(R)-2,3-cyclohexylideneglyceraldehyde, a chiral pool synthon for the synthesis of 2-azido-1,3-diols

Article abstract of DOI:10.1002/hlca.201400344

A new approach was proposed for the synthesis of 2-azido-1,3-diols from easily available and inexpensive chiral pool synthon (R)-2,3-O-cyclohexylidene-D-glyceraldehyde, through Mitsunobu azidation of 1,2-diols. Both C(2) and C(1) azides in variable ratios

Full text of DOI:10.1002/hlca.201400344

Helvetica Chimica Acta – Vol. 98 (2015)
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(R)-2,3-Cyclohexylideneglyceraldehyde, a Chiral Pool Synthon for the
Synthesis of 2-Azido-1,3-diols
by Abdul Rouf*, Mushtaq A. Aga, Brijesh Kumar, and Subhash C. Taneja*
CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu-180001, India
(e-mail: drsctaneja@gmail.com, sctaneja@iiim.ac.in, roufdr99@gmail.com)
A new approach was proposed for the synthesis of 2-azido-1,3-diols from easily available and
inexpensive chiral pool synthon (R)-2,3-O-cyclohexylidene-d-glyceraldehyde, through Mitsunobu
azidation of 1,2-diols. Both C(2) and C(1) azides in variable ratios were obtained in alkyl substituted
diols with C(2) as the major one.
Introduction. – 1,2-Azido alcohols are widely employed in organic synthesis as
versatile precursors for the preparation of 1,2-amino alcohols [1], amino acids [2],
aziridines [3], triazoles [4], 2-oxazolidinones [5], oxazines [6], and oxazolidines [7].
They are also useful intermediates for the preparation of several target compounds, like
carbohydrates/nucleosides [8], peptidomimetics [9], and pseudopeptides [10]. Besides,
organic azides are well known substrates in organic synthesis [11], widely applied in
click chemistry [12], and used as fluorescent probes [13]. Chiral 2-amino-1,3-diols,
which can be easily obtained from 2-azido-1,3-diols are the essential constituents of
antibiotics [14], antiviral glycosidase inhibitors [15], sphingolipids [15b][16], and
dihydrosphingosines [17].
A number of chemical methods exist in the literature for the synthesis of azido
alcohols, the most predominant one is the direct opening of epoxides [18], while other
methods involve the synthesis through solid phase approach [19], hydroazidation of
aldehydes [20], azidation from 1,2-diols [21], and regioselective azide substitution of
diols [22].
Herein, we report the development of an alternate and facile process for the
synthesis of 2-azido-1,3-diols as diastereoisomeric mixtures from commercially
available and inexpensive starting chiral pool, (R)-2,3-cyclohexylideneglyceraldehyde.
Recently, we have also successfully utilized cyclohexylideneglyceraldehyde for the
synthesis of the antidepressant drug reboxetine [23] and the antihypertensive
doxazosin [24].
Results and Discussion. – The synthesis of chiral 2-azido-1,3-diol, involves the
utilization of the commercially available and inexpensive sugar d-mannitol (1) as a
starting material, which possesses the desired chirality. The protection of d-mannitol
was accomplished with cyclohexanone in DMSO, with TsOH as a catalyst to form
1,2,5,6-di-O-cyclohexylidene-d-mannitol (2), which is stable and easy to handle. The
intermediate 2 was cleaved into (R)-2,3-O-cyclohexylidene-d-glyceraldehyde (3) by
ꢀ 2015 Verlag Helvetica Chimica Acta AG, Zürich

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scissoring with NaIO4 in Et2O/H2O in 95% yield [25]. The aldehyde 3, is an ideal
synthon and has multifarious advantages [26][25b], and it can be readily converted into
the target molecules.
Thus, Grignard reaction of aldehyde (R)-3 with various alkyl halides (such as
methyl, ethyl, propyl, butyl, pentyl, hexyl and decyl halides) in dry THF afforded a
mixture of syn- and anti-alkyl glycerol diastereoisomers 4a – 4g in 83 – 90% yield in
variable ratios. The diastereoisomeric products were inseparable by CC, therefore, the
mixture of diastereoisomers were directly used for further transformations. The OH
group of the Grignard product was protected by benzylation to form 5a – 5g, followed
by cyclohexylidene deprotection with TsOH in MeOH affording the diols 6a – 6g. The
diols 6a – 6g were finally converted into the respective azido alcohol regioisomers 7a –
7g and 8a – 8g via Mitsunobu azidation reaction [21b], using Ph3P, DIAD, and TMSN3
as a source of nucleophile in toluene as a solvent, followed by silyl deprotection under
acidic conditions (tetrabutylammonium fluoride, TBAF). It was observed that by
Mitsunobu azidation, the 2-azidoalcohols 7a – 7g were formed as the major products,
while the 1-azidoalcohols 8a – 8g were obtained as the minor products (Scheme 1).
Details of the reaction, the products, and the corresponding yields are given in the
Table.
Scheme 1. Synthesis of Azido Alcohols 7 and 8

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Table. Azido Alcohols Obtained during Mitsunobu Azidation
Entry
R
Product ratio 7: 8
Yield of 7 [%]
Total yield 7 þ 8 [%]
1
2
3
4
5
6
7
Me
Et
Pr
4 : 1
4 : 1
3 : 1
3 : 1
2 : 1
2 : 1
2 : 1
58
68
60
60
59
59
59
73
85
80
80
90
90
90
Bu
Pent
Hex
Dec
For the Mitsunobu azidation, various solvents, like CH2Cl2, THF, and toluene were
tested to optimize the formation of (2S,3RS)-2-azido-3-(benzyloxy)nonan-1-ol, where-
in toluene gave the best results.
In case of the aryl-substituted diols 9a and 9b, the azidation occurred regioselec-
tively at the primary OH group, probably due to steric hindrance (Scheme 2). In our
previous work, we have reported a methodology for a Mitsunobu chlorination. In that
work, we have explained that in sterically hindered diols (aryl-substituted diols) and
sugars, the nucleophilic substitution generally occurs regioselectively at the primary
OH group [23].
The azido alcohols can be easily transformed into azido acids by oxidation. The 2-
azidoalcohols 7f and 7g were oxidized to corresponding azido aldehydes (55 – 60%
yields) 11f and 11g by DessÀMartin periodinane oxidizing reagent and thereafter,
converted to the corresponding azido acids 12f and 12g by the oxidizing agent oxone
(KHSO5, potassium peroxomonosulfate) in DMF in 50 – 60% yields (Scheme 3).
Scheme 2. Synthesis of Azido Alcohols 10
Scheme 3. Synthesis of Azido Acids 12

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The mechanism of the regioselective substitution in diols, as proposed by Mathieu-
Pelta et al., occurs through the intermediacy of dioxaphospholanes [21]. The two
conformational isomeric dioxaphospholanes 13a and 13b formed by the reaction of 1,2-
diols with Ph3P and DIAD, undergo a rapid interconversion through pseudorotation.
The silylation at the more basic PÀO apical O-atom leads to the formation of
(silyloxy)phosphonium ions 15a and 15b and subsequent SN2 displacement of Ph3PO by
an azide ion affords the formation of the C(2) azido regioisomer 16a as the major
product with inversion of configuration and C(1) azido regioisomer 16b as the minor
product (Scheme 4). When the R group of the 1,2-diol is changed from Me to C10H21,
the regioselectivity (16a/16b ratio) decreases.
Scheme 4. Mechanism of Mitsunobu Azidation in Diols

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Figure. Possible applications of azido alcohols
These azido alcohols can be used as valuable synthetic intermediates for the
synthesis of a diversity of bioactive compounds, like amino alcohols, azido acids, azido
aldehydes, triazoles, sphingosines, peptides, etc., as summarized in the Figure.
Conclusions. – An efficient and new methodology has been developed for the
synthesis of 2-azido-1,3-diols as diastereoisomeric mixtures from the synthon (R)-
cyclohexylideneglyceraldehyde. In this methodology, the Mitsunobu reaction was
successfully used for the azidation of alkyl substituted diols affording the C(2) and C(1)
azides in variable ratios, while in the aryl substituted diols, the C(1) azide was
regioselectively formed.
The authors (A. R., M. A. A., and B. K.) thank CSIR and UGC, New Delhi for the award of senior
fellowships. The authors are declaring the institutional publication number IIIM/1618/2013.
Experimental Part
General. Reagents and solvents used were mostly Lab grade quality. Chemicals were purchased from
Aldrich Chemicals, Mumbai. All reactions under anh. conditions were carried out under N2 atmosphere
using freshly dried solvents. The org. extracts were dried over anh. Na2SO4. Silica gel-coated aluminum

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plates from Merck were used for TLC. Silica gel ¼ SiO2. CC ¼ column chromatography. IR Spectra:
PerkinElmer FT-IR spectrometer-Spectrum two. NMR Spectra: Bruker 400 and 500 MHz spectrometers
with TMS as the internal standard; chemical shifts are expressed in parts per million (d ppm). HR-MS:
Q-TOF LC/MS, Agilent Technologies 6540. The diastereoisomeric ratios were calculated on the basis of
NMR.
2,3-O-Cyclohexylidene-d-glyceraldehyde (¼(2R)-1,4-Dioxaspiro[4.5]decane-2-carbaldehyde; 3).
Sodium metaperiodate (NaIO4; 7.3 g) and 200 mg of tetrabutylammonium bromide (TBAB) in H2O
(60 ml) were added to a soln. of 10.0 g of 1,2,5,6-di-O-cyclohexylidene-d-mannitol (¼(1S,2S)-1,2-
di[(2R)-1,4-dioxaspiro[4.5]dec-2-yl]ethane-1,2-diol; 2) in Et2O (100 ml), and the mixture was stirred for
3 h at r.t. After the completion of the reaction, the org. layer was separated, and the aq. layer was
extracted with Et2O (3 Â 35 ml). The combined Et2O soln. was washed with H2O (1 Â 35 ml) and dried.
The solvent was evaporated under vacuum to give the title compound (R)-3 in 95% yield (19.0 g) as a
colorless viscous liquid. B.p. 90 – 948 (2 mm Hg) ([27]: 90 – 938 (2 mm Hg)). [a]2D5 ¼ þ61.2 (c ¼ 3.4,
benzene). 1H-NMR (500 MHz, CDCl3): 1.43 – 1.80 (m, 10 H); 3.90 – 4.22 (m, 2 H); 4.40 (m, 1 H); 9.7 (s,
1 H). 13C-NMR (125 MHz, CDCl3): 23.8; 25.0; 34.7; 36.2; 65.7; 98.4; 110.7; 202.2. HR-ESI-MS: 171.1019
([M þ H]þ, C9H15Oþ3 ; calc. 171.1016).
Grignard Reaction of Aldehyde 3 with Alkyl Halides, General Procedure. The alkyl bromides
(29.2 mmol, 4 equiv.) were added dropwise over 15 min at r.t. under N2 in the presence of a crystal of I2 to
Mg turnings (29.20 mmol, 4 equiv.) placed in a reaction vessel, comprising 60 ml anh. THF, while in the
case of alkyl iodides the reaction was carried out without I2. After the formation of the Grignard reagent
(indicated by warming of reaction vessel), the soln. was cooled to À 108 and cyclohexylideneglycer-
aldehyde (7.30 mmol, 1 equiv.) in THF (20 ml) was added dropwise to the mixture. The mixture was
stirred at r.t. for 18 h and then cooled to 08 before the addition of sat. aq. NH4Cl (30 ml). The soln. was
extracted three times with AcOEt (3 Â 40 ml), the org. layers were combined, dried, and the solvent
evaporated under reduced pressure. The crude products were purified by CC (SiO2; 0 – 15% AcOEt/
hexane) to provide a mixture of syn- and anti-diastereoisomers in 83 – 90%.
(2R,3RS)-1,2-Cyclohexylidenebutane-1,2,3-triol (¼1-[(2R)-1,4-dioxaspiro[4.5]dec-2-yl]ethanol; 4a):
syn/anti 1:1. Yield 83%. Colorless oil. IR (CHCl3): 950, 1060, 1120, 1180, 1290, 1340, 1380, 1460, 2948,
1
3450. H-NMR (400 MHz, CDCl3): 0.94 (d, J ¼ 6.8, 3 H); 1.32 – 1.80 (m, 10 H); 3.72 – 3.76 (m, 1 H);
3.77 – 4.23 (m, 3 H). 13C-NMR (125 MHz, CDCl3): 19.5; 22.6; 23.4; 37.5; 68.8; 69.4; 83.4; 109.9. HR-ESI-
MS: 209.1144 ([M þ Na]þ, C10H18NaO3þ ; calc. 209.1154).
(2R,3RS)-1,2-Cyclohexylidenepentane-1,2,3-triol (¼4,5-O-Cyclohexane-1,1-diyl-1,2-dideoxy-d-glyc-
ero-pentitol; 4b). syn/anti 1:1. Yield 84%. Transparent liquid. IR (CHCl3): 946, 1062, 1136, 1180, 1290,
1340, 1380, 1472, 2940, 3457. 1H-NMR (400 MHz, CDCl3): 1.00 (t, J ¼ 7.5, 3 H); 1.32 – 1.47 (m, 3 H); 1.48 –
1.72 (m, 9 H); 3.64 – 3.73 (m, 1 H); 3.80 – 3.91 (m, 1 H); 3.97 (dd, J ¼ 6.4, 7.8, 1 H); 4.04 (ddd, J ¼ 5.1, 8.4,
11.2, 1 H). 13C-NMR (125 MHz, CDCl3): 8.8; 22.8; 23.6; 23.8; 24.5; 33.5; 34.8; 63.2; 71.0; 76.8; 108.1. HR-
ESI-MS: 223.1300 ([M þ Na]þ, C11H20NaO3þ ; calc. 223.1310).
(2R,3RS)-1,2-Cyclohexylidenehexane-1,2,3-triol (¼1-[(2R)-1,4-Dioxaspiro[4.5]dec-2-yl]butan-1-ol;
4c). syn/anti 27:73. Yield 85%. Transparent liquid. IR (CHCl3): 955, 1056, 1130, 1180, 1280, 1336, 1380,
1460, 2950, 3453. 1H-NMR (400 MHz, CDCl3): 0.91 (dt, J ¼ 8.3 (for syn-isomer), 19.9 (for anti-isomer),
3 H); 1.26 (t, J ¼ 7.1, 1 H); 1.30 – 1.48 (m, 3 H); 1.49 – 1.72 (m, 10 H); 2.06 (s, OH); 3.75 – 3.84 (m, 1 H);
3.89 (t, J ¼ 7.6, 1 H); 3.95 (t, J ¼ 7.1, 1 H); 3.99 – 4.05 (m, 1 H). 13C-NMR (125 MHz, CDCl3): 13.3; 20.6;
21.8; 22.1; 32.2; 36.7; 65.1; 65.9; 79.7; 109.9. HR-ESI-MS: 237.1456 ([M þ Na]þ, C12H22NaO3þ ; calc.
237.1467).
(2R,3RS)-1,2-Cyclohexylideneheptane-1,2,3-triol (¼1-[(2R)-1,4-Dioxaspiro[4.5]dec-2-yl]pentan-1-
ol; 4d). syn/anti 9 :11. Yield 85%. Transparent liquid. IR (CHCl3): 950, 1060, 1130, 1180, 1285, 1340,
1
1380, 1460, 2950, 3450. H-NMR (400 MHz, CDCl3): 0.91 (t, J ¼ 6.5, 3 H); 1.24 – 1.75 (m, 16 H); 3.70 –
3.75 (m, 1 H); 3.84 – 3.87 (m, 1 H); 3.93 – 4.15 (m, 2 H). 13C-NMR (125 MHz, CDCl3): 10.8; 22.2; 23.8;
25.4; 27.9; 31.1; 36.3; 37.2; 67.5; 69.2; 80.1; 109.4. HR-ESI-MS: 251.1616 ([M þ Na]þ, C12H24NaO3þ ; calc.
251.1623).
(2R,3RS)-1,2-Cyclohexylideneoctane-1,2,3-triol (¼1-[(2R)-1,4-Dioxaspiro[4.5]dec-2-yl]hexan-1-ol;
4e). syn/anti 9 :11. Yield 88%. Transparent liquid. IR (CHCl3): 950, 1060, 1130, 1180, 1285, 1340, 1380,
1460, 2940, 3450. 1H-NMR (400 MHz, CDCl3): 0.85 (t, J ¼ 6.5, 3 H); 1.23 – 1.73 (m, 18 H); 2.04 (s, OH);

Helvetica Chimica Acta – Vol. 98 (2015)
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3.75 – 4.22 (m, 4 H). 13C-NMR (125 MHz, CDCl3): 10.1; 24.3; 24.9; 25.8; 26.9; 31.5; 32.4; 35.8; 37.1; 67.9;
69.4; 80.2; 111.3. HR-ESI-MS: 265.1773 ([M þ Na]þ, C14H26NaO3þ ; calc. 265.1780).
(2R,3RS)-1,2-Cyclohexylidenenonane-1,2,3-triol (¼1-[(2R)-1,4-Dioxaspiro[4.5]dec-2-yl]heptan-1-
ol; 4f). syn/anti 36 :64. Yield 90%. Transparent liquid. IR (CHCl3): 950, 1060, 1130, 1180, 1285, 1340,
1380, 1460, 2950, 3450. 1H-NMR (400 MHz, CDCl3): 0.82 (t, J ¼ 6.7, 6 H); 1.25 – 1.72 (m, 40 H); 2.25 (s,
OH); 3.58 – 3.61 (m, 1 H, anti-isomer); 3.70 – 3.75 (m, 1 H, syn-isomer); 3.82 – 3.85 (m, 1 H, anti-isomer);
3.95 – 3.98 (m, 2 H, syn-isomer); 3.99 – 4.01 (m, 1 H, anti-isomer); 4.03 – 4.12 (m, 1 H, anti-isomer); 4.14 –
4.17 (m, 1 H, syn-isomer). 13C-NMR (125 MHz, CDCl3): 14.4; 22.5; 24.1; 24.7; 25.1; 26.9; 26.9; 29.1; 29.4;
32.2; 33.4; 34.6; 35.6; 62.0; 62.6; 71.2; 79.9; 110.2; 110.4. HR-ESI-MS: 279.1925 ([M þ Na]þ,
C15H28NaOþ3 ; calc. 279.1936).
(2R,3RS)-1,2-Cyclohexylidenetridecane-1,2,3-triol (¼1-[(2R)-1,4-Dioxaspiro[4.5]dec-2-yl]undecan-
1-ol; 4g). syn/anti 1:4. Yield 90%. Transparent liquid. IR (CHCl3): 955, 1060, 1115, 1179, 1295, 1345,
1380, 1460, 2934, 3450. 1H-NMR (400 MHz, CDCl3): 0.87 (t, J ¼ 6.2, 3 H); 1.20 – 1.80 (m, 28 H); 2.09 (s,
OH); 3.70 – 4.23 (m, 4 H). 13C-NMR (100 MHz, CDCl3): 9.6; 20.7; 21.5; 21.9; 25.3; 30.4;, 30.9; 31.3; 35.7;
67.2; 67.8; 67.9; 85.1; 109.3; 109.5. HR-ESI-MS: 335.2557 ([M þ Na]þ, C19H36NaO3þ ; calc. 335.2562).
Benzyl Protection. NaH (1.2 equiv.) was added to the soln. of alcohol (4a – 4g) in anh. THF at 08.
After 20 min, benzyl bromide (1.2 equiv.) was added, and the mixture stirred for 3 – 5 h, until the
protection was completed as indicated by TLC. The mixture was extracted with AcOEt (3 Â 20 ml) and
washed with H2O (2 Â 15 ml). The AcOEt layer was washed with brine (1 Â 15 ml), dried over anh.
Na2SO4 and purified by CC (SiO2; 0 – 10% AcOEt/hexane) to obtain the benzyl protected pure
compound in 85 – 90%.
(2R,3RS)-3-Benzyloxy-1,2-cyclohexylidenedioxybutane (¼(2R)-2-[1-(Benzyloxy)ethyl]-1,4-dioxa-
spiro[4.5]decane; 5a). syn/anti 1:1. Yield 85%. Transparent liquid. IR (CHCl3): 959, 1102, 1209, 1457,
1645, 2855, 3088. 1H-NMR (400 MHz, CDCl3): 0.95 (d, J ¼ 7.0, 3 H); 1.37 – 1.68 (m, 10 H); 3.92 – 3.96 (m,
2 H); 4.00 – 4.12 (m, 1 H); 4.18 – 4.26 (m, 1 H); 4.58 (s, 2 H); 7.20 – 7.45 (m, 5 H). 13C-NMR (100 MHz,
CDCl3): 17.7; 22.3; 22.6; 23.4; 24.0; 36.5; 66.3; 73.1; 74.8; 82.5; 109.6; 127.4; 128.6; 128.5; 139.1; 139.9. HR-
ESI-MS: 299.1616 ([M þ Na]þ, C17H24NaO3þ ; calc. 299.1623).
(2R,3RS)-3-Benzyloxy-1,2-cyclohexylidenedioxypentane (¼ 3-O-Benzyl-4,5-O-cyclohexane-1,1-diyl-
1,2-dideoxy-d-glycero-pentitol; 5b). syn/anti 1:1. Yield 85%. Colorless oil. IR (CHCl3): 959, 1102, 1209,
1457, 1645, 3088. 1H-NMR (400 MHz, CDCl3): 0.95 (t, J ¼ 6.8, 3 H); 1.24 – 1.28 (m, 1 H); 1.34 – 1.37 (m,
2 H); 1.50 – 1.74 (m, 9 H); 3.87 – 3.94 (m, 1 H); 4.00 – 4.06 (m, 2 H); 4.12 – 4.17 (m, 1 H); 4.50 – 4.56 (m,
2 H); 7.24 – 7.45 (m, 5 H). 13C-NMR (100 MHz, CDCl3): 10.2; 22.3; 22.7; 23.4; 23.8; 25.4; 36.3; 36.4; 68.4;
74.7; 77.6; 83.5; 108.8; 127.7; 128.3; 138.7; 139.3. HR-ESI-MS: 313.1773 ([M þ Na]þ, C18H26NaO3þ ; calc.
313.1780).
(2R,3RS)-3-Benzyloxy-1,2-cyclohexylidenedioxyhexane (¼(2R)-2-[1-(Benzyloxy)butyl]-1,4-dioxa-
spiro[4.5]decane; 5c). syn/anti 27:73. Yield 86%. Transparent liquid. IR (CHCl3): 955, 1112, 1239,
1454, 1646, 2978. 1H-NMR (400 MHz, CDCl3): 0.90 (t, J ¼ 6.6, 3 H); 1.28 – 1.74 (m, 14 H); 3.87 – 3.94 (m,
1 H); 4.05 – 4.24 (m, 3 H); 4.56 (m, 2 H); 7.24 – 7.45 (m, 5 H). 13C-NMR (125 MHz, CDCl3): 8.6; 19.3;
21.6; 22.6; 24.1; 31.5; 36.2; 62.2; 62.9; 68.6; 77.5; 81.4; 109.3; 128.1; 129.2; 130.3; 139.2; 139.5. HR-ESI-MS:
327.1932 ([M þ Na]þ, C19H28NaOþ3 ; calc. 327.1936).
(2R,3RS)-3-Benzyloxy-1,2-cyclohexylidenedioxyheptane (¼(2R)-2-[1-(Benzyloxy)pentyl]-1,4-dioxa-
spiro[4.5]decane; 5d). syn/anti 9 :11. Yield 88%. Transparent liquid. IR (CHCl3): 950, 1142, 1209, 1444,
1646, 2856, 2978. 1H-NMR (500 MHz, CDCl3): 0.87 (t, J ¼ 6.8, 3 H); 1.24 – 1.68 (m, 16 H); 3.80 – 3.83 (m,
1 H); 3.91 – 3.95 (m, 1 H); 4.00 – 4.07 (m, 1 H); 4.11 – 4.16 (m, 1 H); 4.51 – 4.56 (m, 2 H); 7.33 – 7.38 (m,
5 H). 13C-NMR (125 MHz, CDCl3): 11.1; 23.4; 24.3; 25.1; 27.8; 35.5; 36.3; 64.5; 75.0; 77.3; 78.3; 80.1; 81.1;
109.3; 128.3; 129.1; 129.5; 138.5. HR-ESI-MS: 341.2083 ([M þ Na]þ, C20H30NaO3þ ; calc. 341.2093).
(2R,3RS)-3-Benzyloxy-1,2-cyclohexylidenedioxyoctane (¼(2R)-2-[1-(Benzyloxy)hexyl]-1,4-dioxa-
spiro[4.5]decane; 5e). syn/anti 9 :11. Yield 88%. Transparent liquid. IR (CHCl3): 950, 1102, 1201, 1404,
1656, 2858, 2948. 1H-NMR (400 MHz, CDCl3): 0.92 (t, J ¼ 6.8, 3 H); 1.25 – 1.72 (m, 18 H); 3.21 – 3.27 (m,
1 H); 3.26 – 4.25 (m, 3 H); 4.56 (s, 2 H); 7.64 – 7.68 (m, 5 H). 13C-NMR (125 MHz, CDCl3): 8.6; 24.8; 24.9;
25.6; 26.9; 29.6; 30.3; 37.7; 38.6; 67.7; 74.4; 80.5; 83.2; 110.4; 130.2; 130.5; 140.6. HR-ESI-MS: 355.2243
([M þ Na]þ, C21H32NaOþ3 ; calc. 355.2249).

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(2R,3RS)-3-Benzyloxy-1,2-cyclohexylidenedioxynonane (¼(2R)-2-[1-(Benzyloxy)heptyl]-1,4-dioxa-
spiro[4.5]decane; 5f). syn/anti 36 :64. Yield 90%. Transparent liquid. IR (CHCl3): 970, 1110, 1241, 1424,
1656, 2853, 2928. 1H-NMR (400 MHz, CDCl3): 0.82 – 0.87 (m, 3 H); 1.16 – 1.40 (m, 10 H); 1.41 – 1.75 (m,
10 H); 3.61 – 3.64 (m, 1 H); 3.90 – 3.94 (m, 1 H); 4.00 – 4.21 (m, 2 H); 4.56 (s, 2 H); 7.40 – 7.85 (m, 5 H).
13C-NMR (125 MHz, CDCl3): 10.1; 20.1; 20.8; 21.7; 21.8; 22.4; 23.1; 24.4; 25.8; 36.5; 37.4; 63.8; 75.9; 79.2;
110.0; 128.3; 128.8; 129.5; 139.5. HR-ESI-MS: 369.2401 ([M þ Na]þ, C22H34NaO3þ ; calc. 369.2406).
(2R,3RS)-3-Benzyloxy-1,2-cyclohexylidenedioxytridecane (¼(2R)-2-[1-(Benzyloxy)undecyl]-1,4-di-
oxaspiro[4.5]decane; 5g). syn/anti 1:4. Yield 90%. Colorless liquid. IR (CHCl3): 950, 1102, 1201, 1404,
1656, 2858, 2948. 1H-NMR (400 MHz, CDCl3): 0.98 (t, J ¼ 6.6, 3 H); 1.22 – 1.46 (m, 18 H); 1.46 – 1.78 (m,
10 H); 3.60 – 3.64 (m, 1 H); 3.68 – 3.72 (m, 1 H); 3.78 – 3.83 (m, 1 H); 3.81 – 3.85 (m, 1 H); 4.50 – 4.54 (m,
2 H); 7.50 – 7.53 (m, 5 H). 13C-NMR (125 MHz, CDCl3): 13.2; 14.1; 22.6; 23.3; 23.4; 24.1; 24.2; 25.2; 25.5;
30.8; 30.8; 31.3; 31.9; 34.9; 36.4; 36.6; 65.6; 65.7; 72.0; 72.9; 78.4; 80.6; 109.8; 110.0; 127.4; 127.7; 127.9;
128.2; 138.7; 138.9. HR-ESI-MS: 425.3026 ([M þ Na]þ, C26H42NaO3þ ; calc. 425.3032).
Deprotection of Cyclohexylidene Group. A mixture of the benzyl protected compound (5a – 5g;
12.76 mmol) and TsOH (20 mol-%) in MeOH (30 ml) was stirred at 508 until the starting material
disappeared (as monitored by TLC, 8 h). The mixture was concentrated in vacuo, treated with H2O (1 Â
25 ml) and extracted with AcOEt (3 Â 25 ml). A NaHCO3 soln. (20%, 20 ml) was added to remove the
excess TsOH, and the org. layer was dried and concentrated in vacuo. The residue was subjected to CC
(SiO2; 0 – 50% AcOEt/hexane) to obtain the pure product.
(2R,3RS)-3-O-Benzylbutane-1,2,3-triol (¼(2R)-3-(Benzyloxy)butane-1,2-diol; 6a). syn/anti 1:1.
Yield 82%. Transparent liquid. IR (CHCl3): 950, 1102, 1201, 1404, 1656, 2858, 2948, 3400. 1H-NMR
(400 MHz, CDCl3): 1.03 (d, J ¼ 6.2, 3 H); 3.53 (d, J ¼ 7.0, 1 H); 3.71 – 3.81 (m, 3 H); 4.55 (s, 2 H); 7.19 –
7.39 (m, 5 H). 13C-NMR (125 MHz, CDCl3): 11.2; 63.5; 71.5; 71.9; 75.5; 128.0; 129.5; 129.8; 139.4. HR-
ESI-MS: 219.0987 ([M þ Na]þ, C11H16NaO3þ ; calc. 219.0997).
(2R,3RS)-3-O-Benzylpentane-1,2,3-triol (¼ 3-O-Benzyl-1,2-dideoxy-d-glycero-pentitol; 6b). syn/anti
1:1. Yield 82%. Colorless oil. IR (CHCl3): 950, 1067, 1201, 1404, 1656, 2858, 3400. 1H-NMR (400 MHz,
CDCl3): 0.98 (t, J ¼ 6.8, 2 H); 1.52 – 1.72 (m, 4 H); 3.52 – 3.85 (m, 3 H); 3.90 – 3.93 (m, 1 H); 4.58 (s, 2 H);
7.30 – 7.38 (m, 5 H). 13C-NMR (125 MHz, CDCl3): 17.8; 26.7; 26.9; 65.7; 66.0; 77.6; 78.4; 86.3; 86.9; 131.2;
131.8; 132.1; 142.3; 142.7. HR-ESI-MS: 233.1149 ([M þ Na]þ, C12H18NaO3þ ; calc. 33.1154).
(2R,3RS)-3-O-Benzylhexane-1,2,3-triol (¼(2R)-3-(Benzyloxy)hexane-1,2-diol; 6c). syn/anti 27:73.
Yield 85%. Transparent liquid. IR (CHCl3): 950, 1067, 1201, 1404, 1656, 2888, 3380. 1H-NMR (400 MHz,
CDCl3): 0.80 – 0.89 (m, 3 H); 1.26 – 1.52 (m, 3 H); 1.61 – 1.66 (m, 1 H); 3.25 (s, OH); 3.61 – 3.65 (m, 1 H);
3.71 – 3.75 (m, 3 H); 4.58 (s, 2 H); 7.41 – 7.46 (m, 5 H). 13C-NMR (125 MHz, CDCl3): 9.2; 19.6; 33.2; 33.9;
64.3; 64.7; 73.6; 74.9; 80.6; 81.3; 129.2; 129.7; 130.1; 139.1; 139.6. HR-ESI-MS: 247.1322 ([M þ Na]þ,
C13H20NaOþ3 ; calc. 247.1310).
(2R,3RS)-3-O-Benzylheptane-1,2,3-triol (¼(2R)-3-(Benzyloxy)heptane-1,2-diol; 6d). syn/anti 9 :11.
Yield 86%. Transparent liquid. IR (CHCl3): 950, 1201, 1496, 1656, 2858, 3108, 3405. 1H-NMR (400 MHz,
CDCl3): 0.95 (t, J ¼ 6.2, 3 H); 1.37 – 1.46 (m, 6 H); 1.65 (s, OH); 3.42 – 3.49 (m, 1 H); 3.60 – 3.72 (m, 3 H);
4.41 – 4.49 (m, 2 H); 7.31 – 7.36 (m, 5 H). 13C-NMR (100 MHz, CDCl3): 9.5; 19.6; 23.5; 28.4; 29.1; 65.3;
75.9; 80.0; 129.3; 129.6; 129.9; 139.4; 139.8. HR-ESI-MS: 261.1460 ([M þ Na]þ, C14H22NaO3þ ; calc.
261.1467).
(2R,3RS)-3-O-Benzyloctane-1,2,3-triol (¼(2R)-3-(Benzyloxy)octane-1,2-diol; 6e). syn/anti 9 :11.
Yield 90%. Transparent liquid. IR (CHCl3): 957, 1107, 1224, 1454, 1656, 2908, 3406. 1H-NMR (400 MHz,
CDCl3): 0.91 – 0.95 (m, 3 H); 1.27 – 1.50 (m, 4 H); 1.52 – 1.73 (m, 4 H); 3.27 – 3.40 (qq, J ¼ 4.6, 5.6, 11.3,
12.7, 2 H); 3.50 – 3.53 (m, 1 H); 3.72 (q, J ¼ 4.6, 11.3, 1 H); 4.50 – 4.57 (m, 2 H); 7.22 – 7.45 (m, 5 H).
13C-NMR (100 MHz, CDCl3): 9.2; 23.6; 24.5; 26.2; 30.3; 64.4; 71.2; 72.9; 74.3; 129.2; 129.8; 139.2. HR-
ESI-MS: 275.1619 ([M þ Na]þ, C15H24NaO3þ ; calc. 275.1623).
(2R,3RS)-3-O-Benzylnonane-1,2,3-triol (¼(2R)-3-(Benzyloxy)nonane-1,2-diol; 6f). syn/anti 36 :64.
Yield 92%. Transparent liquid. IR (CHCl3): 950, 1067, 1201, 1404, 1656, 2858, 2952, 3400. 1H-NMR
(400 MHz, CDCl3): 0.90 (t, J ¼ 6.8, 3 H); 1.50 – 1.72 (m, 10 H); 2.75 (s, OH); 3.51 – 3.88 (m, 4 H); 4.54 (s,
2 H); 7.41 – 7.45 (m, 5 H). 13C-NMR (100 MHz, CDCl3): 14.6; 23.5; 26.2; 30.5; 32.4; 64.2; 73.1; 82.3; 128.8;
129.4; 139.2. HR-ESI-MS: 289.1774 ([M þ Na]þ, C16H26NaO3þ ; calc. 289.1780).

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(2R,3RS)-3-O-Benzyltridecane-1,2,3-triol (¼(2R)-3-(Benzyloxy)tridecane-1,2-diol; 6g). syn/anti
1:4. Yield 92%. Colorless thick oil. IR (CHCl3): 950, 1067, 1201, 1404, 1656, 2858, 2903, 3390.
1H-NMR (400 MHz, CDCl3): 0.88 (t, J ¼ 6.6, 3 H); 1.22 – 1.49 (m, 18 H); 2.09 (s, OH); 3.64 (q, J ¼ 2.3, 4.6,
1 H); 3.75 (q, J ¼ 6.4, 12.8, 1 H); 3.76 – 3.82 (m, 1 H); 4.00 – 4.14 (m, 1 H); 4.50 – 4.54 (m, 2 H); 7.23 – 7.45
(m, 5 H). 13C-NMR (100 MHz, CDCl3): 14.1; 22.7; 25.3; 29.4; 29.8; 30.1; 30.3; 31.9; 64.1; 72.5; 73.2; 79.9;
127.8; 127.9; 128.5; 138.3. HR-ESI-MS: 345.2395 [M þ Na]þ, C20H34NaO3þ ; calc. 345.2406).
General Procedure for the Azidation of 1,2-Diols. To a soln. of a diol (1.0 mmol) and Ph3P (342 mg,
1.3 mmol) in 18 ml of dry toluene was injected DIAD (1.5 mmol) at 08. Stirring the yellow mixture at this
temp. for 20 min under N2 was followed by injection of Me3SiN3 (1.3 mmol). (Note: Me3SiN3 is sensitive
to H2O, releasing toxic hydrazoic acid on hydrolysis. Therefore, Me3SiN3 should be used only in a well-
ventilated hood, and skin contact should be avoided). The mixture (either a clear soln. or sometimes a
suspension) was stirred at the same temp. for 2 h and then allowed to warm to r.t. After the removal of
the solvent, the residue was dissolved in 3 ml THF and treated with 2.5 ml of a 1m tetrabutylammonium
fluoride (TBAF) soln. in THF containing 5 wt-% of H2O. The brown mixture was stirred at r.t. until all of
the silyloxy azides 16a-OTMS and 16b-OTMS were consumed completely (TLC). Concentration of the
solvent gave a slurry, which was dissolved in CH2Cl2 (3 Â 30 ml) and washed with brine (1 Â 30 ml) and
dried, concentrated in vacuo to give the regiomeric mixture 7a – 7g and 8a – 8g in 73 – 90%. The mixtures
were separated by CC over SiO2 using 0 – 12% AcOEt/hexane to obtain 7a – 7g.
(2S,3RS)-2-Azido-3-(benzyloxy)butan-1-ol (7a). syn/anti 1:1. Yield 58%. Transparent liquid. IR
(CHCl3): 1018, 1098, 1272, 1454, 1667, 2101, 2856, 2930, 3064, 3435. 1H-NMR (400 MHz, CDCl3): 0.98 (d,
J ¼ 6.1, 3 H); 3.40 – 3.72 (m, 4 H); 4.51 – 4.56 (m, 2 H); 7.41 – 7.46 (m, 5 H). 13C-NMR (100 MHz,
CDCl3): 17.3; 54.4; 59.3; 72.5; 73.6; 128.6; 128.9; 129.4; 138.7. HR-ESI-MS: 244.1057 ([M þ Na]þ,
C11H15N3NaOþ2 ; calc. 244.1062).
(2S,3RS)-2-Azido-3-(benzyloxy)pentan-1-ol (7b). syn/anti 1:1. Yield 68%. Transparent liquid. IR
1
(CHCl3): 1028, 1099, 1273, 1453, 1496, 2100, 2852, 2922, 3392. H-NMR (400 MHz, CDCl3): 0.98 (m,
3 H); 1.41 – 1.46 (m, 2 H); 3.54 – 3.77 (m, 4 H); 4.56 (s, 2 H); 7.51 – 7.54 (m, 5 H). 13C-NMR (100 MHz,
CDCl3): 11.3; 23.2; 23.4; 60.6; 69.6; 73.6; 77.0; 127.7; 127.9; 128.2; 129.1; 137.3; 137.8. HR-ESI-MS:
258.1211 ([M þ Na]þ, C12H17N3NaOþ2 ; calc. 258.1218).
(2S,3RS)-2-Azido-3-(benzyloxy)hexan-1-ol (7c). syn/anti 27:73. Yield 60%. Transparent liquid. IR
1
(CHCl3): 1027, 1208, 1454, 1496, 1604, 1723, 2101, 2871, 2930, 2958, 3434. H-NMR (400 MHz, CDCl3):
0.98 (t, J ¼ 6.3, 3 H); 1.35 – 1.55 (m, 4 H); 3.38 – 3.42 (m, 1 H); 3.72 – 4.23 (m, 3 H); 4.58 (s, 2 H); 7.51 –
7.56 (m, 5 H). 13C-NMR (100 MHz, CDCl3): 12.0; 16.3; 30.1; 63.8; 64.0; 72.8; 78.5; 127.7; 128.1; 128.5;
137.5. HR-ESI-MS: 272.1371 ([M þ Na]þ, C13H19N3NaO2þ ; calc. 272.1375).
(2S,3RS)-2-Azido-3-(benzyloxy)heptan-1-ol (7d). syn/anti 9 :11. Yield 60%. Transparent liquid. IR
1
(CHCl3): 1027, 1208, 1454, 1496, 1604, 1723, 2101, 2871, 2930, 2958, 3434. H-NMR (400 MHz, CDCl3):
0.98 (t, J ¼ 6.2, 3 H); 1.35 – 1.65 (m, 6 H); 3.38 – 3.43 (m, 1 H); 3.67 – 4.23 (m, 3 H); 4.55 (s, 2 H); 7.52 –
7.57 (m, 5 H). 13C-NMR (100 MHz, CDCl3): 11.6; 19.3; 29.9; 30.1; 64.7; 66.0; 72.8; 79.5; 128.7; 129.1;
129.5; 137.6. HR-ESI-MS: 286.1527 ([M þ Na]þ, C14H21N3NaO2þ ; calc. 286.1531).
(2S,3RS)-2-Azido-3-(benzyloxy)octan-1-ol (7e). syn/anti 9 :11. Yield 59%. Transparent liquid. IR
(CHCl3): 1028, 1100, 1273, 1495, 1587, 2101, 2850, 2921, 3400. 1H-NMR (400 MHz, CDCl3): 0.92 – 0.95 (m,
3 H); 1.11 – 1.41 (m, 8 H); 3.39 (dd, J ¼ 6.8, 12.7, 1 H); 3.47 (dd, J ¼ 4.7, 12.7, 1 H); 3.60 (d, J ¼ 5.2, 1 H);
3.67 – 3.77 (m, 1 H); 4.57 (s, 2 H); 7.31 – 7.41 (m, 5 H). 13C-NMR (100 MHz, CDCl3): 13.2; 20.1; 25.1; 29.1;
29.5; 58.5; 65.4; 72.2; 79.5; 128.3; 129.0; 129.4; 139.4. HR-ESI-MS: 300.1681 ([M þ Na]þ, C15H23N3NaO2þ ;
calc. 300.1688).
(2S,3RS)-2-Azido-3-(benzyloxy)nonan-1-ol (7f). syn/anti 36 :64. Yield 59%. Transparent liquid. IR
(CHCl3): 1028, 1098, 1272, 1454, 1667, 2101, 2856, 2930, 3064, 3435. 1H-NMR (400 MHz, CDCl3): 0.95 (t,
J ¼ 6.0, 3 H); 1.22 – 1.62 (m, 10 H); 3.52 – 4.32 (m, 4 H); 4.55 (s, 2 H); 7.40 – 7.46 (m, 5 H). 13C-NMR
(100 MHz, CDCl3): 14.3; 22.3; 25.3; 29.7; 30.7; 31.9; 59.3; 65.0; 72.1; 81.2; 128.4; 128.7; 129.0; 139.2. HR-
ESI-MS: 314.1840 ([M þ Na]þ, C16H25N3NaO2þ ; calc. 314.1844).
(2S,3RS)-2-Azido-3-(benzyloxy)tridecan-1-ol (7g). syn/anti 1:4. Yield 59%. Transparent liquid. IR
(CHCl3): 1103, 1269, 1374, 1454, 1657, 1746, 2102, 2854, 2925, 3400. 1H-NMR (400 MHz, CDCl3): 0.95 (t,
J ¼ 7.3, 3 H); 1.23 – 1.52 (m, 6 H); 1.53 – 1.78 (m, 12 H); 3.52 – 4.35 (m, 4 H); 4.60 – 4.65 (m, 2 H); 7.41 –

832
Helvetica Chimica Acta – Vol. 98 (2015)
7.45 (m, 5 H). 13C-NMR (100 MHz, CDCl3): 15.4; 22.4; 25.4; 27.1; 29.3; 31.2; 60.0; 71.2; 73.2; 80.5; 128.2;
128.5; 129.3; 138.3. HR-ESI-MS: 370.2466 ([M þ Na]þ, C20H33N3NaO2þ ; calc. 370.2470).
Oxidation of Azido-Alcohols – General Procedure. The azido alcohols (7f and 7g; 1 equiv.) were
dissolved in anh. CH2Cl2, and DessÀMartin periodinane (1.3 equiv.) was slowly added at 08. The mixture
stirred for 3 – 4 h and after completion of the reaction as indicated by TLC, the reaction was quenched
with H2O (1 Â 20 ml). The extraction was carried out with CH2Cl2 (3 Â 20 ml), and the org. solvent
washed with NaHCO3 (10%, 20 ml), Na2S2O3 (10%, 15 ml), and brine (10 ml), resp. The org. solvent was
dried (anh. Na2SO4) and removed under reduced pressure to obtain the aldehyde.
The aldehyde (1 equiv.) obtained as described above was dissolved in DMF (0.1m). Potassium
peroxomonosulfate (KHSO5; Oxone; 1 equiv.) was added in one portion and the mixture was stirred at
r.t. for 8 – 10 h until the consumption of starting material was indicated by TLC. 1n HCl was used to
dissolve the salts, and AcOEt (3 Â 15 ml) was added to extract the products. The org. extract was washed
with 1n HCl and brine (1 Â 10 ml), dried, then the solvent was removed under reduced pressure to obtain
the crude product, which was purified by CC to give the azido acids (SiO2; 0 – 20% MeOH/CHCl3).
(2R,3RS)-2-Azido-3-(benzyloxy)nonanoic Acid (12f). syn/anti 36 :64. Yield 50%. Semi-solid. IR
(CHCl3): 1113, 1260, 1334, 1430, 1615, 1667, 2103, 2850, 2924, 2505 – 3380. 1H-NMR (400 MHz, CDCl3):
0.88 (t, J ¼ 6.9, 3 H); 1.27 – 1.32 (m, 3 H); 1.51 – 1.57 (m, 7 H); 2.82 – 2.87 (m, 1 H); 3.31 – 3.37 (m, 1 H);
4.51 – 4.56 (m, 2 H); 7.58 – 5.63 (m, 5 H). 13C-NMR (100 MHz, CDCl3): 11.1; 21.8; 25.0; 29.7; 29.9; 31.2;
73.1; 73.7; 75.7; 75.7; 128.3; 129.4; 129.6; 138.2; 177.6. HR-ESI-MS: 328.1630 ([M þ Na]þ,
C16H23N3NaOþ3 ; calc. 328.1637).
(2R,3RS)-2-Azido-3-(benzyloxy)tridecanoic Acid (12g). syn/anti 1:4. Yield 60%. Semi-solid. IR
(CHCl3): 1103, 1209, 1354, 1452, 1634, 1696, 2102, 2830, 2922, 2500 – 3381. 1H-NMR (400 MHz, CDCl3):
0.96 (t, J ¼ 6.9, 3 H); 1.41 – 1.75 (m, 18 H); 2.51 – 2.56 (m, 1 H); 3.67 – 3.69 (m, 1 H); 4.52 – 4.58 (m, 2 H);
7.24 – 7.44 (m, 5 H). 13C-NMR (100 MHz, CDCl3): 13.3; 21.3; 23.4; 25.4; 26.2; 28.6; 30.1; 30.3; 31.2; 74.9;
75.6; 75.7; 77.5; 128.3; 130.4; 130.5; 139.2; 139.3; 178.2. HR-ESI-MS: 384.2257 ([M þ Na]þ,
C20H31N3NaOþ3 ; calc. 384.2263).
REFERENCES
[1] J. H. Schrittwieser, F. Coccia, S. Kara, B. Grischek, W. Kroutil, N. dꢁAlessandro, F. Hollmann, Green
Chem. 2013, 15, 3318.
[2] M. Caron, P. R. Carlier, K. B. Sharpless, J. Org. Chem. 1988, 53, 5185.
[3] A. Breuning, R. Vicik, T. Schirmeister, Tetrahedron: Asymmetry 2003, 14, 3301.
´
[4] L. S. Campbell-Verduyn, W. Szymanski, P. C. Postema, R. A. Dierckx, P. H. Elsinga, D. B. Janssen,
B. L. Feringa, Chem. Commun. 2010, 46, 898; H. Sharghi, M. H. Beyzavi, A. Safavi, M. M.
Doroodmand, R. Khalifeh, Adv. Synth. Catal. 2009, 351, 2391; C. FranÅois-Endelmond, T. Carlin, P.
Thuery, O. Loreau, F. Taran, Org. Lett. 2010, 12, 40.
[5] F. De Moliner, S. Crosignani, A. Galatini, R. Riva, A. Basso, ACS Comb. Sci. 2011, 13, 453.
[6] G. Madhusudhan, M. S. Reddy, Y. N. Reddy, V. Vijayalakshmi, M. Suribabu, V. Balraju, Indian J.
Chem., Sect. B 2010, 49, 978.
[7] D. Blomberg, M. Hedenstrçm, P. Kreye, I. Sethson, K. Brickmann, J. Kihlberg, J. Org. Chem. 2004,
69, 3500.
[8] D. M. Coe, P. L. Myers, D. M. Parry, S. M. Roberts, R. Storer, J. Chem. Soc., Chem. Commun. 1990,
151; E. F. V. Scriven, K. Turnbull, Chem. Rev. 1988, 88, 297.
[9] J. Ramos, J. A. Soderquist, Arkivoc 2001, iv, 43.
[10] M. Hedenstrçm, L. Holm, Z. Q. Yuan, H. Emtenäs, J. Kihlberg, Bioorg. Med. Chem. Lett. 2002, 12,
841.
[11] S. Bräse, C. Gil, K. Knepper, V. Zimmermann, Angew. Chem., Int. Ed. 2005, 44, 5188.
ˇ
[12] A. Kolarovic, M. Schnürch, M. D. Mihovilovic, J. Org. Chem. 2011, 76, 2613.
[13] M. Sawa, T.-L. Hsu, T. Itoh, M. Sugiyama, S. R. Hanson, P. K. Vogt, C.-H. Wong, Proc. Natl. Acad.
Ssi. U.S.A. 2006, 103, 12371.
[14] J. Boruwa, J. C. Borah, S. Gogoi, N. C. Barua, Tetrahedron Lett. 2005, 46, 1743; S. Hajra, A.
Karmakar, T. Maji, A. K. Medda, Tetrahedron 2006, 62, 8959.

Helvetica Chimica Acta – Vol. 98 (2015)
833
[15] a) A. B. Hughes, A. J. Rudge, J. Nat. Prod. Rep. 1994, 11, 135; b) P.-H. Liang, W.-C. Cheng, Y.-L.
Lee, H.-P. Yu, Y.-T. Wu, Y.-L. Lin, C.-H. Wong, ChemBioChem 2006, 7, 165.
[16] Y. A. Hannun, L. M. Obeid, J. Biol. Chem. 2002, 277, 25847.
[17] K. Thevissen, U. Hillaert, E. M. K. Meert, K. K. Chow, B. P. A. Cammuea, S. Van Calenbergh,
I. E. J. A. FranÅois, Bioorg. Med. Chem. Lett. 2008, 18, 3728.
[18] E. Ballerini, P. Crotti, I. Frau, D. Lanari, F. Pizzoa, L. Vaccaro, Green Chem. 2013, 15, 2394; K. Hang,
H. Wang, V. Stepanenko, M. De Jesffls, C. Torruellas, W. Correa, M. Ortiz-Marciales, J. Org. Chem.
2011, 76, 1883; M. Jafarpour, A. Rezaeifard, M. Aliabadi, Helv. Chim. Acta 2010, 93, 405.
[19] C.-H. Dong, Y.-T. Zhang, G. Huang, J.-J. Dong, H.-X. Liu, X.-H. Tian, J. Wanga, Z.-G. Lv, L.-N.
Song, W.-Q. Yu, Chin. Chem. Lett. 2013, 24, 845.
[20] K. Banert, C. Berndt, S. Firdous, M. Hagedorn, Y.-H. Joo, T. Rüffer, H. Lang, Angew. Chem., Int. Ed.
2010, 49, 10206.
[21] I. Mathieu-Pelta, S. A. Evans Jr., J. Org. Chem. 1992, 57, 3409; L. He, M. Wanunu, H.-S. Byun, R.
Bittman, J. Org. Chem. 1999, 64, 6049.
[22] L. He, H.-S. Byun, R. Bittman, J. Org. Chem. 2000, 65, 7627; K. Smithies, M. E. B. Smith, U.
Kaulmann, J. L. Galman, J. M. Ward, H. C. Hailes, Tetrahedron: Asymmetry 2009, 20, 570.
[23] A. Rouf, M. A. Aga, B. Kumar, S. K. Yousuf, S. C. Taneja, Org. Biomol. Chem. 2013, 11, 6195.
[24] A. Rouf, M. A. Aga, B. Kumar, S. C. Taneja, Tetrahedron Lett. 2013, 54, 6420.
[25] a) A. Chattopadhyay, J. Org. Chem. 1996, 61, 6104; b) V. R. Mamdapur, A. Chattopadhyay, J. Org.
Chem. 1995, 60, 585; c) T. Suzuki, E. Sato, K. Unno, T. Kametani, J. Chem. Soc., Perkin Trans. 1 1986,
2263.
[26] J. Jurczak, S. Pikul, T. Bauer, Tetrahedron 1986, 42, 447.
[27] T. Sugiyama, H. Sugawara, M. Watanabe, K. Yamashita, Agric. Biol. Chem. 1984, 48, 1841.
Received October 31, 2014