Syn-dihydroxylation of alkenes using a sterically demanding cyclic diacyl peroxide

Article abstract of DOI:10.1021/acs.joc.9b01748

The syn-dihydroxylation of alkenes is a highly valuable reaction in organic synthesis. Cyclic acyl peroxides (CAPs) have emerged recently as promising candidates to replace the commonly employed toxic metals for this purpose. Here, we demonstrate that the structurally demanding cyclic peroxide spiro[bicyclo[2.2.1]heptane-2,4′-[1,2]dioxolane]-3′,5′-dione (P4) can be effectively used for the syn-dihydroxylation of alkenes. Reagent P4 also shows an improved selectivity for dihydroxylation of alkenes bearing β-hydrogens as compared to other CAPs, where both diol and allyl alcohol products compete with each other. Furthermore, the use of enantiopure P4 (labeled P4′) demonstrates the potential of P4′ for a metal-free asymmetric syn-dihydroxylation of alkenes.

Full text of DOI:10.1021/acs.joc.9b01748

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Article
Syn-Dihydroxylation of Alkenes Using A
Sterically Demanding Cyclic Diacyl Peroxide
Afsaneh Pilevar, Abolfazl Hosseini, Jonathan Becker, and Peter R. Schreiner
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01748 • Publication Date (Web): 09 Sep 2019
Downloaded from pubs.acs.org on September 13, 2019
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Syn-Dihydroxylation of Alkenes Using A Sterically Demanding
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Cyclic Diacyl Peroxide
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Afsaneh Pilevar,┴ Abolfazl Hosseini,┴ Jonathan Becker,‡ and Peter R. Schreiner*,┴
┴Institute of Organic Chemistry, Justus Liebig University, Heinrich-Buff-Ring 17, 35392 Giessen, Germany
‡Institute of Inorganic and Analytical Chemistry, Justus Liebig University, Heinrich-Buff-Ring 17, 35392 Giessen,
Germany
Abstract. The syn-dihydroxylation of alkenes is a highly valuable reaction in organic synthesis. Cyclic
acyl peroxides (CAPs) have emerged recently as promising candidates to replace the commonly employed
toxic metals for this purpose. Here we demonstrate that the structurally demanding cyclic peroxide
spiro[bicyclo[2.2.1]heptane-2,4′-[1,2]dioxolane]-3′,5′-dione (P4) can be effectively used for the syn-
dihydroxylation of alkenes. Reagent P4 also shows an improved selectivity for dihydroxylation of alkenes
bearing β-hydrogens as compared to other CAPs, where both diol and allyl alcohol products compete with
each other. Furthermore, the use of enantiopure P4 (labeled P4') demonstrates the potential of P4' for a
metal-free asymmetric syn-dihydroxylation of alkenes.
O
1)
O
O
R2
Sterically demanding cyclic peroxide
Improved syn-selectivity
Capable of asymmetric induction
Enhanced selectivity for dihydroxylation
Ar
HO
Ar
O
R2
R1
R1= alkyl, H
R2= alkyl, Ar, H
2) Hydrolysis
R1
OH
of alkene bearing -hydrogens
23 examples
22–94%
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Introduction. The selective oxidation of olefins to the corresponding syn-diols has been the subject of intensive
research.1 Vicinal syn-diols are a common motif in a number of pharmaceutical and biologically active
compounds as well as versatile intermediates in organic syntheses.2 The syn-dihydroxylation of alkenes is
generally performed using stoichiometric or catalytic amounts of transition metals, especially osmium and
ruthenium based catalysts.1a,3 However, the cost, toxicity, and environmental issues associated with these metals
prompted scientists to develop sustainable metal-free strategies for alkene dioxygenation. While the metal free
epoxidation of alkenes has been well established,4 alkene syn-dioxygenation remains a difficult task.
Recently, efficient organocatalytic syn-diacetoxylation of alkenes using aryl iodides as catalysts was reported, but
these reactions often proceed with low diastereoselectivities.5 Diacetoxylation of alkenes using PhI(OAc)2 as
oxidant requires strong acid catalyst (e.g., HOTf) and occurs with low diastereoselectivity.6 Although recent
efforts have led to some improvements,7 literature precedents show that cyclic acyl peroxides (CAPs) are highly
promising candidates for this purpose in terms of cost, atom economy, and prospects on stereoselectivity.
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The chemistry of cyclic acyl peroxides (CAPs) has received strong impetus with the discovery of phthaloyl
peroxide8 and the thermolysis as well as photolysis of CAPs in general has been the subject of numerous
studies over the last decades from both the synthetic and mechanistic point of view.9 Notwithstanding the
pioneering work of Greene and Adam,10 the reactivity of cyclic peroxides toward nucleophiles as well as
olefins still does not yet fully exploit the potency for novel carbon-oxygen bond forming reactions.11
Dioxiranes12 are known to give epoxides upon reaction with alkenes whereas 1,2-dioxetanes13 and dimethyl
α-peroxy lactones produce mixtures of peroxides, cycloadducts, and ene products.11e,11f Concurrently, with
the growing attention for metal free organic reactions, CAPs have become attractive because of their potent
ability in dioxygenation of electron-rich olefins under mild conditions. A few known CAPs have been
employed with phthaloyl and cyclopropyl malonoyl peroxides resulting in appreciably increased
reactivity,14 with the latter being superior due to its higher relative reactivity, diastereoselectivity, and ease
of preparation.15 Tomkinson et al. demonstrated that the backbone structure of aliphatic CAPs plays a key
role in reactivity and selectivity of a given reaction; cyclopropyl malonoyl peroxide hereby is particularly
efficient.14a,14b,16 Despite the great efforts made by Tomkinson and Siegel et al.14c for the metal free syn-
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dihydroxylation of alkenes using established CAPs, there still remain some challenges concerning (1) the
diastereoselectivities, (2) substrate scope, and (3) an asymmetric variant. Therefore, the synthesis and
application of new peroxides with features that fulfill the above requirement remains a challenging task that
must also take into account stability and safety. Additionally, simple manipulations of vicinal di-acids as
starting materials do not necessarily deliver the corresponding cyclic peroxides due to an inappropriate
torsion angle or O–O bond distance as well as their inherent propensity for decarboxylation.14c,17 For
instance, a phenyl group can readily be incorporated into P3, however, the resulting peroxide P5 is unstable
and gradually decomposes at room temperature. The low stability of P5 could be attributed to the shortened
O–O bond that increases the electrostatic repulsion of the peroxy oxygen lone pairs (Scheme 1).17-18
Furthermore, the shortened O–O bond in P5 implies a higher conjugation between the carbonyl group and
peroxy oxygen that increases its electron density. It was reported that the increase in the ring strain (CO–
C–CO angles) of the peroxide directly translates into increased reactivity.14a Although this could explain
the reactivity trend of P1 vs. P3, it is insufficient to explain the low stability of P5. We reason that the
difference between internal CO–C–CO angles in the dicarboxylic acid starting materials and the resulting
peroxides could also be taken as an indicator for peroxide stability;19 for instance, this angle is 10.7 °14a,20 in
P1, about twice as large as in P5 (5.2 °).
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Scheme 1. Comparison of O–O bond length, C(CO)2 inner angle and CO–O bond length (determined by
single‐crystal X‐ray diffraction) in different CAPs.
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
P2
O
P3
P1
P4
P5
1.476
1.476
1.471
1.467
1.466
O-O bond (Å):
C(CO)2 angle:
107.56
1.390
104.01
1.392
102.34
1.377
102.02
1.382
102.51
1.375
CO-O bond (Å):
Here we address several of the above-mentioned challenges with a readily prepared and safe CAP that
proved highly versatile in olefin dioxygenation.
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RESULTS AND DISCUSSION
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We recently synthesized strained cyclic peroxide P4 and applied it to the direct hydroxylation of aromatic
substrates with good yields and appreciable regioselectivities.15a This promising results encouraged us to
evaluate P4 in alkene oxidation using trans-stilbene as the model substrate (Table 1). Various solvents were
used and CHCl3 gave the best results in terms of yield and diastereoselectivity of the resulting diol (Table
1, entries 1–5). Variation of temperature and the amount of peroxide as well as water did not affect the
reaction much (Table 1, entries 6–9). In general, acceptable diastereoselectivities were observed in our
initial screening although P4 showed low reactivity at room temperature. It has been recently shown that
fluorinated alcohols have beneficial effect on the rate and selectivity of alkene oxidation using CAPs21 and
we observed that perfluoro alcohols offered an appreciable increase in yield and selectivity using P4 as
oxidant. The yield for our test reaction increased to 50% with a 32:1 syn:anti ratio upon addition of 1 equiv
of 2,2,2-trifluoroethanol (TFE). Further improvements were achieved when 3 equiv of TFE were added.
Hexafluoroisopropanol (HFIP) on the other hand improved the yield but not the selectivity under the same
conditions (Table 1, entries 10–13).
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Table 1. Optimization of the dihydroxylation using peroxide P4.
O
1) Solvent (0.25 M)
rt/24 h
OH
Ph
O
O
Ph
Ph
+
Ph
2) Hydrolysis
OH
2a
O
1a
P4
no.
1
solvent
CHCl3
Toluene
EtOAc
THF
P4 (equiv)
H2O (equiv)
additive (equiv)
yield (%)a
syn:antib
28:1
29:1
n.d.
1.2
1.2
1.2
1.2
1.2
1.2
1
1
1
1
1
1
–
–
–
–
–
–
38
28
2
3
13c
14c
27
4
n.d.
5
CH3CN
CHCl3
17:1
27:1
6d
36
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CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
1.2
1
2
1
1
1
1
1
1
1
1
1
1
–
32
35
35
50
70
73c
88
68
89
90
92
21:1
28:1
20:1
32:1
34:1
28:1
29:1
35:1
42:1
39:1
39:1
8
–
9
1.5
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
–
10
11
12
13
14
15
16
17
TFE (1)
TFE (3)
HFIP (1)
HFIP (3)
PFB (1)
PFB (3)
PFB (6)
PFB (10)
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a Yield of isolated product. b Ratio determined by NMR. c Yield by NMR. d Reaction at 40 °C.
Significant improvement was finally achieved using 3 equiv of perfluoro-tert-butyl alcohol (PFB) at room
temperature, leading to the formation of 2a in 89% yield and a 42:1 syn:anti ratio (Table 1, entries 14–17).
Therefore, the optimal conditions were established as alkene (1 equiv), P4 (1.2 equiv), PFB (3 equiv) in
CHCl3 at room temperature.
Having optimized the reaction conditions, we next explored the substrate scope, and a variety of substituted
olefins were subjected to our standard conditions (Table 2). Treatment of styrene with P4 in a chloroform-
PFB mixture at room temperature produced 1-phenylethane-1,2-diol in 93% yield of isolated product (Table
2, entry 1). Similarly, styrenes bearing electron donating groups afforded high yields of the corresponding
products (Table 2, entries 2–4). Sterically hindered 2,4,6-trimethylstyrene, however, led to lower
conversion presumably due to the reduced accessibility of the double bond (Table 2, entry 5). Less
nucleophilic para and ortho-chlorostyrenes also furnish the corresponding diols in high yields (Table 2,
entries 6 and 7) while electron-deficient styrenes, such as p-cyanostyrene, react more slowly (Table 2,
entries 8 and 9).
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As shown in Table 2, the dihydroxylation of internal olefins provides access to products containing vicinal
stereogenic centers with good to high diastereocontrol. A rather challenging substrate, cis‐stilbene, afforded
excellent yield but modest diastereoselectivity. The diastereoselectivity was improved to a 5:1 syn:anti ratio
when the reaction was carried out in a toluene / PFB solvent mixture (1:1) at –15 °C, whereas no
improvement was achieved using cyclopropyl malonoyl peroxide (Table 2, entry 10). Dihydroxylation of
trans-β-methylstyrene afforded the desired product in 90% yield and a 5:1 syn:anti ratio (Table 2, entry 11).
This result is marginally superior to using cyclobutane malonoyl peroxide (80%, 4:1 syn:anti ratio).14b This
effect increases with an isopropyl terminus (81%, 11:1 syn:anti ratio) whereas only a modest change was
observed with cyclobutane malonoyl peroxide (68%, 5:1 syn:anti ratio, Table 2, entry 12),22 indicating that
the steric hindrance of P4 considerably affects the diastereoselectivity of the reaction. The steric sensitivity
is also apparent when 2,2'-dimethyl-trans-stilbene was subjected to oxidation with P4: the syn product was
isolated almost exclusively under the same reaction conditions (Table 2, entry 13); equally, indene provided
exclusively the syn diol product in good yield due to the inherent ring strain that prevents the formation of
the anti product (Table 2, entry 14). Similar to a previous report,23 the reaction of p-vinylthioanisole
preferably oxidized the sulfur atom and the alkene moiety remained intact (Table 2, entry 15). Treatment
of p-ethynylstyrene with P4 (Table 2, entry 16) gave only 27% yield of the corresponding diol. Aliphatic
substrates thus far provide only low yields of the corresponding diols, apparently requiring a completely
new optimization.
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Table 2. Dihydroxylation of alkenes with cyclic peroxide P4.a
O
1) CHCl3, PFB, H2O
rt, 24 h
OH
O
O
R2
R2
+
R1
R1
2) Hydrolysis
OH
2a-q
O
1a-q
no.
1
substrate
product
yield (%)b
93
syn:antic
HO
–
OH
1b
OH
2
94
–
1c
OH
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OH
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3
4
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86
72
–
–
–
–
–
1d
OH
OH
1e
MeO
OH
MeO
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OH
65
1f
OH
OH
80d
71d
1g
Cl
OH
Cl
OH
1h
Cl
OH
Cl
OH
8
9
29e
22e
–
–
1i
1j
NC
OH
NC
OH
O2N
OH
NO2
HO
OH
91
4:1
10
88 (92)f,g
5:1 (3:1)f,g
1k
OH
11
12
90
81
5:1
1l
OH
OH
11:1
1m
OH
OH
13
14
15
80
74
76
>75:1
100:0
–
1n
1o
OH
OH
OH
S
1p
1q
S
O
OH
16
27
–
OH
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a Reaction conditions: Alkene (1 equiv), P4 (1.2 equiv), CHCl3 (0.25 M), PFB (3 equiv), H2O (1 equiv)
5
6
at room temperature for 24 h. b Yield of isolated product. c Ratio determined by NMR. d Reaction after
7
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e
f
g
48 h. Reaction after 72 h. Reaction performed in toluene at –15 °C after 5 d. The numbers in
9
parentheses refer to the reaction using cyclopropyl malonoyl peroxide in toluene at –15 °C after 5 d.
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Alkenes bearing β-hydrogens also are viable substrates, however, oxygenations with CAPs generally result
in competitive formation of allyl alcohols, which decreases the yield of the desired diol.14b Having
established conditions for alkene dihydroxylation, we next investigated the selectivity of P4 in
dihydroxylation of alkenes bearing β-hydrogens (Table 3). In fact, the presence of β-hydrogens allows the
reaction to proceed through an alternative path to give the corresponding allyl alcohol (Scheme 2, 12t). The
optimized conditions in Table 2 were employed for hydroxylation of alkenes bearing β-hydrogens, however,
no difference was observed in the presence or absence of PFB (Table 3, entry 1), and therefore, the reaction
of P4 with alkenes bearing β-hydrogens were carried out without PFB.
Table 3. Dihydroxylation of alkenes bearing β-hydrogens with P4 under wet and dry conditions.a
O
OH
OH
OH
R2
O
O
1) CHCl3, H2O, 40 °C
2) Hydrolysis
R2
+
+
R2
R1
R1
R1
O
1r-w
P4
2r-w
3r-w
“wet”
diol:allyl alc.c
“dry”
time of hyd.
(h)d,e
no.
substrate
Yield
Yield
(%)b
diol:allyl alc.c
1.6:1
(%)b
1
2
3
80 (92)f,g
4:1 (3:1)
4:1
26
24
30
48
48
1r
78
1.6:1
1s
Ph
70 (72)g
2.6:1 (1.2:1)
1:5.5
120
1t
4
81
2:1
20
1:>50
72
1u
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68h
66h
pure dioli
pure dioli
–
–
–
–
48
48
1v
1w
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a Reaction conditions: Alkene (1 equiv), P4 (1.2 equiv), CHCl3 (0.6 M), H2O (1 equiv) at 40 °C, reactions
under dry conditions were performed in toluene. b Yield of isolated product. c Ratio determined by NMR.
d Hydrolysis was performed using a mixture solution of NaOH (2 M) and 1,4-dioxane at 100 °C. e In all
cases the same ratios of diol:allyl alc. were also obtained by hydrolysis of methylated esters in
NaOMe/1,4-dioxane. f Reaction under standard conditions using PFB afforded 82% yield and a ratio of
g
3.7:1 diol:allyl alcohol. Numbers in parentheses refer to the reaction using cyclopropyl malonoyl
peroxide. h Yield of diol product. i No allyl alcohol product observed.
Based on the previously established mechanism,24 water plays a critical role in the dihydroxylation reaction.
However, the presence of β-hydrogens triggered an elimination reaction by the adjacent carboxylate anion
(oxonium intermediate 12t, Scheme 2) for which water is not needed to quench carbocation 12t. Intrigued
by the effect of water on the selectivity of the reaction, both wet and dry conditions were examined. With
this in mind, performing the reactions under dry conditions should promote the formation of allyl alcohols.
In general, better yields of the desired diol products were obtained using P4 under wet conditions. The
selectivity for diol formation is higher than that obtained for cyclobutane (70%, 2.5:1 of diol:allyl alcohol)14b
or cyclopropyl malonoyl peroxides under the same reaction conditions (Table 3, entry 1). Good yields and
selectivities were also observed for alkenes 1s–1u for which P4 proved superior. Interestingly, alkenes 1v
and 1w gave only diol products under the same reaction conditions, without the formation of allyl products
(Table 3, entries 5 and 6). The reactions under dry conditions were performed in dry toluene to avoid the
hydrogen bond interaction.25 The dry reaction conditions work in principle, however, were less efficient in
terms of both yields and selectivities (Table 3).
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Scheme 2. Proposed mechanism for the oxidation of alkene bearing β-hydrogens by P4.
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O
(C20H26O3Na+)
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O
calcd.: 337.1774
–CO2
OH
Ph
found: 337.1775
(C28H36O5Na+)
calcd.: 475.2455
found: 475.2453
O
H
5t
O
OH
Ph
O
O
O
H
H2O
–CO2
O
Ph
(C20H25O2)+
O
O
8t
calcd.: 297.1849
found: 297.1857
O
11t
H2O
O
O
Ph
O
O
O
Ph
O
O
–CO2
P4
+
O
O
O
Ph
O
Ph
O
O
O
O
O
1t
P4
4t
7t
13t
O
H+-Abstraction
H
O
Ph
O
(C28H34O4Na+)
calcd.: 457.2349
found: 457.2336
O
O
12t
Ph
O
O
O
(C21H24O4Na+)
calcd.: 363.1567
found: 363.1567
O
O
CH2N2
Ph
HO
9t
O
10t
6t
Inspection of Table 3 reveals that the preference for diol vs allyl alcohol formation is governed by the nature
of the alkene where the stability of resulting carbocation as well as the steric environment of the β-hydrogens
greatly affects the reaction outcome. For instance, the stabilized carbocation derived from 1r affords high
yield of diol product despite the existence of three β-hydrogens whereas less stable carbocation 4t provides
modest selectivity. Ready formation of the carbocation intermediates derived from alkenes 1v and 1w
assisted by steric hindrance around the β-hydrogens led to the exclusive formation of dihydroxylated
products. Even though the principal mechanism for alkene syn-dihydroxylations with CAPs has been
thoroughly investigated,24 the difficulty in hydrolyzing the resulting esters provoked our curiosity. For
instance, the hydrolysis of the product mixture resulting from the reaction of 1t with P4 (mixture of
dihydroxylated and allylic esters products) using aqueous sodium hydroxide did not proceed even after
prolonged reaction times and elevated temperatures. Further investigation by GC-MS and NMR indicated
that the dihydroxylated products were fully hydrolyzed whereas the allylic esters remained unreactive.
Other bases like LiOH, KOH, and NaOMe/MeOH lead to incomplete hydrolysis of the allylic esters
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products. This unexpected result prompted us to identify the reaction products before hydrolysis (Scheme
2). The products were isolated after a second esterification with diazomethane. Two major allyl alcohol
and diol products (each containing exo and endo) were isolated; the exo-allyl structure was confirmed by X-
ray crystallography. Note that mainly the decarboxylation product (5t, through intermediate 11t) was
obtained in the case of the diol product whereas the allyl oxidation product was isolated as a diester (10t,
through intermediate 12t). Surprisingly, the hydrolysis of the ester 10t was easily accomplished at 100 °C
overnight using a solution of NaOMe/1,4-dioxane, possibly due to its increased solubility in organic media.
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To gain further insight into the underlying mechanism, samples of the reaction mixture were analyzed by
HRMS as illustrated in Scheme 2. We suggest that the intermediate 4t forms in the first step,24 which
undergoes proton elimination to give the corresponding allyl alcohol ester 6t. An alternative pathway is the
addition of water to intermediate 4t and simultaneous decarboxylation to deliver the desired product 5t or
decarboxylation only to form 7t. The latter may hydrolyze or react further with peroxide P4 to give the
desired products after hydrolysis. We reasoned that the formation of allyl product 6t could be controlled by
the ease of proton abstraction that is less favorable in the case of rigid and sterically hindered P4 as compared
to cyclobutane and cyclopropyl malonoyl peroxides. However, further evidence is needed to provide a full
understanding of the mechanistic details.
Despite the considerable improvements in asymmetric metal catalyzed olefin syn-dihydroxylation, a
stereoselective organocatalyzed variant remains elusive. We recently demonstrated a synthetic route for the
preparation of enantiopure peroxide P4 (which we label P4'), we naturally attempted the asymmetric
dihydroxylation of alkenes using P4'. Performing the reaction under conditions used in Table 1 gave no ee
(Table 4, entry 1), therefore subsequent reactions were carried out without the addition of PFB to minimize
the effects of environment on the asymmetric induction (Table 4). The initial results are promising,
demonstrating the potential of P4' as an organic reagent for replacing toxic and expensive metal catalysts,
even though this will require a lot more work. To the best of our knowledge, this is the first example of the
use of a chiral peroxide for the direct enantioenriched syn-dihydroxylation of alkenes.
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Table 4. Assessment of asymmetric syn-dihydroxylation of trans-stilbene using chiral peroxide P4'.
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9
O
1) Solvent
H2O (1 equiv)
OH
O
O
Ph
Ph
+
Ph
Ph
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OH
2) Hydrolysis
O
1 equiv
P4'
(1 equiv)
no.
1d
2
Solvent
T (°C)
Yield (%)a
ee (%)b,c
CHCl3/PFB
CHCl3
RT
40
85
36
38
30
0
9
7
9
3
CHCl3
RT
40
4
Toluene
a Yield of isolated product. b Determined by chiral HPLC. See Supporting Information for details. c ee
of syn dihydroxylated product. d According to standard conditions of Table 2.
In conclusion, we have developed a high yielding olefin syn-dihydroxylation reaction enabled by a sterically
demanding cyclic peroxide. High diastereoselectivities were observed for the dihydroxylation of a wide
range of olefins with good to excellent yields. The diastereoselectivity was significantly boosted when
sterically encumbered substrates were employed, a result that we ascribe to the bulky nature of P4.
Moreover, the promising preliminary results for an asymmetric syn-dihydroxylation indicates the potential
of reagents such as P4 for developing a metal free variant of the well-established asymmetric syn-
dihydroxylation of alkenes. Furthermore, this might be advantageously realized using chiral hydrogen bond
donors, considering the low background reaction of P4. Future work will continue to explore the ability of
the P4 and related structures in the development of an asymmetric variant.
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EXPERIMENTAL SECTION
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General Remarks. All chemicals were purchased from TCI, Sigma Aldrich, Alfa Aesar, and Acros
Organics in reagent grade and used without further purification. Alkenes 1m,26 1q,27 1u, 1v, 1w were
prepared according to literature procedures.28 Peroxides P4 and P4' were synthesized according to our
previous report.15a All solvents were distilled before usage. Flash column chromatography was performed
using MN silica gel 60 M (0.040 – 0.063 mm) or Büchi Reveleris Silica columns (0.040 mm). Analytical
thin-layer chromatography (TLC) was performed using precoated polyester sheets Polygram® SIL
G/UV254 from Macherey Nagel with a fluorescence indicator. Visualization of the TLC plate was
accomplished by UV lamp at 254 nm, 5% phosphomolybdic acid in ethanol. Nuclear magnetic resonance
(NMR) spectra were recorded on Bruker AV600 or AV400 spectrometers at 298 K. Chemical shifts (δ)
were expressed in ppm downfield from the internal standard tetramethylsilane (TMS, δ = 0.00 ppm) or to
the respective solvent residual peaks (CDCl3: δ = 7.26 ppm; DMSO-d6: δ = 2.50 ppm) and were reported as
(s = singlet, d = doublet, t = triplet, q = quartet, dd = doublet of doublet, m = multiplet, br = broad, etc). The
coupling constants (J) were recorded in Hz. The progress of reactions was monitored by NMR or GC-MS
analyses with a Quadrupol-MS HP MSD 5971(EI) and HP 5890A GC equipped with a J & W Scientific
fused silica GC column (30 m × 0.250 mm, 0.25 micron DB–5MS stationary phase: 5% phenyl and 95%
methyl silicone) using He (4.6 grade) as carrier gas; T-program standard 60 – 250 °C (15 °C/min heating
rate), injector and transfer line 250 °C. HRMS were collected on a Bruker Mikro-TOF (ESI).
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CAUTION: Organic peroxides are potentially dangerous compounds, the procedures must be handled with
sufficient care; avoid exposure to strong heat or mechanical shock.
Preparation of Peroxide P5
Urea hydrogen peroxide (0.76 g, 8.05 mmol) was added to methanesulfonic acid (2.33 mL) and stirred in a
water bath for 3 min. Indane-2,2-dicarboxylic acid29 (0.56 g, 2.7 mmol) was added to the solution and the
reaction stirred for 24 h in water bath.14a A mixture of ice/ethyl acetate (7 g/8 mL) was added to the reaction
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mixture and stirred for 5 min. The phases were separated and the aqueous layer was extracted with ethyl
acetate (3 × 8 mL). The combined organic layers were successively washed with NaHCO3 (2 × 4 mL) and
brine (5 mL), dried over MgSO4, filtered, and the solvent was removed under reduced pressure yielding P5
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1
(0.5 g, 91%) as a white solid. H{13C} NMR (400 MHz, CDCl3): δ = 7.25 – 7.18 (m, 4H), 3.59 (s, 4H) ppm;
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13C{1H} NMR (100 MHz, CDCl3): δ = 174.4, 137.2, 128.2, 124.4, 46.3, 42.5 ppm.
General Procedure for Alkene Dihydroxylation
Alkene (0.5 mmol) was placed inside a 4 mL vial (screw top with solid green Thermoset cap with PTFE
liner) equipped with a magnetic stirrer bar. CHCl3 (2 ml), PFB (0.21 ml, 1.5 mmol), water (9 μl, 0.5 mmol)
and P4 (0.11 g, 0.6 mmol) were subsequently added. The liner was sealed and the material was stirred at
room temperature for the indicated time. The reaction mixture was then diluted with EtOAc (10 mL) and
stirred with a saturated solution of Na2S2O5 (10 mL) for 2 h. After separation of the layers, the aqueous
phase was extracted with EtOAc (2 × 10 mL). The combined organic extracts were washed with brine (10
mL) and concentrated under reduced pressure. The residue was hydrolyzed using a mixture of NaOH (1 M,
10 ml) and THF (10 ml) at 60 °C (oil bath) for 24 h. THF was removed under reduced pressure and the
basic phase was extracted with EtOAc (2 × 10 mL), washed with brine, dried over Na2SO4, filtered and
concentrated to give the crude product. The resultant crude mixture was then purified by column
chromatography over silica gel.
General Procedure for the Dihydroxylation of Alkenes Bearing β-Hydrogens
Alkene (1 mmol) was placed inside a 4 mL vial (screw top with solid green Thermoset cap with PTFE liner)
equipped with a magnetic stirrer bar. CHCl3 (1.6 mL), water (0.018 g, 1 mmol) and P4 (0.22 g, 1.2 mmol)
were subsequently added. The liner was sealed and the vial was placed inside an oil bath heated to 40 °C
for 24 h. The reaction mixture was then cooled to room temperature and diluted with EtOAc (15 mL) and
stirred with a saturated solution of Na2S2O5 (15 mL) for 2 h. After separation of the layers, the aqueous
phase was extracted with EtOAc (2 × 10 mL). The combined organic extracts were washed with brine (10
mL) and concentrated under reduced pressure. The residue was hydrolyzed using a mixture of NaOH (2 M,
15 ml) and 1,4-dioxane (15 mL) at 100 °C (oil bath) for the indicated time. 1,4-dioxane was removed under
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reduced pressure and the basic phase was extracted with EtOAc (2 × 10 mL), washed with brine, dried over
Na2SO4, filtered and concentrated to give the crude product. The resultant crude mixture was then purified
by column chromatography over silica gel.
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Characterization data for alkenes 1m, 1q, 1u, 1v, 1w:
[(1E)-3-Methyl-1-butenyl]-benzene (1m): Colorless oil (0.28 g, 13%; pentane as an eluent); 1H{13C} NMR
(400 MHz, CDCl3): δ = 7.38 – 7.14 (m, 5H), 6.33 (d, J = 16.1 Hz, 1H), 6.19 (dd, J = 15.9, 6.7 Hz, 1H), 2.52
– 2.40 (m, 1H), 1.09 (d, J = 6.8 Hz, 6H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 138.0, 128.5, 126.8,
126.8, 126.0, 31.5, 22.5 ppm.26
1-Ethynyl-4-vinylbenzene (1q): Yellow oil (two steps, 0.53 g, 41%; pentane as an eluent); H{13C} NMR
1
(400 MHz, CDCl3): δ = 7.46 (d, J = 8.3 Hz, 2H), 7.36 (d, J = 8.0 Hz, 2H), 6.70 (dd, J = 17.6, 10.9 Hz, 1H),
5.78 (d, J = 17.6 Hz, 1H), 5.31 (d, J = 10.9 Hz, 1H), 3.11 (s, 1H) ppm; 13C{1H} NMR (100 MHz, CDCl3):
δ = 138.0, 136.1, 132.3, 126.1, 121.3, 115.1, 83.7, 77.7 ppm.27
1-Methylene-1,2,3,4-tetrahydronaphthalene (1u): Colorless oil (1.4 g, 65%; pentane as an eluent); 1H{13C}
NMR (400 MHz, CDCl3): δ = 7.67 – 7.60 (m, 1H), 7.19 – 7.06 (m, 3H), 5.46 (d, J = 0.9 Hz, 1H), 4.94 (q, J
= 1.4 Hz, 1H), 2.83 (t, J = 6.5 Hz, 2H), 2.56 – 2.50 (m, 2H), 1.91 – 1.83 (m, 2H) ppm; 13C{1H} NMR (100
MHz, CDCl3): δ = 143.5, 137.4, 134.8, 129.3, 127.6, 125.9, 124.3, 107.9, 33.3, 30.5, 23.9 ppm.30
3-Methyl-2-phenyl-1-butene (1v): Colorless oil (1.7 g, 77%; pentane as an eluent); 1H{13C} NMR (400 MHz,
CDCl3): δ = 7.37 – 7.22 (m, 5H), 5.14 (s, 1H), 5.03 (t, J = 1.4 Hz, 1H), 2.89 – 2.77 (m, 1H), 1.10 (d, J = 6.8
Hz, 6H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 155.8, 142.9, 128.1, 127.1, 126.6, 110.0, 32.3, 22.1
ppm.31
1-Cyclohexyl-1-Phenylethene (1w): Colorless oil (2.2 g, 78%; pentane as an eluent); H{13C} NMR (400
1
MHz, CDCl3): δ = 7.36 – 7.27 (m, 4H), 7.26 – 7.22 (m, 1H), 5.13 (d, J = 1.3 Hz, 1H), 5.00 (t, J = 1.4 Hz,
1H), 2.47 – 2.36 (m, 1H), 1.88 – 1.74 (m, 4H), 1.74 – 1.66 (m, 1H), 1.39 – 1.25 (m, 2H), 1.25 – 1.09 (m,
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3H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 155.0, 143.0, 128.1, 127.0, 126.6, 110.3, 42.6, 32.7, 26.9,
5
6
26.5 ppm.32
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(±)-Hydrobenzoin (2a): Colorless solid (0.1 g, 89%; n-hexane/ethyl acetate 4:1 as an eluent); 1H{13C} NMR
(400 MHz, CDCl3): δ = 7.25 – 7.20 (m, 6H), 7.17 – 7.09 (m, 4H), 4.71 (s, 2H), 2.86 (s, 2H) ppm; 13C{1H}
NMR (100 MHz, CDCl3): δ = 139.8, 128.2, 128.0, 126.9, 79.1 ppm.14a
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1-Phenylethane-1,2-diol (2b): Colorless solid (0.06 g, 93%; n-hexane/ethyl acetate 3:1 as eluent); 1H{13C}
NMR (400 MHz, CDCl3): δ = 7.39 – 7.27 (m, 5H), 4.82 (dd, J = 8.2, 3.5 Hz, 1H), 3.76 (dd, J = 11.3, 3.5
Hz, 1H), 3.66 (dd, J = 11.3, 8.2 Hz, 1H), 2.74 (br s, 1H), 2.36 (br s, 1H) ppm; 13C{1H} NMR (100 MHz,
CDCl3): δ = 139.5, 127.5, 127.0, 125.0, 73.7, 67.1 ppm.14a
1-p-Tolylethane-1,2-diol (2c): Colorless solid (0.07 g, 94%; n-hexane/ethyl acetate 3:1 as eluent); 1H{13C}
NMR (400 MHz, CDCl3): δ = 7.24 (d, J = 8.1 Hz, 2H), 7.16 (d, J = 7.8 Hz, 2H), 4.76 (dd, J = 8.3, 3.5 Hz,
1H), 3.75 – 3.59 (m, 2H), 2.96 (s, 1H), 2.59 (s, 1H), 2.34 (s, 3H) ppm; 13C{1H} NMR (100 MHz, CDCl3):
δ = 137.9, 137.6, 129.3, 126.1, 74.7, 68.2, 21.2 ppm.33
1-o-Tolylethane-1,2-diol (2d): Colorless solid (0.06 g, 86%; n-hexane/ethyl acetate 3:1 as eluent); 1H{13C}
NMR (400 MHz, CDCl3): δ = 7.49 (dd, J = 7.4, 1.7 Hz, 1H), 7.25 – 7.12 (m, 3H), 5.06 (dt, J = 8.4, 2.9 Hz,
1H), 3.77 – 3.68 (m, 1H), 3.66 – 3.57 (m, 1H), 2.54 (d, J = 3.0 Hz, 1H), 2.34 (s, 3H), 2.27 (dd, J = 7.4, 4.3
Hz, 1H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 138.5, 134.8, 130.5, 127.8, 126.3, 125.7, 71.4, 66.9,
19.0 ppm.34
1-(4-Methoxyphenyl)ethane-1,2-diol (2e): Colorless solid (0.06 g, 72%; n-hexane/ethyl acetate 3:1 as
eluent); 1H{13C} NMR (400 MHz, CDCl3): δ = 7.31 – 7.24 (m, 2H), 6.92 – 6.85 (m, 2H), 4.75 (dd, J = 8.2,
13
3.7 Hz, 1H), 3.80 (s, 3H), 3.73 – 3.60 (m, 2H), 2.80 (br s, 1H), 2.51 (br s, 1H) ppm; C{1H} NMR (100
MHz, CDCl3): δ = 158.4, 131.6, 126.3, 112.9, 73.3, 67.0, 54.3 ppm.34
1-Mesitylethane-1,2-diol (2f): Colorless solid (0.06 g, 65%; n-hexane/ethyl acetate 3:1 as eluent); 1H{13C}
NMR (400 MHz, CDCl3): δ = 6.83 (s, 2H), 5.25 (dd, J = 9.8, 3.8 Hz, 1H), 3.96 (dd, J = 11.5, 9.9 Hz, 1H),
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3.60 (dd, J = 11.5, 3.8 Hz, 1H), 2.49 (br s, 2H), 2.40 (s, 6H), 2.25 (s, 3H) ppm; 13C{1H} NMR (100 MHz,
CDCl3): δ = 137.2, 136.7, 132.5, 130.2, 72.7, 64.7, 20.7, 20.8 ppm.14a
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1-(4-Chlorophenyl)ethane-1,2-diol (2g): Pale yellow solid (0.07 g, 80%; n-hexane/ethyl acetate 3:1 as
eluent); 1H{13C} NMR (400 MHz, CDCl3): δ = 7.28 – 7.18 (m, 4H), 4.72 (dd, J = 8.2, 3.4 Hz, 1H), 3.66 (dd,
J = 11.3, 3.4 Hz, 1H), 3.53 (dd, J = 11.3, 8.2 Hz, 1H), 2.54 (br s, 2H) ppm; 13C{1H} NMR (100 MHz,
CDCl3): δ = 138.9, 133.7, 128.7, 127.5, 74.0, 67.9 ppm.34
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1-(2-Chlorophenyl)ethane-1,2-diol (2h): Pale yellow solid (0.06 g, 71%; n-hexane/ethyl acetate 3:1 as
eluent); 1H{13C} NMR (400 MHz, CDCl3): δ = 7.60 (dd, J = 7.7, 1.8 Hz, 1H), 7.36 – 7.28 (m, 2H), 7.26 –
7.21 (m, 1H), 5.25 (dd, J = 7.9, 3.1 Hz, 1H), 3.91 (dd, J = 11.4, 3.1 Hz, 1H), 3.58 (dd, J = 11.4, 7.9 Hz, 1H),
2.34 (br s, 2H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 137.8, 131.9, 129.4, 129.0, 127.6, 127.1, 71.4,
66.2 ppm.34
1-(4-Cyanophenyl)ethane-1,2-diol (2i): Colorless solid (0.02 g, 29%; n-hexane/ethyl acetate 3:1 as eluent);
1H{13C} NMR (400 MHz, Acetone-d6): δ = 7.95 – 7.89 (m, 2H), 7.58 – 7.52 (m, 2H), 7.43 (br s, 1H), 6.82
(dd, J = 17.7, 10.9 Hz, 1H), 6.61 (br s, 1H), 5.92 (dd, J = 17.7, 0.9 Hz, 1H), 5.34 (dd, J = 10.9, 0.9 Hz, 1H)
ppm; 13C{1H} NMR (100 MHz, Acetone-d6): δ = 168.6, 141.4, 137.3, 134.8, 128.9, 127.0, 116.2 ppm.2a
1-(3-Nitrophenyl)ethane-1,2-diol (2j): Colorless oil (0.02 g, 22%; n-hexane/ethyl acetate 3:1 as eluent);
1H{13C} NMR (400 MHz, Acetone-d6): δ = 8.31 (t, J = 2.0 Hz, 1H), 8.15 – 8.10 (m, 1H), 7.87 – 7.83 (m,
1H), 7.62 (t, J = 7.9 Hz, 1H), 4.93 – 4.86 (m, 1H), 4.76 (d, J = 4.0 Hz, 1H), 4.03 (t, J = 5.9 Hz, 1H), 3.75 –
13
3.61 (m, 2H) ppm; C{1H} NMR (100 MHz, Acetone-d6): δ = 149.1, 146.4, 133.6, 130.1, 122.7, 121.8,
74.1, 68.4 ppm.34
meso-Hydrobenzoin (2k): Colorless solid (0.1 g, 91%; n-hexane/ethyl acetate 3:1 as eluent); 1H{13C} NMR
13
(400 MHz, CDCl3): δ = 7.27 – 7.14 (m, 10H), 4.74 (s, 2H), 2.14 (s, 2H) ppm; C{1H} NMR (100 MHz,
CDCl3): δ = 139.8, 128.2, 128.1, 127.1, 78.1 ppm.14a
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1-Phenyl-1,2-propanediol (2l): White solid (0.07 g, 90%; n-hexane/ethyl acetate 3:1 as an eluent); 1H{13C}
NMR (400 MHz, CDCl3): δ = 7.37 – 7.25 (m, 5H), 4.33 (d, J = 7.5 Hz, 1H), 3.88 – 3.78 (m, 1H), 3.01 (br
6
7
8
13
s, 2H), 1.02 (d, J = 6.3 Hz, 3H) ppm; C{1H} NMR (100 MHz, CDCl3): δ = 140.1, 127.5, 127.1, 125.9,
9
78.5, 71.2, 17.7.14b
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3-Methyl-1-phenyl-1,2-butanediol (2m): Colorless oil (0.07 g, 81%; n-hexane/ethyl acetate 3:1 as eluent);
1H{13C} NMR (400 MHz, CDCl3): δ = 7.38 – 7.28 (m, 5H), 4.62 (d, J = 6.3 Hz, 1H), 3.48 (t, J = 5.3 Hz,
1H), 2.75 (s, 1H), 2.33 (s, 1H), 1.65 – 1.57 (m, 1H), 0.95 (dd, J = 6.9, 3.6 Hz, 6H) ppm; 13C{1H} NMR (100
MHz, CDCl3): δ = 141.6, 128.5, 127.9, 126.6, 80.4, 75.1, 29.2, 20.1, 16.3 ppm.
1,2-Di-o-tolylethane-1,2-diol (2n): White solid (0.1 g, 80%; n-hexane/ethyl acetate 3:1 as eluent); 1H{13C}
NMR (400 MHz, CDCl3): δ = 7.61 – 7.59 (m, 2H), 7.22 – 7.09 (m, 4H), 6.92 – 6.90 (m, 2H), 4.95 (s, 2H),
3.02 (s, 2H), 1.65 (s, 6H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 138.0, 135.9, 130.2, 127.7, 127.2,
125.9, 74.6, 18.8 ppm.
2,3-Dihydro-1H-indene-1,2-diol (2o): Colorless solid (0.05 g, 74%; n-hexane/ethyl acetate 3:1 as eluent);
1H{13C} NMR (400 MHz, CDCl3): δ = 7.45 – 7.39 (m, 1H), 7.31 – 7.21 (m, 3H), 5.03 – 4.95 (m, 1H), 4.54
– 4.45 (m, 1H), 3.12 (dd, J = 16.3, 5.8 Hz, 1H), 2.95 (dd, J = 16.4, 3.6 Hz, 1H), 2.61 (br s, 1H), 2.52 (br s,
1H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 142.0, 140.1, 128.9, 127.2, 125.4, 125.1, 76.0, 73.5, 38.7
ppm.14a
1-(Methylsulfinyl)-4-vinylbenzene (2ps): Colorless solid (0.06 g, 76%; n-hexane/ethyl acetate 3:1
8:1 as
eluent); 1H{13C} NMR (400 MHz, CDCl3): δ = 7.63 – 7.60 (m, 2H), 7.57 – 7.52 (m, 2H), 6.74 (dd, J = 17.6,
10.9 Hz, 1H), 5.84 (dd, J = 17.6, 0.7 Hz, 1H), 5.37 (dd, J = 10.9, 0.7 Hz, 1H), 2.72 (s, 3H) ppm; 13C{1H}
NMR (100 MHz, CDCl3): δ = 144.8, 140.5, 135.7, 127.1, 123.8, 116.2, 44.0 ppm.35
1-(4-Ethynylphenyl)ethane-1,2-diol (2q): Colorless solid (0.02 g, 27%; n-hexane/ethyl acetate 3:1 as eluent);
1H{13C} NMR (400 MHz, CDCl3): δ = 7.49 (d, J = 7.8 Hz, 2H), 7.33 (d, J = 7.9 Hz, 2H), 4.82 (dd, J = 8.2,
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3.4 Hz, 1H), 3.75 (dd, J = 11.3, 3.5 Hz, 1H), 3.62 (dd, J = 11.3, 8.1 Hz, 1H), 3.08 (s, 1H), 2.52 (br s, 2H)
ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 141.2, 132.3, 126.0, 121.8, 83.3, 77.4, 74.3, 67.9 ppm.36
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2-Phenyl-1,2-propanediol (2r): Colorless oil (0.1 g, 64%; n-hexane/ethyl acetate 3:1 as eluent); H{13C}
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NMR (400 MHz, CDCl3): δ = 7.46 – 7.42 (m, 2H), 7.39 – 7.33 (m, 2H), 7.30 – 7.24 (m, 1H), 3.76 (dd, J =
11.1, 4.1 Hz, 1H), 3.60 (dd, J = 11.1, 7.7 Hz, 1H), 2.79 (s, 1H), 2.15 (dd, J = 7.9, 4.7 Hz, 1H), 1.51 (s, 3H)
ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 145.0, 128.4, 127.2, 125.1, 74.9, 71.1, 26.0 ppm.37
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2-Phenylprop-2-en-1-ol (3r): Colorless oil (0.02 g, 16%); H{13C} NMR (400 MHz, CDCl3): δ = 7.47 –
7.42 (m, 2H), 7.39 – 7.27 (m, 3H), 5.47 (s, 1H), 5.35 (d, J = 1.1 Hz, 1H), 4.55 (s, 2H), 1.64 (br s, 1H) ppm;
13C{1H} NMR (100 MHz, CDCl3): δ = 147.3, 138.5, 128.5, 128.0, 126.1, 112.6, 65.1 ppm.38
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2-p-Tolylpropane-1,2-diol (2s):White solid (0.1 g, 62%; n-hexane/ethyl acetate 3:1 as eluent); H{13C}
NMR (400 MHz, CDCl3): δ = 7.34 – 7.29 (m, 2H), 7.17 (d, J = 8.0 Hz, 2H), 3.74 – 3.68 (m, 1H), 3.56 (dd,
13
J = 11.5, 6.2 Hz, 1H), 3.02 (s, 1H), 2.58 (br s, 1H), 2.34 (s, 3H), 1.49 (s, 3H) ppm; C{1H} NMR (100
MHz, CDCl3): δ = 142.1, 136.8, 129.1, 125.1, 74.8, 71.0, 26.0, 21.0 ppm.39
2-(p-Tolyl)prop-2-en-1-ol (3s): Colorless oil (0.02 g, 16%); 1H{13C} NMR (400 MHz, CDCl3): δ = 7.38 –
7.33 (m, 2H), 7.17 (d, J = 8.0 Hz, 2H), 5.44 (s, 1H), 5.31 (q, J = 1.4 Hz, 1H), 4.53 (s, 2H), 2.36 (s, 3H), 1.62
13
(s, 1H) ppm; C{1H} NMR (100 MHz, CDCl3): δ = 147.1, 137.8, 135.6, 129.2, 125.9, 111.8, 65.1, 21.1
ppm.40
1-Phenylcyclohexane-1,2-diol (2t): White solid (0.1 g, 51%; n-hexane/ethyl acetate 3:1 as eluent); 1H{13C}
NMR (400 MHz, CDCl3): δ = 7.52 – 7.45 (m, 2H), 7.39 – 7.33 (m, 2H), 7.27 – 7.22 (m, 1H), 3.96 (ddd, J
= 11.2, 4.5, 2.6 Hz, 1H), 2.62 (d, J = 1.8 Hz, 1H), 1.90 – 1.78 (m, 3H), 1.76 – 1.58 (m, 4H), 1.56 – 1.48 (m,
1H), 1.45 – 1.32 (m, 1H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 146.4, 128.5, 127.0, 125.1, 75.8,
74.5, 38.5, 29.2, 24.4, 21.1 ppm.41
2-Phenyl-2-cyclohexen-1-ol (3t): White solid (0.03 g, 19%); 1H{13C} NMR (400 MHz, CDCl3): δ = 7.49 –
7.44 (m, 2H), 7.36 – 7.30 (m, 2H), 7.28 – 7.22 (m, 1H), 6.16 (dd, J = 4.7, 3.4 Hz, 1H), 4.73 – 4.69 (m, 1H),
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2.32 – 2.11 (m, 2H), 2.00 – 1.92 (m, 1H), 1.90 – 1.63 (m, 4H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ =
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140.2, 139.1, 128.7, 128.6, 127.1, 126.0, 65.5, 31.6, 26.1, 17.4 ppm.42
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1-hydroxy-1-hydroxymethyl-1,2,3,4-tetrahydronaphthalene (2u): White solid (0.1 g, 54%; n-hexane/ethyl
acetate 3:1 as eluent); 1H{13C} NMR (400 MHz, CDCl3): δ = 7.57 – 7.49 (m, 1H), 7.25 – 7.16 (m, 2H), 7.14
– 7.06 (m, 1H), 3.76 – 3.58 (m, 2H), 2.90 – 2.71 (m, 2H), 2.46 – 2.23 (m, 3H), 1.97 – 1.68 (m, 3H) ppm;
13C{1H} NMR (100 MHz, CDCl3): δ = 139.2, 137.7, 128.9, 127.7, 126.7, 126.3, 73.1, 69.1, 33.3, 29.7, 20.2
ppm.43
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1-Hydroxymethyl-3,4-dihydronaphthalene (3u): Colorless oil (0.04 g, 27%); H{13C} NMR (400 MHz,
CDCl3): δ = 7.37 – 7.33 (m, 1H), 7.25 – 7.14 (m, 3H), 6.12 (t, J = 4.5 Hz, 1H), 4.53 (s, 2H), 2.78 (t, J = 8.1
13
Hz, 2H), 2.37 – 2.28 (m, 2H), 1.51 (br s, 1H) ppm; C{1H} NMR (100 MHz, CDCl3): δ = 136.5, 136.1,
133.1, 127.8, 127.2, 127.1, 126.5, 122.8, 64.0, 27.9, 22.9 ppm.44
3-Methyl-2-phenylbutane-1,2-diol (2v): Colorless oil (0.12 g, 68%; n-hexane/ethyl acetate 3:1 as eluent);
1H{13C} NMR (400 MHz, CDCl3): δ = 7.44 – 7.32 (m, 4H), 7.29 – 7.23 (m, 1H), 3.98 (d, J = 11.2 Hz, 1H),
3.81 (d, J = 11.3 Hz, 1H), 2.66 (s, 1H), 2.11 – 1.97 (m, 1H), 1.61 (br s, 1H), 0.92 (d, J = 6.8 Hz, 3H), 0.75
(d, J = 6.9 Hz, 3H) ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 142.9, 128.2, 127.0, 126.2, 79.3, 68.4, 35.2,
17.4, 16.7 ppm.45
1-Cyclohexyl-1-phenylethane-1,2-diol (2w): White solid (0.15 g, 66%; n-hexane/ethyl acetate 3:1 as eluent);
1H{13C} NMR (400 MHz, CDCl3): δ = 7.42 – 7.31 (m, 4H), 7.28 – 7.22 (m, 1H), 3.96 (d, J = 10.9 Hz, 1H),
3.81 (dd, J = 11.2, 7.6 Hz, 1H), 2.72 (s, 1H), 1.85 – 1.54 (m, 6H), 1.47 – 1.38 (m, 1H), 1.28 – 0.9 (m, 5H)
ppm; 13C{1H} NMR (100 MHz, CDCl3): δ = 143.1, 128.1, 126.9, 126.2, 79.2, 68.1, 45.6, 27.2, 26.8, 26.6,
26.5, 26.3 ppm.45
Methylated ester intermediate (10t): White solid (0.06 g, 16%; n-hexane/ethyl acetate 16:1 as eluent);
1H{13C} NMR (400 MHz, CDCl3): (mixture of endo/exo) δ = 7.33 – 7.25 (m, 4H), 7.24 – 7.17 (m, 1H), 6.32
– 6.23 (m, 1H), 5.99 – 5.91 (m, 1H), 3.19 – 3.03 (s, 3H), 2.83 – 2.74 (m, 1H), 2.35 – 2.14 (m, 4H), 1.99 –
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1.62 (m, 5H), 1.52 – 1.17 (m, 5H), 1.06 – 0.96 (m, 1H) ppm; C{1H} NMR (100 MHz, CDCl3): (major
5
6
isomer) δ = 171.8, 171.4, 139.6, 135.0, 131.2, 128.3, 127.0, 125.6, 67.7, 61.2, 51.9, 43.4, 39.6, 38.9, 36.3,
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28.8, 27.7, 25.9, 25.1, 17.3 ppm.
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Ester intermediate (5t): White solid (0.17 g, 54%); 1H{13C} NMR (400 MHz, CDCl3): (mixture of endo/exo)
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δ = 7.50 – 7.15 (m, 5H), 5.42 – 5.13 (m, 1H), 2.57 – 1.64 (m, 10H), 1.54 – 0.22 (m, 10H) ppm; C{1H}
NMR (100 MHz, CDCl3): δ = 173.6, 173.6, 146.2, 146.1, 128.3, 128.3, 126.9, 126.8, 124.7, 124.6, 76.4,
75.9, 75.5, 75.4, 46.0, 45.8, 40.6, 40.2, 40.1, 39.9, 39.8, 39.6, 36.9, 31.7, 31.5, 29.0, 29.0, 27.4, 27.3, 24.5,
24.2, 24.2, 23.8, 21.1, 21.1 ppm. HRMS (ESI) m/z: [M + Na]+ calcd for C20H26O3Na 337.1774, found
337.1775.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI:
10.1021/acs.joc.xxx
Copies of H and 13C NMR spectra, X-ray crystallographic data for compound P5 (CIF), X-ray
1
crystallographic data for compound 10t (CIF), and copies of chiral HPLC chromatographs for compound
2a (PDF)
AUTHOR INFORMATION
Corresponding Author
*E-mail: prs@uni-giessen.de
ORCID
Peter R. Schreiner: 0000-0002-3608-5515
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was supported by the Justus Liebig University.
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