Stereoselective routes for the total synthesis of (+)-cryptocarya diacetate

Article abstract of DOI:10.1002/hlca.200800355

A stereoselective total synthesis of (+)-cryptocarya diacetate (1) was achieved by two different routes (Schemes 2 and 3). The sequences involve LiAlH₄/LiI reduction, ring-closing metathesis, Prins cyclization, Wacker oxidation, and Wittig olefination reactions as key steps.

Full text of DOI:10.1002/hlca.200800355

Helvetica Chimica Acta – Vol. 92 (2009)
967
Stereoselective Routes for the Total Synthesis of (þ)-Cryptocarya Diacetate
by Gowravaram Sabitha*, Nandyala M. Reddy, Muddala N. Prasad, and Jhillu S. Yadav
Organic Division I, Indian Institute of Chemical Technology, Hyderabad 500007, India
(phone: þ 91-40-27160512; fax: þ 91-40-27160512; e-mail: gowravaramsr@yahoo.com)
A stereoselective total synthesis of (þ)-cryptocarya diacetate (1) was achieved by two different
routes (Schemes 2 and 3). The sequences involve LiAlH4/LiI reduction, ring-closing metathesis, Prins
cyclization, Wacker oxidation, and Wittig olefination reactions as key steps.
Introduction. – The 1,3-diol structural unit is a common motif in many natural
products. Cryptocarya diacetate (1) is the simplest example of such natural products. It
is an a,b-unsaturated lactone isolated by Drewes and co-workers [1] in 1995 from the
leaves and bark of the South African plant Cryptocarya latifolia which have been long
sought after for their legendary magical and medicinal properties [2]. These properties
range from the treatment of headaches and morning sickness to that of cancer,
pulmonary diseases, and various bacterial and fungal infections. The structure of
cryptocarya diacetate (1) has been unambiguously established by using NMR spectral
techniques (COSY, HECTOR, DQFCOSY, HSQC, and HMBC). Other natural
products containing the 1,3-diol and 5,6-dihydro-2H-pyran-2-one moieties [3a], such as
cryptocarya triacetate (2) [1] and passifloricin A (3) [3b] having antifungal activity
have also been isolated.
The preparation of 1,3-diol moieties is a challenge for the synthetic chemist.
Because of its interesting structural feature and legendary medicinal properties,
cryptocarya diacetate (1) has been the target of several syntheses. Earlier synthetic
approaches for the preparation of 1 use Sharpless asymmetric epoxidation [4], enantio-
and regioselective Sharpless dihydroxylation [5], an iterative Jacobsen hydrolytic
kinetic resolution (HKR) [6], Jacobsenꢀs hydrolytic kinetic resolution of a multi-
configurational synthon, and diastereoselective ketone reduction as the key steps for
installing the chiral centers of the 1,3-diol system [7]. The synthesis of 1 was reported
from our group [8] by an iterative Prins cyclization and reductive cleavage sequence.
Our ongoing project on synthesizing bioactive natural lactones [9] prompted us to
explore the simple strategies for the synthesis of cryptocarya diacetate (1) as shown in a
ꢁ 2009 Verlag Helvetica Chimica Acta AG, Zꢂrich

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retrosynthetic plan, i.e., by Route a from 6 via 5 and 4 and by Route b from 10 via 9 – 7
(Scheme 1).
Scheme 1. Retrosynthetic Plan of 1
In Route a, the target molecule 1 could be synthesized from 4 through 5 via
oxidation, allylation and diastereoselective reduction, acrylation, and ring-closing
metathesis (RCM). Accordingly, the required compound 5 was prepared from
commercially available propargyl alcohol (¼ prop-2-yn-1-ol; 6) (Scheme 2) following
the same procedure as that used for its enantiomer [9a]. Alcohol 5 was then oxidized to
the corresponding aldehyde in 88% yield with Dess – Martin periodinane in CH2Cl2
followed by conversion into a mixture 11a/11b of isomeric homoallylic alcohols under
Barbier conditions (zinc, allyl bromide, sat. NH4Cl in THF) in 82% yield. The
diastereoisomer mixture 11 was converted into an enantiomerically enriched alcohol 4
by adopting an oxidation/selective reduction protocol. Accordingly, the mixture 11 was
oxidized with Dess – Martin periodinane in CH2Cl2 at room temperature for 1 h to
afford a b,g-unsaturated ketone 12 in 88% yield. Compound 12 was subjected to ꢃsynꢀ-
stereoselective reduction with 3 equiv. of LiAlH4 in the presence of 3 equiv. of LiI [9a]
in Et2O at ꢀ 1008 to provide the desired ꢃsynꢀ-alcohol 4 in 84% yield (ꢃsynꢀ/ꢃantiꢀ
selectivity 95 :5). Alcohol 4 was transformed into its acrylate ester 13 in 84% yield by
treating with acryloyl chloride (¼ prop-2-enoyl chloride), catalytic amounts of DMAP
(¼ N,N-dimethylpyridin-4-amine), and Et3N in CH2Cl2. Ring-closing olefin metathesis
[10] of 13 in refluxing CH2Cl2 for 3 h in the presence of Grubbsꢀ catalyst
(¼ benzylidenedichlorobis(tricyclohexylphosphine)ruthenium(IV); 10 mol-%) pro-
duced the isopropylidene-protected lactone 14 in 86% yield as a single diastereoisomer.
Next, removal of the acetonide group was accomplished by heating 14 in 80% aqueous
AcOH for 3 h at 608. The crude diol was directly acylated after solvent removal by
addition of Ac2O in pyridine. This one pot protocol provided excellent yields of
optically active cryptocarya diacetate (1), which had spectral data identical to that of
the isolated material.

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Scheme 2. Synthesis of 1 from Prop-2-yn-1-ol (6) (Route a)
a) Dess – Martin periodinane (¼acetic acid 1,1’’,1’’-(3-oxo-1l5-1,2-benziodoxol-1(2H)-ylidyne) ester),
CH2Cl2, r.t., 1 h; 88%. b) Allyl bromide, Zn, THF, 4 h; 82%. c) Dess – Martin periodinane, CH2Cl2, r.t.,
1 h; 88%. d) LiAlH4/LiI 1:1, Et2O, ꢀ 1008 ! r.t., 1 h; 84%. e) Acryloyl chloride, Et3N, DMAP, 08 ! r.t.,
2 h; 70%. f) 10 mol-% of Grubbsꢀ catalyst, CH2Cl2, r.t., 3 h; 86%. g) AcOH/H2O 4 :1, 3 h, 608, then
Ac2O/pyridine, DMAP; 76%.
In Route b (Scheme 3), the stereoselective synthesis of (þ)-cryptocarya diacetate
(1) by the Prins-cyclization methodology was considered. Accordingly, Cu-mediated
opening of (2S)-2-[(benzyloxy)methyl]oxirane (10) [11] with vinylmagnesium bromide
in THF afforded homoallylic alcohol 15, which on treatment with lithium in liquid NH3
underwent debenzylation to produce diol 16. Prins cyclization of 16 with 3-
(benzyloxy)propanal in the presence of CF3COOH followed by hydrolysis of the
resulting trifluoroacetate yielded the desired trisubstituted pyran derivative 9.
Tosylation of 9 with 1.1 equiv. of tosyl chloride (¼4-methylbenzenesulfonyl chloride;
TsCl) in the presence of Et3N in CH2Cl2 produced the primary 4-methylbenzenesul-
fonate 17a in 95% yield. Silyl protection of the secondary-alcohol function with t-
BuMe2SiCl and 1H-imidazole in the presence of a catalytic amount of DMAP afforded
compound 17b in 92% yield. Compound 17b, on exposure to NaI in refluxing acetone,
was converted into the corresponding iodo derivative 18 in 24 h. The latter, on exposure
to unactivated Zn in refluxing EtOH, furnished the open-chain key intermediate 8 with
the ꢃantiꢀ-1,3-diol system. To get the 1,3-diol with the required ꢃsynꢀ-configuration, the
OH group of 8 needed to be inverted, which was performed under standard Mitsunobu
conditions [12] (DEAD (¼diethyl diazene-1,2-dicarboxylate), Ph3P, and 4-nitro-
benzoic acid in dry THF, followed by hydrolysis of the resultant ester with K2CO3 in
MeOH) and procured the inverted alcohol 19 in 75% yield. Desilylation of 19 with
(Bu4N)F gave the 1,3-diol which was converted to acetonide 20 under conventional
conditions with 2,2-dimethoxypropane in DMSO and the catalyst TsOH; the structure
of ꢃsynꢀ-diol 20 was further confirmed [13] by 13C-NMR spectroscopy. From 20, methyl
ketone 7 was obtained under modified Wacker-oxidation [14] conditions (0.1 equiv. of
PdCl2, 0.2 equiv. of Cu(OAc)2 · H2O in AcNMe2/H2O 7:1) in 77% yield. ꢃsynꢀ-

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Scheme 3. Synthesis of 1 from 2-{(Benzyloxy)methyl]oxirane 10 (Route b)
a) CH2¼CHMgBr, CuCN, ꢀ 788 ! 408, 4 h; 92%. b) Li, liq. NH3, THF, ꢀ 308, 20 min, 75%. c) 3-
(Benzyloxy)propanal, CF3COOH, CH2Cl2, K2CO3, MeOH, r.t., 0.5 h; 65%. d) Et3N, TsCl, CH2Cl2,
08 ! r.t., 3 h; 95%. e) t-BuMe2SiCl, 1H-imidazole, DMAP (cat.), CH2Cl2, r.t.; 92%. f) NaI, acetone,
reflux, 24 h; 95%. g) Unactivated Zn, EtOH, reflux, 1 h; 93%. h) 4-NO2C6H4COOH, EtOOCN¼N-
COOEt, Ph3P, THF, 08 ! r.t., 30 min, then K2CO3, MeOH, r.t., 4 h; 72%. i) (Bu4N)F, THF, 08 ! r.t., 4 h;
90%. j) Acetone dimethyl acetal, TsOH, DMSO, 2 h; 94%. k) PdCl2, Cu(OAc)2 · H2O, O2, DMF/H2O
7:1, r.t., 3 to 4 h; 77%. l) LiAlH4/LiI 1:1, Et2O, ꢀ 1008 ! r.t., 1 h; 84%. m) Ac2O/pyridine, DMAP
(cat.), CH2Cl2, r.t.; 94%. n) Pd/C, H2, AcOEt, r.t.; 95%. o) 1. IBX (¼1-hydroxy-1,2-benziodoxol-3-(1H)-
one 1-oxide), DMSO, 08, 6 h; 94%; 2. (CF3CH2O)2P(O)CH2COOMe, KN(SiMe3)2, THF, ꢀ 808, 0.5 h;
78%. p) 1. 0.1n HCl, MeOH; 86%; 2. ZnCl2, THF, reflux; 80%; 3. Ac2O/pyridine, CH2Cl2, DMAP (cat.),
r.t.; 85% over three steps.
Stereoselective reduction of 7 with 3 equiv. of LiAlH4 in the presence of 3 equiv. of LiI
[9a] in Et2O at ꢀ 1008 provided the desired ꢃsynꢀ-compound 21 in 84% yield (ꢃsynꢀ/
ꢃantiꢀ selectivity 95 :5). The secondary OH group of 21 was acetylated (Ac2O/pyridine
in CH2Cl2 at r.t.), followed by the removal of the benzyl protecting group (Pd/C, H2, in
AcOEt at r.t.) to get alcohol 22b in 95% yield. Oxidation of 22b to the corresponding
aldehyde in 94% was achieved with IBX (¼1-hydroxy-1,2-benziodoxol-3(1H)-one 1-
oxide) in DMSO. For the synthesis of the d-lactone, the connecting moiety had to be a
C2 unit with (Z)-configuration, which was built by a modified Wadsworth – Emmons
reaction of the aldehyde with methyl 2-[bis(2,2,2-trifluoroethoxy)phosphinyl]acetate in

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the presence of KN(SiMe3)2 in THF; thus exclusively the unsaturated (Z)-configurated
ester 23 was obtained. After hydrolyzing the acetonide with dilute acid, the
lactonization of the hydroxy ester was achieved by treating with ZnCl2 in THF under
reflux to give a hydroxylactone. Finally the OH group was acetylated with Ac2O/
pyridine in CH2Cl2 to provide the target molecule 1.
In conclusion, two different synthetic routes were used to install the chiral centers
of the 1,3-diol system of (þ)-cryptocarya diacetate (1), thus accomplishing its
stereoselective synthesis.
N. M. K. R. and M. N. P. thank the CSIR, New Delhi, for the award of fellowships.
Experimental Part
FC ¼ Flash chromatography; CC ¼ column chromatography. M.p.: Bꢀchi-R-535 apparatus; uncor-
rected. Optical rotations: Jasco DIP-370 polarimeter; at 208. IR Spectra: Perkin-Elmer FTIR-240-c
spectrophotometer; KBr optics; ˜n in cmꢀ1. 1H- and 13C-NMR Spectra: Varian Unity-200 and Bruker 300
spectrometer; in CDCl3 with SiMe4 as internal standard; d in ppm, J in Hz. MS: Finnigan MAT-1020 mass
spectrometer; at 70 eV; in m/z.
1-[(4R,6S)-2,2,6-Trimethyl-1,3-dioxan-4-yl]pent-4-en-2-ol (¼(4R,6S)-2,2,6-Trimethyl-a-(prop-2-en-
1-yl)-1,3-dioxane-4-ethanol; 11a/11b). To a soln. of Dess – Martin periodinane (1.95 g, 4.59 mmol) in
CH2Cl2 (4 ml) at r.t. was added a soln. of alcohol 5 (500 mg, 2.87 mmol) in CH2Cl2 (4 ml). After 1 h
stirring, the mixture was diluted with Et2O (10 ml) and washed once with 10% Na2S2O3/sat. aq. NaHCO3
soln. 1:1. The aq. layer was extracted with Et2O (3 ꢁ 15 ml), the combined org. extract washed once with
brine, dried (MgSO4), and concentrated, and the residue purified by FC (10% AcOEt/hexane) to give
the corresponding aldehyde (439 mg, 88%) as a colorless oil. To a stirred soln. of this aldehyde (225 mg,
1.30 mmol) in THF (10 ml) at 08 was added activated Zn (171 mg, 2.61 mmol) and dropwise allyl bromide
(0.22 ml, 2.61 mmol). After stirring at r.t. for 1 h, the mixture was quenched with sat. NH4Cl soln. (5 ml),
and the org. compound was extracted into AcOEt (3 ꢁ 20 ml). The combined org. phase was washed with
H2O (1 ꢁ 20 ml) and brine (1 ꢁ 20 ml), dried (Na2SO4), and concentrated and the crude product purified
by CC (SiO2 (60 – 120 mesh), AcOEt/hexane 1:9): 11a/11b (182 mg, 82%). Colorless liquid. IR (KBr):
3455, 3040, 2969, 2912, 1482, 1340, 1120, 725. 1H-NMR (CDCl3, 200 MHz): 5.88 – 5.71 (m, 1 H); 5.20 – 5.0
(m, 2 H); 4.20 – 4.04 (m, 1 H); 4.02 – 3.62 (m, 2 H); 2.25 – 2.11 (m, 2 H); 1.59 – 1.50 (m, 2 H); 1.44 (s, 3 H);
1.36 (s, 3 H); 1.30 – 1.19 (m, 2 H); 1.17 – 1.11 (m, 3 H). LC-MS: 237 ([M þ Na]þ).
1-[(4S,6S)-2,2,6-Trimethyl-1,3-dioxan-4-yl]pent-4-en-2-one (12). To a soln. of Dess – Martin period-
inane (541 mg, 1.27 mmol) in CH2Cl2 (4 ml) at r.t. was added a soln. of 11a/11b (182 mg, 0.85 mmol) in
CH2Cl2 (4 ml). After 1 h stirring, the mixture was diluted with Et2O (10 ml) and washed once with 10%
Na2S2O3/sat. aq. NaHCO3 soln. 1:1. The aq. layer was extracted with Et2O (3 ꢁ 15 ml), the combined org.
extract washed once with brine, dried (MgSO4), and concentrated, and the residue purified by FC (10%
AcOEt/hexane): 12 (158 mg, 88%). Colorless oil. [a]2D5 ¼ þ12.3 (c ¼ 0.024, CHCl3). IR (neat): 1716,
1
1378, 1260, 830. H-NMR (CDCl3, 300 MHz): 5.99 – 5.84 (m, 1 H); 5.23 – 5.10 (m, 2 H); 4.35 – 4.24 (m,
1 H); 4.05 – 3.93 (m, 1 H); 3.18 (d, J ¼ 6.8, 2 H); 2.68 (dd, J ¼ 6.7, 15.8, 2 H); 2.41 (dd, J ¼ 6.04, 15.86,
2 H); 1.61 – 1.54 (m, 1 H); 1.45 (s, 3 H); 1.35 (s, 3 H); 1.30 – 1.03 (m, 1 H); 1.16 (d, J ¼ 6.0, 3 H). 13C-NMR
(300 MHz, CDCl3): 206.6; 130.2; 118.8; 98.6; 65.5; 64.8; 48.6; 38.3; 30.0; 21.9; 19.6.
(2R)-1-[(4R,6S)-2,2,6-Trimethyl-1,3-dioxan-4-yl]pent-4-en-2-ol (¼(aR,4R,6S)-2,2,6-Trimethyl-a-
(prop-2-en-1-yl)-1,3-dioxane-4-ethanol; 4). To a soln. of 12 (150 mg, 0.70 mmol) in dry Et2O (10 ml) at
r.t. under N2 was added LiI (293 mg, 2.19 mmol), and the mixture was stirred at ꢀ 408 for 30 min. The
resulting mixture was then cooled to ꢀ 1008, LiAlH4 (80 mg, 2.12 mmol) was added, and the mixture was
stirred for 30 min. The mixture was then cooled to 08, diluted with Et2O, and quenched by dropwise
addition of sat. aq. Na2SO4 soln. (10 ml). The solid material was filtered and washed several times
thoroughly with hot AcOEt. The combined org. phase was dried (Na2SO4) and concentrated, and the
residue purified by CC (SiO2): 4 (127 mg, 84%). Clear liquid. [a]2D5 ¼ þ9.48 (c ¼ 0.065, CHCl3). IR
(KBr): 3450, 3050, 2974, 2912, 1497, 1339. 1H-NMR (CDCl3, 200 MHz): 5.95 – 5.71 (m, 1 H); 5.16 – 5.03

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(m, 2 H); 4.19 – 3.78 (m, 3 H); 3.54 – 3.41 (br. s, 1 H); 2.35 – 2.09 (m, 2 H); 1.66 – 1.51 (m, 1 H); 1.48 (s,
3 H); 1.30 – 1.20 (m, 1 H); 1.16 (d, J ¼ 5.5, 3 H). 13C-NMR (CDCl3, 300 MHz): 134.8; 117.2; 98.6; 70.9;
70.1; 65.0; 42.3; 41.9; 38.8; 30.2; 22.1; 19.9. LC-MS: 237 ([M þ Na]þ).
(1R)-1-{[(4S,6S)-2,2,6-Trimethyl-1,3-dioxan-4-yl]methyl}but-3-en-1-yl Prop-2-enoate (13). Prop-2-
enoyl chloride (0.096 ml, 1.19 mmol) was added dropwise under N2 to a soln. of 4 (170 mg, 0.79 mmol),
Et3N (0.221 ml, 1.58 mmol), and DMAP (5 mg) in dry CH2Cl2. The mixture was stirred at r.t. for 1 h.
After completion of the reaction, the mixture was diluted with CH2Cl2, washed with brine, and extracted
twice with CH2Cl2. The org. phases were washed with 1m aq. HCl and brine, dried (Na2SO4), and
concentrated. The crude product was purified by CC (SiO2 (60 – 120 mesh)): pure 13 (178 mg, 84%).
Liquid. IR (KBr): 3071, 2974, 2856, 1724, 1638, 1453. 1H-NMR (CDCl3, 200 MHz): 6.37 (td, J ¼ 1.6, 17.1,
1 H); 6.15 – 5.99 (m, 1 H); 5.84 – 5.60 (m, 2 H); 5.28 – 4.98 (m, 3 H); 3.99 – 3.70 (m, 2 H); 2.43 – 2.28 (m,
2 H); 1.70 – 1.44 (m, 2 H); 1.30 (s, 3 H); 1.40 – 1.19 (m, 2 H); 1.12 (d, J ¼ 6.2, 3 H). LC-MS: 271 ([M þ
Na]þ).
(6R)-5,6-Dihydro-6-{[(4S,6S)-2,2,6-trimethyl-1,3-dioxan-4-yl]methyl}-2H-pyran-2-one
(14).
Grubbsꢀ catalyst (37 mg, 0.063 mmol, 10 mol-%) was dissolved in CH2Cl2 (10 ml) and added dropwise
to a refluxing soln. of 13 (170 mg, 0.63 mmol) in CH2Cl2 (100 ml). Refluxing was continued for 3 h by
which time all of the starting material was consumed (TLC). The solvent was evaporated and the crude
product purified by CC (SiO2, hexane/AcOEt 70 :30): 14 (130 mg, 86%). IR (KBr): 2975, 1728, 1440,
1250, 1032, 944, 810, 753. 1H-NMR (CDCl3, 300 MHz): 6.89 – 6.80 (m, 1 H); 6.03 – 5.97 (m, 1 H); 4.69 –
4.52 (m, 1 H); 4.22 – 4.05 (m, 1 H); 4.03 – 3.89 (m, 1 H); 2.52 – 2.26 (m, 2 H); 2.07 – 1.97 (m, 1 H); 1.87 –
1.23 (m, 3 H); 1.44 (s, 3 H); 1.34 (s, 3 H); 1.34 (s, 3 H); 1.16 (d, J ¼ 6.1, 3 H). LC-MS: 263 ([M þ Na]þ).
Cryptocarya Diacetate (¼(6R)-6-[(2S,4S)-2,4-Bis(acetyloxy)pentyl]-5,6-dihydro-2H-pyran-2-one;
1). To AcOH/H2O 4 :1 (10 ml), 14 (100 mg, 0.41 mmol) was added, and the mixture was heated to
608. After 3 h, the solvent was evaporated, and the resulting diol was added to CH2Cl2 (10 ml), Ac2O
(0.5 ml, 6.66 mmol), pyridine (0.5 ml), and a cat. amount of DMAP. The mixture was stirred for 1 h.
Then, sat. NaHCO3 soln. (1 ml) was added. The aq. layer was extracted with Et2O (3 ꢁ 10 ml), the
combined org. phase dried (Na2SO4), the solvent evaporated, and the crude product purified by CC
(SiO2, hexane/AcOEt 4 :1): 1 (88 mg, 75%). Colorless liquid. [a]2D5 ¼ þ54.6 (c ¼ 0.3, CHCl3) ([1]: [a]2D5
¼
1
þ55.8 (c ¼ 1.06, CHCl3)). IR (neat): 2970, 1735, 1430, 1365, 1235, 1042, 981, 755. H-NMR (300 MHz,
CDCl3): 6.88 (ddd, J ¼ 3.0, 6.8, 9.8, 1 H); 6.03 (ddd, J ¼ 0.7, 3, 9.8, 1 H); 5.11 (dddd, J ¼ 4.6, 6, 7.2, 9.1,
1 H); 5.02 – 4.95 (m, 1 H); 4.5 (ddd, J ¼ 3.7, 6.8, 11, 1 H); 2.5 (ddd, J ¼ 1, 5, 18, 1 H); 2.39 – 2.25 (m, 1 H);
2.16 (ddd, J ¼ 1, 4.2, 6, 1 H); 2.07 (s, 3 H); 2.04 (s, 3 H); 2.00 (ddd, J ¼ 6, 8, 14.1, 1 H); 1.96 (ddd, J ¼ 4, 6.6,
14.1, 1 H); 1.79 (ddd, J ¼ 6, 8, 14.3, 1 H); 1.27 (d, J ¼ 6.8, 3 H). 13C-NMR (300 MHz, CDCl3): 20.1; 21.0;
29.3; 39.2; 40.5; 67.6; 67.8; 74.9; 121.4; 144.6; 163.7; 170.5; 170.6. LC-MS: 307 ([M þ Na]þ).
(2S)-2-[(Benzyloxy)methyl]oxirane (¼ Benzyl (S)-Glycidyl Ether; 10). To the (R,R)-(salen)cobalt-
(II) precatalyst (151 mg, 0.250 mmol, 0.5 mol-%), sequentially (ꢂ)-benzyl glycidyl ether ((ꢂ)-10; 8.20 g,
50.0 mmol) and AcOH (57 ml, 1.0 mmol, 0.02 equiv.) were added. After the mixture turned from a red
suspension to a dark brown soln., it was cooled to 08, and THF (0.5 ml) followed by H2O (495 ml,
27.5 mmol, 0.55 equiv.) were added. The mixture was allowed to warm to r.t. over 2 h and stirred for an
additional 20 h. Distillation of the mixture at 758/11 Torr gave unreacted 10 (3.77 g, 46%). Colorless oil.
1
TLC (SiO2, 20% AcOEt/hexane): Rf 0.6. [a]2D5 ¼ ꢀ5.2 (c ¼ 2.0, CHCl3). H-NMR (CDCl3, 300 MHz):
7.35 – 7.28 (m, 5 H); 4.60 (d, J ¼ 12.0, 1 H); 4.55 (d, J ¼ 12.0, 1 H); 3.76 (dd, J ¼ 11.2, 2.8, 1 H); 3.42 (dd,
J ¼ 11.2, 5.8, 1 H); 3.18 (m, 1 H); 2.78 (dd, J ¼ 4.5, 4.2, 1 H); 2.60 (dd, J ¼ 4.5, 2.5, 1 H). 13C-NMR
(CDCl3, 75 MHz): 140.0; 128.5; 127.8; 73.3; 70.9; 50.9; 44.3. LC-MS: 165 ([M þ H]þ).
(2S)-1-(Benzyloxy)pent-4-en-2-ol (15). To Mg (1.18 g, 48.78 mmol) in dry THF (35 ml) at r.t. was
sequentially added 1,2-dibromoethane (3 drops) and, dropwise, freshly prepared vinyl bromide (3.45 ml,
48.78 mmol). After 0.5 h stirring, CuCN (10.9 mg, 5 mol-%) was added. Then, the mixture was cooled to
ꢀ 788, 10 (4.0 g, 24.39 mmol) in THF (6 ml) was added, and the mixture was warmed to ꢀ 408 and stirred
for 4 h. After quenching with sat. NH4Cl soln. (30 ml) and extraction with AcOEt (2 ꢁ 30 ml), the
combined org. phase was washed with brine (20 ml), dried (Na2SO4), and concentrated. Purification by
CC afforded 15 (4.30 g, 92%). Colorless liquid. TLC (SiO2, 20% AcOEt/hexane): Rf 0.45. [a]2D5 ¼ ꢀ2.32
1
(c ¼ 1.2, CHCl3). IR (neat): 3360, 3021, 1637, 1494, 1450. H-NMR (CDCl3, 300 MHz): 7.31 (m, 5 H);
5.91 – 5.69 (m, 1 H); 5.20 – 4.93 (m, 2 H); 4.52 (s, 2 H); 4.00 – 3.63 (m, 1 H); 3.49 (dd, J ¼ 9.5, 3.7, 1 H);

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3.32 (dd, J ¼ 9.5, 6.5, 1 H); 2.48 (br. s, 1 H); 2.23 (t, J ¼ 6.7, 2 H). 13C-NMR (CDCl3, 75 MHz): 138.3;
134.2; 128.5; 127.9; 127.7; 117.7; 73.8; 73.4; 69.7; 37.9. LC-MS: 215 ([M þ Na]þ).
(2S)-Pent-4-ene-1,2-diol (16). To a soln. of Li (3.72 g, 104.1 mmol) in liq. NH3 (25 ml) was added 15
(4.0 g, 20.8 mmol) in dry THF (8 ml). The mixture was stirred for 20 min and quenched with solid NH4Cl
(5.5 g). Ammonia was allowed to evaporate, and to the residual mixture, Et2O was added. The mixture
was filtered through Celite, the filtrate dried (Na2SO4) and concentrated, and the residue purified by CC:
16 (1.59 g, 75%). Colorless oil. TLC (SiO2, 80% AcOEt/hexane): Rf 0.25. [a]2D5 ¼ þ3.6 (c ¼ 2.8, CHCl3).
IR (neat): 3388, 2927, 1645, 1440, 1075. 1H-NMR (CDCl3, 300 MHz): 5.91 – 5.63 (m, 1 H); 5.13 – 5.04 (m,
2 H); 3.75 – 3.55 (m, 2 H); 3.38 (dd, J ¼ 11.0, 7.6, 1 H); 3.16 (br. s, 2 H); 2.18 (t, J ¼ 6.0, 2 H). 13C-NMR
(CDCl3, 75 MHz): 135.1; 117.2; 71.3; 66.0; 37.5. LC-MS: 125 ([M þ Na]þ).
3-(Benzyloxy)propan-1-ol. Under N2, a 60% dispersion of NaH in mineral oil (10.7 g, 447.3 mmol)
was washed thoroughly with dry hexane. Then DMF (600 ml) was added and the mixture cooled to 08. To
the formed suspension was added dropwise within 15 min the soln. of propane-1,3-diol (20 g, 263.1 mmol)
in dry DMF (40 ml). After the addition, the temp. of the mixture was raised to r.t. and kept at r.t. for 4 h.
Then, at 08, cat. amounts of (Bu4N)I followed by benzyl bromide (31.25 ml, 263.1 mmol) within 10 min
were added, and the mixture was stirred at r.t. for 4 h. Thereafter, cold H2O (60 ml) was added cautiously,
and the aq. phase was extracted with AcOEt (3 ꢁ 60). The combined org. extract was washed with H2O
and brine and concentrated, and the residue subjected to CC: pure 3-(benzyloxy)propan-1-ol (34.9 g,
80%). Colorless liquid. TLC (SiO2, 50% AcOEt/hexane): Rf 0.5. 1H-NMR (CDCl3, 300 MHz): 7.43 – 7.13
(m, 5 H); 4.50 (s, 2 H); 3.75 (t, J ¼ 5.5, 2 H); 3.63 (t, J ¼ 5.5, 2 H); 1.78 (m, 2 H). LC-MS: 189 ([M þ
Na]þ).
3-(Benzyloxy)propanal. To a soln. of 3-(benzyloxy)propan-1-ol (30 g, 182.9 mmol) in dry CH2Cl2
(300 ml) at 08 was added Celite and then portionwise pyridinium chlorochromate (PCC; 78.86 g,
365.8 mmol). The mixture was brought to r.t., stirred for 2.5 h, diluted with Et2O, and filtered through a
pad of Celite, which was washed with excess of Et2O. The filtrate was concentrated and the residue
purified by CC: 3-(benzyloxy)propanal (23.1 g, 78%). Colorless liquid. TLC (SiO2, 20% AcOEt/
hexane): Rf 0.4. IR (neat): 2858, 1722, 1098, 740, 698. 1H-NMR (CDCl3, 300 MHz): 9.78 (s, 1 H); 7.40 –
7.20 (m, 5 H); 4.44 (s, 2 H); 3.70 (dt, J ¼ 7.0, 1.3, 2 H); 2.65 – 2.50 (m, 2 H).
(2S,4R,6S)-6-[2-(Benzyloxy)ethyl]tetrahydro-4-hydroxy-2H-pyran-2-methanol (9). CF3COOH
(37.5 ml, 490.1 mmol) was added slowly to a soln. of 16 (2.5 g, 24.5 mmol) and 3-(benzyloxy)propanal
(12.0 g, 73.5 mmol) in CH2Cl2 (90 ml) at r.t. under N2. The mixture was stirred for 3 h, then sat. NaHCO3
soln. (200 ml) was added, and the pH was adjusted to > 7 by addition of Et3N. The aq. layer was extracted
with CH2Cl2 (4 ꢁ 70 ml) and the combined org. phase concentrated. The residue was dissolved in MeOH
(40 ml) and stirred with K2CO3 (6.77 g) for 30 min. MeOH was then evaporated, and H2O (30 ml) was
added. The mixture was extracted with CH2Cl2 (3 ꢁ 30 ml), the combined org. phase dried (Na2SO4) and
evaporated, and the residue purified by CC (SiO2): 9 (3.65 g, 56%). Gummy liquid. TLC (SiO2, 80%
AcOEt/hexane): Rf 0.2. [a]2D5 ¼ ꢀ12.9 (c ¼ 0.04, CHCl3). IR (neat): 3410, 2922, 2854, 1736, 1453, 1368,
1244, 1096, 1029, 742, 699. 1H-NMR (CDCl3, 300 MHz): 7.36 – 7.17 (m, 5 H); 4.47 (q, J ¼ 12.5, 14.7, 2 H);
4.02 – 3.66 (m, 1 H); 3.66 – 3.30 (m, 6 H); 1.98 – 1.59 (m, 3 H); 1.57 – 1.30 (m, including two OH, 3 H);
1.28 – 1.06 (m, 2 H). 13C-NMR (CDCl3, 75 MHz): 138.2; 128.3; 127.6; 75.9; 72.8; 72.7; 67.5; 66.5; 65.5;
40.9; 36.6; 35.9. LC-MS: 289 ([M þ Na]þ).
{(2S,4R,6S)-6-[2-(Benzyloxy)ethyl]tetrahydro-4-hydroxy-2H-pyran-2-yl}methyl 4-Methylbenzene-
sulfonate (17a). To the soln. of 9 (2.0 g, 7.51 mmol) in dry CH2Cl2 (15.0 ml), Et3N (2.09 ml, 15.0 mmol)
was added at 08. Then, 4-methylbenzenesulfonyl chloride (1.57 g, 8.27 mmol) was added over 2 h. The
mixture was allowed to warm to r.t. and stirred for 3 h. Then the mixture was treated with aq. 1n HCl
(10 ml) and extracted with CH2Cl2 (3 ꢁ 30 ml). The org. layers were washed with sat. NaHCO3 soln.
(15 ml) and H2O (15 ml). The combined org. phase was dried (Na2SO4) and concentrated and the residue
subjected to FC: 17a (3.0 g, 95%). Gummy liquid. TLC (SiO2, 80% AcOEt/hexane): Rf 0.5. [a]D25
¼
1
ꢀ22.3 (c ¼ 1, CHCl3). IR (neat): 3405, 2922, 2856, 1450, 1146, 973. H-NMR (CDCl3, 300 MHz): 7.74
(d, J ¼ 8.3, 2 H); 7.34 – 7.19 (m, 7 H); 4.43 (AB, J ¼ 12.1, 14.4, 2 H); 4.0 – 3.86 (m, 2 H); 3.70 (tt, J ¼ 3.8,
9.8, 1 H); 3.36 – 3.55 (m, 4 H); 2.43 (s, 3 H); 1.85 (dd, J ¼ 3.0, 12.8, 2 H); 1.68 (q, J ¼ 6.0, 13.0, 2 H); 1.17 –
1.0 (qd, J ¼ 3.8, 12.1, 2 H). 13C-NMR (CDCl3, 75 MHz): 144.6; 138.2; 132.7; 129.6; 128.1; 127.7; 127.4;
127.3; 72.7; 72.5; 71.9; 67.1; 66.2; 40.5; 36.5; 35.7; 21.4. LC-MS: 443 ([M þ Na]þ).

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Helvetica Chimica Acta – Vol. 92 (2009)
{(2S,4R,6S)-6-[2-(Benzyloxy)ethyl]-4-{[(tert-butyl)dimethylsilyl]oxy}tetrahydro-2H-pyran-2-yl}-
methyl 4-Methylbenzenesulfonate (17b). To a stirred soln. of 17a (3.0 g, 7.1 mmol) in CH2Cl2 (15 ml), 1H-
imidazole (1.45 g, 21.3 mmol) was added at 08 and stirred for 15 min. (tert-Butyl)chlorodimethylsilane
(1.23 g, 7.8 mmol) was added to the mixture at 08 and stirred for 2 h. After completion of the reaction
(TLC monitoring), the mixture was directly concentrated and the residue subjected to CC: pure 17b
(3.5 g, 92.1%). 1H-NMR (CDCl3, 300 MHz): 7.79 – 7.71 (m, 2 H); 7.32 – 7.18 (m, 7 H); 4.44 (s, 2 H); 3.98 –
3.86 (m, 2 H); 3.77 – 3.66 (m, 1 H); 3.54 – 3.38 (m, 4 H); 2.44 (s, 3 H); 1.78 – 1.60 (m, 4 H); 1.40 – 1.22 (m,
2 H); 0.85 (s, 9 H); 0.02 (s, 6 H). 13C-NMR (CDCl3, 75 MHz): 144.5; 138.5; 133.1; 129.6; 128.3; 127.6;
127.6; 127.48; 72.9; 72.7; 72.6; 68.1; 66.3; 41.3; 37.3; 35.9; 25.7; 21.5; 18.0; ꢀ 4.5; ꢀ 4.6. LC-MS: 535 ([M þ
1]þ).
{(2S,4R,6S)-2-[2-(Benzyloxy)ethyl]tetrahydro-6-(iodomethyl)-2H-pyran-4-yl]oxy}(tert-butyl)dime-
thylsilane (18). NaI (4.7 g, 31.5 mmol) was added to a soln. of 17 (3.4 g, 6.3 mmol) in acetone (50 ml) and
heated under reflux for 24 h. The acetone was evaporated, and to the residue, H2O (15 ml) and AcOEt
(20 ml) were added. The org. layer was dried (Na2SO4) and concentrated, and the residue chromato-
graphed: 18 (2.9 g, 93%). Colorless liquid. TLC (SiO2, 10% AcOEt/hexane): Rf 0.7. IR (neat): 3360,
1
2935, 2850, 1146, 735. H-NMR (CDCl3, 300 MHz): 7.33 – 7.24 (m, 5 H); 4.49 (s, 2 H); 3.84 – 3.25 (m,
5 H); 3.11 (d, J ¼ 6.2, 2 H); 2.07 – 1.93 (m, 1 H); 1.81 – 1.67 (m, 3 H); 1.34 – 1.01 (m, 2 H); 0.87 (s, 9 H);
0.04 (s, 6 H). 13C-NMR (CDCl3, 75 MHz): 138.63; 128.39; 127.7; 127.5; 75.1; 73.2; 72.6; 68.4; 66.6; 41.6;
41.3; 36.1; 25.8; 18.1; 9.20; ꢀ 4.3.
(3S,5S)-1-(Benzyloxy)-5-{[(tert-butyl)dimethylsilyl]oxy}oct-7-en-3-ol (8). To a soln. of 18 (2.8 g,
5.7 mmol) in EtOH (30 ml), commercial Zn dust (5.4 g, 85.5 mmol) was added. The mixture was
refluxed for 4 h and then cooled to 258. Addition of solid NH4Cl (2.0 g) and Et2O (60 ml) followed by
stirring for 5 min gave a gray suspension. The suspension was filtered through Celite, the filtrate
concentrated, and the residue purified by FC: 8 (1.9 g, 91.3%). Colorless liquid. TLC (SiO2, 10% AcOEt/
hexane): Rf 0.4. [a]2D5 ¼ ꢀ35.1 (c ¼ 1, CHCl3). IR: 3358, 2860, 1428, 1105, 740, 705, 508. 1H-NMR (CDCl3,
300 MHz): 7.32 – 7.21 (m, 5 H); 5.81 – 5.66 (m, 1 H); 5.07 – 4.98 (m, 2 H); 4.5 (q, J ¼ 2.2, 12.8, 2 H); 4.08 –
3.98 (m, 2 H); 3.68 – 3.54 (m, 2 H); 3.19 (br. s, 1 H); 2.28 (t, J ¼ 6.7, 2 H); 1.80 – 1.39 (m, 4 H); 0.89 (s,
9 H); 0.09 (s, 3 H); 0.08 (s, 3 H). 13C-NMR (CDCl3, 75 MHz): 138.1; 134.7; 128.3; 127.5; 117.2; 73.08; 70.2;
68.2; 66.8; 42.4; 41.6; 37.4; 25.8; ꢀ 4.48; ꢀ 4.86. LC-MS: 387 ([M þ Na]þ).
(3R,5S)-1-(Benzyloxy)-5-{[(tert-butyl)dimethylsilyl]oxy}oct-7-en-3-ol (19). To a stirred soln. of 8
(1.3 g, 10.56 mmol) in toluene (10 ml) was added triphenylphosphine (1.76 g, 6.6 mmol) and 4-
nitrobenzoic acid (1.12 g, 6.6 mmol). The mixture was cooled to ꢀ 788, and slowly diethyl diazene-1,2-
dicarboxylate (1.69 ml, 10.56 mmol) was added. The mixture was slowly brought to ꢀ 208 and stirred for
1 h. Then, the mixture was concentrated, and MeOH (20 ml) and K2CO3 (1.6 g, 12 mmol) were added.
After 1 h stirring, the mixture was filtered through a plug of Celite and washed with AcOEt. The
combined org. phase was concentrated, and the residue subjected to CC: pure 19 (1.2 g, 92%). IR (neat):
1
3360, 2872, 1445, 758, 508. H-NMR (300 MHz, CDCl3): 7.34 – 7.19 (m, 5 H); 5.86 – 5.66 (m, 1 H); 5.03
(dd, J ¼ 11.8, 1.1, 2 H); 4.49 (s, 2 H); 4.0 – 3.80 (m, 2 H); 3.69 – 3.55 (m, 2 H); 3.22 (br. s, 1 H); 2.33 – 2.16
(m, 2 H); 1.74 – 1.51 (m, 4 H); 0.90 (s, 9 H); 0.09 (s, 6 H). LC-MS: 387 ([M þ Na]þ).
(3R,5S)-1-(Benzyloxy)oct-7-ene-3,5-diol. To a stirred soln. of 19 (1.2 g, 3.1 mmol) in THF, (Bu4N)F
(3.1 ml, 3.1 mmol) was added slowly at 08. After completion of the reaction (TLC monitoring), the
mixture was concentrated, and the residue subjected to CC: pure (3R,5S)-1-(benzyloxy)oct-7-ene-3,5-
diol (0.8 g, 95.2%). [a]D ¼ ꢀ5.4 (c ¼ 1, CHCl3). IR (neat): 3384, 2928, 2864, 1438, 1094. 1H-NMR
(300 MHz, CDCl3): 7.27 (m, 5 H); 5.03 – 5.13 (m, 2 H); 4.5 (s, 2 H); 4.05 (m, 1 H); 3.90 – 3.85 (m, 1 H);
3.65 (m, 2 H); 2.2 (m, 2 H); 1.52 (m, 4 H). LC-MS: 273 ([M þ Na]þ).
(4R,6S)-4-[2-(Benzyloxy)ethyl]-2,2-dimethyl-6-(prop-2-en-1-yl)-1,3-dioxane (20). To a stirred soln.
of (3R,5S)-1-(benzyloxy)oct-7-ene-3,5-diol (0.8 g, 2.7 mmol) in dry DMSO (4 ml), 2,2-dimethoxypro-
pane (10 ml) and a cat. amount of 4-methylbenzenesulfonic acid were added and stirred at r.t. for 1 h.
Then, Et3N (1 ml) was added, the mixture stirred for 10 min and diluted with AcOEt (20 ml), the org.
layer washed with H2O (2 ꢁ 5 ml) and brine (2 ꢁ 5 ml), dried (Na2SO4), and concentrated, and the
residue purified by CC: 20 (0.8 g, 94%). Colorless liquid. [a]D ¼ þ5.9 (c ¼ 1.0, CHCl3). IR (neat): 2935,
1
1620, 1455, 1239, 1180, 950, 763, 720. H-NMR (300 MHz, CDCl3): 7.29 – 7.24 (m, 5 H); 5.8 – 5.68 (m,
1 H); 5.1 – 5.08 (m, 2 H); 4.46 (d, J ¼ 2.3, 2 H); 4.01 – 3.96 (m, 1 H); 3.9 – 3.72 (m, 1 H); 3.6 – 3.4 (m, 2 H);

Helvetica Chimica Acta – Vol. 92 (2009)
975
2.35 – 2.05 (m, 2 H); 1.76 – 1.61 (m, 2 H); 1.49 (t, J ¼ 3, 1 H); 1.43 (t, J ¼ 3.1, 1 H); 1.40 (s, 3 H); 1.32 (s,
3 H). 13C-NMR (75 MHz, CDCl3): 19.9; 30.1; 40.7; 66.0; 66.4; 68.3; 73.0; 116.7; 127.6; 127.4; 128.3; 134.1.
LC-MS: 313 ([M þ Na]þ).
1-{(4R,6R)-6-[2-(Benzyloxy)ethyl]-2,2-dimethyl-1,3-dioxan-4-yl}propan-2-one (7). A suspension of
20 (0.8 g, 2.7 mmol), PdCl2 (48 mg, 0.27 mmol), and Cu(OAc)2 · H2O (109 mg, 0.54 mmol) in AcNMe2/
H2O 7:1 (6 ml) was placed under O2 (balloon) and stirred at r.t. for 6 h. The mixture was diluted with
Et2O, washed with H2O and brine, dried (Na2SO4), and concentrated. The residue was purified by FC: 7
1
(0.60 g, 66%). Colorless oil. IR (neat): 3085, 2935, 1724, 1436, 1055, 720. H-NMR (CDCl3, 300 MHz):
7.39 – 7.17 (m, 5 H); 4.45 (s, 2 H); 4.31 – 4.13 (m, 1 H); 4.05 – 3.86 (m, 1 H); 3.60 – 3.41 (m, 2 H); 2.64 (dd,
J ¼ 8.1, 15.4, 1 H); 2.38 (dd, J ¼ 5.1, 16.1, 1 H); 2.14 (s, 3 H); 1.79 – 1.44 (m, 4 H); 1.31 (s, 3 H); 1.27 (s,
3 H). 13C-NMR (CDCl3, 75 MHz): 206.9; 138.4; 128.3; 127.6; 127.5; 98.6; 72.6; 66.1; 65.8; 65.6; 50.0; 36.7;
36.4; 31.0; 30.1; 19.7. LC-MS: 329 ([M þ Na]þ).
(2S)-1-{(4S,6R)-6-[2-(Benzyloxy)ethyl]-2,2-dimethyl-1,3-dioxan-4-yl}propan-2-ol (¼(aS,4S,6R)-6-
[2-(Benzyloxy)ethyl]-a,2,2-trimethyl-1,3-dioxane-4-ethanol; 21). To a soln. of 7 (500 mg, 1.6 mmol) in
dry Et2O (10 ml) at r.t. under N2 was added LiI (650 mg, 4.8 mmol), and the mixture was stirred at ꢀ 408
for 30 min. After cooling to ꢀ 1008, LiAlH4 (134 mg, 4 mmol) was added, and the mixture was stirred for
30 min. The mixture was then warmed to 08, diluted with Et2O, and quenched by dropwise addition of sat.
aq. Na2SO4 soln. (6 ml). The solid material was filtered and washed thoroughly with AcOEt. The
combined org. phase was dried (Na2SO4) and concentrated, and the residue purified by CC: 21 (450 mg,
1
89%). Liquid. [a]D ¼ þ11.4 (c ¼ 1, CHCl3). IR (neat): 3443, 2991, 1452, 1378, 1134, 864, 766. H-NMR
(300 MHz, CDCl3): 7.27 – 7.23 (m, 5 H); 4.43 (s, 2 H); 3.90 – 4.13 (m, 3 H); 3.40 – 3.71 (m, 2 H); 1.62 – 1.74
(m, 2 H); 1.44 (s, 3 H); 1.35 (s, 3 H); 1.17 – 1.59 (m, 4 H); 1.13 (d, J ¼ 6.5, 3 H). 13C-NMR (CDCl3,
75 MHz): 138.6; 128.5; 127.8; 127.0; 98.8; 73.1; 67.3; 66.2; 65.2; 43.7; 37.4; 30.3; 29.8; 25.1; 23.5; 20.1. LC-
MS: 308 (Mþ).
(1S)-2-{(4S,6R)-6-[2-(Benzyloxy)ethyl]-2,2-dimethyl-1,3-dioxan-4-yl}-1-methylethyl
Acetate
(¼(aS,4S,6R)-6-[2-(Benzyloxy)ethyl]-a,2,2-trimethyl-1,3-dioxane-4-ethanol Acetate; 22a). To a stirred
soln. of 21 (0.3 g, 0.95 mmol) in CH2Cl2 was added pyridine (1 ml), Ac2O (0.2 ml, 2.05 mmol), and
DMAP (cat.), and the mixture was stirred for 3 h. The mixture was diluted with CH2Cl2 (10 ml), washed
with H2O (1 ꢁ 5 ml) and brine (1 ꢁ 5 ml), dried (Na2SO4), and concentrated. The crude product was
purified by CC (AcOEt/hexane 1:9): 22a (0.32 g, 94%). Colorless liquid. [a]D ¼ þ12.8 (c ¼ 1, CHCl3). IR
(neat): 2940, 1736, 1375, 1274, 1202, 748. 1H-NMR (300 MHz, CDCl3): 7.26 – 7.24 (m, 5 H); 5.03 (m, 1 H);
4.45 (s, 2 H); 3.73 – 4.05 (m, 2 H); 3.50 – 3.48 (m, 2 H); 2.0 (s, 3 H); 1.64 – 1.89 (m, 2 H); 1.09 – 1.52 (m,
4 H); 1.38 (s, 3 H); 1.3 (s, 3 H); 1.2 (d, J ¼ 6.0, 3 H). 13C-NMR (CDCl3, 75 MHz): 171.4; 138.1; 128.2;
127.0; 126.9; 98.4; 73.1; 67.7; 65.1; 64.2; 43.9; 36.9; 36.2; 30.0; 29.8; 20.9; 20.0; 19.1. LC-MS: 350 (Mþ).
(1S)-2-[(4S,6R)-6-(2-Hydroxyethyl)-2,2-dimethyl-1,3-dioxan-4-yl]-1-methylethyl
Acetate
(¼(a4S,4S,6R)-a4,2,2-Trimethyl-1,3-dioxane-4,5-diethanol 4-Acetate; 22b). To a stirred soln. of 22a
(0.3 g, 0.84 mmol) in AcOEt (1 ml) was added 10% Pd/C. The mixture was stirred under H2 for 12 h and
then filtered through Celite. The filtrate was concentrated: 22b (0.216 g, 95%). Colorless liquid. [a]D ¼
þ14.2 (c ¼ 1, CHCl3). IR (neat): 3453, 2985, 2943, 1730, 1375, 1230, 936, 729. 1H-NMR (400 MHz,
CDCl3): 5.05 – 5.02 (m, 1 H); 3.88 – 4.05 (m, 2 H); 3.72 (ddq, J ¼ 1.4, 3.6, 6.6, 2 H); 1.69 – 1.66 (m, 1 H);
2.0 (s, 3 H); 1.72 – 1.51 (m, 1 H); 1.40 (s, 3 H); 1.36 (s, 3 H); 1.24 – 1.46 (m, 4 H); 1.2 (d, J ¼ 6.6, 3 H).
13C-NMR (CDCl3, 75 MHz): 170.3; 98.7; 69.3; 67.5; 65.4; 60.8; 42.7; 38.0; 36.7; 30.5; 30.1; 21.3; 19.4. LC-
MS: 261 ([M þ 1]þ).
Methyl (2Z)-4-{(4R,6S)-6-[(2S)-2-(Acetyloxy)propyl]-2,2-dimethyl-1,3-dioxan-4-yl}but-2-enoate
(23). To a stirred soln. of 22b (0.21 g, 0.78 mmol) in dry DMSO (1 ml) was added IBX (0.330 g,
1.2 mmol) at 08, and the mixture was stirred for 6 h. Then the mixture was quenched with sat. NaHCO3
soln. (1 ml), filtered, and washed with AcOEt (2 ꢁ 5 ml). The org. phase was washed with H2O (1 ꢁ
10 ml) and brine (1 ꢁ 10 ml), dried (Na2SO4), and concentrated: aldehyde (0.19 g, 94%). The crude
aldehyde was used as such without purification. To a stirred soln. of methyl 2-[bis(2,2,2-trifluoroethoxy)-
phosphinyl]acetate (0.36 g, 0.9 mmol) and [18]crown-6 (0.9 g, 03.5 mmol) in dry THF (1 ml) at ꢀ 788 was
added potassium bis(trimethylsilyl)amide (¼ potassium 1,1,1,3,3,3-hexamethyldisilazanide; 1 ml,
0.6 mmol), and the mixture was stirred for 30 min at ꢀ 788. Then, the crude aldehyde (0.19 g) in dry
THF (1 ml) was added, and the mixture was stirred for 30 min at ꢀ 788. The reaction was quenched by

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Helvetica Chimica Acta – Vol. 92 (2009)
adding sat. NH4Cl soln. (2 ml) and stirring at r.t. for 10 min. Then, the mixture was extracted with AcOEt
(2 ꢁ 8 ml), the combined org. phase washed with H2O (1 ꢁ 10 ml) and brine (1 ꢁ 6 ml), dried (Na2SO4),
and concentrated, and the residue purified by CC (SiO2 (60 – 120 mesh), AcOEt/hexane 1:9): pure 23
(0.15 g, 60%). [a]D ¼ þ29.1 (c ¼ 1.0, CHCl3). IR (neat): 2935, 2859, 1722, 1650, 1455, 1340, 1160, 856, 752.
1H-NMR (300 MHz, CDCl3): 6.38 (ddd, J ¼ 1.4, 2.5, 6.1, 1 H); 5.8 (dd, J ¼ 2.1, 6.9, 1 H); 3.77 – 3.95 (m,
2 H); 5.07 – 5.01 (m, 1 H); 3.70 (s, 3 H); 2.92 – 2.88 (m, 1 H); 2.6 – 2.65 (m, 1 H); 2.0 (s, 3 H); 1.35 – 1.59
(m, 10 H), 1.19 (d, J ¼ 6.0, 3 H). 13C-NMR (75 MHz, CDCl3): 19.3; 20.0; 20.7; 21.2; 30.4; 35.7; 36.9; 42.8;
50.3; 65.4; 67.7; 67.8; 68.3; 120.5; 146.0; 145.8. LC-MS: 314 (Mþ).
Cryptocarya Diacetate (1). A soln. of 23 (0.1 g, 0.3 mmol) in 80% AcOH/H2O (0.6 ml) was stirred at
r.t. for 4 h. The mixture was concentrated, and the residue dissolved in benzene (2 ml). Then, 4-
methylbenzenesulfonic acid (cat.) was added, and the mixture stirred at r.t. for 3 h. After concentration,
the crude product was dissolved in CH2Cl2 (3 ml), and pyridine (0.3 ml), Ac2O (0.1 ml), and DMAP
(cat.) were added. The mixture was stirred at r.t. for 2 h, then diluted with CH2Cl2 (4 ml), washed with
H2O (3 ml) and brine (3 ml), dried (Na2SO4), and concentrated. The residue was purified by CC (SiO2
(60 – 120 mesh), AcOEt/hexane 3 :2): 1 (81 mg, 91%). Colorless liquid. Spectral data: identical with
those of the natural product.
REFERENCES
[1] S. E. Drewes, B. M. Schlapelo, M. M. Horn, R. Scott-Shaw, O. Sandor, Phytochemistry 1995, 38, 1427.
[2] J. Jodynis-Liebert, M. Murias, E. Błoszyk, Planta Med. 2000, 66, 199.
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Received September 15, 2008