 (6 H, s, 2 ¥ CH3), 7.22–7.34 (10 H, m, 2 ¥ Ph) ppm. 13C
NMR (diastereomeric mixture, CDCl3, 75.5 MHz): d 26.8, 27.8,
52.9, 53.1, 118.4, 118.7, 126.5, 126.8, 129.1, 129.3, 129.5, 133.8,
134.0, 193.6, 194.3 ppm. IR (solid-state, diastereomeric mixture):
n 3059.3, 2936.3, 2239.1, 1728.6, 1595.6, 1490.0, 1446.9, 760.2,
695.5 cm-1.
Solution photolysis
Ketone (4–8 mg) was dissolved in 1 mL C6D6 and the solution was
deoxygenated with argon for 10 min. The solution was photolyzed
using a medium-pressure Hg Hanovia lamp and the reaction
1
progress was monitored by H NMR. No attempts were made
to isolate and characterize the products.
d,l-2,4-Dimethyl-3-oxo-2,4-diphenylpentanedinitrile (d,l-2a)
1
Solid-state photolysis
White solid. H NMR (CDCl3, 300 MHz): d 1.85 (6 H, s, 2 ¥
CH3), 7.40–7.55 (6 H, m, 2 ¥ Ph), 7.51–7.55 (4 H, m, 2 ¥ Ph) ppm.
13C NMR (CDCl3, 75.5 MHz): d 27.9, 53.1, 118.4, 126.6, 129.4,
129.6, 134.1, 193.7 ppm. IR (solid-state): n 3059.0, 2989.0, 2238.3,
1727.7, 1595.3, 1489.7, 1446.8, 760.5, 695.7 cm-1. mp 142–143◦.
Ketone (4–8 mg) was crushed between 2 microscope slides and
photolyzed using a medium-pressure Hg Hanovia lamp. The
reaction was monitored by 1H NMR.
d,l-2,3-Dimethyl-2,3-diphenylsuccinonitrile (d,l-5a)
2,4-Diethyl-3-oxo-2,4-diphenylpentanedinitrile (2b)
White soild. 1H NMR (CDCl3, 300 MHz): d 2.10 (6 H, s, 2 ¥ CH3),
White solid. Major diastereomer (76%): 1H NMR (CDCl3,
300 MHz): d 0.77 (6 H, t, J = 7 Hz, 2 ¥ CH3), 2.11 (2 H, dq,
J = 14, 7 Hz, 2 ¥ CHCH3) 2.26 (2 H, dq, J = 14, 7 Hz, 2 ¥
CHCH3), 7.37–7.56 (10 H, m, 2 ¥ Ph) ppm. Minor diastereomer
(24%): 1H NMR (CDCl3, 300 MHz): d 0.95 (6 H, t, J = 7 Hz, 2 ¥
CH3), 2.12 (2 H, dq, J = 14, 7 Hz, 2 ¥ CHCH3), 2.47 (2 H, dq, J =
14, 7 Hz, 2 ¥ CHCH3), 7.11–7.30 (10 H, m, 2 ¥ Ph) ppm. 13C NMR
(diastereomeric mixture, CDCl3, 75.5 MHz): d 9.4, 9.4, 32.9, 33.6,
59.8, 59.9, 117.3, 117.5, 127.1, 127.3, 128.8, 129.3, 129.4, 132.2,
132.3, 192.1, 194.1 ppm. IR (solid-state, diastereomeric mixture):
n 3054.8, 2983.3, 2239.6, 1726.8, 1595.4, 1490.5, 1449.2, 765.7,
696.4 cm-1.
7.06–7.10 (4 H, m, 2 ¥ Ph), 7.19–7.33 (6 H, m, 2 ¥ Ph) ppm. 13
C
NMR (CDCl3, 75 MHz): d 23.4, 50.8, 120.8, 127.8, 128.2, 129.1,
134.8 ppm. The spectral data match literature data.19
d,l-2,3-Diethyl-2,3-diphenylsuccionitrile (d,l-5b)
1
White soild. H NMR (CDCl3, 500 MHz): d 0.96 (6 H, t, 7 Hz,
2 ¥ CH3), 2.51 (2 H, q, 7 Hz, 2 ¥ CHCH3), 2.51 (2 H, q, 7 Hz, 2 ¥
CHCH3), 7.05–7.25 (10 H, m, 2 ¥ Ph) ppm. 13C NMR (CDCl3,
125 MHz): d 10.1, 28.3, 57.6, 120.2, 128.3, 128.7, 132.4 ppm. IR
(solid-state): n 3067.2, 2982.6, 2240.0, 1601.4, 1494.8, 1449.5.6,
733.8, 693.3 cm-1.
d,l-2,4-Diethyl-3-oxo-2,4-diphenylpentanedinitrile (d,l-2b)
Acknowledgements
1
White solid. H NMR (CDCl3, 300 MHz): d 0.77 (6 H, t, J =
We are grateful to the National Science Foundation for support
through grants CHE-0844455, DMR0605688 and creativity ex-
tension DMR0937243.
7 Hz, 2 ¥ CH3), 2.11 (2 H, dq, J = 14, 7 Hz, 2 ¥ CHCH3), 2.26
(2 H, dq, J = 14, 7 Hz, 2 ¥ CHCH3), 7.42–7.45 (6 H, m, 2 ¥ Ph),
7.53–7.56 (4 H, m, 2 ¥ Ph) ppm. 13C NMR (CDCl3, 75.5 MHz): d
9.6, 33.8, 60.1, 117.4, 127.3, 129.5, 129.6, 129.6, 132.4, 192.3 ppm.
IR (solid-state): n 3055.1, 2983.8, 2239.6, 1726.6, 1595.6, 1490.6,
1449.2, 765.8, 696.5 cm-1. mp 153–156◦.
Notes and references
1 (a) E. A. Peterson and L. E. Overman, Contiguous stereogenic
quaternary carbons: a daunting challenge in natural product synthesis,
Proc. Natl. Acad. Sci. U. S. A., 2004, 101, 11943–11948; (b) B. Dutta, N.
Gilboa and I. Marek, Highly diastereoselective preparation of homoal-
lylic alcohols containing two contiguous quaternary stereocenters in
acyclic systems from simple terminal alkynes, J. Am. Chem. Soc., 2010,
132, 5588–5589; (c) T. Yoshino, H. Morimoto, G. Lu, S. Matsunaga
and M. Shibasaki, Construction of contiguous tetrasubstituted chiral
carbon stereocenters via direct catalytic asymmetric aldol reaction of
a-isothiocyanato esters with ketones, J. Am. Chem. Soc., 2009, 131,
17082–17083; (d) F. Xue, S. Zhang, L. Liu, W. Duan and W. Wang,
Organocatalytic enantioselective cross-aldol reactions of aldehydes
with isatines: formation of two contiguous quaternary centered 3-
substituted 3-hydroxyindol-2-ones, Chem.–Asian J., 2009, 4, 1664–
1667; (e) L. E. Overman and D. A. Watson, Diastereoselection in
the formation of contiguous quaternary carbon stereocenters by the
intramolecular Heck reaction, J. Org. Chem., 2006, 71, 2600–2667.
Dimethyl 2,4-dimethyl-3-oxo-2,4-diphenylpentanedioate (2d)
White solid. Major diastereomer (61%): 1H NMR (CDCl3,
300 MHz): d 1.73 (6 H, s, 2 ¥ CH3), 3.65 (6 H, s, 2 ¥ OCH3),
7.23–7.35 (10 H, m, 2 ¥ Ph) ppm. Minor diastereomer (39%):
1H NMR (CDCl3, 300 MHz): d 1.76 (6 H, s, 2 ¥ CH3), 3.63
(6 H, s, 2 ¥ OCH3), 7.23–7.35 (10 H, m, 2 ¥ Ph) ppm. 13C
NMR (diastereomeric mixture, CDCl3, 75.5 MHz): d 23.7, 24.6,
52.2, 52.5, 64.6, 65.0, 125.2, 127.5, 127.6, 127.8, 128.2, 128.4,
138.4, 138.6, 172.0, 172.2, 202.9, 203.3 ppm. IR (solid-state,
diastereomeric mixture): n 3010.6, 2956.6, 1721.8, 1703.2, 1598.8,
1496.6, 1261.0, 1111.0, 693.1 cm-1.
1486 | Photochem. Photobiol. Sci., 2011, 10, 1480–1487 This journal is
The Royal Society of Chemistry and Owner Societies 2011
©

2 (a) Y. Inoue, Asymmetric photochemical reactions in solution, Chem.
Rev., 1992, 92, 741–770; (b) J. Svoboda and B. Ko¨nig, Templated pho-
tochemistry: toward catalysts enhancing the efficiency and selectivity
of photoreactions in homogeneous solutions, Chem. Rev., 2006, 106,
5413–5430; (c) R. G. Weiss, V. Ramamurthy and G. S. Hammond,
Photochemistry in organized and confining media: a model, Acc. Chem.
Res., 1993, 26, 530–536; (d) R. S. H. Liu and G. S. Hammond, Reflection
on medium effects on photochemical reactivity, Acc. Chem. Res., 2005,
38, 396–403; (e) L. M. Campos and M. A. Garcia-Garibay, Reactive
intermediates in crystals: form and function, in Reactive Intermediates,
ed. M. S. Platz, M. Jones and R. Moss, Hoboken, NJ, 2007, ch. 7, pp.
271–331.
3 (a) M. Nishijima, T. C. S. Pace, A. Nakamura, T. Mori, T. Wada,
C. Bohne and Y. Inoue, Supramolecular photochirogenesis with
biomolecules. Mechanistic studies on the enantiodifferentiation for
the photocyclodimerization of 2-anthracenecarboxylate mediated by
bovine serum albumin, J. Org. Chem., 2007, 72, 2707–2715; (b) C. L. D.
Gibb, A. K. Sundaresan, V. Ramamurthy and B. C. Gibb, Templation
of the excited-state chemistry of a-(n-alkyl) dibenzyl ketones: how
guest packing within a nanoscale suptramolecular capsule influences
photochemistry, J. Am. Chem. Soc., 2008, 130, 4069–4080; (c) P.
Montes-Navajas and H. Garcia, Cucurbituril complexation enhances
intersystem crossing and triplet lifetime of 2,4,6-triphenylpyrylium ion,
J. Phys. Chem. C, 2010, 114, 2034–2038.
4 (a) N. J. Turro, From boiling stones to smart crystals: supramolecular
and magnetic isotope control of radical-radical reactions in zeolites,
Acc. Chem. Res., 2000, 33, 637–646; (b) J. C. Scaiano and H.
Garc´ıa, Intrazeolite photochemistry: toward supramolecular control of
molecular photochemistry, Acc. Chem. Res., 1999, 32, 783–793; (c) V.
Ramamurthy and M. A. Garcia-Garibay, Zeolites as supramolecular
hosts for photochemical transformations, in Supramolecular Chemistry,
ed. G. Alberti and T. Bein, Elsevier, New York, 1996, vol. 7, ch. 24, pp.
693–719.
5 (a) J. Xu and R. G. Weiss, Enantioselectivity of prochiral radical-pair
recombinationsReaction cavity differentiation in polyethylene films,
Org. Lett., 2003, 5, 3077–3080; (b) T. Mori, Y. Inoue and R. G. Weiss,
Enhanced photodecarboxylation of an aryl ester in polyethylene films,
Org. Lett., 2003, 5, 4661–4664.
11 (a) T. Choi, K. Peterfy, S. I. Khan and M. A. Garcia-Garibay,
Molecular control of solid-state reactivity and biradical formation
from crystalline ketones, J. Am. Chem. Soc., 1996, 118, 12477–12478;
(b) T. Choi, D. Cizmeciyan, S. I. Kahn and M. A. Garcia-Garibay,
An efficient solid-to-solid reaction via a steady-state phase separation
mechanism, J. Am. Chem. Soc., 1995, 117, 12893–12894; (c) K. Peterfy
and M. A. Garcia-Garibay, Generation and reactivity of a triplet
1,4-biradical confomationally trapped in a crystalline cyclopentanone,
J. Am. Chem. Soc., 1998, 120, 4540–4541.
12 (a) M. J. E. Resendiz and M. A. Garcia-Garibay, Hammett analysis
of photodecarbonylation in crystalline 1,3-diarylacetones, Org. Lett.,
2005, 7, 371–374; (b) T. Choe, S. I. Khan and M. A. Garcia-Garibay,
Combination vs. disproportionation in dialkyl biradicals. Selectivity
reversal in a crystalline solid, Photochem. Photobiol. Sci., 2006, 5, 449–
451; (c) F. Family and M. A. Garcia-Garibay, Photodecarbonylation
of ketodiacids as ammonium salts: efficient formation of C-C bonds
between adjacent quaternary centers in the crystalline state, J. Org.
Chem., 2009, 74, 2476–2480.
13 D. Ng, Z. Yang and M. A. Garcia-Garibay, Total synthesis of ( )-
herbertenolide by stereospecific formation of vicinal quaternary centers
in a crystalline ketone, Org. Lett., 2004, 6, 645–647.
14 A. Natarajan, D. Ng, Z. Yang and M. A. Garcia-Garibay, Par-
allel syntheses of (+)- and (-)-a-cuparenone by radical combina-
tion in crystalline solids, Angew. Chem., Int. Ed., 2007, 46, 6485–
6487.
15 (a) M. J. E. Resendiz, A. Natarajan and M. A. Garcia-Garibay,
Diastereoselective synthesis and spin-dependent photodecarbonylation
of di(3-phenyl-2-pyrrolidinon-3-yl)ketones: synthesis of nonadjacent
and adjacent stereogenic quaternary centers, Chem. Commun., 2008,
193–195; (b) M. J. E. Resendiz, F. Family, K. Fuller, L. M. Campos, S. I.
Khan, N. V. Lebedeva, M. D. E. Forbes and M. A. Garcia-Garibay,
Radical reactions with double memory of chirality (2MOC) for the
enantiospecific synthesis of adjacent stereogenic quaternary centers in
solution: cleavage and bonding faster than radical rotation, J. Am.
Chem. Soc., 2009, 131, 8425–8433.
16 E. Vedejs, A. W. Kruger, N. Lee, S. T. Sakata, M. Stec and E.
Suna, Enantioselective enolate protonation with chiral anilines: scope,
structural requirements, and mechanistic implications, J. Am. Chem.
Soc., 2000, 122, 4602–4607.
6 (a) V. Ramamurthy and K. Venkatesan, Photochemical reactions of
organic crystals, Chem. Rev., 1987, 87, 433–481; (b) J. N. Gamlin, R.
Jones, M. Leibovitch, B. Patrick, J. R. Scheffer and J. Trotter, The ionic
auxiliary concept in solid state organic photochemistry, Acc. Chem.
Res., 1996, 29, 203–209; (c) M. A. Garcia-Garibay, Engineering carbene
rearrangements in crystals: from molecular information to solid-state
reactivity, Acc. Chem. Res., 2003, 36, 491–498; (d) J. R. Scheffer, Crystal
lattice control of unimolecular photorearrangements, Acc. Chem. Res.,
1980, 13, 283–290; (e) L. R. MacGillivray, G. S. Papaefstathiou, T.
Friscic, T. D. Hamilton, D. K. Bucar, Q. Chu, D. B. Varshney and I. G.
Georgiev, Supramolecular control of reactivity in the solid state: from
templates to ladderanes to metal–organic frameworks, Acc. Chem. Res.,
2008, 41, 280–291.
17 (a) D. Weiss, The Norrish type-I reaction in cycloalkanone photo-
chemistry, in Organic Photochemistry, ed. A. Padwa, Marcel Deker,
New York, 1981, vol. 5, pp. 347–420; (b) C. Bohne, Norrish type
I processes of ketones: selected examples and synthetic applications,
in CRC Handbook of Organic Photochemistry and Photobiology, ed.
W. M. Horspool and P. S. Song, CRC Press, Boca Raton, FL, 1995, pp.
423–429.
18 N. V. Lebedeva, V. F. Tarasov, M. J. E. Resendiz, M. A. Garcia-Garibay,
R. C. White and M. D. E. Forbes, The missing link between molecular
triplets and spin-polarized free radicals: room temperature triplet states
of nanocrystallline radical pairs, J. Am. Chem. Soc., 2010, 132, 82–
84.
7 (a) S. Shiraki and M. A. Garcia-Garibay, Carbon–carbon bond
formation by the photoelimination of small molecules in solution and
in crystals, in Handbook of Synthetic Photochemistry, ed. A. Albini
and M. Fagnini, Wiley-VCH, Weinheim, 2010, ch. 2, pp. 25–66;
(b) C. J. Mortko and M. A. Garcia-Garibay, Stereospecific synthesis
of compounds with adjacent chiral quaternary centers in solid-to-
solid reactions, in Topics in Stereochemistry, ed. S. E. Denmark and
J. S. Siegel, Wiley-Interscience, Hoboken, NJ, 2006, vol. 25, ch. 7, 205–
253.
8 (a) M. Veerman, M. J. E. Resendiz and M. A. Garcia-Garibay,
Large-scale photochemical reactions of nanocrystalline suspensions:
a promising green chemistry method, Org. Lett., 2006, 8, 2615–1617;
(b) C. J. Mortko and M. A. Garcia-Garibay, Green chemistry strategies
using crystal-to-crystal photoreactions: stereoselective synthesis and
decarbonylation of trans-a,a’-dialkenoylcyclohexanones, J. Am. Chem.
Soc., 2005, 127, 7994–7995.
9 M. A. Garcia-Garibay and L. Campos, Photochemical decarbonyla-
tion of ketones: recent advances and reactions in crystalline solids,
in The Handbook of Organic Photochemistry and Photobiology, ed.
W. Horspool, CRC Press, Boca Raton, FL, 2003, ch. 48.
10 M. A. Garcia-Garibay, The entropic enlightenment of organic pho-
tochemistry: strategic modifications of intrinsic decay pathways using
an information-based approach, Photochem. Photobiol. Sci., 2010, 9,
1574–1588.
19 L. I. Peterson, Meso-dl isomerization of 2,3-dimethyl-2,3-
diphenylsuccinonitrile, J. Am. Chem. Soc., 1967, 89, 2677–2681.
20 R. L. Huang and L. Kum-Tatt, Synthetic estrogens. Part II. The
synthesis of tetra-alkyldibenzyls and substituted succinonitriles by free-
radical dimerisation, J. Chem. Soc., 1954, 2570–2577.
21 Y. L. Lam, L. L. Koh and H. H. Huang, Crystal structures of
meso- and ( )-2,3-dicyano-2-3-diphenylbutane and 3,4-dicyano-3,4-
diphenylhexane, J. Chem. Res., Synop., 1991, 212–213.
22 C. de Luca, A. Inesi and L. Rampazzo, Electroreduction of methyl 2-
bromo-2-phenylpropanoate on a vitreous carbon electrode: meso- and
DL-dimethyl 2,3-dimethyl-2,3-diphenylsuccinate, J. Chem. Soc., Perkin
Trans. 2, 1982, 1403–1407.
23 (a) K. Biswas and S. Woodward, Stereoselective 1,4-addition of
Grignard reagents to a,b-enamdes using a combined chiral auxillary-
catalyst approach, Tetrahedron: Asymmetry, 2008, 19, 1702–1708;
(b) K. Ogura, S. Mitamura, K. Kishi and G. Tsuchihashi, A new syn-
thesis of 2-arylpropanoates using methyl methylthiomethyl sulfoxide,
Synthesis, 1979, 880–882.
24 (a) H. Brunner and P. Schmidt, Naproxen derivatives by enantioselec-
tive decarboxylation, Eur. J. Org. Chem., 2000, 2119–2133; (b) M. E.
Ellison, D. Ng, H. Dang and M. A. Garcia-Garibay, Enantiospecific
synthesis of vicinal stereogenic tertiary and quaternary centers by
combination of configurationally-trapped radical pairs in crystalline
solids, Org. Lett., 2003, 5, 2531–2534.
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