Vanadyl species-catalyzed complementary β-oxidative carbonylation of styrene derivatives with aldehydes

Article abstract of DOI:10.1039/c4ob02621g

A series of oxometallic species and metal acetylacetonates (acac) was examined as catalysts for oxidative carbonylation of styrene with benzaldehyde using t-butylhydroperoxide as the co-oxidant in warm acetonitrile. Among them, VO((acac)₂ and vanadyl(iv) chloride were found to be the only catalyst class to achieve cross-coupling processes by judiciously tuning the ligand electronic attributes, leading to β-hydroxylation- and β-peroxidation-carbonylation of styrene, respectively, in a complementary manner. Mechanistic studies indicated that vanadyl-associated acyl radicals generated by t-butoxy radical-assisted, homolytic cleavage of the aldehyde C-H bond were involved in tandem processes with an exclusive syn diastereoselectivity in the case of β-methylstyrene. This journal is

Full text of DOI:10.1039/c4ob02621g

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Vanadyl species-catalyzed complementary
β-oxidative carbonylation of styrene derivatives
with aldehydes†
Cite this: DOI: 10.1039/c4ob02621g
Wen-Chieh Yang,b Shiue-Shien Weng,*a Anandhan Ramasamy,b Gobi Rajeshwaren,b
Yi-Ya Liaob and Chien-Tien Chen*b
A series of oxometallic species and metal acetylacetonates (acac) was examined as catalysts for oxidative
carbonylation of styrene with benzaldehyde using t-butylhydroperoxide as the co-oxidant in warm aceto-
nitrile. Among them, VO((acac)2 and vanadyl(IV) chloride were found to be the only catalyst class to
achieve cross-coupling processes by judiciously tuning the ligand electronic attributes, leading to
β-hydroxylation– and β-peroxidation–carbonylation of styrene, respectively, in a complementary manner.
Mechanistic studies indicated that vanadyl-associated acyl radicals generated by t-butoxy radical-assisted,
homolytic cleavage of the aldehyde C–H bond were involved in tandem processes with an exclusive
syn diastereoselectivity in the case of β-methylstyrene.
Received 18th December 2014,
Accepted 18th December 2014
DOI: 10.1039/c4ob02621g
www.rsc.org/obc
limiting their extensive application. To meet this ultimate
need, an efficient and direct β-oxidative carbonylation of
Introduction
Transition metal-catalyzed direct vicinal difunctionalization of alkenes remains to be explored. Along this line, several
alkenes is one of the most attractive strategies because it seminal studies on the β-amino and β-hydroxy carbonylation
allows precise and regioselective installation of two substitu- of olefins have been developed in recent years.4,5
ents across a CvC double bond. Among them, oxidative
double functionalization of alkenes (e.g., dihydroxylation,1a,b forward approach for the synthesis of α,β-unsaturated ketones
aminohydroxylation,1c and oxidative difunctionalization1d,e
by copper(II)-catalyzed direct coupling of alkenes with the alde-
Very recently, Lei and co-workers developed a straight-
)
has become an important tactic in organic synthesis. These hyde Csp2–H bond in the presence of the tert-butyl hydroperox-
new advances enable chemists to assemble complex building ide (TBHP) oxidant,6 which provided a complementary means
blocks of biological and medicinal interests in a single oper- to access this type of product through the radical-mediated oxi-
ation from common alkene feedstock.1 In the last decade, sig- dative coupling as compared to some existing powerful coup-
nificant advances have been achieved in the carbonylation of ling manipulations.7 By utilizing the iron(II) triggered radical
olefins catalyzed by transition metal complexes derived from and Fenton process, Taniguchi8 and Li9 independently identi-
Rh, Co, Ru and Pd.2 On the other hand, Caddick and co- fied unique and efficient synthetic protocols for β-hydroxy and
workers have revealed an impressive radical-type hydroacyl- β-peroxy carbonyl compounds from vinyl arenes and aldehydes
ation of activated alkenes under aerobic and catalyst-free con- in the presence of O2 or the TBHP co-oxidant [eqn (1) and (2)].
ditions, which demonstrate the power of the oxidative cross- Among these studies, acyl radicals (or alkoxycarbonyl radicals)
coupling strategy in view of its environmental benignity, oper- were formed as reactive intermediates by the redox Fenton
ational efficiency and simplicity.3 However, these carbonyl- cycle and triggered the tandem acyl radical–alkene–oxidant
ation methodologies were mainly utilized to construct (oxygen or TBHP) three-component coupling reactions.
β-unfunctionalized ketones; further functionalization of the However, high loadings of the expensive iron phthalocyanine
inert C(sp3)–H bond at the carbon β to the carbonyl is required (Fe(Pc)) and carbazates were required. In addition, further oxi-
for building up further molecular complexity, thus somewhat dation at the 2° hydroxyl groups of the products may limit the
synthetic utility of the former system.
aDepartment of Chemistry, ROC Military Academy, Kaoshiung, Taiwan
bDepartment of Chemistry, National Tsing Hua University, Hsinchu, Taiwan.
E-mail: ctchen@mx.nthu.edu.tw
†Electronic supplementary information (ESI) available: Experimental pro-
ð1Þ
cedures, structural proof, and spectral data for all new compounds. See DOI:
10.1039/c4ob02621g
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Table 1 Vanadyl species-catalyzed selective β-hydroxylation- or β-per-
oxidation–carbonylation of styrene: optimization of reaction conditionsa
ð2Þ
ð3Þ
Yield of
Yield of
Entry
Catalyst
3ab (%)
4ab (%)
1
2
3
4
5
6
7
8
VO(OTf)2–5H2Oc
VOCl2–3H2O
Trace
5
71
80
6
β-Hydroxycarbonyl compounds, the well-known aldol pro-
ducts,10 constitute key structural templates in many poly-
ketides11 and are also valuable for the subsequent synthesis of
syn- or anti-1,3-diols through judicious reduction on the
ketone moiety.12 As part of our continuing efforts in vanadyl
species mediated oxidative coupling chemistry13 and recent
interests in the functionalization of C–H bonds, herein we
describe two new classes of oxidative β-peroxy-carbonylation
and β-hydroxy-carbonylation of alkenes, respectively, catalyzed
by two individual oxovanadium/TBHP systems by varying only
the vanadyl counter ions. In contrast to the two iron-catalyzed
processes mentioned above,6,7 this new complementary combi-
nation of catalytic methods provides an expedient tool to selec-
tively access either radical process using the same set of
coupling reagents with judicious tuning of the electrostatic
attributes of a given vanadyl catalyst [eqn (3)]. Vanadyl species
have been well adopted to catalyze reactions like polymeriz-
ation, oxidations of alcohols, amines, and sulfides, as well as
allylic alcohol and olefin epoxidation.14,15 Despite the in situ
perbenzoic acid generation by aerobic oxidation of benz-
aldehyde for olefin epoxidation catalyzed by vanadyl species,16
their ability as catalysts for aldehyde C–H activation remains
elusive even with ample success particularly in 3° C–H acti-
vation.17 To our delight several vanadyl species turned out to
efficiently catalyze the oxidative coupling between styrene
derivatives and aldehydes without resorting to any halides or
halide equivalents.5
We started out by using styrene 1a and benzaldehyde 2a
(3.0–5.0 equiv.) as a test coupling system in the presence of
anhydrous TBHP (3.0 equiv. in decane) with a diverse array of
oxometallic species at 80 °C. Among these oxometallic species
and solvents examined, group 5B oxovanadium species were
found to be the most chemoselective and efficient catalysts
compared to group 6B (e.g., 13–18% yields by CrO2Cl2 and
MoO2Cl2) and group 4B (e.g., <3% by TiOCl2 and HfOCl2) in
acetonitrile (see ESI, Table S1†). Notably, the structural identi-
ties of the β-oxidative carbonylation products catalyzed by the
vanadyl catalysts highly depend on their counter ion attributes
and thus the amphoteric nature of the resulting vanadyl
species (i.e., VvO vs. +V–O−). Namely, more electronegative
counter anions (e.g., −OTf and Cl−) and thus more electron-
deficient vanadyl species led to the β-peroxidative carbonyla-
tion product 4a (68–80% yields as in entries 1, 2 and 11
of Table 1). On the other hand, more basic counter anions
VOCl2–3H2O/bipyd
VOCl2–3H2O/phene
VOCl2–3H2O/salenf
VO(OAc)2–3H2Og
37
23
68
32
75
73
43
58
Trace
7
6
Trace
Trace
Trace
Trace
68
h
VO(acac)2
i
VO(tmhd)2
j
9
VO(hfacac)2
VO(dbm)2
k
10
11
12
13
14
15
16
17
18
q
VOCl3
—
VO(OiPr)3l
64
<5
q
VO(acac)2
82 (84)m
89
—
—
—
—
q
VO(acac)2ll,,mm,n(5 mol%)
VO(acac)2l,m,o
VO(acac)2
q
65
72
Trace
Trace
q
VO(acac)2/BHTp
VOCl2–3H2Oo
—
q
43
a Reaction conditions: styrene (1 mmol), aldehyde (5 mmol), 5 M tert-
BuOOH in decane (3 mmol), MeCN (2 mL), 80 °C. b Isolated yield.
c OTf: trifluoromethanesulfonate. d bipy: 2,2′-bipyridine (2.5 mol%).
e phen: 1,10-phenanthroline (2.5 mol%). f salen: N,N′-bis(salicylidene)-
ethylenediamine (2.5 mol%). g OAc: acetate. h acac: acetylacetone.
i tmhd: 2,2,6,6-tetramethyl heptan-2,5-dione. j hfacac: 1,1,1,5,5,5-
hexafluoropentan-2,5-dione. k dbm: dibenzoylmethane. l 3.0 equiv. of
70% tert-BuOOH in water was used. m Slow addition of TBHP over
30 min. n 65 °C. o Styrene/aldehyde/tert-BuOOH(aq.) ratio: 1/3/2, 80 °C.
p One equiv. of 2,6-di-tert-butyl-4-methylphenol (BHT) was added. q Not
detected.
(e.g., acetylacetonate analogues and Oi-Pr) and thus more
electron-rich vanadyl species furnished the carbonylative
β-hydroxylation product 3a (43–75% yields in entries 7–10
and 12).
Among the three vanadyl species bearing electronegative
ligands (i.e., −OTf, Cl−, and AcO−) examined, VOCl2–3H2O pro-
vided the best yield of 4a (80%, entry 2), despite with a trace
amount (5%) of β-hydroxyketone 3a isolated. Increasing the
electron density of the vanadyl centre by adding basic, biden-
tate ligands like 2,2′-bipyridine or 1,10-phenanthroline
resulted in a significant loss of catalytic activities with a rever-
sal of product distribution (37 and 23% yields of 3a as in
entries 3 and 4). Further increasing the electron density of the
vanadyl centre by employing the covalent Salen-type (N,N’-bis-
(salicylidene)ethylenediamine) ligand improved the yield of 3a
to 68% (entry 5), along with a discernible amount of β-peroxy-
ketone 4a (7%). Vanadyl species which bears weakly basic
acetate counter anions also led to preferential formation of 3a
albeit in poorer yield (32%, entry 6).
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Based on these ligand effects, we further optimized the pro-
duction of 3a in the model reaction using tetradentate, oxo-
vanadium bis(acetylacetonate) [VO(acac)2] and its derivatives.
As expected, oxovanadium β-diketonate species bearing more
basic ligands predominantly gave the β-hydroxylation product
3a in 43–75% yields. Notably, the product yields are pro-
portional to the basicity of the β-diketonate ligand (i.e., acac−
≈ tmhd− > dbm− > hfacac−; entries 7–10 in Table 1). Therefore,
the less hindered VO(acac)2 was selected as the best catalyst in
view of its catalytic reactivity, commercial price, and avail-
ability (75% yield, entry 7). It should be noted that metal acetyl-
acetonates derived from Fe(II), Co(II), Cu(II), Rh(II), and Pd(II)
did not provide any discernible product 3a under similar con-
ditions, indicating the essential role of the VvO unit in deli-
vering the hydroxyl group at the β-position. Oxidovanadium(V)
catalysts such as VOCl3 and VO(OPri)3 also showed similar
ligand effects. Namely, more Lewis acidic VOCl3 led to the
β-peroxidation product 4a (68% yield), whereas more basic
VO(OPri)3 furnished the β-hydroxyketone 3a (64% yield; entries
11 and 12) albeit with less catalytic efficiencies presumably
due to its moisture sensitivity.
The final optimized condition for the β-hydroxylative
carbonylation of styrene was to use 3.0 equiv. of 70% aqueous
TBHP instead of dry TBHP in the presence of 5.0 equiv. of
benzaldehyde with 2.5 mol% of VO(acac)2 at 80 °C. The
desired β-hydroxyketone 3a was afforded in 84% yield (Table 1,
entry 13). Slow addition of aqueous TBHP over 30 min and
doubled catalyst loading (i.e., 5 mol%) further increased the
yield of 3a to 89% and the β-peroxidation was completely sup-
pressed [cf. entry 13 (parenthesis) with entry 14]. The yield of
3a was reduced to 65% when the reaction temperature was
lowered to 65 °C (entry 15). Decreasing the substrate and
oxidant stoichiometry to 1.0/3.0/2.0 (styrene/benzaldehyde/
Scheme 1 Substrate scope in the VO(acac)2-catalyzed β-hydroxy-
carbonylation of styrene derivativesa. aReaction conditions: 1 (1 mmol),
2 (5 mmol), VO(acac)2 (0.025 mmol), 70% aqueous t-BuOOH (3 mmol),
TBHP) reduced the yield of 3a by 10–12% (entry 16). Therefore, acetonitrile (2 mL), 80 °C, under N2. Yields of the isolated products are
given. b5 mol% of VO(acac)2 was used. cAr = 3,4-di-methylphenyl.
dReaction temperature: 90 °C.
2.0 equiv. of TBHP was still sufficient to achieve a satisfactory
production of β-hydroxyketone 3a. These results indicated that
the β-peroxidation pathway can be suppressed with insufficient
loading of TBHP or with a more basic catalyst. Notably, when
(3b–e) in 74–86% isolated yields albeit with 30%–50% longer
reaction time due to the steric and/or electronic effects of the
substituent. Notably, these products are somewhat acid sensi-
tive. They tend to undergo dehydration to form the corres-
ponding enones (30–34%) even upon standing in CDCl3 for
24 h. Electron-deficient, halogen- or cyano-containing, as well
as hetero-aromatic aldehydes (1f–k) were well adapted to the
reaction conditions. The desired products 3f–k were obtained
in 58–73% yields in a shorter reaction time (40 min to 1 h).
Aliphatic aldehydes proved more recalcitrant due to facile
decomposition of the incipient acyl radicals to the corres-
ponding alkyl radicals under the reaction conditions.20 Beside
aliphatic aldehydes bearing 1° alkyl groups (e.g., pentanal),
those with α-branching groups (e.g., isopropyl and cyclohexyl
in 1l,m) also showed satisfactory results. Higher catalyst
loading (5 mol%) and a longer reaction time (1.5 h) were
required to achieve satisfactory yields (60–65%) of products
3l,m. Nevertheless, these two cases turned out to be the only
2,6-di-tert-butyl-4-methylphenol (BHT, 1.0 equiv.), a radical
scavenger,18 was introduced, the test reaction completely shut
down, suggesting the involvement of a radical process of this
coupling reaction (entry 17). In contrast, the chemical yield of
the VO(Cl)2-catalyzed β-peroxidation was dropped to half (i.e.,
43%) with the reduced substrate and oxidant stoichiometry
(entry 18), which revealed that a larger excess of TBHP (at least
3 equiv.) is essential to facilitate the β-peroxidation pathway.
The fully optimized β-hydroxycarbonylation protocol proved
amenable to a diverse range of aldehyde and styrene type sub-
strate combinations (Scheme 1). In marked contrast, Pd(II)
catalyzed, β-hydroxyphosphonylation and β-hydroxy-carboxyl-
ation of styrene proceeded in only 34% and 42% isolated
yields, respectively, along with extensive dehydration and/or
hydroxyl oxidation (37% yield).8,19 Aromatic aldehydes bearing
electron-donating or -stabilizing groups such as methyl (1b–c),
methoxy (1d), and benzo-fused (1d) substrates reacted most
efficiently, affording the corresponding β-hydroxyketones
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successful aliphatic aldehyde examples reported to date. In
contrast, both pivaldehyde (a 3° alkyl group) and phenyletha-
nal (a benzyl group) led to the α-hydroxyalkylation products in
68% yields (see ESI†).
Styrenyl substrates bearing p-substituents (1n–q), α-methyl-,
α-phenyl-, and β-methyl-styrenes, were also investigated. It was
found that the coupling efficiencies to p-substituted styrenes
were satisfactory in all cases except for 1q which bears the
p-methoxy group. The products of pharmaceutical interests
(i.e., 3n–3p and 3q) were isolated in good (73–84%) and moder-
ate (56%) yields, respectively.21 To our expectation, α-substi-
tuted styrenes like 1r and 1s were high yielding substrates
(87–91% yield) presumably due to the involvement of even
more stable 3° radical intermediates and complete prevention
of over oxidation. Furthermore, the more challenging sub-
strate, trans-β-methyl styrene, was also able to produce the
corresponding coupling product 3t with an exclusive syn
diastereoselectivity even at an elevated temperature (100 °C)
and a longer reaction time (2 h) in propanonitrile presumably
due to the β-methyl steric effect [eqn (4a)].
ð4aÞ
Scheme 2 Substrate scope in the VOCl2-catalyzed β-peroxidative
carbonylation of styrene derivativesa. aReaction conditions: 1 (1 mmol),
2 (5 mmol), VO(Cl)2 (0.025 mmol), t-BuOOH (3 mmol, 5 M in decane),
acetonitrile (2 mL), 80 °C, under N2. Yields of the isolated products are
given.
ð4bÞ
By taking advantage of the differential catalytic activity
between the two final vanadyl catalysts, we also carried out
the complementary functionalization of styrene derivatives
(Scheme 2). Their β-peroxidative carbonylations using 2.5 mol
% of VOCl2 under the established conditions (Table 1, entry 2,
styrene/benzaldehyde/TBHP, 1/5/3) were performed for the
same substrate classes. Comparative results are compiled in
Scheme 2. There was no direct correlation between the yields
of the peroxide products and the electronic characteristics of
aldehyde reactants because minor epoxide formation from the
initial coupling products was observed in several cases. Beside
electron rich or hindered cases (1d and 1h), most aromatic
aldehydes led to the products 4b–h in 73–75% yields which
59–72% yields. Expectedly, α-methyl and α-phenyl styrenes
afforded even better yields (72–93%) in the β-peroxy ketone
formation (4q–s).
ð5Þ
On the other hand, the reaction of trans-β-methyl styrene
were comparable to or slightly higher than those catalyzed by with p-tolualdehyde led to the corresponding coupling product
FeCl2. In the cases of hetero-aromatic and aliphatic aldehydes 3t′ with 1 : 1 (syn : anti) diastereoselectivity at 100 °C for 2 h
which were not studied before, the peroxides 4i–k were in propanonitrile [eqn (4b)]. The result indicated a different
furnished in 72–78% yields. As a potentially useful extension, operating mechanism involved in the V(O)Cl2 catalyzed
acetonide-protected glyceraldehyde was tested under similar reaction.
reaction conditions. The desired, volatile products 4t were
Notably, treatment of 4a with 3.0 equiv. TBHP in the pres-
produced in 78% conversion (in 30% isolated yield) as ence of 5, 10, 25, and even 100 mol% VO(acac)2 afforded less
a 1 : 1 mixture of diastereomers [eqn (5)].22 p-Substituted than 5% of 3a [eqn (6)]. Furthermore, the cross-coupling reac-
styrenes led to the β-peroxy carbonylated products 4l–p in tions between p-tolualdehyde (or o-tolualdehyde) and styrene
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in the presence of 1 equiv. of 4a led only to 3b (or 3c) with a
negligible amount of 3a under similar catalytic conditions
[eqn (7)]. Both control experiments ruled out the possibility of
4a as the intermediate en route to 3a in the β-carbonylative
hydroxylation of styrene [eqn (6)]. Furthermore, when 1.0
equiv. of di-tert-butyl azodicarboxylate (DtBAD) was added to
the individual peroxidation and the hydroxylation reaction as a
radical trapping reagent,23 the coupling product 5 between
benzoyl radicals and DtBAD was obtained in 78–83% yields in
both cases along with the desired products 3a and 4a in 11
and 16% yields. The results strongly implicated that both the
reactions proceeded through the radical mechanism [eqn (8)].
ð6Þ
Scheme 3 Plausible complementary mechanisms.
ð7Þ
carbonylation product 4 formation and bring back the initial
vanadyl(IV) catalyst 6 [Scheme 3, (a)→(b)→(c)→(d)].
Conversely, the vanadyl(V) hydroxide 8 may act as a source
of hydroxyl radicals26 in the chemoselective hydroxylation of
radical 10, presumably due to its increased stability under the
influence of basic or electron-rich ligand(s).27 This hypothesis
is consistent with our observations that the formation of
t-BuOO• via vanadyl(V) hydroxide 8-induced decomposition of
TBHP [step (b)] can be suppressed by reducing the amount of
TBHP (Table 1, entry 13, parenthesis) or increasing the loading
of the V(O)(acac)2 catalyst (Table 1, entry 14). In addition, the
product distribution of VOCl2 mediated catalysis was reversed
from peroxy 4 to the corresponding β-hydroxyketone 3 when
the incipient 8 was stabilized by introducing basic or covalent
ligand(s) (Table 1, entries 3–5). These results support the
important role of 8 in the hydroxylation pathway.
To support the increased stability of vanadyl(V) hydroxide 8
under the influence of the acac ligand, a control sample with
an equal amount of VO(acac)2 and TBHP in refluxing aceto-
nitrile was maintained for 1 h. Complex 8 (VO(acac)2–OH) was
indeed formed as evidenced by electrospray ionization mass
analysis of the mixture (see ESI†). Furthermore, the addition
of α-methylstyrene to that reaction mixture for 4 h led to the
formation of 1,2-di-t-butylperoxylation and 1,2-dihydroxylation
products, 11a and 11d, in 27% and 33% yields along with
1-hydroxy-2-t-butylperoxy and 1-hydroxy-2-t-butoxy adducts,
11b and 11c, in 4 and 16% yields [eqn (8)]. The formation of
11c further supports the formation of t-butoxy radicals
and vanadyl(V) hydroxide 8 through pathway (a). Therefore, the
V(O)(acac)2-catalyzed hydroxylation–carbonylation of styrene
ð8Þ
Several mechanistic features governing vanadium-catalyzed
oxygen transfer reactions such as epoxidation, C–H bond
hydroxylation, and other oxidation reactions have been docu-
mented.15,24 Among them, vanadyl alkylperoxy complex 7 gen-
erated by vanadyl(IV) 6-triggered, Haber–Weiss decomposition
of TBHP [steps (a) and (b) in Scheme 3] is widely considered as
the key intermediate in vanadyl(IV)/TBHP catalytic systems;25
complex-7 is oxidatively decomposed to vanadyl(V) hydroxide 8
through homolytic cleavage of the O–O bond with concomitant
electron transfer [step (a)]. Vanadyl(V) hydroxide 8 further
reacts with an additional TBHP to produce t-butylperoxy radi-
cals [t-BuOO•, step (b)] with a concomitant formation of H2O.
The two-step decomposition of TBHP coupled with a one-elec-
tron change of the vanadyl centre associated with the Haber–
Weiss mechanism may be responsible for the chemoselective
carbonylative peroxidation. Firstly, hydrogen atom abstraction
of an aldehyde by the t-butoxy radical (t-BuO•) produced by
step (a) would afford an acyl radical 9. The subsequent
addition of 9 to a styrene type substrate would produce a more
stable, benzylic type radical 10 [step (c)]. Radical 10 would be
trapped by an incipient t-BuOO• to facilitate the peroxidation–
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may proceed through a direct coupling of 8 with benzylic
radical 10 [Scheme 3, (a)→(c)→(e)] to afford β-hydroxyketone 3
with concomitant release of the initial catalyst 6 and com-
pletion of the catalytic cycle.
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ð8Þ
Conclusions
In conclusion, we have developed tandem and complementary
β-hydroxylation–carbonylation and β-peroxidation–carbonyla-
tion of styrenes by simply adjusting the ligand environment of
a vanadyl centre. Notably, V(O)(acac)2 is the only acac-bearing,
oxometallic species that works for this chemistry. Other met-
allic acac species like Fe(acac)2, Fe(acac)3, Co(acac)2, Cu(acac)2,
Rh(acac)2, and Pd(acac)2 did not lead to any discernible
β-hydroxyketone product 3a under similar reaction conditions.
Conversely, moisture tolerant VOCl2 serves as an alternative
catalytic system for FeCl2 and provides an additional advan-
tage for aliphatic aldehydes bearing 2° alkyl groups. The new
complementary methodologies are attractive because the desir-
able β-hydroxy and β-peroxyketones can be provided selectively
by using the same set of coupling partners. The exclusive syn
selectivity observed in eqn (4) also suggests that vanadyl
species-associated radicals might be involved in the coupling
reaction. Further investigations on the detailed mechanisms
and asymmetric variants of this radical, oxidative coupling
transformation are underway.
Acknowledgements
Financial support from the Ministry of Science of Technology
of Taiwan (NSC 101-2113-M-007-009-MY3) was greatly
acknowledged.
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