Synthesis of (±)-4-alkanolides from pent-4-enoic acid

Article abstract of DOI:10.1007/s11172-008-0103-y

Synthesis of (±)-4-hexanolide, (±)-4-nonanolide, and (±)-4-dodecanolide, racemic forms of the insect signal substances, has been accomplished by cationic cyclization of pent-4-enoic acid and its amide in the key step.

Full text of DOI:10.1007/s11172-008-0103-y

Russian Chemical Bulletin, International Edition, Vol. 57, No. 3, pp. 657—659, March, 2008
657
Synthesis of (± ±)ꢀ)ꢁalꢁnoaides from pent)ꢀ)enoic ꢁcid
T. M. Ugurchieva, A. V. Lozanova, M. V. Zlokazov, and V. V. Veselovsky
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
4
7 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. Eꢀmail: ves@ioc.ac.ru
Synthesis of (± ±ꢀ4ꢀheꢁanolide, (± ±ꢀ4ꢀnonanolide, and (± ±ꢀ4ꢀdodecanolide, raceꢂic forꢂs of
the insect signal substances, has been accoꢂplished by cationic cyclization of pentꢀ4ꢀenoic acid and
its aꢂide in the key step.
Key words: pentꢀ4ꢀenoic acid, broꢂination, cationic cyclization, hydrolysis, (± ±ꢀ5ꢀbroꢂoꢀ
ꢂethyltetrahydrofuranꢀ2ꢀone, ꢂethyl (± ±ꢀ4,5ꢀepoꢁypentanoate, crossꢀcoupling, organocuprates,
(± ±ꢀ4ꢀheꢁanolide, (± ±ꢀ4ꢀnonanolide, (± ±ꢀ4ꢀdodecanolide, lactones, pheroꢂones.
1
Earlier, we reported on a new approach to the syntheꢀ
sis of natural butanolides based on cationic cyclization of
αꢀsubstituted pentꢀ4ꢀenoic acid dialkylaꢂides (1± into
iꢂiniuꢂ salts (2±. Hydrolysis of the latter gives
the corresponding butyrolactones (3±, which in their funcꢀ
tionalization pattern are the prospective synthons of soꢂe
natural ꢂetabolites (Scheꢂe 1±. In further developꢂent
of this approach, it becaꢂe necessary, in particular, to
study a possibility of a cheꢂoselective elongation of
the side carbon chain in lactones 3 by the crossꢀcoupling
with participation of the broꢂoꢂethyl group. It should
be noted that eꢁaꢂples of such transforꢂation are known
Scheme 1
2
3
only for the ꢂore reactive iodide and tosylate. Thereꢀ
fore, the first stage of the present study deals with a quest
of the ways of solving of this probleꢂ with the use of
siꢂple ꢂodel coꢂpound.
(
± ±ꢀ5ꢀBroꢂoꢀ4ꢀpentanolide (ꢀ±, obtained by us by
broꢂineꢀassisted cationic cyclization of unsaturated
aꢂide 5 into iꢂiniuꢂ salt 6 followed by its hydrolysis,
served as a ꢂodel for optiꢂization of conditions for
the indicated transforꢂations. Approꢁiꢂately in the saꢂe
yield, lactone ꢀ can be obtained directly froꢂ pentꢀ4ꢀ
enoic acid (7± by halolactonization upon treatꢂent with
NBS in aq. THF.
A crossꢀcoupling of broꢂolactone ꢀ with a diꢂethylꢀ
cuprate reagent leads to (± ±ꢀ4ꢀheꢁanolide 8ꢁ in 34%
yield (Scheꢂe 2±. A condensation of organocuprates with
epoꢁy ester 9 (cf. Ref. 4±, obtained froꢂ broꢂolactone ꢀ
in one step, gave soꢂewhat higher yield (~40%± of lacꢀ
tone 8ꢁ. This reaction also turned out to be ꢂore efficient
in the preparation of alkylbutyrolactones 8b,c. The yields
of (± ±ꢀ4ꢀnonanolide 8b and (± ±ꢀ4ꢀdodecanolide 8c were
1
—3: n = 0, 1, 2
Reꢁgents ꢁnd conditions: i. Br , CH C1 , 0 °C; ii. 1± SOC1 , DMF
2
2
2
2
(cat.±, 80—100 °C; 2± pyrrolidine, THF, 20 °C; iii. NaOAc•3H O,
2
aq. MeCN, 20 °C; iv. NBS, aq. THF, 15—20 °C.
of 8c — defensive secretion of rove beetle Bredius
mandibularis.5b
7
2 and 64%, respectively. As it is known, an optically
active (R±ꢀ(+± forꢂ of lactone 8ꢁ is a coꢂponent of
the pheroꢂone of beetle Trogoderma glabrum,5 of 8b —
seꢁ pheroꢂone of rice weevil Sitophilus Zeamais, and
The structure of the earlier unknown salt 6 was conꢀ
firꢂed both by physical and cheꢂical data and by eleꢀ
ꢂental analysis. The earlier described coꢂpounds ꢀ, 5,
ꢁ
6
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 644—646, March, 2008.
066ꢀ5285/08/5703ꢀ657 © 2008 Springer Science+Business Media, Inc.
1

6
58
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 3, March, 2008
Ugurchieva et al.
Scheme 2
with ꢂ.p. 110—115 °C (decoꢂp.± (CH Cl —Et O±. Found (%±:
2
2
2
C, 35.00; H, 4.98; Br, 50.75; N, 4.63. C H Br NO. Calculated (%±:
9
15
2
–1
C, 34.53; H, 4.83; Br, 51.05; N, 4.47. IR (KBr±, ν/cꢂ : 660, 852,
1
2
1
016, 1044, 1140, 1232, 1272, 1352, 1408, 1424, 1456, 1700, 2448,
1
940, 3360. H NMR, δ: 2.14 (ꢂ, 4 H, 2 CH CH N±; 2.43 (dddd,
2
2
H, HC(4±, J = 7.4 Hz, 7.4 Hz, 10.0 Hz, 12.7 Hz±; 2.77 (dddd, 1
H, H´C(4±, J = 4.9 Hz, 7.4 Hz, 10.0 Hz, 12.7 Hz±; 3.49 (ddd, 1 H,
HC(3±, J = 4.9 Hz, 10.0 Hz, 18.0 Hz±; 3.38—4.05 (ꢂ, 7 H, H´C(3±
H CBr, 2 CH N±; 5.53 (dddd, 1 H, HC(5±, J = 5.0 Hz, 5.0 Hz,
2
2
7
.4 Hz, 7.4 Hz±.
± ±)5)Bromomethyatetrꢁhydrofurꢁn)2)one (ꢀ±. A. A solution of
(
R = Me (a), Bu (b), nꢀC H (c)
7
15
salt 6 (6.7 g, 21.4 ꢂꢂol± and NaOAc•3H O (3.2 g, 23.5 ꢂꢂol± in
2
a ꢂiꢁture of MeCN (55 ꢂL± and H O (5 ꢂL± was stirred for 5 h at
Reꢁgents ꢁnd conditions: i. 1± MeLi, CuI, Et O, 0 °C, 2± ꢀ, Et O,
2
2
2
2
0 °C and concentrated in vacuo followed by eꢁtraction of the residue
–
70 °C → 0 °C; ii. 1± MeONa, MeOH, 20 °C, 2± AcOH, 20 °C;
t
n
with MeOBu . The eꢁtract was washed with 2 M HCl and brine,
dried with Na SO , concentrated in vacuo. The residue was distilled
iii. MeMgBr, CuI or MeLi, CuCN, Et O—THF, –30 °C; Bu MgCl
2
or C H MgBr, CuCN, THF, 0 °C.
2
4
7
15
to obtain lactone ꢀ (3.44 g, 90%± as colorless liquid with b.p.
1
8
0—84 °C (0.08 Torr±. H NMR, δ: 2.01—2.22 and 2.34—2.51
and 9, as well as raceꢂic lactones 8ꢁ—c were characterized
by coꢂparison of the spectra of obtained saꢂples with
those available in the literature.
(both ꢂ, 1 H each, 2 H C(3±±; 2.53—2.68 (ꢂ, 2 H, H C(4±±; 3.53
2
2
and 3.55 (both d, 1 H each, H CBr, J = 5.1 Hz±; 4.74 (dddd, 1 H,
2
HC(5±, J = 5.1 Hz, 5.1 Hz, 6.7 Hz, 6.7 Hz± (cf. Ref. 8±.
B. NꢀBroꢂosucciniꢂide (17.1 g, 114.0 ꢂꢂol± was added in
portions to a stirred solution of acid 7 (8.76 g, 87.4 ꢂꢂol± in
a ꢂiꢁture of THF (90 ꢂL± and water (10 ꢂL± for 10 ꢂin at 15 °C.
The reaction ꢂiꢁture was stirred for 2 h at 20 °C followed by
concentration in vacuo, then the residue was eꢁtracted with benꢀ
zene—light petroleuꢂ (2 : 1, v/v, 100 ꢂL±. The eꢁtract was washed
with water (2×50 ꢂL± and brine, dried with Na SO , concentrated
Experimentꢁa
IR spectra were recorded on a Specord Mꢀ80 spectroꢂeter.
H NMR spectra were recorded on a Bruker ACꢀ200 spectroꢂeter
1
relatively to the solvent signal (CDCl , δ 7.27±. The R values were
3
H
f
2
4
ꢂeasured on the plates with a fiꢁed layer of SiO (Silufol±, visualizaꢀ
in vacuo. The residue was distilled to obtain lactone ꢀ (9.38 g, 60%±
as colorless liquid with b.p. 82—88 °C (0.1 Torr±, virtually identical
( H NMR± to the one described in the preceding procedure.
2
tion was perforꢂed by spraying with saturated solution of phosphoꢀ
ꢂolybdic acid in EtOH and subsequent heating. Melting points
were deterꢂined on a Kofler apparatus. Coluꢂn chroꢂatography
was perforꢂed on Silica gеl 60 (0.04—0.06 ꢂꢂ (Fluka±±. Solvents,
including light petroleuꢂ with b.p. 40—70 °C, were purified and
1
Methya (± ±)ꢀ,5)epoxypentꢁnoꢁte (9±. Lactone ꢀ (1.25 g,
7.0 ꢂꢂol± was added in one portion to a solution of NaOMe,
prepared froꢂ Na (0.21 g, 9.1 ꢂgꢀat.± and MeOH (15 ꢂL±, with
stirring at 20 °C (Ar±. The reaction ꢂiꢁture was stirred for 20 ꢂin,
then quenched with AcOH (1.5 ꢂL±, concentrated at atꢂospheric
dried according to standard procedures, Br was distilled over
2
P O . Pentꢀ4ꢀenoic acid (7±, SOCl , pyrrolidine, MeLi, CuCN,
2
5
2
n
t
CuI, MeI, Bu Cl, and nꢀheptyl broꢂide were purchased froꢂ
Acros Organics.
pressure, and the residue was eꢁtracted with MeOBu . The eꢁtract
was washed with water and brine, dried with Na SO , and concenꢀ
2
4
N)(Pent)ꢀ)enoya±pyrroaidine (5±. A ꢂiꢁture of acid 7 (5 g,
trated. The residue was distilled to obtain epoꢁy ester 9 (0.62 g,
68%± as colorless liquid with b.p. 85—88 °C (25 Torr±. H NMR, δ:
1
4
9.9 ꢂꢂol±, SOCl (9 g, 75.7 ꢂꢂol±, and DMF (0.3 ꢂL± was
2
heated under stirring at 80—100 °C (Ar± for 5 h followed by
1.66—2.04 (ꢂ, 2 H, H C(3±±; 2.45 (t, 2 H, H C(2±, J = 7.5 Hz±;
2
2
distillation to obtain the acyl chloride (5 g, 42.2 ꢂꢂol± with b.p.
2.48 (dd, 1 H, HC(5±, J = 2.7 Hz, 4.9 Hz±; 2.74 (dd, 1 H, H´C(5±,
J = 4.0 Hz, 4.9 Hz±; 2.96 (dddd, 1 H, HC(4±, J = 2.7 Hz, 4.0 Hz,
4.6 Hz, 6.5 Hz±; 3.67 (s, 3 H, MeO± (cf. Ref. 9±.
(± ±)ꢀ)ꢂexꢁnoaide (8ꢁ±. A. An etheral solution of MeLi (0.77 M,
9.5 ꢂL, 7.3 ꢂꢂol± was added to a stirred suspension of CuI (0.76 g,
120—123 °C. The acyl chloride without additional purification was
dissolved in THF (20 ꢂL± and added to a stirred solution of
pyrrolidine (5.97 g, 84.0 ꢂꢂol± in THF (50 ꢂL± at 0 °C (Ar±.
The reaction ꢂiꢁture was stirred for 2 h at 20 °C, then washed with
water, 2 M solution of HCl, and brine, dried with Na SO , and
4.0 ꢂꢂol± in Et O (2 ꢂL± for 15 ꢂin at 0 °C (Ar±. Then, a solution
2
4
2
concentrated in vacuo. A distillation of the residue gave aꢂide 5
of broꢂolactone ꢀ (0.36 g, 2 ꢂꢂol± in Et O (2 ꢂL± was added
2
1
(
5.8 g, 76%± with b.p. 110 °C (0.7 Torr±. H NMR, δ: 1.88 (ꢂ, 4 H,
dropwise to thus obtained and cooled to –70 °C virtually colorless
solution for 5 ꢂin. The reaction ꢂiꢁture was stirred for 2 h at
–70 °C, 1.5 h at –30 °C, and 2 h at 0 °C, then quenched with
2
2
CH CH N±; 2.36 (ꢂ, 4 H, H C(2±, H C(3±±; 3.42 (ꢂ, 4 H,
2 2 2 2
CH N±; 4.96 (ddd, 1 H, HC=, J = 1.1 Hz, 1.6 Hz, 10.0 Hz±; 5.03
2
(
=
ddd, 1 H, HC=, J = 1.6 Hz, 3.3 Hz, 17.2 Hz±; 5.86 (dddd, 1 H,
HC—C, J = 6.4 Hz, 6.4 Hz, 10.0 Hz, 17.2 Hz± (cf. Ref. 7±.
± ±)N)(5)Bromomethyatetrꢁhydrofurꢁn)2)yaidene±pyrroaidinium
bromide (6±. A solution of Br2 (8.48 g, 5.3 ꢂꢂol± in CH Cl2
saturated aq. NH Cl and eꢁtracted with EtOAc. The eꢁtract was
4
washed with water and brine, dried with Na SO , and concentrated
2
4
(
in vacuo. The residue was subjected to chroꢂatography on SiO2,
eluting with light petroleuꢂ—ethyl acetate (17 : 3±, to obtain lactone
2
t
(
15 ꢂL± was added to a stirred solution of aꢂide 5 (8.01 g, 5.0
8ꢁ (80 ꢂg, 34%± as colorless oil with R 0.54 (MeOBu —light
f
1
ꢂꢂol± in CH Cl (30 ꢂL± for 30 ꢂin at 0 °C (Ar±. The reaction
petroleuꢂ, 3 : 1±. H NMR, δ: 1.01 (t, 3 H, Me, J = 7.4 Hz±; 1.65
2
2
ꢂiꢁture was kept for 15 ꢂin at this teꢂperature and concentrated
in vacuo to ~ 15 ꢂL followed by addition of THF (50 ꢂL± to
the residue. The crystals forꢂed were filtered off and washed with
THF on the filter to obtain salt 6 (13.77 g, 84%± as colorless crystals
(ꢂ, 1 H, CH CH , J = 6.5 Hz, 7.4 Hz, 9.4 Hz±; 1.74 (ꢂ, 1 H,
3
2
CH CH , J = 6.6 Hz, 7.4 Hz, 9.4 Hz±; 1.87 (dddd, 1 H, HC(4±,
3
2
J = 7.8 Hz, 8.7 Hz, 9.5 Hz, 12.3 Hz±; 2.32 (dddd, 1 H, H´C(4±,
J = 6.5 Hz, 6.5 Hz, 7.0 Hz, 12.3 Hz±; 2.5 (dd, 1 H, HC(3±,

Synthesis of (± ±ꢀ4ꢀalkanolides
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 3, March, 2008
659
J = 6.5 Hz, 7.0 Hz±; 2.55 (dd, 1 H, H´C(3±, J = 8.7 Hz, 9.5 Hz±; 4.44
the reaction ꢂiꢁture and chroꢂatography under the described above
(
dddd, 1 H, HC(5±, J = 6.5 Hz, 6.6 Hz, 6.6 Hz, 7.8 Hz± (cf. Ref. 10±.
conditions. The yield was 0.25 g (64%±, colorless oil with R 0.37
(MeOBu —light petroleuꢂ, 1 : 1±. H NMR, δ: 0.88 (br.t, 3 H, Me,
f
t
1
B. A solution of MeMgBr in Et O (2.72 M, 2.2 ꢂL, 6.0 ꢂꢂol±
2
was added to a stirred suspension of CuI (0.61 g, 3.2 ꢂꢂol± in THF
7 ꢂL± for 5 ꢂin at 0 °C (Ar±. After 30 ꢂin, the ꢂiꢁture was cooled
to –50 °C followed by addition to it a solution of epoꢁy ester 9
0.26 g, 2 ꢂꢂol± in THF (1.5 ꢂL±. The reaction ꢂiꢁture was stirred
J = 6.8 Hz±; 1.18—1.95 (ꢂ, 15 H, 7 CH , HC(4±±; 2.32 (ꢂ, 1 H,
H´C(4±±; 2.50 (dd, 1 H, HC(3±, J = 6.6 Hz, 7.0 Hz±; 2.54 (dd, 1 H,
H´C(3±, J = 8.9 Hz, 9.5 Hz±; 4.48 (ꢂ, 1 H, HC(5±± (cf. Ref. 4a±.
2
(
(
for 2 h at –30 °C, quenched with saturated aq. NH Cl, and treated
as in the preceding eꢁperiꢂent. Chroꢂatography of the obtained
4
References
product on SiO by elution with CH Cl gave lactone 8ꢁ (94 ꢂg,
2
2
2
1
1. (a± A. V. Lozanova, T. M. Ugurchieva, M. V. Zlokazov, A. V.
Stepanov, V. V. Veselovsky, Mendeleev Commun., 2006, 15;
4
2%±, virtually identical (R , H NMR± to the described above
f
saꢂple.
(
b± A. V. Lozanova, T. M. Ugurchieva, V. V. Veselovsky, Izv.
Akad. Nauk, Ser. Khim., 2007, 124 [Russ. Chem. Bull., Int. Ed.,
007, 56, 130]; (c± T. M. Ugurchieva, A. V. Lozanova, M. V.
Zlokazov, V. V. Veselovsky, Izv. Akad. Nauk, Ser. Khim., 2007,
544 [Russ. Chem. Bull., Int. Ed., 2007, 56, 1485].
. (a± H. Takahata, Y. Uchida, T. Moꢂose, J. Org. Chem., 1995,
0, 5628; (b± G. D. Monache, D. Misiti, P. Salvatore, G. Zappia,
Tetrahedron Asymmetry, 2000, 11, 1137.
3. U. Ravid, R. M. Silverstein, L. R. Sꢂith, Tetrahedron, 1978,
ꢀ, 1449.
C. A solution of MeLi in Et O (1.6 M, 3.75 ꢂL, 6.0 ꢂꢂol± was
2
added to a stirred suspension of CuCN (0.29 g, 3.2 ꢂꢂol± in THF
2
(
4 ꢂL± for 10 ꢂin at 0 °C (Ar±, after 20 ꢂin, the ꢂiꢁture was cooled
to –50 °C followed by addition to it a solution of epoꢁy ester 9
0.26 g, 2 ꢂꢂol± in THF (1.5 ꢂL±. The reaction ꢂiꢁture was stirred
1
(
2
for 2 h at –30 °C, quenched with saturated aq. NH Cl, and treated
4
6
as described above to obtain lactone 8ꢁ (90 ꢂg, 40%±, virtually
1
identical (R , H NMR± to the described above saꢂple.
f
n
(
± ±)ꢀ)ꢃonꢁnoaide (8b±. A solution of Bu MgCl in THF (2.0 M,
3
2
.6 ꢂL, 5.1 ꢂꢂol± was added to a stirred suspension of CuCN
4
. (a± S. Chattopadhyay, R. Maꢂdapur, M. S. Chadha, Tetraheꢀ
dron, 1990, ꢀ6, 3667; (b± G. C. PaddonꢀJones, C. J. Moore,
D. J. Brecknell, W. A. Koenig, W. Kitching, Tetrahedron Lett.,
(
0.23 g, 2.55 ꢂꢂol± in THF (3 ꢂL± for 5 ꢂin at 0 °C (Ar±. The
reaction ꢂiꢁture was stirred for 20 ꢂin, then, a solution of epoꢁy
ester 9 (0.22 g, 1.7 ꢂꢂol± in THF (0.5 ꢂL± was added to it at 0 °C
1
997, 38, 3479.
followed by the quenching with saturated aq. NH Cl after 1 h. The
4
t
5. K. Mori, in The Total Synthesis of Natural Products, Ed. J. A.
Siꢂon, John Wiley and Sons, New York, 1992, Vol. 9; (a± p. 216;
aqueous layer was separated and eꢁtracted with MeOBu . A coꢂꢀ
bined organic layer was sequentially washed with saturated aq.
NH Cl, water, and brine and dried with Na SO . A concentrated
(
b± p. 234.
4
2
4
6
. H. Raꢂa Mohan, A. S. Rao, Org. Prep. Proc. Int., 1993, 25, 321.
in vacuo residue was subjected to chroꢂatography on SiO .
2
t
7. K. D. Moeller, P. W. Wang, S. Tarazi, M. R. Marzabadi, P. L.
Wong, J. Org. Chem., 1991, 56, 1058.
8. H. Mattes, C. Benezra, J. Org. Chem., 1988, 53, 2732.
A gradient elution of the latter with light petroleuꢂ—MeOBu (froꢂ
t
1
0 to 40% of MeOBu ± gave lactone 8b (0.19 g, 72%± as colorless oil
t
1
with R 0.30 (MeOBu —light petroleuꢂ, 1 : 1±. H NMR, δ: 0.87
f
9
. P.ꢀT. Ho, N. Davies, Synthesis, 1983, 462.
(
br.t, 3 H, Me, J = 6.6 Hz±; 1.19—1.95 (ꢂ, 9 H, 4 CH , HC(4±±;
2
1
0.K. Mori, H. Mori, T. Sugai, Tetrahedron, 1985, ꢀ1, 919.
2
2
.31 (dddd, 1 H, H´C(4±, J = 5.8 Hz, 5.8 Hz, 6.7 Hz, 13.3 Hz±;
.50 (dd, 1 H, HC(3±, J = 6.6 Hz, 7.1 Hz±; 2.54 (dd, 1 H, H´C(3±,
J = 8.6 Hz, 9.5 Hz±; 4.48 (ꢂ, 1 H, HC(5±± (cf. Ref. 6±.
± ±)ꢀ)ꢄodecꢁnoaide (8c±. Lactone 8c was obtained siꢂilarly
(
froꢂ epoꢁy ester 9 (0.26 g, 2.0 ꢂꢂol± and cuprate reagent, prepared
froꢂ CuCN (0.27 g, 3.0 ꢂꢂol± in THF (1 ꢂL± and 1.0 M solution
of nꢀC H MgBr (6 ꢂL± in THF (6.0 ꢂꢂol±, after treatꢂent of
Received December 4, 2007;
in revised form December 17, 2007
7
15