A new approach to (-)-swainsonine by ruthenium-catalyzed ring rearrangement

Article abstract of DOI:10.1021/jo025589u

A new enantioselective synthesis of the idolizidine alkaloid (-)-swainsonine 1 in 40% overall yield starting from the known oxazolidinone 6 is described. Throughout the synthesis, the high efficiency of metal-catalyzed reactions is illustrated. The key step is a new ruthenium-catalyzed metathesis rearrangement reaction. In this ring-closing/ring-opening tandem process, stereocenters are transferred from a ring to the olefinic side chain of the formed heterocycle. The metathesis precursor was obtained by palladium-catalyzed desymmetrization of cyclopentenediol. The synthesis was completed by functionalization of the terminal double bond, cyclization of the second ring, and diastereoselective dihydroxylation.

Full text of DOI:10.1021/jo025589u

J . Org. Chem. 2002, 67, 4325-4329
4325
A New Ap p r oa ch to (-)-Sw a in son in e by Ru th en iu m -Ca ta lyzed
Rin g Rea r r a n gem en t
Nicole Buschmann, Anke Ru¨ckert, and Siegfried Blechert*
Institut fu¨r Chemie, Technische Universita¨t Berlin, Strasse des 17. J uni 135, D-10623 Berlin, Germany
blechert@chem.tu-berlin.de
Received February 4, 2002
A new enantioselective synthesis of the idolizidine alkaloid (-)-swainsonine 1 in 40% overall yield
starting from the known oxazolidinone 6 is described. Throughout the synthesis, the high efficiency
of metal-catalyzed reactions is illustrated. The key step is a new ruthenium-catalyzed metathesis
rearrangement reaction. In this ring-closing/ring-opening tandem process, stereocenters are
transferred from a ring to the olefinic side chain of the formed heterocycle. The metathesis precursor
was obtained by palladium-catalyzed desymmetrization of cyclopentenediol. The synthesis was
completed by functionalization of the terminal double bond, cyclization of the second ring, and
diastereoselective dihydroxylation.
Sch em e 1. Ru th en iu m -Ca ta lyzed Rin g
Rea r r a n gem en t
In tr od u ction
During the past decade, the synthetic potential of ring-
closing metathesis (RCM) as a mild and catalytic C-C
bond-forming method has been well recognized.1 RCM is
widely used in the synthesis of small, medium, and large
rings. However, the application of RCM to the synthesis
of chiral carbo- or heterocycles is often limited by the
accessibility of the chiral acyclic precursor dienes. To
avoid complicated multistep syntheses of such chiral
acyclic dienes, a new concept for the synthesis of chiral
carbo- and heterocyclessa ring rearrangement domino
process shas recently been developed.2 In these ruthe-
nium-catalyzed metathesis reactions a carbocycle is
transformed into a heterocyclic product by an intra-
molecular ring-closing/ring-opening domino metathesis
(Scheme 1).
Due to the reversibility of the metathesis cycloaddition/
cycloreversion sequences of the rearrangement, the reac-
tion is thermodynamically controlled. The ratio of start-
ing material to rearrangement product is therefore
determined by the difference of free energy of formation
of product and reactant.
The ring-rearrangement reaction of chiral carbocycles,
e.g., cyclopentene derivatives, offers significant advan-
tages over RCM methodology. Enantiomerically pure
cyclopentene precursors are readily accessible in contrast
to chiral acyclic dienes. The palladium-catalyzed allylic
substitution of cyclopentene derivatives offers one pos-
sibility for the synthesis of such carbocycles.3 In the
metathesis rearrangement, a stereocenter is transferred
from the carbocycle into the side chain of the formed
heterocycle, thus incorporating the desired chiral moi-
eties into the product (Scheme 1).
We recently applied the ruthenium-catalyzed ring
rearrangement in the synthesis of (-)-halosaline2b and
(+)-dumetorine. Herein, we report a ruthenium-catalyzed
ring rearrangement of a chiral cyclopentene precursor
and demonstrate the efficiency of this flexible concept
in the synthesis of the polyhydroxylated indolizidine
alkaloide (-)-swainsonine 1. Swainsonine was first iso-
lated from the fungus Rhizoctonia leguminicolain4 in
1973 and has since attracted great attention from both
biological and synthetic points of view.5 It is found to be
an effective inhibitor of R-D-mannosidases, including the
glycoprotein-processing enzyme mannosidase II.6 It also
exhibits important antimetastatic, antitumor-prolifera-
tive, anticancer, and immunoregulating activity.6 Swain-
sonine was the first inhibitor to be selected for testing
as an anticancer drug, reaching phase I clinical trials.
Due to its promising biological profile, much effort has
been devoted to the development of efficient syntheses
of this azasugar analogue.7
Retrosynthetic analysis reveals that the target mol-
ecule 1 may arise from functionalized dihidropyrrolidine
* To whom correspondence should be addressed. Tel: +49-30-
31422255. Fax: +49-30-31423619.
(1) For recent reviews, see: (a) Fu¨rstner, A. Angew. Chem. 2000,
112, 3140-3172; Angew. Chem., Int. Ed. 2000, 39, 3012-3043. (b)
Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413-4450. (c)
Armstrong, S. J . Chem. Soc., Perkin Trans. 1 1998, 317-388. (d)
Fu¨rstner, A. Top. Organomet. Chem. 1998, 1, 37-72. (e) Schuster, M.;
Blechert, S. Angew. Chem. 1997, 109, 2124-2144; Angew. Chem., Int.
Ed. Engl. 1997, 36, 2036-2056.
(2) For examples, see: (a) Stragies, R.; Blechert, S. J . Am. Chem.
Soc. 2000, 122, 9584-9591. (b) Stragies, R.; Blechert, S. Tetrahedron
1999, 55, 8179-8188. (c) Weatherhead, G. S.; Ford, J . G.; Alexanian,
E. J .; Schrock, R. R.; Hoveyda, A. H. J . Am. Chem. Soc. 2000, 122,
1828-1829.
(3) (a) Trost, B. M.; Patterson, D. E. J . Org. Chem. 1998, 63, 1339-
1341. (b) Trost, B. M.; van Vranken, D. L. Chem. Rev. 1996, 96, 395-
422. (c) Trost, B. M.; Van Vranken, D. L.; Bingel, C. J . Am. Chem.
Soc. 1992, 114, 9327-9343.
(4) Guengerich, F. P.; DiMari, S. J .; Broquist, H. P. J . Am. Chem.
Soc. 1973, 95, 2055-2056.
(5) For a review concerning synthesis and biological activity of
swainsonine and other glycosidase inhibitors, see: Nishimura, Y. In
Studies in Natural Products Chemistry; Atta-ur-Rahman, Ed.; Elsevi-
er: Amsterdam, 1992; Vol. 10, pp 495-583.
(6) For a recent review, see: El Nemr, A. Tetrahedron 2000, 56,
8579-8629.
10.1021/jo025589u CCC: $22.00 © 2002 American Chemical Society
Published on Web 05/15/2002

4326 J . Org. Chem., Vol. 67, No. 12, 2002
Buschmann et al.
Sch em e 2. Retr osyn th etic An a lysis
essential to shift the rearrangement equilibrium com-
pletely toward the product. In contrast, rearrangement
of the benzyl ether analogue of 9 afforded an starting
material/product ratio of 18:1. We would propose that the
superiority of the TBDMS group is due to increased steric
interactions between substituents, thus facilitating ring
opening. In addition, dimerization of products could be
suppressed by introduction of this large substituent on
the hydroxy group. Excess ethylene as an additive in the
metathesis increased the yield and avoided side product
formation.2b When the reaction was performed with a
0.05 M concentration of 9 in CH2Cl2 using 5 mol % of the
commercially available “Grubbs’ catalyst” (benzylidene-
bis-(tricyclohexylphosphine)ruthenium dichloride) and
excess ethylene, an isolated yield of up to 98% was
achieved. When the amount of catalyst was reduced to 1
mol %, the isolated yield decreased to 89%. For the
essential removal of all ruthenium impurities from the
product,8 1.5 equiv (relative to the amount of Grubb’s
catalyst) of lead tetraacetate was added to the reaction
mixture after complete conversion of 9. Subsequent
filtration of the reaction mixture through a pad of silica
gel and washing with CH2Cl2 yielded the desired product
10 as a colorless solid. Stereochemical integrity of the
two chiral centers was completely preserved in this
rearrangement.
Sch em e 3. Rea gen ts a n d Con d ition sa
a
Key: (a) KOH, MeOH, 70 °C, 60 min, 98%; (b) CH2dCHCH2Br,
K2CO3, DMF, rt, 12 h, 99%; (c) TBDMSOTf, 2,6-lutidine, CH2Cl2,
98%; (d) 5 mol % (Cl2(PCy3)2RuCHPh (Cy ) cyclohexyl)), CH2dCH2,
CH2Cl2, 40 °C, 1 h, 98%.
For the formation of the six-membered ring system,
the terminal double bond needed to be functionalized
appropriately (Scheme 4). Selective hydroboration with
9-BBN followed by oxidative workup with NaOH/H2O2
provided the terminal alcohol. If the rearrangement
product 10 was simply chromatographed without using
lead tetraacetate to remove all traces of ruthenium, these
remaining impurities lead to no conversion in the hydro-
boration. Decomposition of starting material was ob-
served. Subsequent deprotection of the tosyl group was
accomplished by using freshly prepared sodium amalgam
in methanolic phosphate buffer without isolation of the
secondary amine.9 All attempts to induce cyclization by
in situ activation of the terminal alcohol were unsuccess-
ful. Therefore, the amine was selectively protected as the
allyl carbamate by treatment of the crude detosylated
product with allyl chloroformate and sodium hydroxide
in CH2Cl2/H2O. Subsequent mesylation of the primary
alcohol provided the cyclization precursor 13. The allyl
oxycarbonyl group was then deprotected by polymer-
bound Pd(PPh3)4, and subsequent nucleophilic substitu-
tion of the mesylate by the freed amino group provided
indolizidine derivative 14 in 95% yield after simple
filtration through basic alumina. The utilization of
soluble Pd(PPh3)4 was not feasible, since the indolizidine
derivative 14 was not stable after chromatography using
silica gel. Decomposition took place within a few hours.
With the indolizidine derivative 14 now established,
only the surprisingly nontrivial oxidation of the alkene
remained to complete the synthesis. Introduction of the
cis-dihydroxy functionality in the 1- and 2-positions of
14 was planned to be carried out according to the
procedure of Mukai et. al., who reported a selectivity of
88:12 in favor of the desired configuration using OsO4,
NMO, acetone, and water at room temperature.10 How-
2, which itself could be readily prepared via a ruthenium-
catalyzed ring rearrangement as the key step in our
synthetic strategy. The metathesis precursor 3 is readily
available by asymmetric palladium-catalyzed allylic ami-
nation of meso-diol 5 (Scheme 2). Unlike most synthetic
approaches using starting materials from the chiral pool,
both enantiomers of 4 would be available by this strategy.
Resu lts a n d Discu ssion
An enantiomerically pure oxazolidinone derivative 6
serves as the initial chiral material in our synthesis
(Scheme 3). The efficiency of palladium-catalyzed desym-
metrization of meso-bis-carbamate substrates, which can
be generated in situ by reaction of a diol with 2 equiv of
p-tosyl isocyanate, has been demonstrated by Trost.3
Oxazolidinone derivative 6 was prepared on large scale,
using in situ generated bis-carbamate of 5, 3 equiv of
NEt3, and 2.5 mol % of the chiral palladium catalyst at
-50 to 0 °C. The catalyst was prepared from ligand
L* ) (1R,2R)-(+)-1,2-diaminocyclohexane-N,N′-bis(2′-di-
phenyphosphinobenzoyl) and tris(dibenzylideneacetone)-
dipalladium(0) choroform complex in THF. HPLC analy-
sis revealed an enantiomeric excess (ee) of the corre-
sponding oxazolidinone 6 of greater than 97%. Recrystalli-
zation from dichlormethane/hexanes increased the ee to
>99%. The metathesis precursor 9 was then obtained in
high yield by a standard sequence of carbamate hydroly-
sis, amide alkylation, and protection of the secondary
alcohol as TBDMS ether in 95% overall yield.
As shown in Scheme 3, the ruthenium-catalyzed me-
tathesis successfully converted 9 into the desired dihy-
dropyrrole 10. Correlating well with previous findings,2b
the sterically demanding TBDMS ether proved to be
(7) For some recent syntheses of (-)-swainsonine, see: (a) Zhao, H.;
Hans, S.; Cheng, X.; Mootoo, D. R. J . Org. Chem. 2001, 66, 1761-
1767. (b) de Vicente, J .; Arrayas, R. G.; Canada, J .; Carretero, J . C.
Synlett 2000, 53-56, (c) Trost, B. M.; Patterson, D. E. Chem. Eur. J .
1999, 5, 3279-3284.
(8) Paquette, L. A.; Schloss, J . D.; Efremov, I.; Fabris, F.; Gallou,
F.; Mendez-Andino, J .; Yang, J . Org. Lett. 2000, 2, 1259-1261.
(9) Chavez, F., Sherry, A. D. J . Org. Chem. 1989, 54, 2990-2992.
(10) Mukai, C.; Sugimoto, Y.; Miyazawa, K.; Yamaguchi, S.;
Hanaoka, M. J . Org. Chem. 1998, 63, 6281-6287.

Enantioselective Synthesis of (-)-Swainsonine
J . Org. Chem., Vol. 67, No. 12, 2002 4327
Sch em e 4a
Con clu sion
In summary, the concept of ring-closing/ring-opening
tandem metathesis was successfully applied to the
synthesis of the polyhydroxylated indolizidine alkaloid
(-)-swainsonine 1, which was obtained in 40% yield over
12 steps starting from 6. Our strategy enables the synthe-
sis of enantiomerically pure heterocycles carrying a func-
tionalized side chain amenable to further manipulations.
Exp er im en ta l Section
Gen er a l Meth od s. All reagents were obtained commer-
cially and were used without further purification. All reactions
were carried out under an inert atmosphere (N2) unless
otherwise indicated. Anhydrous tetrahydrofuran was obtained
by distillation from sodium benzophenone, dichlormethane
from calcium hydride, and methanol from magnesium. The
enantiomeric excesses were determined by chiral HPLC
analyses with a CHIRACEL OJ column using hexane/isopropyl
alcohol mixtures as eluent.
(3a S,6a R)-3-(Tolu en e-4-su lfon yl)-3,3a ,6,6a -tetr a h yd r o-
cyclop en t-4-en oxa zol-2-on e (6). To a solution of the meso-
diol 5 (7.00 g, 69.92 mmol) in 120 mL of THF was added tosyl
isocyanate (34.45 g, 174.67 mmol) at room temperature. The
mixture was then stirred at 60 °C for 1 h. The reaction was
allowed to cool to room temperature, and 29 mL (21.05 g,
208.06 mmol) of triethylamine was added. The resulting white
slurry was cooled to -50 °C, and an orange solution of tris-
(dibenzylideneacetone)dipalladium(0) chloroform complex (1.81
g, 1.75 mmol) and (3.63 g, 5.24 mmol) ligand L* ) (1R,2R)-
(+)-1,2-diaminocyclohexane-N,N′-bis(2′-diphenyphosphinoben-
zoyl) in 25 mL of THF was slowly added. The orange reaction
mixture was stirred mechanically at -50 °C for 1 h, stepwise
warmed over a period of 5 h until 0 °C, and subsequently
stirred overnight at room temperature. Solvent was removed
under vacuum, and the crude product was purified by flash
chromatography, eluting with 3:2 hexanes/EtOAc, to yield the
desired product 6 (17.89 g, 92%) as a white solid (97% ee, as
determined by chiral HPLC, Chiralcel OJ -column, 50:50
hexane/2-propanol, 1 mL/min, 210 and 245 nm, (-) 12.9 min,
(+) 19.9 min). The enantiomeric excess was improved to >99%
(11.13 g, 57% yield) by recrystallization from dichloromethane/
a
Reagents and conditions: (a) (i) 9-BBN, THF, 0-55 °C, 8 h,
(ii) NaOH/H2O2, EtOH, 60 min, reflux, 83%; (b) (i) Na/Hg, MeOH,
reflux, 120 min, (ii) NaOH, CH2dCHCH2CO2Cl, CH2Cl2/H2O, rt,
60 min, 89%; (c) MsCl, NEt3, CH2Cl2, 0 °C, 2 h, 98%; (d) Pd0, NEt3,
dimedone, THF, 3 h, rt, 3 h 60 °C, 95%; (e) (i) AD-mix-R,
CH3SO2NH2, 5 °C, 1 week, (ii) TBAF, THF, rt, 24 h, (iii) Ac2O,
pyridine, DMAP, CH2Cl2, rt, 24 h, 68% (13:14 ) 20:1); (f) Amberlite
IRA-401, MeOH, rt, 2 h, 96%.
ever, in our hands, these results could not be reproduced.
Unfortunately, after desilylation and described protection
as triacetates, we observed almost no diastereoselectivity
(ratio of 15/16 ) 50:50-42:58).11
hexanes. 6: mp 119-122 °C (lit.3 mp 121-125 °C); [R]20
)
D
+141.27 (c ) 0.865, CH2Cl2) (lit.3 99% ee, [R]20 ) +114 (c )
D
2.52, CH2Cl2)); 1H NMR (400 MHz, CDCl3) δ 2.45 (s, 3H), 2.69
(br d, J ) 19 Hz, 1H), 2.81 (br dd, J ) 19, 7 Hz, 1H), 5.11
(ddd, J ) 7, 7, 1 Hz, 1H), 5.29 (br d, J ) 7 Hz, 1H), 6.00 (br d,
J ) 7 Hz, 1H), 6.04 (br d J ) 7 Hz, 1H), 7.35 (d, J ) 8 Hz,
2H), 7.95 (d, J ) 8 Hz, 2H); 13C NMR (125.8 MHz, CDCl3) δ
21.7 (CH3), 39.0 (CH2), 66.3 (CH), 76.7 (CH), 128.0 (CH), 128.3
(CH), 129.7 (CH), 133.8 (CH), 135.0 (Cq), 145.5 (Cq), 151.3 (Cq);
IR (neat, cm-1) 3069, 2925, 2846, 1775, 1596, 1364, 1168, 1143;
LRMS m/z 280 ([M - H]+, <1), 215 (75), 170 (76), 91 (100);
To improve the facial selectivity of the dihydroxylation
reaction an asymmetric oxidation was employed.12 With
use of AD-mix-R, the stereoselectivity of the syn-hydroxyl-
ation was improved, leading to a 20:1 mixture of dia-
stereomeric diols favoring the desired diastereomer.
Dihydroxylation occurred mainly from the face of the
double bond in a trans relationship with regard to H8a.
Since this mixture of diastereomers could not be sepa-
rated by column chromatography, the mixture was de-
silylated and converted into the corresponding triacetates
15 and 16.10 Column chromatography provided 15 (318
mg) and 16 (6 mg) in 65% and 3% yield. Comparison of
spectroscopic data with those previously reported in the
literature for the triacetate of natural (-)-swainsonine
1 and the triacetate of 1,2-di-epi-swainsonine 16 con-
firmed their stereochemical assignments. Finally, basic
hydrolysis of 15 using Amberlite resin (Amberlite IRA-
401) in methanol at room temperature provided (-)-
swainsonine 1 in 96% isolated yield.
HRMS calcd for
280.0641. Anal. Calcd for C13H13NO4S: C, 55.90; H, 4.69; N,
5.01. Found: C, 55,92; H, 4.78; N 5.16.
C
13H14NO4S [M + H+] 280.0644, found
N-((1S,5R)-5-H yd r oxycyclop en t -2-en yl)-4-m et h ylb en -
zen esu lfon a m id e (7). Oxazolidinone 6 (4.01 g, 14.35 mmol)
and potassium hydroxide (2.42 g, 43.06 mmol) were suspended
in 140 mL of methanol and the mixture heated to 70 °C for 2
h. Dichloromethane and saturated NaCl solution were added
to the reaction mixture, the phases were separated, and the
aqueous layer was extracted two times with dichloromethane.
The dichloromethane phase was dried with magnesium sul-
fate, and the solvent was removed under vacuum. The desired
product was purified by chromatography on silica gel using
1:1 hexanes/MTBE to yield 7 (3.55 g, 14.00 mmol, 98%) as a
white solid. 7: mp 59-61 °C; [R]20 ) +13.27 (c ) 0.985,
D
CH2Cl2); 1H NMR (400 MHz, CDCl3) δ 1.75 (br s, 1H), 2.33
(dddd, J ) 18, 4, 2, 2 Hz, 1H), 2.44 (s, 3H), 2.57 (dddd, J ) 18,
6, 4, 2 Hz, 1H), 4.22 (dddd, J ) 6, 6, 4, 2 Hz, 1H), 4.25 (br d,
J ) 6 Hz, 1H), 5.22 (br d, J ) 8 Hz, 1H), 5.35 (ddd, J ) 6, 2,
2, Hz, 1H), 5.80 (ddd, J ) 6, 4, 2 Hz, 1H), 7.32 (d, J ) 8 Hz,
2H), 7.80 (d, J ) 8 Hz, 2H); 13C NMR (125.8 MHz, CDCl3) δ
(11) A diastereomeric ratio of 20:80 (favoring the undesired config-
uration) was recently reported using the even more bulky TIPS
protecting group on the C8 oxygen; see ref 7b.
(12) Kolb, H. C.; Van Nieuwenhze, M. S.; Sharpless, K. B. Chem.
Rev. 1994, 94, 2483-2547.

4328 J . Org. Chem., Vol. 67, No. 12, 2002
Buschmann et al.
21.5 (CH3), 40.1 (CH2), 61.4 (CH), 70.3 (CH), 127.2 (CH), 129.0
(CH), 129.8 (CH), 131.8 (CH), 137.3 (Cq), 143.6 (Cq); IR (neat,
cm-1) 3495, 3273, 3064, 2924, 1598, 1437, 1327, 1158; LRMS
m/z 253 ([M+], <1), 197 (19), 155 (21), 98 (100), 91 (80); HRMS
calcd for C12H15NO3S [M+] 253.0773, found 253.0778. Anal.
Calcd for C12H15NO3S: C, 56.90; H, 5.97; N, 5.53. Found: C,
56.78; H, 5.96; N, 5.68.
solid. 10: mp 77-79 °C; [R]20D ) -205.22 (c ) 0.938, CH2Cl2);
1H NMR (400 MHz, CDCl3) δ 0.10 (s, 3H), 0.15 (s, 3H), 0.86
(s, 9H), 2.24 (dddd, J ) 14, 8, 2, 1 Hz, 1H), 2.30 (dddd, J ) 14,
6, 2, 2 Hz, 1H), 2.41 (s, 3H), 4.03 (dddd, J ) 15, 2, 2, 2 Hz,
1H), 4.10 (dddd, J ) 15, 5, 2, 2 Hz, 1H), 4.22 (ddd, J ) 8, 6, 2
Hz, 1H), 4.36 (m, 1H), 5.11 (ddd, J ) 10, 2, 1 Hz, 1H), 5.12
(ddd, J ) 18, 2, 2 Hz, 1H), 5.59 (dddd, J ) 6, 2, 2, 2 Hz, 1H),
5.62 (dddd, J ) 6, 2, 2, 1 Hz, 1H), 5.87 (dddd, J ) 18, 10, 8, 6
Hz, 1H), 7.29 (d, J ) 8 Hz, 2H), 7.65 (d, J ) 8 Hz, 2H); 13C
NMR (125.8 MHz, CDCl3) δ -4.6 (CH3), -4.5 (CH3), 18.0 (Cq),
21.5 (CH3), 25.8 (CH3), 40.2 (CH2), 56.1 (CH2), 71.2 (CH,), 74.1
(CH,), 117.3 (CH2), 125.8 (CH), 125.9 (CH), 127.5 (CH), 129.7
(CH), 134.3 (Cq), 134.7 (CH), 143.4 (Cq); IR (neat, cm-1) 2927,
2855, 1641, 1599, 1339, 1160; LRMS m/z 392 ([M+ - CH3], 3),
350 (89), 222 (29), 213 (17), 185 (100), 91 (29), 73 (93); HRMS
calcd for C20H30NO3SSi [M+ - CH3] 392.1716, found 392.1716.
Anal. Calcd for C21H33NO3SSi: C, 61.87; H, 8.16; N, 3.44.
Found: C, 61.97; H 8.05; N, 3.66.
N-Allyl-N-((1S,5R)-5-h yd r oxycyclop en t-2-en yl)-4-m eth -
ylben zen esu lfon a m id e (8). Amine 7 (9.65 g, 38.08 mmol),
potassium carbonate (7.89 g, 57.12 mmol), and allyl bromide
(4.8 mL, 6.86 g, 56.74 mmol) were suspended in 50 mL of DMF
and the mixture stirred overnight at room temperature.
Dichloromethane and a saturated NaCl solution were added
to the suspension, and the aqueous layer was extracted two
times with dichloromethane. The combined organic layers were
dried with MgSO4, and the solvent was removed under
vacuum. The residue was purified by a short column filtration
on silica gel using 1:1 hexanes/MTBE to yield 8 (11.01 g, 37.53
mmol, 99%) as a white solid. 8: mp 34-35 °C; [R]20D ) +75.49
(c ) 0.865, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ 2.34 (dddd,
J ) 18, 4, 4, 2 Hz, 1H), 2.43 (s, 3H), 2.65 (dddd, J ) 18, 7, 3,
2 Hz, 1H), 3.71 (dddd, J ) 16, 6, 2, 2 Hz, 1H), 4.01 (br dd, J
) 16, 6 Hz, 1H), 4.47 (ddd, J ) 7, 7, 4 Hz, 1H), 4. 61 (br d, J
) 7 Hz, 1H), 5.11 (ddd, J ) 10, 2, 2 Hz, 1H), 5.14 (ddd, J )
18, 2, 2 Hz, 1H), 5.39 (ddd, J ) 6, 3, 2 Hz, 1H), 5.84 (dddd, J
) 18, 10, 6, 6 Hz, 1H), 5.89 (ddd, J ) 6, 4, 2 Hz, 1H), 7.31 (d,
J ) 8 Hz, 2H), 7.75 (d, J ) 8 Hz, 2H); 13C NMR (125.8 MHz,
CDCl3) δ 21.5 (CH3), 39.8 (CH2), 48.6 (CH2), 65.7 (CH), 70.7
(CH), 117.2 (CH2), 126.8 (CH), 127.3 (CH), 129.7 (CH), 133.5
(CH), 135.8 (CH), 137.1 (Cq), 143.5 (Cq); IR (neat, cm-1) 3525,
3065, 2925, 1640, 1598, 1332, 1157; LRMS m/z 293 ([M+], 2),
(R)-4-(ter t-Bu tyld im eth ylsila n yloxy)-4-[(S)-1-(tolu en e-
4-su lfon yl)-2,5-d ih yd r o-1H-p yr r ol-2-yl]bu ta n -1-ol (11). Al-
kene 10 (2.53 g, 6.21 mmol) was dissolved in 130 mL of THF
and cooled to 0 °C, and a 0.5 M solution of 9-BBN-H (14 mL,
7.00 mmol) was slowly added. The reaction mixture was
allowed to warm to room temperature and then heated to 55
°C, and stirring was continued for 8 h. Two hundred milliliters
of ethanol, 12 mL of a 6 M solution of sodium hydroxide, and
7 mL of a 30% hydrogen peroxide solution were then added,
and the solution was refluxed for 1 h. The solvent was
concentrated, MTBE and saturated NaCl solution were added,
and the aqueous layer was extracted three times with MTBE.
The combined organic layers were dried with MgSO4, and the
solvent was removed under vacuum. The residue was purified
by column chromatography on silica gel eluting with 3:2-1:1
hexanes/MTBE to yield the alcohol 11 (2.19 g, 5.15 mmol, 83%)
237 (48), 155 (19), 138 (100), 91 (61); HRMS calcd for C15H19
-
-
NO3S [M+] 293.1086, found 293.1088. Anal. Calcd for C15H19
NO3S: C, 61.41; H, 6.53; N, 4.77. Found: C, 61.38; H, 6.43;
N, 4.93.
as a colorless solid. 11: mp 79-81 °C; [R]20 ) -208.02 (c )
D
N-Allyl-N-[(1S,5R)-5-(ter t-b u t yld im et h ylsila n yloxy)-
cyclop en t-2-en yl]-4-m eth ylben zen esu lfon a m id e (9). To a
solution of the alcohol 8 (6.43 g, 21.91 mmol) and 2,6-lutidine
(6.5 mL, 6.00 g, 55.99 mmol) in 20 mL of dichloromethane was
added dropwise tert-butyldimethylsilyl trifluoromethane-
sulfonate (5.5 mL, 6.37 g, 24.08 mmol). The reaction was
stirred overnight at room temperature, concentrated in a
vacuum, and purified by column chromatography on silica gel
eluting with 8:2 hexanes/MTBE to yield the protected alcohol
0.935, C6H6); 1H NMR (500 MHz, C6D6) δ 0.28 (s, 3H), 0.46 (s,
3H), 1.08 (s, 9H), 1.51-1.79 (m, 4H), 1.93 (s, 3H), 3.48 (m, 2H),
4.06 (dddd, J ) 15, 2, 2, 2 Hz, 1H), 4.15 (dddd, J ) 15, 5, 2, 2
Hz, 1H), 4.46 (ddd, J ) 7, 7, 2 Hz, 1H), 4.52 (dddd, J ) 5, 2,
2, 1 Hz, 1H), 5.17 (dddd, J ) 6, 2, 2, 1 Hz, 1H), 5.37 (dddd, J
) 6, 2, 2, 1 Hz, 1H), 6.85 (d, J ) 8 Hz, 2H), 7.80 (2d, J ) 8 Hz,
2H); 13C NMR (125.8 MHz, C6D6) δ -4.3 (CH3), -4.1 (CH3),
18.3 (Cq), 21.0 (CH3), 26.2 (CH3), 29.4 (CH2), 32.1 (CH2), 56.4
(CH2), 62.5 (CH2), 71.9 (CH), 75.1 (CH), 125.9 (CH), 126.4 (CH),
9 (8.78 g, 21.53 mmol, 98%) as a colorless oil. 9: [R]20
)
127.9 (CH), 129.7 (CH), 135.4 (Cq), 143.1 (Cq); IR (neat, cm-1
)
D
+93.65 (c ) 0.850, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ 0.11
(s, 3H), 0.13 (s, 3H), 0.91 (s, 9H), 2.28 (dddd, J ) 18, 4, 4, 2
Hz, 1H), 2.41 (s, 3H), 2.55 (dddd, J ) 18, 7, 3, 2 Hz, 1H), 3.70
(dddd, J ) 16, 6, 2, 2 Hz, 1H), 4.05 (br dd, J ) 16, 6 Hz, 1H),
4.50 (ddd, J ) 7, 7, 4 Hz, 1H), 4.78 (br d, J ) 7 Hz, 1H), 4.96
(ddd, J ) 10, 2, 2 Hz, 1H), 5.05 (ddd, J ) 18, 2, 2 Hz, 1H),
5.43 (ddd, J ) 6, 3, 2 Hz, 1H), 5.72 (dddd, J ) 18, 10, 6, 6 Hz,
1H), 5.83 (ddd, J ) 6, 4, 2 Hz, 1H), 7.25 (d, J ) 8 Hz, 2H),
7.71 (d, J ) 8 Hz, 2H); 13C NMR (125.8 MHz, CDCl3) δ -5.0
(2CH3), -4.7 (2CH3), 18.1 (Cq), 21.4 (CH3), 25.9 (CH3), 41.4
(CH2), 49.1 (CH2), 64.9 (CH), 72.0 (CH), 116.4 (CH2), 127.1
(CH), 128.1 (CH), 129.4 (CH), 132.4 (CH), 136.3 (CH), 139.3
(Cq), 142.5 (Cq); IR (neat, cm-1) 3064, 2928, 2856, 1640, 1599,
1342, 1160; LRMS m/z 392 ([M+ - CH3], 2), 350 (100), 268
3526, 3417, 2928, 2856, 1598, 1344, 1162; LRMS m/z 426
([MH+], <1), 368 (19), 222 (34), 203 (23), 155 (25), 91 (50), 71
(100), 69 (79), 55 (32); HRMS calcd for C21H36NO4SSi [MH+]
426.2134, found 426.2139. Anal. Calcd for C21H35NO4SSi: C,
59.26; H, 8.29; N, 3.29. Found: C, 59.19; H 8.16; N, 3.41.
(S)-2-[(R)-1-(ter t-Bu tyld im eth ylsila n yloxy)-4-h yd r oxy-
bu tyl]-2,5-d ih yd r op yr r ole-1-ca r boxylic Acid Allyl Ester
(12). Alcohol 11 (3.17 g, 7.44 mmol) and K2HPO4‚3H2O (12.08
g, 52.93 mmol) were dissolved in 160 mL of MeOH. Na/Hg (136
g, freshly prepared from 145 g of Hg and 5.3 g of Na) was
added, and the mixture was refluxed for 2 h. The solution was
decanted, H2O was then added, and the aqueous layer was
extracted four times with CH2Cl2. The combined organic layers
were dried with Na2SO4, and solvent was removed under
vacuum. The crude product was then dissolved in 140 mL of
CH2Cl2/H2O (1:1), and with vigorous stirring NaOH (1.80 g,
44.90 mmol) and allyl chloroformate (1.0 mL, 1.17 g, 9.70
mmol) were added. After 1 h, phases were separated and the
aqueous layer was extracted several times with CH2Cl2. The
combined organic layers were dried with Na2SO4 and concen-
trated. The residue was chromatographed on silica gel using
3:2 hexanes/EtOAc to give 12 (2.35 g, 6.62 mmol, 89%) as a
(89), 252 (75), 73 (70); HRMS calcd for C20H30NO3SSi [M+
-
CH3] 392.1716, found 392.1716. Anal. Calcd for C21H33NO3-
SSi: C, 61.87; H, 8.16; N, 3.44. Found: C, 61.88; H, 7.96; N,
3.50.
(S)-2-[(R)-1-(ter t-Bu tyld im eth ylsila n yloxy)bu t-3-en yl]-
1-(tolu en e-4-su lfon yl)-2,5-d ih yd r o-1H-p yr r ole (10). The
metathesis precursor 9 (6.02 g, 14.76 mmol) was dissolved in
300 mL of CH2Cl2, and 500 mL of C2H4 was slowly bubbled
through the solution via a syringe. Cl2(PCy3)2RuCHPh (0.61
g, 0.74 mmol) was then added, and the mixture was stirred at
25 °C for 3 h. Subsequently, lead tetraacetate (0.49 g, 1.11
mmol) was added to the reaction mixture, and stirring was
continued for an additional 14 h. The solvent was removed
under vacuum, and the residue was then purified by column
filtration over 0.30 g of silica gel using dichloromethane to yield
dihydropyrrole 10 (5.90 g, 14.46 mmol, 98%) as a colorless
colorless oil. 12: [R]20 ) -184.75 (c ) 0.885, C6H6); 1H NMR
D
(500 MHz, C6D6) two rotamers (ratio: 3:1) δ 0.16 (s, 3H), 0.17
(s, 3H), 1.03 (s, 9H), 1.50-1.80 (m, 4H), 3.48 (br s, 0.5H), 3.56-
3.61 (m, 1.5H), 4.01-4.12 (m, 1.5H), 4.18 (br dd, J ) 16, 6 Hz,
0.25H), 4.28 (br t, J ) 6 Hz, 0.25H), 4.40 (br d, J ) 16 Hz,
0.25H), 4.49 (br s, 0.25H), 4.57 (br t, J ) 6 Hz, 0.75H), 4.65
(br dd, J ) 13, 6 Hz, 1H), 4.69-4.78 (m, 1.75H), 5.11 (br d, J
) 10 Hz, 1H), 5.26 (br d, J ) 17 Hz, 0.25H), 5.28 (br d, J ) 18

Enantioselective Synthesis of (-)-Swainsonine
J . Org. Chem., Vol. 67, No. 12, 2002 4329
Hz, 0.75H), 5.45 (br dddd, J ) 6, 2, 2, 1 Hz, 0.75H), 5.51 (br d,
J ) 6 Hz, 0.25H), 5.58 (br d, J ) 6 Hz, 0.25H), 5.64 (br dddd,
J ) 6, 2, 2, 1 Hz, 0.75H), 5.94 (dddd, J ) 17, 10, 6, 5 Hz, 1H);
13C NMR (125.8 MHz, C6D6) δ -4.9, -4.7 (CH3), -4.4, -4.3
(CH3), 18.2 (Cq), 26.0 (CH3), 29.5 (CH2), 32.0 (CH2), 54.1, 55.0
(CH2), 62.4 (CH2), 65.7, 65.8 (CH2), 68.7, 69.5 (CH), 71.2, 72.5
(CH), 117.1, 117.3 (CH2), 125.84, 126.1 (CH), 126.4, 126.8 (CH),
133.7, 134.3 (CH), 154.5 (Cq); IR (neat, cm-1) 3434, 2929, 2857,
1707, 1687, 1627; LRMS m/z 356 ([MH+], <1), 298 (18), 240
(6), 152 (32), 73 (62), 71 (100); HRMS calcd for C18H34NO4Si
[MH+] 356.2257, found 356.2254. Anal. Calcd for C18H33NO4-
Si: C, 60.81; H, 9.36; N, 3.94. Found: C, 60.56; H 9.18; N,
4.15.
(S)-2-[(R)-1-(ter t-Bu tyld im eth ylsila n yloxy)-4-m eth a n e-
su lfon yloxybu tyl]-2,5-d ih yd r op yr r ole-1-ca r boxylic Acid
Allyl Ester (13). Alcohol 12 (0.80 g, 2.26 mmol) and triethyl-
amine (0.95 mL, 0.69 g, 6.83 mmol) were dissolved in 40 mL
of CH2Cl2 and cooled to 0 °C. Subsequently, methanesulfonyl
chloride (0.21 mL, 0.31 g, 2.71 mmol) was added dropwise, and
the solution was allowed to warm to rt. After 2 h of stirring at
rt, saturated NaHCO3 solution was added, and the aqueous
phase was extracted three times with dichloromethane. The
organic phases were dried with Na2SO4 and concentrated. The
residue was chromatographed on silica gel using 3:2 hexanes/
1:1 solution of tert-butyl alcohol and water. The mixture was
stirred at room temperature until both phases were clear and
then cooled to 0 °C, whereupon the inorganic salts partially
precipitated. The olefin 14 (0.42 g, 1.64 mmol) was added at
once, and the heterogeneous slurry was stirred vigorously at
3-6 °C for 1 week. The reaction was quenched by addition of
50 mL of a saturated sodium sulfite solution and stirred for
60 min. The reaction mixture was extracted several times with
ethyl acetate, dried with Na2SO4, and concentrated. The
residue was passed through a short pad of silica gel using 10:1
CH2Cl2/MeOH to give a mixture of crude dihydroxylated
products. To a solution of the crude alcohols in 6.5 mL of THF
was added TBAF (4 mL of a 1.0 M solution in THF), and the
reaction mixture was stirred at room temperature for 24 h.
The reaction mixture was concentrated, CH2Cl2 (6.5 mL),
pyridine (1.2 mL, 14.91 mmol), DMAP (40 mg, 0.33 mmol),
and acetic anhydride (0.9 mL, 9.52 mmol) were added, and
stirring was continued overnight at room temperature. The
reaction mixture was then quenched with MeOH and concen-
trated to dryness. Column chromatography on silica gel using
1:1 hexanes/EtOAc afforded a 20:1 mixture of 15/16 (334 mg,
1.12 mmol, 68%) as a yellow oil. The diastereomers were then
separated by chromatography using 2:1 hexanes/EtOAc as
eluent, to give 15 (291 mg) and 16 (15 mg). Compound 15:
[R]20D ) +7.04 (c ) 0.895, MeOH) (lit.13 [R]20D ) +7.0 (c ) 1.77,
MeOH)); 1H NMR (500 MHz, CDCl3) δ 1.18-1.28 (m, 1H),
1.70-1.79 (m, 2H), 1.91 (ddd, J ) 11, 11, 4 Hz, 1H), 1.99 (s,
3H), 2.05 (s, 3H), 2.09 (s, 3H), 2.11-2.17 (m, 2H), 2.58 (dd, J
) 11, 8 Hz, 1H), 3.05 (ddd, J ) 10, 3, 3 Hz, 1H,), 3.16 (br d, J
) 11 Hz, 1H), 4.95 (ddd, J ) 11, 10, 5 Hz, 1H), 5.21 (ddd, J )
8, 6, 2 Hz, 1H), 5.52 (dd, J ) 6, 4 Hz, 1H); 13C NMR (125.8
MHz, CDCl3) δ 20.5 (CH3), 20.6 (CH3), 21.0 (CH3), 23.3 (CH2),
29.8 (CH2), 51.8 (CH2), 59.3 (CH2), 68.1 (CH), 69.2 (CH), 69.8
(CH), 70.2 (CH), 170.0 (Cq), 170.0 (Cq), 170.2 (Cq); IR (neat,
cm-1) 2945, 2801, 1738, 1254, 1237; LRMS m/z 300 ([MH+],
2), 239 (21), 180 (12), 137 (29), 120 (100); HRMS calcd for
EtOAc to give 13 (0.96 g, 2.21 mmol, 98%) as a colorless oil.
1
13: [R]20 ) -154.25 (c ) 0.870, C6H6); H NMR (500 MHz,
D
C6D6) two rotamers (ratio: 3:1) δ 0.11 (br s, 3H), 0.13 (br s,
3H), 1.00 (br s, 9H), 1.34-1.56 (m, 3H), 1.61-1.75 (m, 1H),
2.27 (br s, 0.75H), 2.33 (br s, 2.25H), 3.89 (br s, 0.50H), 3.94
(t, J ) 6 Hz, 1.50H), 3.98-4.20 (m, 2H), 4.33-4.41 (m, 0.5H),
4.45 (br t, J ) 6 Hz, 0.75H), 4.55 (br s, 0.75H), 4.63 (dd, J )
14, 6 Hz, 0.75H), 4.67-4.78 (m, 1.25H), 5.10 (br d, J ) 10 Hz,
0.75H), 5.11 (br d, J ) 10 Hz, 0.25H), 5.25 (br d, J ) 17 Hz,
0.25H), 5.26 (br d, J ) 17 Hz, 0.75H), 5.41-5.55 (m, 2H), 5.93
(dddd, J ) 17, 10, 6, 6 Hz, 1H); 13C NMR (125.8 MHz, C6D6) δ
-4.9, -4.7 (CH3), -4.4, -4.4 (CH3), 18.1 (Cq), 26.0 (CH2), 26.0
(CH3), 31.3 (CH2), 36.6 (CH3), 54.1, 55.0 (CH2), 65.6, 65.9 (CH2),
68.9, 69.3 (CH2), 68.6, 69.4 (CH), 70.7, 72.0 (CH), 117.1, 117.7
(CH2), 125.6, 126.1 (CH), 126.4, 127.1 (CH), 128.5, 133.7 (CH),
154.5, 160.5 (Cq); IR (neat, cm-1) 2929, 2857, 1703, 1628, 1408,
1358, 1176; LRMS m/z 418 ([M+ - CH3], 2), 376 (38), 281 (49),
185 (23), 153 (50), 71 (100); HRMS calcd for C18H32NO6SSi [M+
- CH3] 418.1720, found 418.1720. Anal. Calcd for C19H35NO6-
SSi: C, 52.63; H, 8.14; N, 3.23. Found: C, 52.42; H 8.09; N,
3.28.
C
14H21NO6 [MH+] 300.1447, found 300.1451. Anal. Calcd for
C14H21NO6: C, 56.18; H, 7.07; N, 4.68. Found: C, 56.07; H 7.13;
N, 4.50.
(1S,2R,8R,8a R)-Oct a h yd r oin d olizin e-1,2,8-t r iol [(-)-
Sw a in son in e] (1). To a solution of trisacetate 15 (54.6 mg,
0.182 mmol) in 3 mL of methanol was added Amberlite resin
(50 mg, Amberlite IRA-401(OH)). The reaction mixture was
shaken for 2 h and filtered through a frit, and the resin was
rinsed with methanol. After the filtrate was concentrated, (-)-
swainsonine 1 (30.6 mg, 0.177 mmol, 96%) was obtained as
colorless crystals. NMR spectroscopy indicated complete con-
version, and no further purification was required. 1: mp 143-
(8R,8a S)-8-(ter t-Bu tyld im eth ylsila n yloxy)-3,5,6,7,8,8a -
h exa h yd r oin d olizin e (14). To a mixture of polymer-bound
Pd(0) catalyst (freshly prepared from palladium acetate (0.05
g, 0.23 mmol) and polymer-bound triphenylphosphine (0.77 g,
2.31 mmol) in 25 mL of THF, shaken for 1 h at room
temperature) was added a solution of 13 (1.00 g, 2.31 mmol)
in 55 mL of THF, triethylamine (3 mL, 40.78 mmol) and
dimedone (2.26 g, 16.14 mmol). The mixture was shaken for 3
h at room temperature and subsequently for 3 h at 50 °C. The
suspension was then chromatographed over basic aluminum
oxide using THF as eluent to yield the desired indolizidine 14
145 °C (lit.13 mp 144-145 °C); [R]20 ) -89.74 (c ) 0.575,
D
MeOH) (lit.13 [R]20 ) -87.2 (c ) 2.1, MeOH)); H NMR (500
1
D
MHz, D2O) δ 1.04-1.13 (m, 1H), 1.31-1.42 (m, 1H), 1.53-
1.60 (m, 1H), 1.76 (dd, J ) 10, 4 Hz, 1H), 1.80 (ddd, J ) 12,
11, 4 Hz, 1H), 1.91 (dddd, J ) 12, 3, 3, 3 Hz, 1H), 2.40 (dd, J
) 11, 8 Hz, 1H), 2.71-2.78 (m, 2H), 3.65 (ddd, J ) 11, 10, 5
Hz, 1H), 4.10 (dd, J ) 6, 4 Hz, 1H), 4.20 (ddd, J ) 7, 6, 3 Hz,
1H); 13C NMR (125.8 MHz, D2O, ref MeOH, 49.00) δ 22.9 (CH2),
32.2 (CH2), 51.4 (CH2), 60.3 (CH2), 66.1 (CH), 68.8 (CH), 69.4
(CH), 72.5 (CH); IR (neat, cm-1) 3368, 2942, 2801, 2726, 1347,
1127, 1073; LRMS m/z 173 ([M+], 25), 155 (25), 138 (16), 113
(100), 96 (89); HRMS calcd for C8H15NO3 [M+] 173.1052, found
173.1046. Anal. Calcd for C8H15NO3: C, 55.47; H, 8.73; N, 8.09.
Found: C, 55.30; H 8.72; N 7.84.
(0.56 g, 2.19 mmol, 95%) as a slightly yellow oil. 14: [R]20
)
D
-91.73 (c ) 0.955, C6H6); 1H NMR (500 MHz, C6D6) δ 0.13 (s,
3H), 0.15 (s, 3H), 1.07 (s, 9H), 1.36 (dddd, J ) 13, 13, 10, 4
Hz, 1H), 1.46-1.53 (m, 1H), 1.62-1.74 (m, 1H), 1.97 (br dddd,
J ) 13, 4, 4, 4 Hz, 1H), 2.32 (ddd, J ) 12, 12, 6 Hz, 1H), 2.81
(br dd, J ) 12, 5 Hz, 1H), 3.09-3.15 (m, 1H), 3.21 (dddd, J )
12, 6, 2, 1 Hz, 1H), 3.62 (dddd, J ) 12, 4, 2, 2 Hz, 1H), 3.68
(ddd, J ) 10, 9, 4 Hz, 1H), 5.77 (dddd, J ) 6, 2, 2, 2 Hz, 1H),
6.26 (br d, J ) 6, Hz, 1H); 13C NMR (125.8 MHz, C6D6) δ -4.5
(CH3), -4.1 (CH3), 18.2 (Cq), 25.1 (CH2), 26.0 (CH3), 35.0 (CH2),
49.0 (CH2), 58.3 (CH2), 72.5 (CH), 74.8 (CH), 128.8 (CH), 131.4
(CH); IR (neat, cm-1) 2929, 2856, 2778, 1616; LRMS m/z 253
([M+], <1), 196 (100), 154 (22), 120 (30), 75 (12); HRMS calcd
for C14H27NOSSi [M+] 253.1862, found 253.1866. Anal. Calcd
for C19H35NOSSi: C, 66.34; H, 10.74; N, 5.53. Found: C, 65.97;
H 10.77; N, 5.18.
Ack n ow led gm en t. This work was supported by the
Graduiertenkolleg Synthetische, mechanistische und
reaktionstechnische Aspekte von Metallkatalysatoren
and by the Fond der Chemischen Industrie.
Su p p or tin g In for m a tion Ava ila ble: Proton and carbon
NMR spectra are available for compounds 6-15 and 1. This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O025589U
Acet ic Acid (1S,2R,8R,8a R)-1,2-Dia cet oxyoct a h yd r o-
in d olizin -8-yl Ester (15). AD-mix-R (4.29 g) and methane-
sulfonamide (0.18 g, 1.85 mmol) were dissolved in 15 mL of a
(13) Schneider, M. J .; Ungemach, F. S.; Broquist, H. P.; Harris, T.
M. Tetrahedron 1983, 39, 29-32.