Radicals from aldehydes: A convergent access to dienes and δ-lactones

Article abstract of DOI:10.1055/s-2006-941582

A convenient method for the generation of O,S-acetal xanthates from aldehydes has been developed. The corresponding nucleophilic radicals undergo facile addition to unactivated olefins and the resulting adducts can be further elaborated to generate dienes

Full text of DOI:10.1055/s-2006-941582

LETTER
1485
Radicals from Aldehydes: A Convergent Access to Dienes and d-Lactones
A
C
onvergent
h
A
ccess to
D
a
ienes and
d
r
-
Lactone
a
s
njeet K. Bagal, Lucie Tournier, Samir Z. Zard*
Laboratoire de Synthèse Organique associé au CNRS, Ecole Polytechnique, 91128 Palaiseau, France
Fax +33(1)69333851; E-mail: zard@poly.polytechnique.fr
Received 30 January 2006
presence of catalytic anhydrous zinc chloride to generate
1-chloroethyl acetate 3a.4 Treatment of the crude product
mixture with potassium O-ethyl xanthate then cleanly
furnished the desired radical precursor 4a in an overall
yield of 78%. This fast and efficient two-step protocol was
then applied to additional aldehydes in order to assemble
a group of radical precursors 4a–e (Scheme 2).15
Abstract: A convenient method for the generation of O,S-acetal
xanthates from aldehydes has been developed. The corresponding
nucleophilic radicals undergo facile addition to unactivated olefins
and the resulting adducts can be further elaborated to generate
dienes and unsaturated d-lactones.
Key words: aldehydes, xanthates, radical reactions, lactones,
dienes
O
H
OAc
Cl
OAc
EtOC(S)SK
AcCl
R
R
R
Aldehydes are considered as the epitome electrophilic
partners in addition reactions of organometallic reagents,
and thousands of carbinols have been prepared this way.
Through conversion into protected cyanohydrins or
dithianes aldehydes can acquire nucleophilic character,
and such an umpolung has further expanded their syn-
thetic utility.1 In contrast, the use of aldehydes as radical
precursors has remained somewhat limited, especially in
terms of intermolecular radical reactions.2
acetone
or EtOH
ZnCl2
Xa
3
Xa = SC(S)OEt
4a R = Me, 78%
4b R = i-Pr, 89%
4c R = s-Bu, 75%
4d R = n-C9H19, 81%
4e R = c-Hex, 82%
Scheme 2
With xanthates 4 in hand, we next investigated their
ability to undergo group transfer radical addition. Pleas-
ingly, when treated with a substoichiometric amount of
lauroyl peroxide (DLP, 5–25%) and the corresponding
olefin A–F (2 equiv) in refluxing 1,2-dichloroethane
(DCE), xanthates 4 furnished good to excellent yields of
olefin addition adducts 5 (Scheme 3, Table 1).16
We have recently shown that the xanthate 1 derived from
trifluoroacetaldehyde can be applied for the preparation of
a wide variety of a-trifluoromethyl alcohol derivatives 2
by radical addition to unactivated olefins (Scheme 1).3
The high yields of adduct 2 obtained (up to 92%) could be
attributed to the strongly electron-withdrawing tri-
fluoromethyl group which modifies the reactivity of the
corresponding radical to give highly efficient propagation
steps.
R'
5a R = Me
5b R = i-Pr
5c R = s-Bu
5d R = n-C9H19
5e R = c-Hex
OAc R'
OAc
Xa
R
R
Xa
DLP
DCE
4
Xa = SC(S)OEt
1. H2SO4
R
OH
OAc
Xa
OAc
EtOC(S)SK
F3C
F3C
F3C
R
Scheme 3
2. H2SO4
Ac2O
lauroyl
peroxide
(DLP)
1
2
OMe
Xa
Xa = SC(S)OEt
The adducts 5 were isolated as a mixture of diastereomers
with low overall diasteroselectivity being observed during
the radical addition step. In some cases interesting, sepa-
rable minor products of double addition to olefin B could
be isolated, e.g. 5bB¢ and 5eB¢ (entries 4 and 10). More-
over, one-pot radical addition to N-protected allyl-aniline
followed by intramolecular cyclisation provided rapid
access to the functionalised indoline 6 in excellent overall
yield (Scheme 4).5
Scheme 1
However, the question remained as to whether the
presence of an electron-withdrawing group was essential
for successful radical addition, or could parallel chemical
transformations be accomplished with ordinary alde-
hydes.
Our initial target was the xanthate derived from acetalde-
hyde 4a since it was analogous to the trifluorinated
compound 1 (Scheme 2). To this end, a neat mixture of
acetaldehyde and acetyl chloride was stirred in the
DLP (1 equiv)
DCE
OAc
4c
N
N
6 68% dr = 1:1
Boc
Boc
SYNLETT 2006, No. 10, pp 1485–1490
Advanced online publication: 12.06.2006
2
1
.0
6
.2
0
0
6
Scheme 4
DOI: 10.1055/s-2006-941582; Art ID: D02806ST
© Georg Thieme Verlag Stuttgart · New York

1486
S. K. Bagal et al.
LETTER
Table 1 Radical Addition of Xanthates 4a–e to Olefins A–Fa
Entry
1
Substrate
Olefin A–F
Product(s) 5
Xa = SC(S)OEt
Yield (%)b
71
drc
Xa
4a
A
5aA
1:1
C6H13
AcO
AcO
AcO
Xa
Xa
2
3
4a
4a
B
5aB
5aC
78
74
1:1
1:1
OAc
TMS
OAc
Cd
OAc Xa
4
4b
B
5bB
5bB¢
5bC
57
22
70
1:1
Xa
OAc
OAc
1:1:1:1
1:1
OAc
OAc Xa
5
4b
Cd
TMS
OAc Xa
OAc Xa
OAc Xa
6
7
4c
4c
B
E
5cB
5cE
91
95
1:1
1:1
OAc
CO2H
CO2H
8
9
4c
F
5cF
81
81
1:1:1:1
1:1
OAc Xa
OAc Xa
4d
D
5dD
CN
n-C9H19
OAc
10
4e
B
5eB
50
26
1:1
Xa
OAc
OAc
5eB¢
1:1:1:1
OAc
TMS
CN
OAc Xa
OAc Xa
11
4e
Cd
D
5eC
5eD
81
1:1
1:1
12
4e
41 (52)e
C
E
F
A
B
D
Olefins A–F:
C6H13
TMS
OAc
CN
CO2H
CO2H
a For general experimental procedures, see ref. 16.
b Reported yields are of isolated products.
c Diastereomeric ratio was measured after purification by NMR spectroscopy.
d Olefin was used as the reaction solvent due to its volatile nature.
e Reported yield is based upon recovered xanthate 4e.
Synlett 2006, No. 10, 1485–1490 © Thieme Stuttgart · New York

LETTER
A Convergent Access to Dienes and d-Lactones
1487
NHBoc
It may now be concluded that the presence of an electron-
withdrawing group in the xanthate precursor (e.g. 1) is
unnecessary, and simple aldehyde derivatives 4a–e are
sufficiently reactive to undergo radical addition. In order
to ascertain whether ketones could fulfill an analogous
role as radical precursors, we briefly investigated the
reactivity of cyclohexanone and levulinic acid (10).
Me
OH
15 61%
O
DLP (1.1 equiv)
OH
1. concd TFA
2. Et3N
13G
N
H
O
14 71%
O
Zinc chloride catalysed chloroacetylation of cyclohex-
anone to generate 1-chlorocyclohexyl acetate 7 followed
by in situ treatment with potassium O-ethyl xanthate fur-
nished the desired xanthate precursor 8 in reasonable
overall yield (Scheme 5).4,6 Radical addition to allyltri-
methylsilane (olefin C) to afford 9C was higher yielding
than the corresponding transformation with allyl cyanide
(olefin D), possibly due to a side reaction in which the
corresponding radical was reduced.
Scheme 7
or acetonitrile at room temperature, furnished the corre-
sponding dienes 16, 17, and 18, respectively, in high
yields and with high E-selectivity for the g,d-double bond
(Scheme 8).19 In contrast, refluxing an ethanolic solution
of 5dD in the presence of concentrated hydrochloric acid
afforded unsaturated d-lactone 19.20
Xa
O
R
Xa
OAc C or D
concd
HCl
Olefin
OAc Xa
H
R
DBU
1. AcCl, ZnCl2
R'
CN
O
CN
n-C9H19
2. EtOC(S)SK
EtOH
DLP
DCE
n-C9H19
8
OAc
25% (50%)
Xa = SC(S)OEt
n-C9H19
19 62%
5dD
16 60% (E,E:E,Z = 1.4:1)
cylohexanone: R,R' = O
7: R = OAc, R' = Cl
9C R = TMS, 77%
9D R = CN, 30% (38%)
OAc Xa
CN
CN
DBU
Scheme 56,7
5eD
17 81% (E,E:E,Z = 1.3:1)
Xa
Levulinic acid (10) was transformed into xanthate 12 in
90% overall yield by initial thionyl chloride-mediated
conversion to chlorolactone 11, followed by nucleophilic
substitution (Scheme 6).8,17 To our delight, lauroyl perox-
ide (DLP, 5–25%) initiated radical addition of precursor
12 to olefins B–J afforded adducts 13B–J in excellent
yields (Table 2).16,18
DBU
CN
CN
18 79% ( E:Z = 1.1:1)
OAc
Xa = SC(S)OEt
9D
Scheme 8
Facile entry into the d-lactone domain was also obtained
through similar thermal acidic treatment of adducts 5cE
and 5cF (Table 1) to afford cyclisation products 20 and
21, respectively (Scheme 9). The ready introduction of a
methyl substituent is noteworthy since it is ubiquitous
amongst natural products.12,20
Xa
R'
X
1. SOCl2
O
O
O
O
O
O
R
2. EtOC(S)SK
acetone
DLP
DCE
11 X = Cl
12 X = Xa, 90% (2 steps)
13 Xa = SC(S)OEt
OH
10
OAc Xa
Scheme 6
concd HCl
O
O
R
CO2H
reflux
EtOH
5cE R = H
5cF R = Me
The product derived from (–)-b-pinene 13J (entry 5) is
particularly interesting since it was formed after initial
radical addition followed by fragmentation of the cyclo-
butane ring. Furthermore, adduct 13G (entry 2) provided
facile access to the medicinally important azocin-2-one
structural motif 15 through a rapid two-step reaction se-
quence.9 Reductive dexanthylation followed by amine
deprotection and subsequent base induced in situ cyclisa-
tion,10 converted 13G into the desired eight-membered
lactam 15 in good overall yield (Scheme 7).11
R
20 R = H, 65%
21 R = Me, 68%
Scheme 9
More complex dienes can be assembled in a highly con-
vergent and efficient manner by radical addition of a xan-
thate to vinyl pivalate (olefin I). The reaction product is a
new radical precursor having an equivalent O,S-acetal
moiety to the xanthates derived from aldehydes 4a–e.
Thus, xanthates 23, 26, and 13I were prepared in excep-
tional yields from their corresponding precursors 22,13
25,14 and 12 (Table 2, entry 4), respectively (Scheme 10).
Radical addition of 23, 26, and 13I to allyl cyanide (olefin
D) to generate the corresponding addition adducts fol-
lowed by base-induced elimination finally afforded the
Adducts generated by radical addition to allyl cyanide
(olefin D) are of further significance since they provide
new synthetic routes to the valuable building blocks: 1-cy-
anodienes and unsaturated six-membered lactones. Sim-
ply stirring adducts 5dD, 5eD (Table 1) and 9D
(Scheme 5) with DBU (2.2 equiv) in dichloromethane
Synlett 2006, No. 10, 1485–1490 © Thieme Stuttgart · New York

1488
S. K. Bagal et al.
LETTER
Table 2 Radical Addition of Xanthate 12 to Olefinsa
Entry
1
Olefin
Product(s) 13
Xa = SC(S)OEt
Yield (%)b
92
drc
Xa
O
O
O
B
13B
1:1
OAc
Xa
O
2
G
13G
89
1:1
NHBoc
Xa
O
O
3
4
H
I
13H
13I
80
85
1:1
1:1
8
CO2Me
Xa
O
O
PivO
Xa
5
J
13J
71
1:1
O
O
B
G
H
I
J
OPiv
Olefins B–J:
OAc
NHBoc
CO2Me
a For general experimental procedures, see ref. 16.
b Reported yields are of isolated products.
c Diastereomeric ratio was measured after purification.
structurally diverse cyanodienes 24, 27, and 28, respec-
tively, in good overall yields.19 In line with our previous
results (Scheme 8), a high selectivity for the E g,d-double
bond was observed (Scheme 10).
Acknowledgment
We wish to thank Rhodia Chimie Fine for generous financial
support to L.T. and Drs. Jean-Marc Paris and François Metz of
Rhodia for friendly discussions.
In summary, a facile and highly efficient method for the
generation of radicals from aldehydes and their subse-
quent addition to unactivated olefins has been devised.
The addition products have then been demonstrated as ex-
cellent precursors to cyanodienes and unsaturated d-lac-
tones. Since our approach represents an umpolung of the
normal electrophilic reactivity of aldehydes, many of the
key structural units prepared would be tedious to obtain
through existing procedures.
References and Notes
(1) For an example of the use of protected cyanohydrins, see:
(a) Stork, G.; Maldonado, L. J. Am. Chem. Soc. 1971, 93,
5286. (b) Stork, G.; Takahashi, T.; Kawamoto, I.; Suzuki, T.
J. Am. Chem. Soc. 1978, 100, 8272. (c) For an example of
the use of dithianes, see: Smith, A. B. III; Adams, C. M.;
Barbosa, S. A. L.; Degnan, A. P. J. Am. Chem. Soc. 2003,
125, 350.
O
O
O
CN
Xa
CN
D
OPiv
OPiv
I
1.
Ar
24 (E,E:E,Z = 1.3:1)
41% (2 steps)
Ar
Xa
OPiv
Xa
DLP
DCE
DLP, DCE
2. DBU
22
25
23 92%
F
O
O
CN
O
Xa
O
54% (2 steps)
44% (2 steps)
27 (E,E isomer only)
26 89%
Xa
O
O
O
O
O
Xa
PivO
NC
12
Xa = SC(S)OEt
13I 85% dr = 1:1
28 (E,E:E,Z = 3:1)
Scheme 10
Synlett 2006, No. 10, 1485–1490 © Thieme Stuttgart · New York

LETTER
A Convergent Access to Dienes and d-Lactones
1489
(2) (a) Davies, A. G.; Sutcliffe, R. J. Chem. Soc., Perkin Trans.
2 1980, 5, 819. (b) Foulard, G.; Brigaud, T.; Portella, C. J.
Org. Chem. 1997, 62, 9107. (c) Nishida, A.; Kawahara, N.;
Nishida, M.; Yonemitsu, O. Tetrahedron 1996, 52, 9713.
(d) Dondi, D.; Caprioli, I.; Fagnoni, M.; Mella, M.; Albini,
A. Tetrahedron 2003, 59, 947. (e) Stojanovic, A.; Renaud,
P. Helv. Chim. Acta 1998, 81, 353. (f) Giese, B.; Horler, H.
Tetrahedron 1985, 41, 4025.
(3) Tournier, L.; Zard, S. Z. Tetrahedron Lett. 2005, 46, 455.
(4) (a) Ulich, L. H.; Adams, R. J. Am. Chem. Soc. 1921, 43,
660. (b) Luk’yanov, S. M.; Borodaev, S. V.; Borodaeva, S.
V. J. Org. Chem. USSR 1983, 19, 1872.
additional portions (5% mol) every 1.5 h until the xanthate
was completely consumed. The mixture was then cooled to
r.t., concentrated under reduced pressure and purified by
flash chromatography (silica gel). A small layer of basic
alumina was placed on top of the silica to remove any lauric
acid present.
Data for ( )-Xanthate Adduct 5eD.
Rf = 0.2 [PE (40–60)–Et2O, 4:1]. IR (film): nmax = 2929 (s),
2855 (s), 2251 (w), 1735 (s), 1446 (s), 1234 (s), 1051 (s), 733
(s) cm–1. 1H NMR (400 MHz, CDCl3): d = 0.93–1.28 (10 H,
m), 1.36–1.45 (6 H, m), 1.45–1.59 (2 H, m), 1.59–1.80 (10
H, m), 1.97–2.08 (4 H, m), 2.05 (3 H, s), 2.09 (3 H, s), 2.80–
3.05 (4 H, m), 3.78–3.87 (1 H, m), 3.88–3.97 (1 H, m), 4.59–
(5) Ly, T. M.; Quiclet-Sire, B.; Sortais, B.; Zard, S. Z.
Tetrahedron Lett. 1999, 40, 2533.
4.68 (4 H, m), 4.78–4.86 (1 H, m), 4.88–4.97 (1 H, m). 13
C
(6) The reaction yields reported are for preliminary studies and
hence are unoptimised.
(7) Yields based upon recovered starting material are given in
parentheses.
(8) Langlois, D. P.; Wolff, H. J. Am. Chem. Soc. 1948, 70, 2624.
(9) Evans, P. A.; Holmes, A. B. Tetrahedron 1991, 47, 9131;
and references cited therein.
(10) Liard, A.; Quiclet-Sire, B.; Zard, S. Z. Tetrahedron Lett.
1996, 37, 5877.
(11) Vedejs, E.; Stults, J. S. J. Org. Chem. 1988, 53, 2226.
(12) (a) Liu, J. S.; Huang, M. F.; Ayer, W. A.; Arnold, G. F.;
Arnold, E.; Clardy, J. Tetrahedron Lett. 1983, 24, 2351.
(b) Liu, J. S.; Huang, M. F.; Ayer, W. A.; Bigam, G.
Tetrahedron Lett. 1983, 24, 2355. (c) Kirson, I.; Cohen, A.;
Abraham, A. J. Chem. Soc., Perkin Trans. 1 1975, 21, 2136.
(13) Legrand, N.; Quiclet-Sire, B.; Zard, S. Z. Tetrahedron Lett.
2000, 41, 9815.
NMR (100.6MHz, CDCl3): d = 13.8 (2 CH3), 21.1 (2 CH3),
22.6 (CH2), 24.4 (CH2), 25.9 (2 CH2), 26.0 (2 CH2), 26.2
(CH2), 26.3 (CH2), 27.9 (CH2), 28.2 (CH2), 28.5 (CH2), 28.9
(CH2), 33.8 (CH2), 34.3 (CH2), 41.5 (CH), 41.9 (CH), 43.1
(CH), 43.9 (CH), 70.5 (CH2), 70.6 (CH2), 74.4 (2 CH), 116.9
(C), 117.1 (C), 170.5 (C), 171.0 (C), 212.0 (C), 212.3 (C).
MS (EI): m/z (%) = 343 (40) [M+], 283 (100). HRMS: m/z
calcd for C16H25O3NS2: 343.1276. Found: 343.1287 [M+].
(17) Procedure for Preparation of Xanthate 12.
To a flask containing levulinic acid (10, 8 g, 69 mmol, 1
equiv) under nitrogen at 0 °C was added dropwise freshly
distilled SOCl2 (6 mL, 83 mmol, 1.2 equiv) and the resulting
mixture stirred for 1 h. The reaction mixture was then
allowed to warm to r.t. and concentrated in vacuo to afford
crude chloride 11. To a solution of crude chloride 11 in
acetone (70 mL) at 0 °C under nitrogen was added
portionwise potassium O-ethyl xanthate (13.3 g, 83 mmol,
1.2 equiv) and the resulting mixture stirred at r.t. for 18 h
overnight. The mixture was then concentrated under reduced
pressure and diluted with H2O and Et2O. The aqueous layer
was extracted with Et2O and the organic layers were
combined, washed with brine, dried (Na2SO4), filtered and
concentrated in vacuo. Purification by flash chromatography
[PE (40–60)–EtOAc, 9:1] gave xanthate 12 as a yellow oil
(13.7 g, 90%, 2 steps).
(14) Binot, G.; Quiclet-Sire, B.; Saleh, T.; Zard, S. Z. Synlett
2003, 382.
(15) General Procedure for Preparation of Xanthates 4a–e.
To a flask containing freshly fused catalytic ZnCl2 (ca. 5 mg)
under argon was added acetyl chloride (2.4 mmol) and the
mixture cooled to –5 °C to –10 °C. The aldehyde (1 mmol)
was then added dropwise and the resulting reaction mixture
stirred at r.t. for 1 h. The mixture was then concentrated
under reduced pressure to afford crude chloride 3. To a
solution of crude chloride 3 in EtOH or acetone (1 M) at 0
°C under argon was added portionwise potassium O-ethyl
xanthate (1.5 mmol) and the resulting mixture stirred at r.t.
for 18 h overnight. The mixture was then concentrated under
reduced pressure and diluted with H2O and Et2O. The
aqueous layer was extracted with Et2O and the organic layers
were combined, washed with H2O, brine, dried (Na2SO4),
filtered and concentrated in vacuo. Purification by flash
chromatography (silica gel) gave xanthates 4 as yellow oils.
Note that in some cases, using 0.5 equiv of acetyl chloride
gave higher product yields.
Data for ( )-Xanthate 12.
Rf = 0.1 [PE (40–60)–EtOAc, 9:1]. IR (film): nmax = 2981 (s),
2933 (s), 1791 (s), 1241 (s), 1128 (s), 1040 (s), 896 (s) cm–1.
1H NMR (400 MHz, CDCl3): d = 1.50 (3 H, t, J = 7.0 Hz),
1.96 (3 H, s), 2.35–2.42 (1 H, m), 2.63–2.91 (3 H, m), 4.67–
4.77 (2 H, m). 13C NMR (100.6 MHz, CDCl3): d = 13.7
(CH3), 28.6 (CH3), 28.8 (CH2), 35.2 (CH2), 70.2 (CH2), 94.4
(C), 175.1 (C), 209.4 (C). MS (CI): m/z (%) = 238 (100)
+
[MNH4 ], 221 (48) [MH+]. HRMS: m/z calcd for C8H12O3S2:
220.0228. Found: 220.0234 [M+].
(18) Data for ( )-Xanthate Adduct 13H.
Rf = 0.15 [PE (40–60)–Et2O–CH2Cl2, 7.5:1.5:1]. IR (film):
Data for ( )-Xanthate 4e.
nmax = 2829 (s), 2856 (s), 1774 (s), 1737 (s), 1444 (s), 1364
Rf = 0.2 [PE (40–60)–Et2O, 97:3]. IR (film): nmax = 2929 (s),
2855 (s), 1753 (s), 1368 (s), 1221 (s), 1111 (s), 1051 (s) cm–1.
1H NMR (400 MHz, CDCl3): d = 0.93–1.30 (5 H, m), 1.40
(3 H, t, J = 7.0 Hz), 1.61–1.90 (6 H, m), 2.07 (3 H, s), 4.55–
4.70 (2 H, m), 6.57 (1 H, d, J = 5.5 Hz). 13C NMR (100.6
MHz, CDCl3): d = 13.7 (CH3), 20.9 (CH3), 25.8 (2 CH2),
26.0 (CH2), 28.5 (CH2), 28.9 (CH2), 42.0 (CH), 70.1 (CH2),
84.7 (CH), 169.3 (C), 210.7 (C). MS (CI): m/z (%) = 294
(s), 1216 (s), 1052 (s), 734 (s) cm–1. 1H NMR (400 MHz,
CDCl3): d = 1.23–1.50 (17 H, m), 1.46 (6 H, t, J = 7.0 Hz),
1.47 (3 H, s), 1.53 (3 H, s), 1.57–1.97 (9 H, m), 2.00–2.22 (8
H, m), 2.33 (4 H, t, J = 7.5 Hz), 2.36–2.46 (2 H, m), 2.54–
2.75 (4 H, m), 3.69 (6 H, s), 3.78–3.96 (2 H, m), 4.67 (4 H,
q, J = 7.0 Hz). 13C NMR (100.6 MHz, CDCl3): d = 13.8 (2
CH3), 24.8 (CH3), 24.9 (2 CH2), 27.0 (CH3), 27.0 (CH2), 28.6
(CH2), 29.0 (2 CH2), 29.1 (3 CH2), 29.2 (4 CH2), 29.3 (CH2),
32.5 (CH2), 34.0 (2 CH2), 34.7 (2 CH2), 35.9 (CH2), 44.3
(CH2), 45.1 (CH2), 46.7 (CH), 47.3 (CH), 51.3 (2 CH3), 69.9
(CH2), 70.0 (CH2), 85.9 (C), 86.1 (C), 174.2 (2 C), 176.2 (C),
176.3 (C), 214.0 (C), 214.1 (C). MS (CI): m/z (%) = 436
+
(10) [MNH4 ], 277 (10) [MH+], 217 (100). HRMS: m/z calcd
for C12H20O3S2: 276.0854. Found: 276.0845 [M+].
(16) General Procedure for Radical Addition.
A solution of xanthate (1 mmol) and the desired olefin (2
mmol) in 1,2-dichloroethane (DCE, 2 mL) was refluxed for
15 min under nitrogen. Lauroyl peroxide (DLP, 5% mol)
was then added to the refluxing solution, followed by
+
(100) [MNH4 ], 419 (44) [MH+]. HRMS: m/z calcd for
C20H34O5S2: 418.1848. Found: 418.1844 [M+].
Synlett 2006, No. 10, 1485–1490 © Thieme Stuttgart · New York

1490
S. K. Bagal et al.
LETTER
(19) General Procedure for Diene Formation.
To a solution of xanthate (1 mmol) in CH2Cl2 or MeCN (0.1
M) at r.t. under nitrogen was added DBU (2.2 mmol)
dropwise and the resulting mixture stirred for 18 h overnight.
The mixture was then concentrated under reduced pressure
and diluted with H2O and Et2O. The aqueous layer was
extracted with Et2O and the organic layers were combined,
washed several times with sat. aq NH4Cl and then brine,
dried (Na2SO4), filtered and concentrated in vacuo. Purifi-
cation was performed by flash chromatography (silica gel).
Data for ( )-(2E,4E)- and ( )-(2Z,4E)-5-Cyclohexyl-
penta-2,4-dienenitrile (17).
NMR Data for ( )-(2Z,4E)-Isomer.
1H NMR (400 MHz, CDCl3): d = 1.08–1.43 (5 H, m), 1.59–
1.86 (5 H, m), 2.07–2.26 (1 H, m), 5.14 (1 H, d, J = 11.0 Hz),
6.11–6.20 (1 H, m), 6.55 (1 H, dd, J = 15.0, 11.0 Hz), 6.82
(1 H, t, J = 11.0 Hz). 13C NMR (100.6 MHz, CDCl3): d =
24.3 (CH2), 24.5 (2 CH2), 30.7 (2 CH2), 41.1 (CH), 94.8
(CH), 117.1 (CN, very weak), 124.4 (CH), 150.2 (CH),
151.3 (CH).
(20) General Procedure for Lactone Formation.
To a solution of 5dD, 5cE or 5cF (100 mg) in EtOH (10 mL)
at r.t. under nitrogen was added concd HCl (1 mL) and the
resulting mixture refluxed (EtOH) for 72 h. The mixture was
then cooled to r.t., concentrated under reduced pressure and
diluted with Et2O (50 mL). The ethereal phase was washed
with sat. aq K2CO3, dried (MgSO4), filtered and concen-
trated in vacuo. Purification by flash chromatography (silica
gel) gave lactones 19, 20, 21 as yellow oils.
Purification by flash chromatography [PE(40–60)–CH2Cl2,
7:3) gave diene 17 as a pale yellow oil (81%) and as a
mixture of 2 diastereomers in a 2E,4E/2Z,4E ratio of 1.3:1.
Only traces of the 2E,4Z and 2Z,4Z diastereomers could be
detected in the NMR spectra.
Rf = 0.5 and 0.35 [PE (40–60)–CH2Cl2, 1:1]. IR (film):
Data for ( )-6-Isobutyl-3-methyl-5,6-dihydro-pyran-2-
one (21).
n
max = 3039 (m), 2927 (s), 2856 (s), 2214 (s), 1637 (s), 1595
(s), 994 (s), 742 (s) cm–1. MS (CI): m/z (%) = 179 (100)
Rf = 0.2 [PE (40–60)–EtOAc, 9:1]. IR (film): nmax = 2959 (s),
2929 (s), 1726 (s), 1368 (s), 1113 (s), 786 (s) cm–1. 1H NMR
(400 MHz, CDCl3): d = 0.88 (6 H, d, J = 6.5 Hz), 1.26–1.37
(1 H, m), 1.65–1.75 (1 H, m), 1.77–1.92 (1 H, m), 1.86 (3 H,
s), 2.17–2.28 (2 H, m), 4.34–4.46 (1 H, m), 6.49–6.58 (1 H,
m). 13C NMR (100.6 MHz, CDCl3): d = 17.0 (CH3), 22.1
(CH), 23.0 (CH3), 23.9 (CH3), 30.3 (CH2), 44.0 (CH2), 76.4
(CH), 128.4 (C), 139.0 (CH), 166.2 (C). MS (CI): m/z (%) =
[MNH4 ], 162 (1) [MH+]. HRMS: m/z calcd for C11H15N:
+
161.1205. Found: 161.1207 [M+]
NMR Data for ( )-(2E,4E)-Isomer.
1H NMR (400 MHz, CDCl3): d = 1.08–1.43 (5 H, m), 1.59–
1.86 (5 H, m), 2.07–2.26 (1 H, m), 5.28 (1 H, d, J = 16.0 Hz),
6.11–6.16 (2 H, m), 7.01 (1 H, dd, J = 16.0, 10.0 Hz).
13C NMR (100.6 MHz, CDCl3): d = 24.3 (CH2), 24.4
(2 CH2), 30.6 (2 CH2), 41.2 (CH), 96.5 (CH), 115.4 (CN,
very weak), 125.5 (CH), 151.4 (CH), 151.6 (CH).
+
186 (100) [MNH4 ], 169 (100) [MH+].
Synlett 2006, No. 10, 1485–1490 © Thieme Stuttgart · New York