Practical one-pot sequence for the asymmetric synthesis of 1,2 diols from primary alcohols

Article abstract of DOI:10.1016/j.tetlet.2012.11.137

A practical one-pot three-step sequence is reported for the asymmetric synthesis of α-benzoyloxylated alcohols from primary alcohols. Good overall yields (36-52%) and enantioselectivities (91-94% e.e.) are obtained using a commercial organocatalyst in the key oxylation reaction. A simple modification in the protocol allows the formation of enantioenriched γ-benzoyloxylated α,β-unsaturated ester from alcohol. Synthetic utility has been harnessed to the easy preparation of (-)-γ-octalactone from hexan-1-ol.

Full text of DOI:10.1016/j.tetlet.2012.11.137

Accepted Manuscript
Practical one-pot sequence for the asymmetric synthesis of 1,2 diols from pri‐
mary alcohols
Philippe Hermange, François Portalier, Christine Thomassigny, Christine Greck
PII:
S0040-4039(12)02100-4
DOI:
http://dx.doi.org/10.1016/j.tetlet.2012.11.137
TETL 42233
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
12 October 2012
26 November 2012
28 November 2012
Please cite this article as: Hermange, P., Portalier, F., Thomassigny, C., Greck, C., Practical one-pot sequence for
the asymmetric synthesis of 1,2 diols from primary alcohols, Tetrahedron Letters (2012), doi: http://dx.doi.org/
10.1016/j.tetlet.2012.11.137
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Graphical Abstract
Practical One-Pot Sequence for the
Asymmetric Synthesis of 1,2 Diols from
Primary Alcohols
Leave this area blank for abstract info.
Philippe Hermange, François Portalier, Christine Thomassigny and Christine Greck

1
Tetrahedron Letters
journal homepage: www.elsevier.com
Practical one-pot sequence for the asymmetric synthesis of 1,2 diols from primary
alcohols.
Philippe Hermange, François Portalier, Christine Thomassigny and Christine Greck*
ILV- UMR CNRS 8180, Université de Versailles-St-Quentin en Yvelines, 45, avenue des Etats-Unis, 78035 Versailles Cedex, France.
Tel : +33 (0)139254474 ; Fax: +33 (0)139254452. E-mail: greck@chimie.uvsq.fr.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A practical one-pot three-step sequence is reported for the asymmetric synthesis of -
benzoyloxylated alcohols from primary alcohols. Good overall yields (36-52%) and
enantioselectivities (91-94% e.e.) are obtained using a commercial organocatalyst in the key
oxylation reaction.
A simple modification in the protocol allows the formation of
Available online
enantioenriched -benzoyloxylated ,-unsaturated ester from alcohol. Synthetic utility has been
harnessed to the easy preparation of (-)--octalactone from hexan-1-ol.
Keywords:
1,2-Diol
2009 Elsevier Ltd. All rights reserved.
TEMPO
Asymmetric benzoyloxylation
Electrophilic hydroxylation
Organocatalysis
One-pot sequence
Organocatalytic one-pot reactions have attracted much
attention in1the actual context of “Green Chemistry”, by avoiding
both purification procedures and metallic chemicals.1 This
strategy has become a new powerful tool for multi-step and total
syntheses, allowing rapid and stereoselective access to complex
structures from simple starting materials.2 The structural diversity
is often created from carbonyl compounds by an enamine or
iminium activation step, which is followed by the asymmetric
addition of various electrophiles or nucleophiles. Aldehydes
proved to be particularly versatile precursors in these processes
but are known to be sensitive to storage and to degrade in time.
Thus, their formation in situ prior to an organocatalysed
functionalisation would be highly desirable.3 Two strategies have
been recently described for such combination, both starting from
stable alcohols. Alexakis and Mazet reported the one-pot
isomerisation of allylic alcohols to aldehydes catalysed by an
iridium complex and their following organocatalysed-
functionalisation.4 Rueping et al described a ruthenium-based
oxidative system to generate aldehydes which were further
composed of an oxidation, an -oxylation and a subsequent
reduction (Scheme 1).
Scheme 1. One-pot strategy for asymmetric synthesis of
monoprotected 1,2-diols from primary alcohols.
The key step, consisting in the organocatalysed -oxylation of
aldehydes, led to the creation of the chiral centre.7 From the
various oxygen donors described for this reaction, we identified
the readily available and inexpensive benzoylperoxide8 (BPO) as
a suitable reagent. Recently Hayashi showed that a catalytic
amount of diphenylprolinol tert-butyldimethylsilyl ether (20 mol
%) allowed the benzoyloxylation of aldehydes with yield up to
78%.8c Maruoka described also the benzoyloxylation of
aldehydes in the presence of radical scavengers using 2-
tritylpyrrolidine (10 mol%) Indeed, the -acylation of 3-
phenylpropanal led to the product with a yield of 52% by adding
10 mol % of 2,2,6,6-tetramethyl-1-piperidinyl-oxyl (TEMPO).8a.
In our sequence, the choice of the oxidation conditions in the first
involved in
a
series of organocatalysed transformations.5
However, only propargylic and allylic alcohols were compatible
for this oxidation strategy.
In line with our interests on the organocatalysed asymmetric
-functionalisation of carbonyl compounds,6 we aimed to
develop the direct synthesis of monoprotected 1,2-diols from
primary alcohols. A one-pot three-step sequence was proposed,
———

2
Tetrahedron Letters
step was critical as by-products needed to be fully compatible
Scope of this methodology was explored, first demonstrating
that both enantiomers of 4a could be produced by using (S)- or
(R)-catalyst 5, leading to (S)-4a (52% yield, 94% e.e.) and (R)-
4a (49% yield, 93% e.e.) respectively (Table 2, entries 1 and 2).
Then, various primary alcohols were employed as starting
material. Similar results were observed with butan-1-ol 1b (50%
yield, 93% e.e., entry 3). Higher loadings of (S)-5 (20 mol %)
were needed to achieve the three-step sequence in correct yields
when the carbon chain length was increased. After this
modification, product 4c could be formed in 46% yield from
hexan-1-ol 1c with 94% of enantiomeric excess (entry 4).
Applying the same conditions to tetradodecan-1-ol 1d allowed to
secure 4d with a correct yield of 39% (entry 5). The one-pot
procedure also proved to be compatible with functionalities like
alkylchlorides (4e, 44% yield, entry 6), silylethers (4f, 41% yield,
entry 7) or alkenes. The latter one is illustrated with the synthesis
of 4g in 45% yield from oleyl alcohol 1g (entry 8). In all these
cases, e.e. values were maintained to a good level between 91%
and 93% (entries 6-8). Interestingly, such asymmetric induction
was also detected when an existing chiral center was present on
the -position of the starting alcohol. Indeed, using (S)-citronellol
1h with either (S)-5 or (R)-5 lead respectively to (2S,3S)-4h and
(2R,3S)-4h products with similar diastereoisomeric excess of
93% and 94% (entries 9 and 10).
In order to broaden the scope of the one-pot strategy in a
synthetically interesting new direction, olefination has been
considered in the last step. Wittig reaction has been typically
described as a powerful method to employ in situ carbonyl
compounds after alcohol oxidation3a or -oxylation.8c,12 The use
of two equivalents of methyl(triphenylphosphoranylidene)
acetate instead of NaBH4 in the third step was then attempted.
Direct formation of -benzoyloxylated ,-unsaturated esters 8a
and 8c was observed from 3-phenylpropan-1-ol 1a and hexan-1-
ol 1c (Scheme 2). Both yields (54% for 8a, 48% for 8c) and
enantioselectivities (respectively 94% and 95%) were similar to
these obtained for 4a and 4c (Table 2, entry 1 and 4).
with the following steps. Catalytic TEMPO in the presence of the
iodine(III) co-oxidant [bis(acetoxy)iodo]benzene (BAIB) in
dichloromethane was selected. This system is known for smooth
conversion of primary alcohols to aldehydes,9 and minimal
impact was expected from co-produced acetic acid and
iodobenzene on the subsequent steps. We assumed that the
benzoyloxylation reaction could be done in the presence of
TEMPO introduced in the previous oxidation step. A slight
excess of alcohol (1.1 equiv) has been used to ensure full
consumption of PhI(OAc)2 after the first reaction. Furthermore,
an in situ reduction by NaBH4 was envisaged, to afford directly
the desired and stable monoprotected 1,2-diol at the end of the
sequential addition. This simple three-step procedure would fully
satisfy the desired criteria: avoiding workups and purifications of
any aldehydes intermediates, and leading directly to the desired
monoprotected 1,2-diol from the primary alcohol.
Combination of the three steps in a single one-pot procedure
was attempted with 3-phenylpropan-1-ol 1a as a model substrate
and gave the desired product (S)-4a with good yield (49%) and
enantioselectivity (91%, Table 1, entry 1).10 The use of distilled
THF as solvent for the whole sequence allowed a slight increase
of both yield and enantiomeric excess (52% and 94%
respectively, entry 2). Equimolar mixture of BAIB and starting
material 1a in step one gave equivalent results (entry 3).
However, loading of the alcohol was maintained to 1.1
equivalent relative to PhI(OAc)2 to ensure full reproducibility.11
Lower activity was observed for catalyst (S)-6 similarly to
Maruoka’s result8a (40% yield, entry 4). Decreasing the
benzoylperoxide amount from 1.5 to 1.1 equivalent led to the
formation of (S)-4a with identical results (52% yield and 94%
e.e., entry 5) compared to entry 2. The introduction of 20 mol %
of catalyst (S)-5 did not improve the yield and selectivity (entry
6). Finally, (±)-4a was secured in a 57% yield with the racemic
version of Maruoka’s catalyst 78a (entry 7). Due to its commercial
availability in both enantiomeric forms, diphenylprolinol TMS-
ether 5 was preferred for the further experiments.
Finally, synthetic utility of such intermediates was
demonstrated by easy preparation from 8c of the naturally
occurring (S)--octalactone13 9. The three-step sequence includes
a palladium catalysed hydrogenation of the double bond, ester
hydrolysis and intramolecular esterification to give (S)-9 with an
overall yield of 68%. Configuration retention of the chiral centre
was confirmed by optical rotation ([]D -43.1, c 0.8 in MeOH)
and comparison to the literature ([]D -47.1, c 1.0 in MeOH).13b
Table 1. Optimisation of the Oxidation/-Benzoylation/Reduction
sequence.
Entry Solvent
BPO (equiv)
Cat. Yielda (%) e.e.b (%)
1
2
CH2Cl2
THF
THF
THF
THF
THF
THF
1.5
1.5
1.5
1.5
1.1
1.1
1.1
(S)-5
(S)-5
(S)-5
(S)-6
(S)-5
(S)-5
(±)-7
49
52
50
40
52
52
57
91
94
94
92
94
94
0
3c
4
Scheme 2. Reagents and conditions: i) PhI(OAc)2 (1.0 equiv, 0.25 mmol),
TEMPO (10 mol %), 1a or 1c (1.1 equiv) in THF (1.5 mL), rt, 16h; ii) BPO
(1.1 equiv), (S)-5 (10 or 20 mol %) in THF (0.5 mL), rt, 5h; iii) Ph3P=CH-
CO2Me (2 equiv), rt, 16h; iv) Pd/C (10 wt. %), H2 (1 atm), EtOH, rt, 2h; v)
KOH (2M), 90°C, 18h; vi) HCl (6M), 90°C, 2h. a Purified yield. b Determined
by 1H NMR analysis. c Determined by HPLC analysis.
5
6d
7
Reagents and conditions: i) PhI(OAc)2 (1.0 equiv, 0.25 mmol), TEMPO (10
mol %), 1a (1.1 equiv) in solvent (1 mL), rt, 16h; ii) BPO (n equiv), Catalyst
(10 mol %) in THF (1 mL), rt, 5h; iii) NaBH4 (4 equiv), rt, 16h.
a Purified yield.
b Determined by HPLC analysis.
c 1.0 equiv of 1a.
d 20 mol % of (S)-5.

3
Table 2. Scope of the Oxydation/-Benzoyloxylation/Reduction sequence
Entry
1
Alcohol
Catalyst (Loading)
Product
Yielda (%)
52
e.e.b (%)
94
(S)-5 (10 mol %)
1a
1a
(S)-4a
(R)-4a
2
(R)-5 (10 mol %)
49
93
3
4
5
6
7
(S)-5 (10 mol %)
(S)-5 (20 mol %)
(S)-5 (20 mol %)
(S)-5 (20 mol %)
(S)-5 (20 mol %)
50
46
39
44
41c
93
94
91
93
91
1b
1c
1d
(S)-4b
(S)-4c
(S)-4d
(S)-4e
1e
1f
(S)-4f
(S)-4g
8
(S)-5 (20 mol %)
(S)-5 (20 mol %)
45d
36
92
1g
9e
(93% d.e.)
(S)-1h
(2S,3S)-4h
10e
(R)-5 (20 mol %)
20
(94% d.e.)
(S)-1h
(2R,3S)-4h
Reagents and conditions: i) PhI(OAc)2 (1.0 equiv, 0.25 mmol), TEMPO (10 mol %), 1a-h (1.1 equiv) in THF in (1.5 mL), rt, 16h; ii) BPO (1.1 equiv), 5
(x mol %) in THF (0.5 mL), rt, 5h; iii) NaBH4 (4 equiv), rt, 16h.
a Isolated yield.
b Determined by HPLC analysis.
c Isolated with 16 wt. % of 1e.
d Isolated with 20 wt. % of 1g
e BPO (1.5 equiv), CH2Cl2/THF:1/1.
J.; Williams, J. M. J. Adv. Synth. Catal. 2008, 350, 1975-1978. (d)
Kim, H.; Park, Y.; Hong, J.; Kim, H.; Park, Y.; Hong, J. Angew.
Chem., Int. Ed. 2009, 48, 7577-7581. (e) Davi, M.; Lebel, H. Org.
Lett. 2009, 11, 41-44. (f) Brioche, J.; Masson, G.; Zhu, J. Org.
Lett. 2010, 12, 1432-1435.
In conclusion, an easy synthesis of enantioenriched -
benzoyloxylated alcohols via a one-pot three-step sequence has
been described. These monoprotected 1,2-diols were formed
from the corresponding primary alcohol with good overall yields
(up to 52%) and enantioselectivities (>91% e.e.). The procedure
offers numerous practical advantages: no manipulation of often
unstable aldehydes is needed and a simple sequential addition at
room temperature is realised using commercial catalysts and
reagents. Modification of the last step allowed the direct
formation of -benzoyloxylated ,-unsaturated esters, which
synthetic utility harnessed by the expedient transformation of (S)-
8c into (S)--octalactone 9 with a good overall yield (68%).
4. Quintard, A.; Alexakis, A.; Mazet, C. Angew. Chem., Int. Ed.
2011, 50, 2354-2358.
5. (a) Rueping, M.; Sundén, H.; Hubener, L.; Sugiono, E. Chem.
Commun. 2012, 48, 2201-2203. (b) Rueping, M.; Dufour, J.; Maji,
M. S. Chem. Commun. 2012, 48, 3406-3408. (c). Rueping, M;
Sundén, H.; Sugiono, E. Chem. Eur. J. 2012, 18, 3649-3653.
6. (a) Thomassigny, C.; Prim, D.; Greck, C. Tetrahedron Lett. 2006,
47, 1117-1119. (b) Ait-Youcef, R.; Kalch, D.; Moreau, X.;
Thomassigny, C.; Greck, C. Lett. Org. Chem. 2009, 6, 377-380.
(c) Kalch, D.; Ait-Youcef, R.; Moreau, X.; Thomassigny, C.;
Greck, C.Tetrahedron: Asymmetry 2010, 21, 2302-2306. (d)
Desmarchelier, A.; Marrot, J.; Moreau, X.; Greck, C. Org. Biomol.
Chem. 2011, 9, 994-997. (e) Desmarchelier, A.; Yalgin, H.;
Coeffard, V.; Moreau, X.; Greck, C. Tetrahedron Lett. 2011, 52,
4430-4432. (f) Coeffard, V.; Desmarchelier, A.; Morel, B.;
Moreau, X.; Greck, C. Org. Lett. 2011, 13, 5778-5781. (g) Colin,
O.; Hermange, P.; Thomassigny, C.; Greck, C. Tetrahedron Lett.
2012, 53, 1085-1088.
References and notes
1. For recent reviews see: (a) Albrecht, Ł.; Jiang, H.; Jørgensen, K.
A. Angew. Chem. Int. Ed. 2011, 50, 8492-8509. (b) Patil, N. T.;
Shinde V. S.; Gajula, B. Org. Biomol. Chem. 2012, 10, 211-224.
(c) Wende R. C.; Schreiner, P. R. Green Chem. 2012, 14, 1821-
1849.
7. For a review see: (a) Vilaivan, T.; Bhanthumnavin, W. Molecules,
2010, 15, 917-958. For representative examples, see: With
nitrosobenzene: (b) Hayashi, Y.; Yamaguchi, J.; Hibino, K.; Shoji,
M. Tetrahedron Lett. 2003, 44, 8293-8296. (c) Brown, S. P.;
Brochu, M. P.; Sinz, C. J.; MacMillan, D. W. C. J. Am. Chem.
Soc. 2003, 125, 10808-10809. (d) Zhong, G. Angew. Chem. Int.
Ed. 2003, 42, 4247-4250. With N-sulfonyloxaziridine: (e) Tong,
S.-T.; Brimble, M. A.; Barker, D. Tetrahedron 2009, 65, 4801-
4807. With o-quinone: (f) Hernandez-Juan, F. A.; Cockfield, D.
M.; Dixon, D. J. Tetrahedron Lett. 2007, 48, 1605-1608. With O2:
2. For a review, see: (a) Grondal, C.; Jeanty, M.; Enders, D. Nature
Chem. 2010, 2, 167-178. For a recent example, see: (b) Ishikawa,
H.; Suzuki, T.; Hayashi, Y. Angew. Chem. Int. Ed. 2009, 48, 1304-
1307. (c) Ishikawa, H.; Suzuki, T.; Orita, H.; Uchimaru, T.;
Hayashi, Y.Chem. Eur. J. 2010, 16, 12616-12626.
3. For a review on tandem alcohol oxidation processes with MnO2,
see: (a) Taylor, R. J. K.; Reid, M.; Foot, J.; Raw, S. A. Acc. Chem.
Res. 2005, 38, 851-869. For selected examples of one-pot alcohol
oxidation processes, see: (b) Ngouansavanh, T.; Zhu, J. Angew.
Chem. Int. Ed. 2006, 45, 3495-3497. (c) Hall, M. I.; Pridmore, S.

4
Tetrahedron
(g) Córdova, A.; Sundén, H.; Engqvist, M.; Ibrahem, I.; Casas, J.
J. Am. Chem. Soc. 2004, 126, 8914-8915. (g) Ibrahem, I.; Zhao,
G.-L; Sundén, H.; Córdova, A. Tetrahedron Lett. 2006, 47, 4659-
4663.
8. For asymmetric organocatalysed -benzoyloxylations, see: (a) Kano,
T.; Mii, H.; Maruoka, K. J. Am. Chem. Soc. 2009, 131, 3450-
3451. (b) Vaismaa, M. J. P.; Chak Yau, S.; Tomkinson, N. C. O.
Tetrahedron Lett. 2009, 50, 3625-3627. (c) Gotoh, H.; Hayashi, Y.
Chem. Commun. 2009, 3083-3085. (d) Lifchits, O.; Demoulin, N.;
List, B. Angew. Chem. Int. Ed. 2011, 50, 9680-9683. (e) Zhang,
Z.; Zheng, W.; Antilla, J. C. Angew. Chem. Int. Ed. 2011, 50,
1135-1138. (f) Jadhav, M. S.; Righi, P.; Marcantoni, E.;
Bencivenni, G. J. Org. Chem. 2012, 77, 2667-2674.
9. De Mico, A.; Margarita, R.; Parlanti, L.; Vescovi, A.; Piancatelli, G
J. Org. Chem. 1997, 62, 6974-6977.
10. Applying to 1a only steps i and ii of Table 1 lead to 3a in 51%
yield. Applying to 2a (in CH2Cl2) steps ii and iii of Table 1 lead to
4a in 18% yield (91% e.e.). Addition of TEMPO (10 mol %) in
the previous conditions increased the yield of 4a to 48% (90%
e.e.) from 2a.
11. Yield of 4a decreased when second step reactants were introduced
without total PhI(OAc)2 consumption.
12. For recent examples see: (a) Kondekar, N. B.; Kumar, P. Org.
Lett. 2009, 11, 2611-2614. (b) Jha, V.; Kondekar, N. B.; Kumar,
P. Org. Lett. 2010, 12, 2762-2765. (c) Devalankar, D. A.;
Chouthaiwale, P. V.; Sudalai, A. Tetrahedron: Asymmetry 2012,
23, 240-244.
13. (a) Ravid, U.; Silverstein, R. M.; Smith, L. R. Tetrahedron 1978,
34, 1449-1452 and references therein. (b) Yang, H.; Kim, S.
Synlett 2008, 4, 555-560.
Supplementary material
Supplementary material associated with this article can be
found in the online version.