Molybdenum-catalyzed diastereoselective anti-dihydroxylation of secondary allylic alcohols

Article abstract of DOI:10.1021/acs.orglett.9b00735

In this protocol, we report a Mo-catalyzed anti-dihydroxylation of secondary allylic alcohols, providing a general method for the preparation of 1,2,3-triols bearing up to three continuous stereocenters with excellent diastereocontrol. The mechanistic studies reveal that this dihydroxylation reaction consists of two steps and up to excellent diastereomeric ratios of the final triol products can be achieved due to the high level of both diastereocontrol in the initial epoxidation and regiocontrol in the following hydrolysis in situ.

Full text of DOI:10.1021/acs.orglett.9b00735

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Molybdenum-Catalyzed Diastereoselective anti-Dihydroxylation of
Secondary Allylic Alcohols
Shixia Su and Chuan Wang*
Hefei National Laboratory for Physical Science at the Microscale, Department of Chemistry, Center for Excellence in Molecular
Synthesis, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China
S
* Supporting Information
ABSTRACT: In this protocol, we report a Mo-catalyzed anti-
dihydroxylation of secondary allylic alcohols, providing a general
method for the preparation of 1,2,3-triols bearing up to three
continuous stereocenters with excellent diastereocontrol. The
mechanistic studies reveal that this dihydroxylation reaction
consists of two steps and up to excellent diastereomeric ratios of
the final triol products can be achieved due to the high level of
both diastereocontrol in the initial epoxidation and regiocontrol
in the following hydrolysis in situ.
1,2,3-Triols are a characteristic structural motif contained in a
large number of naturally occurring compounds ranging from
sugars to polyketides.1 Conventionally, 1,2,3-triols bearing
three stereogenic centers are synthesized through diastereose-
lective addition of a carbon-centered nucleophile to a carbonyl
moiety bearing two adjacent hydroxylated stereocenters.2 On
the other side, as a plethora of methods have been established
for the synthesis of chiral secondary allylic alcohols in a highly
enantioselective manner,3 the diastereoselective dihydroxyla-
tion of enantioenriched secondary allylic alcohols also provides
an alternative access to optically active 1,2,3-triols. Although
Os-catalyzed syn-dihydroxylation of alkenes has proven to be
very successful for a wide range of substrates,4−6 only moderate
to good diastereoselectivities could be obtained for dihydrox-
ylation of secondary allylic alcohols.7 Excellent results can be
achieved only when an overstoichiometric amount of OsO4 is
employed in the presence of TMEDA as a ligand.8 However,
the toxicity, volatility, and high cost of OsO4 limit the use of
this method in the synthesis of 1,2,3-triols (Scheme 1A). Very
recently, our group reported a Mo-catalyzed proximal selective
direct anti-dihydroxylation of allylic alcohols bearing at least
two olefinic units.9,10 As a continuation of our interest in this
area, we envisage that a diastereoselective anti-dihydroxylation
of secondary allylic alcohols could also be achieved under the
catalysis of molybdenum using environmentally benign hydro-
gen peroxide as the oxidant (Scheme 1B). The challenge of
this reaction lies in not only the diastereocontrol of the initial
epoxidation but also the regiocontrol of the following ring
opening reaction. The lack of control in either of these two
elementary steps will lead to low diastereomeric ratios of the
final products.
For optimization of the reaction conditions, we used racemic
(E)-hept-3-en-2-ol [( )-1a] as the standard substrate (Table
1), which is a very challenging substrate for achieving high
diastereocontrol due to the weak steric effect of the small
methyl group. Initially, we performed the reaction under the
optimum conditions for dihydroxylation of simple primary
allylic alcohols using MoO2(acac)2 as the catalyst and MeCN
as the solvent (entry 1).9 The desired triol was afforded as a
mixture of anti/anti-isomer ( )-2a and syn/anti-isomer
( )-2a′ after reductive workup with Ph2S in an excellent
yield, but the diastereoselectivity of this reaction was very low.
Further screening of solvents and other Mo, V, and W salts as
catalysts failed to deliver significantly improved results.11
Relying on our previous discovery that bishydroxamic acids
(BHA) can be employed as the ligand in Mo-catalyzed
dihydroxylation,9 we decided to explore the influence of BHA
ligands on the outcome of the diastereoselectivity of the
studied reaction. Next, several hydroxamic acids L1−L6 were
tested as ligands, and toluene was chosen as the solvent due to
the high solubility of the BHA ligands in it (entries 2−7,
respectively). In the case of monodentate N-hydroxy-N-
phenylbenzamide (L1) as the ligand, only traces of the
Scheme 1. Os-Catalyzed Diastereoselective syn-
Dihydroxylation of sec Allylic Alcohols (A) and Mo-
Catalyzed anti-Dihydroxylation of sec Allylic Alcohols (B)
Received: February 27, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b00735
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
respectively). Due to the low solubility of the BHA ligand
L6 in these two solvents, the inverse diastereoselectivity could
be attributed to the background reaction catalyzed by
MoO2(acac)2. Moreover, the impact of temperature on the
outcome of this reaction was investigated (entries 15−17).
Decreasing the temperature to 0 °C gave rise to a longer
reaction time to achieve the full consumption of the substrate
( )-1a and decreased diastereoselectivity (entry 15). An
improved result in terms of both efficiency and stereoselectivity
was achieved when the reaction was carried out at 38 °C (entry
16). Further increasing the reaction temperature to 50 °C
resulted in a lower diastereomeric ratio (entry 17). In the
absence of the BHA ligand L6, no desired reaction occurred in
toluene (entry 18).
Table 1. Ligands, Solvents, and Temperature Screening for
the Mo-Catalyzed anti-Dihydroxylation of (E)-Hept-3-en-2-
a
ol
With the optimum reaction conditions in hand, we started to
evaluate the substrate scope of this Mo-catalyzed anti-
dihydroxylation (Scheme 2). First, various disubstituted (E)-
allylic alcohols ( )-1a−q were employed as precursors
affording products ( )-2a, meso-2b, and ( )-2c−q, respec-
tively, in moderate to high yields. As expected, complete
diastereoselectivities were achieved in the most cases, when the
substitution at the C1 position is larger than a methyl group. It
is noteworthy that a series of functional groups were tolerated,
including alkyne [( )-1h], chloride [( )-1l], ester [( )-1m],
terminal olefin [( )-1k], alcohol [( )-1n], and ketone
[( )-1s]. Surprisingly, a complete loss of diastereocontrol
was observed in the case of disubstituted (Z)-allylic alcohols
( )-1t and ( )-1u as substrates. In contrast, the reactions
using terminal and trisubstituted allylic alcohols provided the
products ( )-2v−aa in moderate to complete diastereoselec-
tivities. Remarkably, the anti-products ( )-2y and ( )-2z were
formed predominantly in the case of monosubstituted and
1,2,2-trisubstituted olefins, whereas the generation of syn-
products ( )-2v−x and ( )-2aa was favored for the reactions
employing 1,1-disubstituted and 1,1,2-trisubstituted alkenes as
starting materials. These results demonstrate that a bulky
geminal substitution R3 (lager than H) gives rise to the
preference of formation of the syn-products. Furthermore,
cyclic allylic alcohols ( )-1ab−ae were also investigated as
precursors for this Mo−BHA-catalyzed reaction. In the case of
cyclohexenols 1ab−ad, the cis/trans-diastereomers 2ab−ad,
respectively, were furnished as the only products. The reaction
using cyclohept-2-en-1-ol [( )-1ae] as the substrate yielded a
triol ( )-2ae only in a moderately good diastereomeric ratio.
Moreover, a 5 mmol scale reaction using alcohol ( )-1b was
conducted providing the product meso-2b in a similar yield.
To demonstrate the crucial effect of the BHA ligand on the
diastereocontrol, we chose a panel of representative allylic
alcohols bearing different substitution patterns of the olefinic
unit and used them as precursors in the BHA-free
MoO2(acac)2-catalyzed dihydroxylation (Scheme 2, results
shown in brackets). In the case of E-disubstituted, terminal,
and trisubstituted olefins, all of the BHA-free reactions
delivered the corresponding products ( )-2b, ( )-2w,
( )-2z, and meso-2aa with inverse diastereoselectivities. In
contrast, the reaction utilizing cyclic allylic alcohol ( )-1ab
furnished product ( )-2ab with the same preference of
stereochemistry as the reaction involving a BHA ligand, albeit
with a lower selectivity. Interestingly, a good diastereomeric
ratio (dr of 91:9) was achieved under the BHA ligand-free
conditions for (Z)-allylic alcohol ( )-1t, which turned out to
be an unsuccessful substrate in the Mo−BHA catalytic system.
Encouraged by this result, we decided to optimize the reaction
b
c
entry
ligand
solvent
t (h)
yield (%)
( )-2a:( )-2a′
1
2
3
4
5
6
7
8
−
MeCN
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
DCE
EtOAc
tBuOH
CyH
MeCN
toluene
toluene
toluene
toluene
14
14
14
14
14
14
14
14
14
14
14
14
14
14
96
12
4
90
33:67
d
L1
L2
L3
L4
L5
L6
L7
L8
L6
L6
L6
L6
L6
L6
L6
L6
−
trace
trace
trace
17
trace
85
53
29
76
45
27
75
39
90
88
92
0
nd
nd
nd
d
d
40:60
d
nd
91:9
88:12
82:18
88:12
75:25
45:55
90:10
40:60
86:14
92:8
9
10
11
12
13
14
e
15
f
16
g
17
86:14
−
18
12
a
Unless otherwise specified, reactions were performed on a 0.25
mmol scale of allylic alcohol ( )-1a using 2.5 equiv of 35% aqueous
H2O2, 10 mol % MoO2(acac)2, and 12 mol % ligand in 1.0 mL of
toluene at 34 °C for 14 h. Yields of the isolated product after column
chromatography. Determined by H NMR spectroscopy after flash
chromatography. Not determined. Reaction temperature of 0 °C.
Reaction temperature of 38 °C. Reaction temperature of 50 °C.
b
c
1
d
e
f
g
product were obtained (entry 2). When bidentate BHA L2−
L6 deriving from ethylenediamine were utilized, in the most
cases the reactions also provided the product in very low yields
(entries 3−7, respectively). An exception was observed in the
reaction using BHA L6 as the ligand, and in this case, the
product ( )-2a was furnished in high yield and diastereose-
lectivity (entry 7), which was notably the inverse of the result
obtained under ligand-free conditions. The high efficiency of
this reaction might be attributed to the extreme bulkiness of
L6, which could prevent the coordination of a second L6 to
the Mo center rendering a free site for activation of the
substrate. Furthermore, we performed the reactions using BHA
L7 and L8 as ligands, and the results revealed that both
efficiencies and stereoselectivities diminished with an increase
in distance between two hydroxamic moieties of the ligands
(entries 8 and 9, respectively). Subsequently, a brief solvent
screening was carried out, and no better result was obtained
(entries 10−14). In MeCN and tBuOH, the syn/anti-isomer
was formed as the major product (entries 12 and 14,
B
DOI: 10.1021/acs.orglett.9b00735
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 2. Evaluation of the Substrate Scope of the Mo−BHA-Catalyzed anti-Dihydroxylation of Secondary Allylic
a−c
Alcohols12,
a
Unless otherwise specified, reactions were performed on a 0.25 mmol scale of allylic alcohols 1 using 2.5 equiv of 35% aqueous H2O2, 10 mol %
MoO2(acac)2, and 12 mol % L6 in 1.0 mL of toluene. Reaction temperatures of 34 °C for 2v, 2z, and 2ab; 38 °C for 2a, 2b, 2t, 2aa, and 2ac−ae;
and 40 °C for 2c−s, 2u, and 2w−y. Reaction times of 6 h for 2k; 12 h for 2a, 2f, and 2h; 14 h for 2b, 2c, 2i, 2l, 2m, 2q, 2t−v, 2x−z, and 2ab−ae;
b
c
16 h for 2w and 2aa; and 18 h for 2d, 2e, 2g, 2j, 2o, 2p, and 2r. Yields of the isolated products after column chromatography. The diastereomeric
d
1
ratios were determined by H NMR spectroscopy after flash chromatography. The reaction was performed on a 5 mmol scale of racemic allylic
alcohol ( )-1b. Reactions were performed under ligand-free conditions: 10 mol % MoO2(acac)2 as the catalyst in 1 mL of MeCN at 34 °C for 14
e
f
h. Enantiopure precursor 1ad was employed.
conditions for the (Z)-allylic alcohols.11 After systematic
screening of catalysts, solvents, and temperatures, the best
outcome concerning diastereoselectivity was achieved for the
catalysis of molybdic acid with acetonitrile as the solvent at 30
°C. Under these conditions, a variety of (Z)-allylic alcohols
( )-1t, ( )-1u, and ( )-1af−ai were subjected to the anti-
dihydroxylation reaction, furnishing the triols with the syn/syn-
configuration, mostly in high to complete diastereoselectivities
(Scheme 3). The relatively low diastereoselectivity of ( )-2af
could be attributed to the OH moiety in the homoallylic
position undermining the orienting effect of the allylic alcohol.
By employing our Mo-catalyzed diastereoselective anti-
dihydroxylation as a key step, we completed a five-step
synthesis of benzyl-protected 2-deoxy allonic acid 2aj in
excellent stereoselectivity (dr of >99:1, 96% ee) starting from
commercially available (Z)-but-2-en-1,4-diol and ethyl acetate
(Scheme 4).13 Notably, a high enantiospecificity was achieved
in this Mo-catalyzed dihydroxylation. In addition, during the
progress of dihydroxylation, the hydrolysis of the ester moiety
occurred, which is possibly directed by the β-hydroxyl group,
because no hydrolyzed product was formed in the case of
( )-2m.
Subsequently, several control experiments were conducted
for mechanistic purposes (Scheme 5). First, the crucial
directing effect of the allylic hydroxyl group was confirmed,
because protecting it with methyl led to the complete
shutdown of the dihydroxylation reaction (Scheme 5A).
Furthermore, we noticed the formation of a certain amount
of epoxides in the beginning phase of the Mo-catalyzed
dihydroxylation, indicating this reaction might consist of two
stages, which are the initial epoxidation and the subsequent
hydrolysis. To verify this, we quenched the Mo−BHA-
catalyzed reaction employing (E)-allylic alcohol ( )-1b after
2 h, providing both triol meso-2b and anti-epoxide ( )-2b-1 in
diastereomerically pure form (Scheme 5B). Next, isolated anti-
epoxide ( )-2b-1 was subjected to the standard reaction
conditions yielding triol meso-2b in a diastereomeric ratio of
>99:1 (Scheme 5C). Notably, in the absence of the Mo salt, no
C
DOI: 10.1021/acs.orglett.9b00735
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 3. Evaluation of the Substrate Scope of the HMoO4-
Scheme 5. Control Experiments for the Mo-Catalyzed anti-
Dihydroxylation
Catalyzed anti-Dihydroxylation of Secondary (Z)-Allylic
a−c
Alcohols12,
a
Unless otherwise specified, reactions were performed on a 0.25
mmol scale of allylic alcohols 1 using 2.5 equiv of 35% aqueous H2O2
b
and 10 mol % H2MoO4 in 1.0 mL of MeCN. Yields of the isolated
products after column chromatography. The diastereomeric ratios
were determined by H NMR spectroscopy after flash chromatog-
c
1
raphy.
Scheme 4. Synthesis of Bn-Protected 2-Desoxy Alonic Acid
Using Mo−BHA-Catalyzed anti-Dihydroxylation as a Key
Step
diastereocontrol, a high level of enantiospecificity, and the use
of environmentally benign hydrogen peroxide as the oxidant.
The preliminary mechanistic investigations reveal that this
anti-dihydroxylation consists of an initial epoxidation and the
subsequent hydrolysis. Because of the high level of diastereo-
and regiocontrol in the epoxidation and hydrolysis, respec-
tively, the final triol products can be obtained in excellent
diastereomeric ratios.
ring opening reaction occurred, excluding the uncatalyzed
background reaction. This result confirms a Mo-catalyzed C3
selective ring opening in the hydrolysis step with complete
regioselectivity. In contrast, the reaction using (Z)-allylic
alcohol ( )-1t afforded triol ( )-2t and epoxide ( )-2t-1
both in a 1:1 diastereomeric mixture (Scheme 5D). In the case
of the BHA-free reaction, syn-epoxide ( )-2t-1 was formed as
the single diastereomer (Scheme 5E). In the subsequent
hydrolysis, the formation of a slight amount of the anti/syn-
product was observed, which is attributed to the imperfect
regioselectivity in this epoxide ring opening step (Scheme 5F).
Again, no ring opening product was formed when the reaction
was conducted without MoO2(acac)2.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b00735.
In conclusion, we developed a Mo-catalyzed diastereose-
lective anti-dihydroxylation of secondary allylic alcohols,
providing an efficient entry to 1,2,3-triols with up to three
continuous stereogenic centers. The Mo−BHA catalytic
system enables the highly diastereoselective dihydroxylation
of E-disubstituted, terminal, and trisubstituted alkenes, while
the ligand-free conditions using molybdic acid as the catalyst
allow the synthesis of 1,2,3-triols with the syn/syn-config-
uration with high diastereoselectivities. This reaction is
distinguished by a broad substrate scope, up to excellent
Representative experimental procedures and necessary
characterization data for all new compounds (PDF)
Accession Codes
CCDC 1866250−1866251 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
D
DOI: 10.1021/acs.orglett.9b00735
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Conditions. J. Am. Chem. Soc. 1976, 98, 1986−1987. (b) Cha, J. K.;
Christ, W. J.; Kishi, Y. On Stereochemistry of Osmium Tetroxide
Oxidation of Allylic Alcohol Systems: Empirical Rule. Tetrahedron
Lett. 1983, 24, 3943−3946. (c) Poli, G. The Osmylation of Flexible 3-
Substituted Cyclopentenes. Tetrahedron Lett. 1989, 30, 7385−7388.
(d) Wang, L.; Sharpless, K. B. Catalytic Asymmetric Dihydroxylation
of cis-Disubstituted Olefins. J. Am. Chem. Soc. 1992, 114, 7568−7570.
(e) Sharpless, K. B.; Amberg, W.; Bennani, Y. L.; Crispino, J.;
Hartung, K.-S.; Jeong, H.-L.; Kwong, K.; Morikawa, Z.-M.; Wang, G.
A.; Xu, D.; Zhang, X.-L. The Osmium-Catalyzed Asymmetric
Dihydroxylation: A New Ligand Class and a Process Improvement.
J. Org. Chem. 1992, 57, 2768−2771. (f) VanNieuwenhze, M. S.;
Sharpless, K. B. The Asymmetric Dihydroxylation of cis-Allylic and
Homoallylic Alcohols. Tetrahedron Lett. 1994, 35, 843−846. (g) Xu,
D.; Park, C. Y.; Sharpless, K. B. Study of the Regio- and
Enantioselectivity of the Reactions of Osmium Tetroxide with Allylic
Alcohols and Allylic Sulfonamides. Tetrahedron Lett. 1994, 35, 2495−
2498. (h) Becker, H.; Soler, M. A.; Sharpless, K. B. Selective
Asymmetric Dihydroxylation of Polyenes. Tetrahedron 1995, 51,
1345−1376. (i) Corey, E. J.; Noe, M. C.; Guzman-Perez, A. Kinetic
Resolution by Enantioselective Dihydroxylation of Secondary Allylic
4-Methoxybenzoate Esters Using a Mechanistically Designed
Cinchona Alkaloid Catalyst. J. Am. Chem. Soc. 1995, 117, 10817−
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: chuanw@ustc.edu.cn.
ORCID
Chuan Wang: 0000-0002-9219-1785
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work is supported by “1000-Youth Talents Plan” start-up
funding, the National Natural Science Foundation of China
(Grant 21772183), the Fundamental Research Funds for the
Central Universities (WK2060190086), and the University of
Science and Technology of China.
REFERENCES
■
(1) (a) Davies-Coleman, M. T.; Rivett, D. E. A. Stereochemical
studies on boronolide, an α-pyrone from Tetradenia barberae.
Phytochemistry 1987, 26, 3047−3050. (b) Feige, G. B.; Lumbsch,
H. T.; Huneck, S.; Elix, J. A. Identification of Lichen Substances by a
Standardized High-Performance Liquid Chromatographic Method. J.
Chromatogr. 1993, 646, 417. (c) Angata, T.; Varki, A. Varki, Chemical
Diversity in the Sialic Acids and Related α-Keto Acids: An
Evolutionary Perspective. Chem. Rev. 2002, 102, 439−470. (d) Kiefel,
M. J.; von Itzstein, M. Recent Advances in the Synthesis of Sialic Acid
Derivatives and Sialylmimetics as Biological Probes. Chem. Rev. 2002,
102, 471−490. (e) Fleming, D. M. Zanamivir in the treatment of
Influenza. Expert Opin. Pharmacother. 2003, 4, 799−805. (f) Li, S.;
Hui, X.-P.; Yang, S.-B.; Jia, Z.-J.; Xu, P.-F.; Lu, T.-J. A Straightforward
Route to the Asymmetric Synthesis of 3, 4-Diepipolyoxamic Acid and
its Isomers. Tetrahedron: Asymmetry 2005, 16, 1729−1731.
̈
10824. (j) Dobler, C.; Mehltretter, G. M.; Sundermeier, U.; Beller, M.
Osmium-Catalyzed Dihydroxylation of Olefins Using Dioxygen or Air
as the Terminal Oxidant. J. Am. Chem. Soc. 2000, 122, 10289−10297.
(k) Dupau, P.; Epple, R.; Thomas, A. A.; Fokin, V. V.; Sharpless, K. B.
Osmium-Catalyzed Dihydroxylation of Olefins in Acidic Media: Old
Process, New Tricks. Adv. Synth. Catal. 2002, 344, 421−433.
(l) Ahmed, M. M.; Berry, B. P.; Hunter, T. J.; Tomcik, D. J.;
O’Doherty, G. A. De Novo Enantioselective Syntheses of Galacto-
Sugars and Deoxy Sugars via the Iterative Dihydroxylation of
Dienoate. Org. Lett. 2005, 7, 745−748. (m) Robinson, T. V.;
Taylor, D. K.; Tiekink, E. R. T. Osmium Catalyzed Dihydroxylation of
1,2-Dioxines: A New Entry for Stereoselective Sugar Synthesis. J. Org.
́
Chem. 2006, 71, 7236−7244. (n) Csatayova, K.; Davies, S. G.; Lee, J.
́
(g) Dubost, C.; Marko, I. E.; Ryckmans, T. Org. Lett. 2006, 8,
A.; Roberts, P. M.; Russell, A. J.; Thomson, J. E.; Wilson, D. L. Highly
Diastereoselective and Stereodivergent Dihydroxylations of Acyclic
Allylic Amines: Application to the Asymmetric Synthesis of 3,6-
Dideoxy-3-amino-l-talose. Org. Lett. 2011, 13, 2606−2609.
(6) For a review of Os-free syn-dihydroxylation, see: Bataille, C. J. R.;
Donohoe, T. J. Osmium-free Direct syn-Dihydroxylation of Alkenes.
Chem. Soc. Rev. 2011, 40, 114−128.
5137−5140. (h) Dhage, G. R.; Thopate, S. R. Undemanding
Synthesis of Novel C19 and C17 Analogues of C18-Guggultetrol.
Synlett 2017, 28, 970−972.
(2) (a) Dixon, D. J.; Foster, A. C.; Ley, S. V. A Short and Efficient
Stereoselective Synthesis of the Polyhydroxylated Macrolactone
́
(+)-Aspicilin. Org. Lett. 2000, 2, 123−125. (b) Gulea, M.; Lopez-
Romero, J. M.; Fensterbank, L.; Malacria, M. 1,4-Hydrogen Radical
Transfer as a New and Versatile Tool for the Synthesis of
Enantiomerically Pure 1,2,3-Triols. Org. Lett. 2000, 2, 2591−2594.
(c) Dixon, D. J.; Krause, L.; Ley, S. V. Rapid Assembly of anti,anti-
1,2,3-Triol Motifs via Stereoselective Addition of Organometallics to
Aldehydes Obtained from (R′,R′,S,R)-2,3-Butane Diacetal Protected
Butanetetraol Derivative. J. Chem. Soc., Perkin. Trans. 2001, 1, 2516−
2518. (d) Enders, D.; Breuer, I.; Raabe, G. Asymmetric Synthesis of 2-
Keto-1,3-diols and Protected 1,2,3-Triols Bearing Two Quaternary
Stereocenters. Synthesis 2005, 2005, 3517−3530. (e) Enders, D.;
Herriger, C. Asymmetric Synthesis of 2-Trifluoromethyl-1,2,3-triols.
Eur. J. Org. Chem. 2007, 2007, 1085−1090. (f) Honda, M.;
Nakamura, T.; Sumigawa, T.; Kunimoto, K.-K.; Segi, M. Stereo-
selective Synthesis of 1,2,3-Triol Derivatives from α,β-Unsaturated
Acylsilanes. Heteroat. Chem. 2014, 25, 565−577. (g) Gati, W.;
Yamamoto, H. A Highly Diastereoselective “Super Silyl” Governed
Aldol Reaction: Synthesis of α,β-Dioxyaldehydes and 1,2,3-Triols.
Chem. Sci. 2016, 7, 394−399.
(7) Donohoe, T. J.; Waring, M. J.; Newcombe, N. J. Enhanced
Stereoselectivity in the Catalytic Dihydroxylation of Acyclic Allylic
Alcohols. Synlett 2000, 2000, 149−151.
(8) (a) Donohoe, T. J.; Moore, P. R.; Waring, M. J.; Newcombe, N.
J. The Directed Dihydroxylation of Allylic Alcohols. Tetrahedron Lett.
1997, 38, 5027−5030. (b) Donohoe, T. J.; Newcombe, N. J.; Waring,
M. J. syn Stereocontrol in the Directed Dihydroxylation of Acyclic
Allylic Alcohols. Tetrahedron Lett. 1999, 40, 6881−6885. (c) Dono-
hoe, T. J.; Blades, K.; Moore, P. R.; Waring, M. J.; Winter, J. J. G.;
Helliwell, M.; Newcombe, N. J.; Stemp, G. Directed Dihydroxylation
of Cyclic Allylic Alcohols and Trichloroacetamides Using OsO4/
TMEDA. J. Org. Chem. 2002, 67, 7946−7956. (d) Donohoe, T. J.
Development of the Directed Dihydroxylation Reaction. Synlett 2002,
2002, 1223−1232.
(9) Fan, P.; Su, S.; Wang, C. Molybdenum-Catalyzed Hydroxyl-
Directed Anti-Dihydroxylation of Allylic and Homoallylic Alcohols.
ACS Catal. 2018, 8, 6820−6826.
(10) For a review of anti-dihydroxylation, see: Wang, C. Vicinal anti-
Dioxygenation of Alkenes. Asian J. Org. Chem. 2018, 7, 509−521.
(11) For details of the optimization of the reaction conditions, see
pages 26−32 of the Supporting Information.
(12) For details of the determination of the relative configuration of
triol products, see pages 48−50 of the Supporting Information.
(13) Avi, M.; Gaisberger, R.; Feichtenhofer, S.; Griengl, H. De novo
Synthesis of Pentoses via Cyanohydrins as Key Intermediates.
Tetrahedron 2009, 65, 5418−5426.
(3) Lumbroso, A.; Cooke, M. L.; Breit, B. Catalytic Asymmetric
Synthesis of Allylic Alcohols and Derivatives and Their Applications
in Organic Synthesis. Angew. Chem., Int. Ed. 2013, 52, 1890−1932.
(4) For a review of Os-catalyzed syn-dihydroxylation, see: Kolb, H.
C.; VanNieuwenhze, M. S.; Sharpless, K. B. Catalytic Asymmetric
Dihydroxylation. Chem. Rev. 1994, 94, 2483−2547.
(5) For selected examples of Os-catalyzed syn-dihydroxylation, see:
(a) Sharpless, K. B.; Akashi, K. Osmium Catalyzed Vicinal
Hydroxylation of Olefins by tert-Butyl Hydroperoxide under Alkaline
E
DOI: 10.1021/acs.orglett.9b00735
Org. Lett. XXXX, XXX, XXX−XXX