Total synthesis of chaetomellic anhydrides A and B via a novel succinate to maleate oxidation

Full text of DOI:10.1021/jo9601977

4164
J . Org. Chem. 1996, 61, 4164-4167
Sch em e 1
Tota l Syn th esis of Ch a etom ellic
An h yd r id es A a n d B via a Novel Su ccin a te
to Ma lea te Oxid a tion
Michael J . Kates and J . Herman Schauble*
Department of Chemistry, Villanova University,
Villanova, Pennsylvania 19085
Received J anuary 30, 1996
In a recent paper, we reported a facile two-step in situ
process for oxidation of succinic to maleic-type anhy-
drides, thioanhydrides, and imides in excellent yields.1
Herein, we report utilization of this sequence as the key
steps for the synthesis of both Chaetomellic anhydrides
A and B (8a and 9, respectively). The latter have recently
been isolated from fermentation extracts of the co-
elomycete Chaetomella acutiseta and (as the free acids)
are found to be highly specific farnesyl pyrophosphate
mimics of Ras farnesyl-protein transferase, exhibiting
potent inhibitory activity.2a-f Two alternate syntheses
of Chaetomellic anhydride A have recently been re-
ported.3
give cis-anhydride 5a (J 2,3 ) 9.1 Hz). Evaporation of the
dichloromethane-pentane extract gave a second white
solid diacid, mp 95-96.5 °C, assigned as the threo
isomers 4a , since the latter gave only the corresponding
trans-anhydride 6a (J 2,3 ) 7.5 Hz). The threo 3a to
erythro 4a diastereoselectivity was 3:1 established by
quantitative NMR analysis of the mixture of crude
diacids.
The diastereomeric succinic acids 3b and 4b were also
separable due to their differential solubility in pentane.
Trituration afforded a pentane-insoluble diacid 3b, mp
97.5-99 °C, that reacted with N-methylmorpholine and
methyl chloroformate at 0 °C to afford the cis-anhydride
5b (J 2,3 ) 9.1 Hz); thus, the diacid was assigned the
erythro structures 5b. Evaporation of the pentane
extract resulted in the low-melting waxy solid threo
diacids 4b, identified by conversion to the trans-anhy-
dride 6b (J 2,3 ) 7.5 Hz). The diastereoselectivity of threo
4b to erythro 3b diacids was 2.5:1, obtained by quantita-
tive NMR analysis.
Malonic ester-type syntheses4 were used to construct
the carbon skeletons of both Chaetomellic anhydrides.
Thus, reaction of 1-bromotetradecane or 1-bromo-7-
hexadecyne (10) with dimethyl malonate and sodium
hydride (1:5:2 molar ratio, respectively) in THF-DMF
under reflux afforded only the monoalkyl malonates 1a
and 1b in essentially quantitative yields, relative to the
starting bromides (Scheme 1).5 Ensuing reaction of
monoalkyl malonates 1a ,b with excess methyl 2-bro-
mopropionate and sodium hydride in THF-DMF under
reflux gave triesters 2a and 3b, in yields of 98-99%. It
was requisite that alkylation of dimethyl malonate with
the long chain bromides be carried out prior to alkylation
with methyl 2-bromopropionate, since reaction in the
reverse order afforded dimethyl 2-methyl-3-(methylcar-
boxy)succinate, which, however, failed to undergo further
alkylation.
Hydrolysis and decarboxylation of the triesters 2a and
2b, effected by treatment with 3 M ethanolic potassium
hydroxide/water (3:1 V/V) under reflux for 8-10 h,
followed by acidification to pH ∼2, and heating under
reflux for an additional 18 h, gave mixtures of the
diastereomeric erythro (S*S*; R*R*) and threo (R*S*;
S*R*) succinic acids (3a , 4a and 3b, 4b, respectively),
isolated in yields >90%, relative to the triesters (Scheme
2). Diastereomers 3a and 4a were easily separated by
trituration of the oily crude product with 5% dichlo-
romethane in pentane. The remaining insoluble white
solid diacid, mp 126-127 °C, was assigned the erythro
structures 3a , since it underwent reaction with N-
methylmorpholine and methyl chloroformate at 0 °C to
The vicinal coupling constants J 2,3 observed for the
stereoisomeric anhydride pairs (5a , 6a and 5b, 6b) are
in agreement with those determined using a combination
of MM2 and modified Karplus-type calculations.6 Fur-
thermore, as expected from the calculated differences in
steric energies (g1.5 kcal/mol), the cis-anhydrides 5a and
5b underwent facile conversion to the respective trans
isomers 6a and 6b upon reaction with DBU in dichlo-
romethane.
The oxidative sequence for conversion of succinic-type
anhydrides 5a , 6a and 5b, 6b to maleic anhydrides 8a
and 8b, was carried out by reaction of the anhydrides
with Et3N and TMSOTf (1:3:3 mol ratio) in benzene
under reflux to give the corresponding 3-methyl-4-tet-
radecyl-2,5-bis((trimethylsilyl)oxy)furan (7a ) and 3-(7-
hexadecynyl)-4-methyl-2,5-bis((trimethylsilyl)oxy)furan
(7b) respectively (Scheme 2).1 Subsequent treatment of
intermediate 7a with 1 mol % pure tetra-n-butylammo-
nium bromide in dry methylene chloride, followed by
addition of pure bromine (1 mol equiv) at 0 °C gave
(1) Kates, M. J .; Schauble, J . H. J . Org. Chem. 1995, 60, 6676.
(2) (a) Singh, S. B.; Zink, D. L.; Liesch, J . M. et al. Tetrahedron 1993,
49, 5917. (b) Lingham, R. B.; Silverman, K. C.; Bills, G. F. et al. Appl.
Microbiol. Biotechnol. 1993, 40, 370. (c) Gibbs, J . B.; Pompliano, D.
L.; Mosser, S. D. et al. J . Biol. Chem. 1993, 268, 7617. (d) Singh, S. B.
Merck & Co. Inc. Eur. Pat. Appl. 92203809.6, 1992. (e) Singh, S. B.;
Bills, G. F.; Lingham, R. B.; Silverman, K. C.; Zink, D. L. Merck & Co.
Inc. Eur. Pat. Appl. 92203808.8, 1992. (f) Gill, M. Phytochemistry 1981,
21, 1786.
(3) (a) Singh, S. B. Tetrahedron Lett. 1993, 34, 6521. (b) Branchaud,
B. P.; Slade, R. M. Tetrahedron Lett. 1994, 35, 4071.
(4) van Liemt, W. B. S.; Steggerda, W. F.; Esmeijer, R.; Lugtenburg,
J . Recl. Trav. Chem. Pays-Bas 1994, 113, 153.
(6) (a) MM2 calculations were performed using CSC Chem3D Plus,
Cambridge Scientific Computing Inc, 875 Massachusetts Ave., Sixth
Floor, Cambridge, MA 02139. (b) Modified Karplus-type calculations
were performed using PCMODEL, Serena Software, Box 3076, Bloom-
ington, IN 47402-3076.
(5) Brillon, D.; Deslongchamps, P. Can. J . Chem. 1987, 65, 43.
S0022-3263(96)00197-1 CCC: $12.00 © 1996 American Chemical Society

Notes
J . Org. Chem., Vol. 61, No. 12, 1996 4165
Sch em e 2
Chaetomellic anhydride A (8a ) in 91% isolated yield,
accompanied by anhydride 6a in 6% yield. The latter
results via hydrolysis of 7a .
Similarly, oxidation of 2,5-bis((trimethylsilyl)oxy)furan
7b, using pure NBS rather than bromine as the oxidant,
afforded anhydride B (8b) in 88% yield, accompanied by
hydrolysis product 6b in 9% yield. Reduction of 8b with
hydrogen on Lindlar catalyst in cyclohexane gave Chae-
tomellic anhydride B (9), quantitatively.7
Other naturally occuring 2,3-dialkylmaleic anhydrides
have been reported. These include 2-ethyl-3-methylma-
leic anhydride (11) (from the volatile oil of Paederia
foetida L.8 and from elderberry (Sambucus nigra L. fruit,
Korsør cultivar),9 2-hexyl-3-methylmaleic anhydride (12)
(from the essential oil of Agropyrum repens rhizome,10
and tricarboxylic acid anhydrides 13-15 produced from
stearic acid by Pseudomonas cepacia A-1419, isolated
from soil.11 Such maleic-type anhydrides should also be
accessible from the corresponding succinic-type conge-
ners, via two-step oxidative sequences of the type de-
scribed herein for the syntheses of Chaetomellic anhy-
drides A and B.
Exp er im en ta l Section
Gen er a l In for m a tion . Melting points are uncorrected.
Boiling points were obtained using short path vacuum distilla-
tion and are uncorrected. Starting materials, bromine (99.99+%),
N-bromosuccinimide (99%), tetra-n-butylammonium bromide
(99+%), and solvents were obtained from Aldrich Chemical Co.
Solvent removal was performed by rotoevaporation, and solvents
were dried with MgSO4 unless otherwise indicated. GC analyses
were performed using a 10M Hewlett-Packard HP-1 macrocap-
illary column. 1H and 13C NMR were recorded at 200 and 50.3
MHz, respectively. Full carbon assignments for all intermedi-
ates and Chaetomellic anhydrides A and B, including techniques
used to determine long chain carbon assignments, will be
published separately. Elemental analyses were provided by
Robertson Microlit Laboratories, Inc., P.O. Box 927, Madison,
NJ 07940.
1-Br om o-7-h exa d ecyn e (10). To a stirred solution contain-
ing 20 g (0.145 mol) of 1-decyne, 3 mg of triphenylmethane, and
2.52 mL (0.0145 mol) of HMPA in 400 mL of THF under argon
at -40 °C was added butyllithium (∼58.0 mL, 0.145 mol) until
the solution turned pink-red in color. At that temperature 177
g (0.725 mol) of 1,6-dibromohexane was added and the mixture
heated under reflux for 44 h. The THF was removed in vacuo
and the remaining solution distilled at 134 °C (3.4 torr) to
remove excess dibromide. The residual liquid was dissolved in
150 mL of pentane, washed with 50 mL of water and 50 mL of
brine, and then dried and solvent removed to afford 45.61 g of
crude alkyne. Silica gel column chromatography, using pentane
as eluant, afforded 38.35 g (88%) of 10 as a pale yellow oil: bp
(7) Brillon, D.; Deslongchamps, P. Can. J . Chem. 1987, 65, 56.
(8) Wong, K. C.; Tan, G. L. Flavour Fragrance J . 1994, 9, 25.
(9) Poll, L.; Lewis, M. J . Lebensm.-Wiss. u.-Technol. 1986, 19, 258.
(10) Boesel, R.; Schilcher, H. Planta Med. 1989, 55, 399.
(11) Itoh, S.; Esaki, N.; Masaki, K.; Blank, W.; Soda, K. J . Ferment.
Bioeng. 1994, 77, 513.

4166 J . Org. Chem., Vol. 61, No. 12, 1996
Notes
176 °C (4.0 Torr); 1H NMR (CD2Cl2) δ 0.88 (3H, t, J 15,16 ) 6.7
Hz), 1.29-1.45 (18H, 2 × bs), 1.86 (2H, p, J 2,3 ) 7.1 Hz), 2.09-
2.15 (4H, cm), 3.49 (2H, t, J 1,2 ) 6.9 Hz); 13C NMR (CD2Cl2)
δ14.28, 18.92, 19.01, 23.05, 28.08, 28.26, 29.21, 29.30, 29.51,
29.56, 29.63, 32.23, 33.16, 33.81, 79.89, 80.46.
) 6.7 Hz), 1.20 (3H, d, J ) 7.2 Hz), 1.26 (24H, bs), 1.59 (2H,
bq), 2.60 (1H, dt, J ) 6.2, 8.3 Hz), 2.74 (1H, dq), 10.06 (2H, bs);
13C NMR (CD2Cl2-DMSO) δ 14.26, 14.42, 23.01, 27.26, 28.88,
29.69, 29.83, 29.97, 29.99, 30.00, 30.03 (4C’s), 32.25, 40.97, 47.65,
177.62, 178.25. Anal. Calcd for C19H36O4: C, 69.47; H, 11.04.
Found (mixture of 3a , 4a ): C, 69.20; H,10.94. Succinic acids
3b, 4b were separated by trituration with 100 mL of pentane.
The insoluble white solid 3b was removed by filtration: mp
97.5-99 °C; 1H NMR (CD2Cl2) δ 0.88 (3H, t, J ) 6.7Hz), 1.91
(3H, d, J ) 6.7Hz), 1.26-1.50 (22H, cm), 2.11 (4H, bt), 2.66 (2H,
cm), 10.26 (2H, bs); 13C NMR (CD2Cl2-DMSO) δ 14.25, 15.14,
18.94, 18.97, 22.98, 27.77, 28.97, 29.17, 29.32, 29.44, 29.47, 29.54
(2C’s), 30.79, 32.17, 42.13, 48.67, 80.27, 80.42, 177.20, 178.02.
The filtrate was concentrated to a dark yellow oil, which
crystallized to a low melting white waxy solid (4b): 1H NMR
(CD2Cl2) δ 0.88 (3H, t, J ) 6.7 Hz), 1.27 (3H, d, J ) 7.0 Hz)*,
1.27-1.47 (22H, cm), 2.12 (4H, bt), 2.60 (1H, ddd, J ) 3.9, 8.0,
9.9 Hz), 2.75 (1H, dq), 10.23 (2H, bs), *determined by COSY;
13C NMR (CD2Cl2) δ 14.18, 14.24, 18.95, 19.00, 23.02, 26.98,
28.88, 28.90, 29.21, 29.43, 29.46, 29.52, 29.57, 29.63, 32.23, 40.80,
47.32, 80.05, 80.31, 181.08, 181.63. Anal. Calcd for C21H36O4:
C, 71.55; H, 10.29. Found (mixture 3b, 4b): C, 71.71; H, 10.19.
Gen er a l P r oced u r e for P r ep a r a tion of Cyclic An h y-
d r id es 5a , 6a , 5b, a n d 6b. A solution of appropiate diacid (3a ,
4a , 3b, or 4b) and N-methylmorpholine (20 mmol each) in 50
mL of dry THF was prepared at 0 °C under argon. Methyl
chloroformate (20 mmol) was added and the solution stirred for
15 min at rt. The N-methylmorpholine hydrochloride was
filtered and the filtrate concentrated to afford quantitative yields
of the corresponding succinic anhydrides. Compound 5a was
obtained as a pale yellow oil, crystallizing to a low-melting white
waxy solid: 1H NMR (CD2Cl2) δ 0.88 (3H, t, J ) 6.8 Hz), 1.27
(24H, bs), 1.29 (3H, d, J ) 7.3 Hz), 1.87 (2H, cm), 3.07 (1H, dt,
J ) 6.9 Hz), 3.31 (1H, dq, J ) 9.1 Hz); 13C NMR (CD2Cl2) δ 11.19,
14.27, 23.04, 26.50, 27.52, 29.68, 29.72, 29.75, 29.94, 30.00, 30.05
(2C’S), 30.08 (2C’s), 32.30, 39.13, 44.40, 173.61, 174.67. Com-
Dim eth yl Ma lon a tes 1a a n d 1b. A solution of 6.0 g (0.248
mol) of NaH in 550 mL of THF and 180 mL of DMF was
prepared at 0 °C under argon. To this solution was added slowly,
via syringe, 82.21 g (0.622 mol) of dimethyl malonate at 0 °C.
The mixture was stirred at rt for 15 min, and then bromotet-
radecane (34.4 g, 0.124 mol) or 1-bromo-7-hexadecyne (10) (37.5
g, 0.124 mol) was added and the mixture heated under reflux
for 1.5 h. The THF was removed in vacuo and the residue
diluted with 100 mL water and extracted with 3 × 75 mL of
pentane and 100 mL of pentane/ether (1:1). The combined
extract was dried and concentrated, and excess dimethyl mal-
onate, bp 68 °C (4.5 Torr), was removed by distillation. Alky-
lation using bromotetradecane gave 40.13 g (99%) of a colorless
oil, which crystallized to white solid 1a : mp 43-44 °C; 1H NMR
(CD2Cl2) δ 0.89 (3H, t, J ) 6.7 Hz), 1.26 (24H, bs), 1.85 (2H, bq,
J ) 7.7 Hz), 3.33 (1H, t), 3.70 (6H, s); 13C NMR (CD2Cl2) δ 14.26,
23.09, 27.70, 29.19, 29.66, 29.78, 29.82, 29.98, 30.07, 30.11, 30.12,
30.14, 30.15, 32.36, 51.88, 52.26, 169.88. Alkylation using
bromide 10 gave 43.45 g (99%) of pale yellow oil 1b: 1H NMR
(CD2Cl2) δ 0.88 (3H, t, J ) 7.0 Hz), 1.26-1.45 (16H, cm), 1.85
(2H, bq, J ) 7.5 Hz), 2.11 (4H, cm), 3.34 (1H, t), 3.70 (6H, s);
13C NMR (CD2Cl2) δ 14.13, 18.94, 19.00, 23.06, 27.58, 28.88,
29.13, 29.15, 29.26, 29.43, 29.56, 29.61, 29.68, 32.29, 51.86, 52.32,
80.05, 80.35, 169.87.
Tr iester s 2a a n d 2b. A solution of 5.45 g (0.226 mol) of NaH
in 550 mL of THF and 180 mL of DMF was prepared at 0 °C
under argon. To this solution was added, slowly via syringe,
37.0 g (113 mol) of 1a or 40.0 g (0.113 mol) of 1b at 0 °C and the
mixture stirred at rt for 15 min. Methyl 2-bromopropionate 38.0
g (0.226 mol) was then added and the mixture heated under
reflux for 1.5 h. The THF was removed in vacuo and the
remaining mixture combined with 100 mL of water and ex-
tracted with 3 × 75 mL of pentane and 100 mL of pentane/ether
(1:1). The combined extract was dried and concentrated and the
excess methyl 2-bromopropionate removed by distillation at 56
°C (4.5 Torr) to leave crude 2a or 2b, respectively. Both
compounds were chromatographed on silica gel using CH2Cl2
as eluant. 2a was obtained as a pale yellow oil (45.8 g, 98%):
1H NMR (CD2Cl2) δ 0.88 (3H, t, J ) 6.6 Hz), 1.24 (3H, d, J ) 7.2
Hz), 1.26 (24H, bs), 1.84 (2H, bcm), 3.09 (1H, q, J )7.2 Hz), 3.64
(3H, s), 3.68 (3H, s), 3.70 (3H, s); 13C NMR (CD2Cl2) δ 13.41,
14.24, 23.00, 24.98, 29.58, 29.70, 29.86, 29.94, 29.99 (2C’s), 30.02
(2C’s), 30.24, 32.25, 34.24, 44.02, 51.94, 52.30, 52.36, 59.94,
170.97, 171.27, 174.22. Compound 2b was also obtained as a
pale yellow oil (49.2 g, 99%): 1H NMR (CD2Cl2) δ 0.88 (3H, t, J
) 6.7 Hz), 1.24 (3H, d, J ) 7.2 Hz), 1.24-1.52 (20H, bcm), 1.85
(2H, cm), 2.11 (4H, cm), 3.09 (1H, q), 3.64 (3H, s), 3.69 (3H, s),
3.71 (3H, s); 13C NMR (CD2Cl2) δ13.44, 14.26, 18.92, 18.98, 23.04,
24.94, 28.77, 29.24, 29.42, 29.53, 29.59, 29.65, 29.81, 32.25, 34.19,
44.08, 51.85, 52.21, 52.29, 59.92, 80.08, 80.34, 170.82, 171.07,
174.00.
1
pound 6a crystallized to a white solid: mp 43-44 °C; H NMR
(CD2Cl2) δ 0.88 (3H, t, J ) 6.6 Hz), 1.26 (24H, bs), 1.40 (3H, d,
J ) 7.1 Hz), 1.65 (1H, cm), 1.86 (1H, cm), 2.71 (1H, dt, J ) 5.5,
7.5 Hz), 2.84 (1H, p, J ) 7.5 Hz); 13C NMR (CD2Cl2) δ 14.27,
15.63, 23.06, 27.01, 29.65, 29.67, 29.74, 29.88, 29.97, 30.02 (2C’s),
30.05, 30.07, 30.25, 32.30, 41.51, 48.28, 173.22, 174.08. Com-
pound 5b was a colorless oil: 1H NMR (CD2Cl2) δ 0.88 (3H, t),
1.25-1.51 (20H, cm), 1.41 (3H, d, J ) 7.3 Hz), 1.67 (2H, cm),
2.07-2.15 (4H, cm), 3.07 (1H, dt, J ) 6.8 Hz), 3.23 (1H, dq, J )
9.1 Hz); 13C NMR (CD2Cl2) δ 11.31, 14.25, 18.91, 18.99, 23.00,
26.47, 27.40, 28.75, 29.17, 29.19, 29.35, 29.46, 29.54, 29.57, 32.20,
39.26, 44.51, 80.08, 80.56, 173.51, 174.56. Compound 6b was a
colorless oil: 1H NMR (CD2Cl2) δ 0.88 (3H, t), 1.26-1.54 (20H,
cm), 1.40 (3H, d, J ) 7.1 Hz), 1.68 (1H, bcm), 1.87 (1H, bcm),
2.07-2.15 (4H, bcm), 2.70 (1H, dt, J ) 5.6, 7.5 Hz), 2.84 (1H,
dq, J ) 7.5 Hz); 13C NMR (CD2Cl2) δ 14.43, 15.67, 19.08, 19.16,
23.18, 27.09, 28.94, 29.32, 29.36, 29.51, 29.64, 29.72, 29.76, 30.30,
32.37, 41.47, 48.18, 80.05, 80.52, 173.16, 174.00.
Su ccin a te to Ma lea te Oxid a tion (8a a n d 8b). Excellent
yields of maleic anhydrides were obtained only under rigorously
anhydrous conditions. Mixed anhydrides 5a , 6a or 5b, 6b (15
mmol) were dissolved in 50 mL of dry benzene at 0 °C under
argon in a flame dried two-neck round-bottom flask equipped
with a septum and condenser. Via syringe, triethylamine (45
mmol) was added and the mixture stirred for 15 min, followed
by addition of TMSOTf (45 mmol), and the solution heated under
reflux for 2 h. The formation of 2,5-bis((trimethylsilyl)oxy)furans
7a and 7b was monitored by 1H NMR. The solution of 7a or 7b
was cooled to 0 °C, and a solution of pure tetra-n-butylammon-
nium bromide (1 mol % relative to starting anhydride) in 50 mL
of CH2Cl2 was added via syringe. To furan 7a , pure bromine
(15 mmol) was added slowly by syringe and the reaction mixture
then stirred for 15 min at 0 °C. To furan 7b was added NBS
(15 mmol, 30 mL of 0.5 M stock solution containing NBS in THF
under 5A molecular sieves) and the reaction mixture stirred for
15 min at 0 °C. The crude products were concentrated to thick
dark oils and chromatographed on a silica gel column eluting
with pentane/CH2Cl2 (3:1) to afford 6a (6%) and Chaetomellic
anhydride A (8a ) (91%) as a colorless oil which crystallized at 0
°C to a white waxy solid (one component by GC analysis): 1H
NMR (CD2Cl2) δ 0.88 (3H, t, J ) 6.7 Hz), 1.26 (22H, bs), 1.56
(2H, p, J ) 7.3 Hz), 2.05 (3H, t, J ) 0.7 Hz), 2.44 (2H, t, J ) 7.3
Su ccin ic Acid s 3a , 4a a n d 3b, 4b. Solutions of triesters
2a (32g, 0.079 mol) or 2b (35 g, 0.079 mol) in 300 mL of freshly
prepared 3 M ethanolic KOH and 100 mL of water were heated
1
under reflux for 8-10 h (loss of methyl esters monitored by H
NMR). Additional water (100 mL) was added, and the resulting
solutions were distilled (azeotropic removal of ethanol) until the
temperature of the distillate was 100 °C and gave a negative
response to J ones reagent. The aqueous solutions were acidified
(pH ) 2) with concd HCl and then refluxed for 18 h. The cooled
solutions were saturated with NaCl and extracted with diethyl
ether (3 × 75 mL), dried, and concentrated, affording 3a , 4a
(24.11 g, 92%) or 3b, 4b (26.78 g, 93%). Both mixtures of succinic
acids appeared to be reasonably pure by 1H and 13C NMR.
Succinic acids 3a , 4a were separated by triturating with 100
mL of 5% CH2Cl2 in pentane. The insoluble white solid 3a was
isolated by filtration: mp 126-127 °C; 1H NMR (CD2Cl2) δ 0.88
(3H, t, J ) 6.7 Hz), 1.45 (3H, d, J ) 6.6 Hz), 1.25-1.61 (24H,
cm), 1.81 (2H, bq), 2.56 (2H, cm, high order), 10.56 (2H, bs); 13
C
NMR (CD2Cl2-DMSO) δ 14.12, 15.14, 22.67, 27.59, 29.34, 29.50,
29.52, 29.62, 29.64, 29.66, 29.68 (3C’s), 30.68, 31.90, 41.98, 48.55,
175.75, 176.25. The filtrate was concentrated to afford 4a as a
1
white solid: mp 95-96.5 °C; H NMR (CD2Cl2) δ 0.88 (3H, t, J

Notes
J . Org. Chem., Vol. 61, No. 12, 1996 4167
Hz); 13C NMR (CD2Cl2) δ 9.60, 14.28, 23.09, 24.69, 27.92, 29.62,
29.78, 29.79, 29.87, 30.00, 30.05, 30.08 (2C’s), 30.11, 32.34,
140.93, 145.02, 166.27, 166.68. 1H and 13C data are in agree-
ment with liturature values.2a Anal. Calcd for C19H32O3: C,
73.98; H,10.45. Found: C,73.64; H,10.57.
Cl2) δ 9.52, 14.27, 23.06, 24.63, 27.42, 27.55, 27.85, 29.20, 29.66,
29.70, 29.73, 29.92 (2C’s), 30.15, 32.31, 129.80, 130.36, 140.85,
144.85, 166.14, 166.53. 1H and 13C data are in agreement with
literature values.2a, f Anal. Calcd for C21H32O3: C, 75.86; H, 9.70.
Found: C, 75.60; H, 9.95.
Similarly, column chromatography afforded 6b (9%) and 8b
(88%) as a colorless oil: 1H NMR (CD2Cl2) δ 0.88 (3H, t, J ) 6.8
Hz), 1.25-1.46 (18H, bcm), 1.57 (2H, bp), 2.05 (3H, s), 2.12 (4H,
cm), 2.45 (2H, t, J ) 7.8 Hz); 13C NMR (CD2Cl2) δ 9.51, 14.27,
18.94, 19.01, 23.04, 24.58, 27.77, 28.70, 29.23, 29.26, 29.33, 29.52,
29.59, 29.64, 32.24, 79.97, 80.48, 140.91, 144.75, 166.13, 166.50.
Ack n ow led gm en t. We wish to thank the Quaker
Chemical Foundation, Conshohocken, PA, for partial
support of this research. We also thank Dr. Walter
Boyko, Director of the NMR Laboratory, Villanova
University, for his insightful help with interpretation
of NMR spectra.
R ed u ct ion of 8b t o Ch a et om ellic An h yd r id e B (9).
A
mixture of 0.15 g (10% w/w) of Lindlar catalyst (Pd/CaCO3/PbO)
in 8 mL of cyclohexane was prepared under argon. To this was
added 1.5 g of alkyne 8b and the flask evacuated and subjected
to H2 gas (1 atm, rt) until no further uptake was observed (∼36-
40 h). The solution was then filtered through Celite and
concentrated to give a quantitative yield of the cis-alkene 9
(Chaetomellic anhydride B) as a colorless oil, observed to be one
component by GC analysis: 1H NMR (CD2Cl2) δ 0.88 (3H, t, J
) 6.6 Hz), 1.26-1.38 (18H, cm), 1.56 (2H, p), 2.02 (4H, cm), 2.05
(3H, s), 2.44 (2H, t, J ) 7.9 Hz), 5.35 (2H, cm); 13C NMR (CD2-
Su p p or tin g In for m a tion Ava ila ble: 13C NMR spectra of
compounds 1a ,b, 2a ,b, 5a ,b, 6a ,b, 8b, and 10 (10 pages). This
material is contained in libraries on microfiche, immediately
follows this article in the microfilm version of the journal, and
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J O9601977