Synthesis of (+)-polyoxamic acid and D-sorbitol from simple achiral allylic halides emploing (S,S)-hydrobenzoin as a chiral source

Article abstract of DOI:10.1039/b202823a

Coupling of cis-1-bromo-2-pentene and (S,S)-hydrobenzoin stannylene acetal followed by regio- and stereoselective transformations of the resulting allylic ether gave (+)-polyoxamic acid and a similar procedure was applied to the synthesis of D-sorbitol from trans-1-iodo-2-hexene.

Full text of DOI:10.1039/b202823a

Synthesis of (+)-polyoxamic acid and -sorbitol from simple achiral
D
allylic halides employing (S,S)-hydrobenzoin as a chiral source
Kwan Soo Kim,* Yong Joo Lee, Jin Hwan Kim and Da Kyung Sung
Department of Chemistry, Yonsei University, Seoul 120-749, Korea. E-mail: kwan@yonsei.ac.kr;
Fax: 82-2-364-7050; Tel: +82-2-2123-2640
Received (in Cambridge, UK) 20th March 2002, Accepted 9th April 2002
First published as an Advance Article on the web 18th April 2002
Coupling of cis-1-bromo-2-pentene and (S,S)-hydrobenzoin
stannylene acetal followed by regio- and stereoselective
transformations of the resulting allylic ether gave (+)-poly-
oxamic acid and a similar procedure was applied to the
(2S,3S,5S)-olefin 5 {[a]D +18 (c 1.0)} and its (2S,3S,5R)-
diastereomer (3+1 ratio), which could then be separated by flash
column chromatography. Attempts to direct conversion of
compound 4 by oxypalladation into compound 5 under various
conditions were not successful. Epoxidation of the major olefin
5 with dimethyldioxirane (DMD) was stereoselective to give the
epoxide 6 {[a]D –35 (c 1.0)} and its diastereomeric epoxide in
the ratio of 9+1, which were separated by flash column
chromatography. Ring opening of the major epoxide 6 with
PhSeNa, generated in situ from PhSeSePh and NaBH4, was
completely regioselective to give only one hydroxyselenide,
whereupon oxidation with NaIO4 in the presence of NaHCO3
followed by elimination provided the allylic alcohol 7 {[a]D
+15 (c 1.0)}. Treatment of the compound 7 with trichlor-
oacetonitrile in the presence of DBU produced the tri-
chloroacetimidate 8 {[a]D +5.0 (c 1.0)}. Regioselective iodocy-
clization of the compound 8 with iodine in THF afforded
iodo-1,3-oxazoline 9 {[a]D +28 (c 1.0)}. Transformation of the
iodide 9 into the alcohol was carried out by treatment of 9 with
Amberlite®IRA-900 carbonate form9 in refluxing benzene.
synthesis of -sorbitol from trans-1-iodo-2-hexene.
D
An efficient methodology for the transformation of simple
achiral acyclic allylic halides to chiral acyclic polyhydroxy or
aminopolyhydroxy compounds without the carbon–chain elon-
gation would be of great value for the synthesis of various
important natural products. We have previously reported the
synthesis of enantiopure cyclic polyhydroxy and aminopolyhy-
droxy compounds from achiral cycloalkenes using hydro-
benzoin as a chiral source.1 However, the synthesis of chiral
acyclic polyhydroxy and aminopolyhydroxy compounds from
simple acyclic achiral starting materials by acyclic stereocontrol
poses a greater challenge. One of the most interesting acyclic
aminopolyhydroxy compounds is (+)-polyoxamic acid (1), the
side chain moiety of peptidyl nucleoside antibiotics, polyoxins,2
which inhibit chitin synthetase of Candida albicans, a human
fungal pathogen and of various phytopathogenic fungi as well
and thus have been used as agricultural fungicides.3 Most
synthetic approaches to (+)-polyoxamic acid have used chiral
starting materials4 except Trost’s work mediated by Pd-
catalyzed asymmetric induction with achiral acyclic allylic
substrates.5 Herein we report a new and efficient synthesis of an
acyclic aminopolyhydroxy compound (+)-polyoxamic acid (1)
starting from 1-bromo-2-pentene employing (S,S)-hydroben-
zoin not only as a chiral source but also as the oxygen atom
source. We also report the synthesis of an acyclic polyhydroxy
target molecule,
-sorbitol (2)6 from 1-iodo-2-hexene employ-
D
ing the same methodology.
Synthesis of (+)-polyoxamic acid commenced with the
coupling of cis-1-bromo-2-pentene and the (S,S)-hydrobenzoin
stannylene acetal 3. Direct reaction of cis-1-bromo-2-pentene
with the sodium monoalkoxide of (S,S)-hydrobenzoin, how-
ever, gave not only the desired allylic ether 4 but also a
substantial amount of the diallylic ether, which was the adduct
of one mole of (S,S)-hydrobenzoin and two moles of cis-
1-bromo-2-pentene. (S,S)-Hydrobenzoin7 was, therefore, con-
verted into the (S,S)-hydrobenzoin stannylene acetal 3 by its
reaction with dibutyltin oxide in refluxing methanol for 30 min8
and the crude stannylene acetal 3 was used for the next step
without purification (Scheme 1). Displacement reaction of cis-
1-bromo-2-pentene with the compound 3 in DMF afforded the
allylic ether 4. Intramolecular oxyselenenylation of the com-
pound 4 using PhSeOTf, which was generated in situ from
PhSeBr and AgOTf, provided an inseparable mixture of two
diastereomeric oxyselenides in 92% yield. Oxidation of the
oxyselenides with NaIO4 in the presence of NaHCO3 followed
by elimination of the resulting selenoxide afforded the
Scheme 1 Reagents and conditions: i, Bun2SnO, MeOH, reflux, 30 min; ii,
cis-1-bromo-2-pentene, DMF, rt, 8 h, 91% in 2 steps; iii, PhSeOTf,
CH2Cl2–THF, 278 °C, 2 h, then rt, 1 h, 92%; iv, NaIO4, NaHCO3, MeOH–
H2O, rt, 10 min, then 70 °C, 5 h, 5 and its (2S,3S,5R)-diastereomer (3+1),
90%; v, DMD, acetone, rt, 2 h, 6 and its diastereomeric epoxide (9+1), 83%;
vi, PhSeSePh, NaBH4, EtOH, 60 °C, 2 h, 85%; vii, NaIO4, NaHCO3,
MeOH–H2O, rt, 10 min, then 70 °C, 48 h, 80%; viii, CCl3CN, DBU,
CH2Cl2, reflux, 3 h, 82%; ix, I2, THF, rt, 3 h; 75%; x, Amberlite® IRA-900
carbonate form, benzene, reflux, 4 h, 81%; xi, RuCl3·xH2O (cat.), K2S2O8,
1 M KOH, H2O, rt, 7 h, 81%; xii, H2, Pd(OH)2 (cat.), conc. HCl (trace),
EtOH, 50 psi, rt, 24 h; xiii, Ac2O, MeOH, rt, 38% in 2 steps.
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Oxidation of the resulting alcohol with RuCl3/K2S2O8 provided
the carboxylic acid 10 {[a]D +5.0 (c 1.0)}. Hydrogenolysis of
the compound 10 using Pd(OH)2 as the catalyst in the presence
of a trace amount of conc. HCl gave crude (+)-polyoxamic acid
(1), of which lactonization using acetic anhydride afforded the
known lactone 11 {[a]D –103 (c 1.0)}.4a,h,k
PhSeNa was completely regioselective to give only one
hydroxyselenide. Oxidation of the hydroxyselenide with NaIO4
followed by elimination of the resultant selenoxide provided the
allylic alcohol 15 {[a]D +18 (c 1.0)}. Treatment of the
compound 15 with Bun Li and then with benzyl chloroformate
afforded the carbonate 16 {[a]D +23.4 (c 1.5)}. Intramolecular
oxyselenenylation of 16 with PhSeBr and the subsequent
oxidation of the resultant selenenyl cyclic carbonate followed
by elimination of the resulting selenoxide gave the olefinic
cyclic carbonate 17 {[a]D –23 (c 1.0)}. Dihydroxylation of
olefin 17 with OsO4/NMO afforded the diol, of which cyclic
carbonate group was hydrolysed during the workup process to
afford the tetrol 18 {[a]D –29 (c 1.0)}. Hydrogenolysis of the
Synthesis of -sorbitol was carried out in a similar manner
D
(Scheme 2). Reaction of trans-1-iodo-2-hexene with the
compound 3 in DMF afforded the allylic ether 12 {[a]D –53 (c
2.0)}. Intramolecular oxyselenenylation of the compound 12
with PhSeOTf gave a mixture of two diastereomeric oxy-
selenides. Oxidation of the diastereomeric oxyselenides with
NaIO4 in the presence of NaHCO3 followed by elimination of
the resulting selenoxide provided a mixture of (2S,3S,5S)-olefin
13 {[a]D +13 (c 1.0)} and its (2S,3S,5R)-diastereomer in the
ratio of 7+3, which could be separated by flash chromatography.
Epoxidation of the major olefin 13 with DMD proceeded in a
stereoselective manner to give a separable mixture of the
epoxide 14 {[a]D +33 (c 1.0)} and its diastereomeric epoxide in
the ratio of 9+1. Ring opening of the major epoxide 14 with
compound 18 using Pd(OH)2 as the catalyst gave
(2).
D-sorbitol
In conclusion, we demonstrated that the present methodology
employing (S,S)-hydrobenzoin as the chiral source and as the
oxygen source would be very useful for the synthesis of
important acyclic aminopolyhydroxy and polyhydroxy com-
pounds from simple achiral substances. Another merit of the
present methodology is that an identical procedure using (R,R)-
hydrobenzoin would provide the enantiomers of those obtained
using (S,S)-hydrobenzoin.
This research was supported by a grant from KOSEF-CMDS
(Centre for Molecular Design and Synthesis).
Notes and references
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Scheme 2 Reagents and conditions: i, trans-1-iodo-2-hexene, DMF, rt, 8 h,
95%; ii, PhSeOTf, CH2Cl2–THF, 278 °C, 2 h, then rt, 1 h, 93%; iii, NaIO4,
NaHCO3, MeOH–H2O, rt, 10 min, then 70 °C, 5 h, 13 and its (2S,3S,5R)-
diastereomer (7+3), 91%; iv, DMD, acetone, rt, 2 h, 14 and its
diastereomeric epoxide (9+1), 82%; v, PhSeSePh, NaBH4, EtOH, 60 °C, 2
h, 88%; vi, NaIO4, NaHCO3, MeOH–H2O, rt, 10 min, then CCl4, 70 °C, 12
h, 85%; vii, BunLi, THF, 278 °C, 5 min, then benzyl chloroformate, 278
°C, 1 h, 98%; viii, PhSeBr, CH3CN, 60 °C, 24 h, 62%; ix, NaIO4, NaHCO3,
MeOH–H2O, rt, 10 min, then 70 °C, 48 h, 87%; x, OsO4 (cat.), NMO,
acetone–H2O, 60 °C, 48 h, 60%, xi, H2, Pd(OH)2 (cat.), conc. HCl (trace),
EtOH, 50 psi, rt, 24 h, 68%.
9 G. Cardillo, M. Orena, G. Porzi and S. Sandri, Synthesis, 1981, 793.
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