Lactones 30. Reaction of halolactones with trialkylphosphites

Article abstract of DOI:10.1016/j.tetlet.2006.07.052

The reaction of halolactones with trialkylphosphites in the presence of water afforded dehalogenated lactones.

Full text of DOI:10.1016/j.tetlet.2006.07.052

Tetrahedron Letters 47 (2006) 6875–6877
Lactones 30. Reaction of halolactones with trialkylphosphitesI
*
´
Bartłomiej Pisarski and Czesław Wawrzenczyk
Department of Chemistry, Agricultural University, Norwida 25, Wrocław 50-375, Poland
Received 21 April 2006; revised 4 July 2006; accepted 13 July 2006
Available online 4 August 2006
Abstract—The reaction of halolactones with trialkylphosphites in the presence of water afforded dehalogenated lactones.
ꢀ 2006 Elsevier Ltd. All rights reserved.
Halolactonization of c,d-unsaturated acids or esters is
one of the most often applied methods for the synthesis
of saturated and unsaturated c- and d-lactones.2–6 In the
synthesis of saturated lactones, halolactones are usually
dehalogenated by reduction with tributyltin hydride,7,8
or other organic tin hydrides.9
The reactions of halolactones with trialkylphosphites
were carried out on the 3.5 mmol scale according to
the following procedure: a mixture of halolactone
(3.5 mmol) and triethylphosphite (10.5 mmol) was
heated at 130 ꢁC for 1 h. After that time, the reaction
mixture was cooled to 70–80 ꢁC. Next, distilled water
(5 mmol) was added and the mixture was heated at
150–180 ꢁC for 6–8 h. The reaction progress was moni-
tored by TLC and GC. The products were isolated from
the reaction mixture by column chromatography (silica
gel, hexane–acetone, 4:1). The results of the experiments
are presented in Table 1. Except for the reactions of
chlorolactone 6, the isolated yields are given in Table 1.
During attempts to synthesize lactones with alkyl phos-
phonate groups from iodolactones, via the Arbuzov
reaction, we observed that in the presence of water some
substrates were transformed into dehalogenated lac-
tones.10 This observation led to detailed studies on the
conditions and scope of this reaction and also its
mechanism.
Taking into consideration the results in Table 1
presented it is apparent that slightly higher yields were
observed in the experiments using triethylphosphite.
Comparison of the reactivity of the lactones with differ-
ent halogen atoms indicates that iodolactones and
bromolactones exhibited similar, high reactivity in this
dehalogenation process. GC analysis (HP-5, 30 m,
0.32 mm, 0.25 lm; detector FI 300 ꢁC, initial tempera-
ture 100 ꢁC, then 20 ꢁC/min to 260 ꢁC, then 50 ꢁC/min
to 300 ꢁC, hold 1 min) indicated only a trace amount
of saturated lactone 4a in the product mixture obtained
from the reaction of chlorolactone 6.
Here we present the results of dehalogenation of racemic
iodo-, bromo- and chloro-lactones 1–6. Iodolactones
1–4 were obtained, mainly by iodolactonization of the
corresponding c,d-unsaturated acids: iodolactone 1, as a
mixture of diastereoisomers, from 3-ethyl-4-methyl-4-
pentenoic acid, lactone 2 as a diastereoisomeric mixture
from 3-isobutyl-5-methyl-4-methylene-hexanoic acid,11
lactone 3 from 3-phenyl-4-pentenoic acid,10 and bicyclic
iodolactone
4 from 1,5,5-trimethyl-(2-cyclohexen-1-
yl)acetic acid.7 Bromolactone 5 and chlorolactone 6
were obtained by bromo- and chloro-lactonization of
ethyl (1,5,5-trimethyl-2-cyclohexen-1-yl)acetate with
N-bromosuccinimide (NBS) and N-chlorosuccinimide
(NCS), respectively, according to the procedure
described earlier.12 The structures of iodo-, bromo-
and chloro-lactones 1, 5 and 6 were confirmed from
their spectral (1H NMR and IR) data.13–15
All the lactones prepared are known compounds
(1a,16 2a,11 3a10 and 4a7), the spectroscopic data of
which corresponded with the literature.
Considering the mechanism of this reaction the results
from earlier studies on the dehalogenation of organic
halo compounds employing dimethyl phosphonate as a
source of the hydrogen atom for radical reduction
should be quoted.17,18 The reaction was initiated with
benzoyl peroxide or AIBN, and thus, a free radical
q For Lactones 29, see Ref. 1.
*
Corresponding author. Tel.: +487 1320 5257; e-mail: c-waw@
ozi.ar.wroc.pl
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.07.052

6876
B. Pisarski, C. Wawrzen´czyk / Tetrahedron Letters 47 (2006) 6875–6877
Table 1.
Substrate
Product
Time (h)
Trialkyl phosphite
Yield (%)
I
O
O
6
8
P(OEt)3
P(Oi-Pr)3
80
54
O
O
1a
1
I
O
O
6
8
P(OEt)3
P(Oi-Pr)3
74
54
O
O
2
2a
O
O
O
O
6
7
P(OEt)3
P(Oi-Pr)3
60
55
I
3a
3
I
O
O
O
O
6
8
P(OEt)3
P(Oi-Pr)3
90
89
4a
4
5
Br
Cl
O
O
O
O
4a
4a
6
8
P(OEt)3
P(Oi-Pr)3
92
75
10
12
P(OEt)3
P(Oi-Pr)3
5
3
6
mechanism for this process was proposed.
Triethylphosphite or diethyl phosphonate in combina-
tion with vanadium(III) chloride and zinc was applied
for the dehalogenation of gem-dibromo-cyclopro-
panes.19 All the above methods required an anhydrous
reaction medium and an inert atmosphere.
The trialkoxyphosphonium salt (A) formed in
the reaction of the halolactone with trialkylphosphite
H-O-H
+
CH2-P(OR)3
-
I
I
CH2
O
The dehalogenation observed in the method presented
here proceeds in the presence of water. Studies on this
reaction led to the following observations. The reaction
of halolactones with triethylphosphite without water
led, as usual via Arbuzov reaction, to the corresponding
phosphonates. No reaction of these phosphonates with
water under the conditions of this method was observed.
The formation of an alkyl iodide in the presence of
water was also not observed. The signal at
À0.321 ppm in the 31P NMR spectrum of the reaction
mixture confirms the formation of triethyl phosphate
during the course of this reaction. Taking into consider-
ation these observations the mechanism presented below
can be proposed (Scheme 1).
O
P(OR)3
+
A
O
O
1
- HI
O
H2
H
O
H
P(OR)3
CH2
CH2
O
O
(RO)3P=O
+
B
O
O
1a
Scheme 1.

B. Pisarski, C. Wawrzen´czyk / Tetrahedron Letters 47 (2006) 6875–6877
6877
2.37 (1H, dd, J = 17.3 and 10.1, one of H-3), 2.27–2.47
(1H, m, H-4), 2.66 (1H, dd, J = 17.3 and 8.3, one of H-3),
3.27, 3.34 (2H, 2 · d, J = 11.1, CH2I); 13C NMR
(151 MHz, CDCl3): d 9.4, 12.9, 22.1, 27.3, 34.8, 46.5,
84.9, 174.8; diastereoisomer b, 1H NMR (300 MHz,
CDCl3); d 0.95 (3H, t, J = 7.3, CH3CH2), 1.29–1.70 (2H,
m, CH3CH2), 1.42 (3H, s, CH3), 2.28 (1H, dd, J = 16.8
and 10.1, one of H-3), 2.27–2.47 (1H, m, H-4), 2.73 (1H,
dd, J = 16.8 and 8.0, one of H-3), 3.36, 3.46 (2H, 2 · d,
J = 11.1, CH2I); 13C NMR (150 MHz, CDCl3): d 12.7,
14.4, 20.7, 23.4, 35.0, 45.0, 85.1, 174.3; IR (film, cmÀ1):
1775 (s), 1382 (m), 1255 (s), 1160 (s), 957 (s); Anal. Calcd
for C8H13IO2: C, 35.84; H, 4.89. Found: C, 36.27; H, 5.13.
14. Data for 5: crystals, mp 110–113 ꢁC; 1H NMR (600 MHz,
CDCl3): d 1.01; 1.17 (6H, two s, (CH3)2C), 1.19 (3H, s,
CH3-6), 1.36 (1H, d, J = 14.9, one of CH2-5), 1.70 (1H,
dd, J = 14.9 and 2.2, one of CH2-5), 1.79 (1H, dd, J = 13.8
and 13.2, H-3 axial), 2.02 (1H, ddd, J = 13.8, 4.1 and 2.2,
H-3 equatorial), 2.13; 2.76 (2H, 2 · d, J = 17.5, CH2-7),
4.02 (1H, ddd, J = 13.2, 9.2 and 4.1, H-2), 4.22 (1H, d,
J = 9.2, H-1); 13C NMR (150 MHz, CDCl3): d 26.8, 30.7,
33.3, 33.5, 40.5, 40.9, 45.2, 46.4, 49.4, 90.8, 175.2; IR (KBr,
cmÀ1): 1784 (s), 1454 (m), 1143 (s), 1024 (s), 989 (s), 696
(m); Anal. Calcd for C11H17BrO2: C, 50.59; H, 6.56.
Found: C, 50.56; H, 6.87.
is, in the presence of water, converted into trialkoxy-
hydroxyphosphonate (B). This unstable compound is
converted into the corresponding lactone and trialkyl
phosphate or its products of hydrolysis. Further studies
on the mechanism of this reaction and its wider applica-
tion are in progress.
References and notes
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15. Data for 6: crystals, mp 97–98 ꢁC, 1H NMR (600 MHz,
CDCl3): d 1.07, 1.12 (6H, two s, (CH3)2C), 1.26 (3H, s,
CH3-6), 1.40 (1H, d, J = 15.0, one of CH2-5), 1.69 (1H,
dd, J = 13.7 and 12.6, axial H-3), 1.70 (1H, dd, J = 15.0
and 2.2, one of CH2-5), 1.95 (1H, ddd, J = 13.7, 4.1 and
2.2, equatorial H-3), 2.20; 2.60 (2H, 2 · d, J = 17.5, CH2-
7), 4.02 (1H, ddd, J = 12.6, 8.7 and 4.1, H-2), 4.14 (1H, d,
J = 8.7, H-1); 13C NMR (150 MHz, CDCl3): d 26.8, 30.5,
32.4, 33.4, 40.6, 41.1, 45.2, 45.3, 58.3, 90.4, 175.3; IR (KBr,
cmÀ1): 1786 (s), 1455 (m), 1157 (s), 991 (m), 742 (m); Anal.
Calcd for C11H17ClO2: C, 60.97; H, 7.91. Found: C, 61.08;
H, 7.98.
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13. Data for 1: oil, diastereoisomeric mixture (62% of diaste-
reoisomer a and 38% of diastereoisomer b): diastereoiso-
mer a, 1H NMR (300 MHz, CDCl3): d 0.97 (3H, t, J = 7.3,
CH3CH2), 1.29–1.70 (2H, m, CH3CH2), 1.57 (3H, s, CH3),