Asymmetric synthesis of enantiomerically pure 7-isopropenyl-4a-methyl-3-methyleneoctahydrochromen-2-ones

Article abstract of DOI:10.1016/j.tetasy.2007.10.039

Four stereoisomers of 7-isopropenyl-4a-methyl-3-methyleneoctahydrochromenon-2-one have been obtained for the first time. The key step of the synthesis involves asymmetric Michael addition of chiral enamines derived from dihydrocarvone to acrylate 1. Absolute configurations were established by X-ray analysis.

Full text of DOI:10.1016/j.tetasy.2007.10.039

Available online at www.sciencedirect.com
Tetrahedron: Asymmetry 18 (2007) 2712–2718
Asymmetric synthesis of enantiomerically pure 7-isopropenyl-4a-
methyl-3-methyleneoctahydrochromen-2-ones
a
a
b
Henryk Krawczyk,a, Marcin Sliwinski, Jacek Ke˛dzia, Jakub Wojciechowski
´
*
´
and Wojciech M. Wolfb,*
a
_
Institute of Organic Chemistry, Technical University (Politechnika), 90-924 Ło´dz´, Zeromskiego 116, Poland
b
_
Institute of General and Ecological Chemistry, Technical University (Politechnika), 90-924 Ło´dz´, Zeromskiego 116, Poland
Received 10 October 2007; accepted 23 October 2007
Abstract—Four stereoisomers of 7-isopropenyl-4a-methyl-3-methyleneoctahydrochromenon-2-one have been obtained for the first time.
The key step of the synthesis involves asymmetric Michael addition of chiral enamines derived from dihydrocarvone to acrylate 1. Abso-
lute configurations were established by X-ray analysis.
ꢀ 2007 Elsevier Ltd. All rights reserved.
1. Introduction
acids with KBH4, lactonization, and finally Horner–
Wadsworth–Emmons reaction of the resulting 2-diethoxy-
phosphoryl-d-valerolactones with formaldehyde provided
the corresponding a-methylene-d-valerolactones with enan-
tiomeric excesses exceeding 95% ee.
The asymmetric Michael reaction of enamines derived
from enantiomerically pure 1-phenylethylamine and 2-
substituted cycloalkanones to electron-deficient olefins
has attracted much attention over the past decades as a
versatile method for the construction of enantiomerically
enriched 2,2-disubstituted cycloalkanones.1 A number of
them have been synthesized by this method and utilized
for the preparation of organic molecules containing a chi-
ral quaternary stereogenic center. Moreover, a version of
this reaction that utilizes enamines formed from 2-substi-
tuted cycloalkanones containing a stereogenic center in
the ring represents a direct approach to the diastereoselec-
tive synthesis of enantiomerically pure 2,2-disubstituted
cycloalkanones. Several examples of such an addition
employing (R)- and (S)-dihydrocarvone, and 3(R),2(RS)-
dimethylcyclohexanone have been reported.2
Based on this research and the importance of the a-methyl-
ene-d-valerolactone motif in natural products,4 we decided
to explore further the potential of acrylate 1. We
envisioned that the use of enamines derived from chiral,
properly substituted cycloalkanones would give access
to enantiomerically pure a-methylene-d-valerolactones.
Dihydrocarvone was selected as a model ketone since it is
easily available in both enantiomeric forms.5 Herein, we
report the first diastereoselective synthesis of four enantio-
merically pure 3-methyleneoctahydrochromen-2-ones der-
ived from (R)- and (S)-dihydrocarvone. These derivatives
could be attractive precursors for the synthesis of bio-
logically active compounds.6
Our own studies led us to discover the potential of dicyclo-
hexylammonium 2-(diethoxyphosphoryl)acrylate 1 as a
Michael acceptor in this type of asymmetric addition. We
have shown that the resulting 2-diethoxyphosphoryl-3-(2-
oxocycloalkyl)propanoic acids can be used as chiral
synthons for the preparation of enantiomerically enriched
a-methylene-d-valerolactones.3 Treatment of these oxo-
2. Results and discussion
The four starting enamines 3, 8, 12, and 16 were prepared
by reacting (R)- and (S)-dihydrocarvone 2 and 7 with (R)-
and (S)-1-phenylethylamine by the reported method.2f
Schemes 1–4 outline transformation of enamines 3, 8,
12, and 16 to the corresponding a-methylene-d-valero-
lactones 6, 11, 15, and 19, respectively. The enamines
proved useful as good substrates for the reaction with salt
*
Corresponding authors. Tel.: +48 (42) 631 3104; fax: +48 (42) 636
5530; e-mail: henkrawc@p.lodz.pl
0957-4166/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.10.039

H. Krawczyk et al. / Tetrahedron: Asymmetry 18 (2007) 2712–2718
2713
O
Me
H
Ph
N
Me
H
Ph
(EtO)2P
CO2NH2(C6H11)2
O
NH
Me
a
1
Me
Me
2
3
b, c
O
O
O
O
O
P(OEt)2
Me
O
O
P(OEt)2
H
H
e
d
CO2H
Me
Me
6
5
4
Scheme 1. Reagents and conditions: (a) (S)-1-phenylethylamine, p-TSA (cat), toluene, reflux, 12 h, 90%; (b) benzene, rt, 48 h; (c) Dowex 50W, acetone/
water, 85%; (d) MeOH, KBH4 (2 equiv), rt, 24 h, 90%; (e) t-BuOK (1 equiv), (HCHO)n (5 equiv), Et2O, rt, 1 h, 85%.
O
Ph
H
Me
N
Ph
H
Me
NH
(EtO)2P
CO2NH2(C6H11)2
O
Me
a
1
Me
Me
7
8
b, c
O
O
O
O
O
P(OEt)2
Me
O
O
P(OEt)2
H
H
e
d
CO2H
Me
Me
11
10
9
Scheme 2. Reagents and conditions: (a) (R)-1-phenylethylamine, p-TSA (cat), toluene, reflux, 12 h, 90%; (b) benzene, rt, 48 h; (c) Dowex 50W, acetone/
water, 85%; (d) MeOH, KBH4 (2 equiv), rt, 24 h, 90%; (e) t-BuOK (1 equiv), (HCHO)n (5 equiv), Et2O, rt, 1 h, 85%.
1. Addition reactions of enamines 6, 11, 15, and 19 to salt 1
proceeded smoothly in benzene at room temperature.
Complete consumption of the salt was observed after 2
days. The crude products were transformed into the corre-
sponding oxoacids by ion-exchange chromatography in
high yield.
Single crystal X-ray analysis revealed that acid 4 is a single,
enantiomerically pure diastereoisomer and its absolute
configuration is 2S,(1R,4R) (Fig. 1). The cyclohexanone
ring exhibits an almost ideal chair conformation. The
Cremer and Pople7 puckering parameters for the ring
˚
atom sequence C1/C2/C3/C7/C8/C9 are Q = 0.515(5) A,
h = 6.5(6)ꢁ, u = 162.2(6)ꢁ. The isopropenyl and methyl
substituents are located in equatorial positions. The ethyl
substituent bearing the diethoxyphosphoryl and carboxylic
groups is placed axially with the endocyclic C9–C11 bond
making an angle of 9.7(2)ꢁ with the normal to the Cremer
and Pople plane (C1, C2, C7, C8). The position of the car-
boxylic group is further stabilized by the nonbonding intra-
molecular electrostatic interaction with the exocyclic
carbonyl group. This Coulombic attraction follows from
the perpendicular arrangement of the carbonyl groups
(Motif II, according to Allen’s classification8) and involves
the oppositely charged O5 (ꢀ0.58 e) and C1 (0.44 e) atoms.
It is well known that the stereogenic center existing in
synthons 3, 8, 12, and 16 may have some impact on the dia-
stereoselective outcome of addition. The best results with
respect to diastereoselectivity were achieved when enam-
ines 3 and 8 were used as the Michael donors. The corre-
sponding oxoalkanoic acids 4 and 9 were isolated as
single diastereoisomers. As expected, the use of enamines
12 and 16 as the Michael donors resulted in moderate dia-
stereoselectivity and led to the formation of mixtures of
isomeric oxoacids 13:4 and 17:9 in a 6:1 ratio. The latter re-
sult is most likely due to the incompatibility of steric effects
with electronic effects in the corresponding transition
states.2
˚
The respective interatomic distance 3.068(4) A is shorter
than the sum of the oxygen and carbon van der Waals radii

2714
H. Krawczyk et al. / Tetrahedron: Asymmetry 18 (2007) 2712–2718
O
Ph
H
Me
N
Ph
H
Me
NH
(EtO)2P
CO2NH2(C6H11)2
O
1
Me
Me
O
Me
a
2
12
b, c
O
O
O
Me
Me
P(OEt)2
P(OEt)2
+
CO2H
CO2H
d
13
4
ratio 6 : 1
O
O
O
O
O
O
P(OEt)2
P(OEt)2
O
O
O
O
e, f
H
H
H
H
+
+
Me
Me
Me
Me
14
5
15
6
Scheme 3. Reagents and conditions: (a) (R)-a-phenylethylamine, p-TSA (cat), toluene, reflux, 12 h, 90%; (b) benzene, rt, 48 h; (c) Dowex 50W, acetone/
water, 80%; (d) MeOH, KBH4 (2 equiv), rt, 24 h, 90%; (e) t-BuOK (1 equiv), (HCHO)n (5 equiv), Et2O, rt, 1 h, 85%; (f) column chromatography.
O
Me
H
Ph
N
Me
H
Ph
(EtO)2P
CO2NH2(C6H11)2
O
NH
1
Me
Me
O
Me
a
7
16
b, c
O
O
O
Me
Me
P(OEt)2
P(OEt)2
+
CO2H
CO2H
d
17
9
ratio 6 : 1
O
O
O
O
O
O
P(OEt)2
P(OEt)2
O
O
O
O
e, f
H
H
H
H
+
+
Me
Me
Me
Me
18
10
19
11
Scheme 4. Reagents and conditions: (a) (S)-a-phenylethylamine, p-TSA (cat), toluene, reflux, 12 h, 90%; (b) benzene, rt, 48 h; (c) Dowex, acetone/water,
80%; (d) MeOH, KBH4 (2 equiv), rt, 24 h, 90%; (e) t-BuOK (1 equiv), (HCHO)n (5 equiv), Et2O, rt, 1 h, 85%; (f) column chromatography.
9
˚
3.22 A. Atomic charges derived from electrostatic poten-
tial were calculated using GAUSSIAN 0310 at the MP2/6-
311+G(d,p) level for the X-ray determined coordinates.
Grid points were selected according to the CHELPG pro-
cedure of Breneman and Wiberg.11 In the crystal hydrogen
bonds between the carboxylic group and phosphoryl bond

H. Krawczyk et al. / Tetrahedron: Asymmetry 18 (2007) 2712–2718
2715
were used directly for the next step. Standard procedures
were applied for the transformation of oxoacids obtained
into the corresponding a-methylene-d-valerolactones.
Chemoselective reduction of oxoacids 4 and 9 with KBH4
in methanol provided directly a-phosphono-d-valerolac-
tones 5 and 10, respectively. Under the same conditions,
the mixtures of oxoacids 13:4 and 17:9 were converted into
mixtures of the corresponding a-phosphono-d-valerolac-
tones 14:5 and 18:10 in a 6:1 ratio.
All attempts to separate the diastereoisomers by column
chromatography were unsuccessful. At this stage we were
unable to determine the diastereoselectivity of the reduc-
tion. Finally, the HWE reaction of phosphonolactones 5,
10, 14:5 and 18:10, performed with excess of paraformalde-
hyde in diethyl ether in the presence of t-BuOK afforded
the corresponding a-methylene-d-valerolactones 6, 11,
15:6 and 19:11, respectively. The mixtures of diastereoiso-
meric lactones 15 and 6, and 19 and 11 were separated
by column chromatography.
The relative and absolute configuration of the enantiomeri-
cally pure 3-methyleneoctahydrochroman-2-ones obtained
was established by X-ray analysis of the trans-lactone
1513 and cis-lactone 11.14 The absolute stereochemistry of
the trans-lactone 15 was determined to be 4a(S),7(R),8a(R),
(Fig. 2) meaning that the lactone 19 is undoubtedly the
4a(R),7(S),8a(S) isomer. The absolute configuration of
cis-lactone 11 was determined to be 4a(S),7(S),8a(S)
(Fig. 3). Therefore, the absolute configuration of lactone
6 must be 4a(R),7(R),8a(R). These findings provide a clear
evidence that the reduction of the oxoacids 4, 9, 13, and 17
proceeded with complete diastereocontrol through the
axial attack of hydride anion on the carbonyl group and
proved the relative configuration of the ring junction in
the lactones obtained.
Figure 1. The crystal structure of acid 4. The methyl C15 atom is
disordered and was refined in two partially occupied positions. The picture
shows sites for which the occupation factor was 0.73(3). The less occupied
positions have not been shown for clarity. Displacement ellipsoids are
drawn at the 50% probability level. H atoms are represented by circles of
an arbitrary radius.
link molecules into an infinite chain running in the b-axis
direction [O6–H6 = 0.82 A, O6–H6ꢁ ꢁ ꢁO40(x,y + 1,z) =
˚
˚
0
167ꢁ, O6ꢁ ꢁ ꢁO4 = 2.567(4) A].
The (R)-absolute configuration at the quaternary stereo-
genic center in acid 4 is fully consistent with the transi-
tion-state model proposed for similar Michael additions12
and with the results of our earlier work.3 As a consequence
of this, the stereochemistry at the quaternary stereogenic
center in acids 9, 13, and 17 was assigned to be (S), (S),
and (R), respectively.
3. Conclusions
In summary, the chemistry described herein expands
the potential of acrylate 1 in asymmetric Michael reac-
tions and provides facile entry to enantiomerically pure
3-methyleneoctahydrochromen-2-ones. The method is
expected to find further applications in the synthesis of
The mixtures of diastereoisomeric oxoacids 13:4 and 17:9
could not be separated by column chromatography and
Figure 2. The molecular structure of 15 as published in Ref. 13. Displacement ellipsoids are drawn at the 50% probability level. H atoms are represented
by circles of an arbitrary radius.

2716
H. Krawczyk et al. / Tetrahedron: Asymmetry 18 (2007) 2712–2718
4.72 (s, 1H, @CH), 4.78 (s, 1H, @CH); 13C NMR (CDCl3):
d = 15.90 (d, 3JCP = 3.8, CH3CH2OP), 16.11 (d,
3JCP = 3.8, CH3CH2OP), 20.92 (CH3), 21.12 (CH3), 25.75
2
(CH2), 33.34 (d, JCP = 5.04, CH2), 38.13 (CH2), 40.95
1
(d, JCP = 128, CHP), 43.21 (CH22), 45.91 (CH), 48.25
3
(d, JCP = 12.0, C), 63.00 (d, JCP = 6.3, CH2OP),
2
63.61 (d, JCP = 6.3, CH2OP), 109.00 (@CH2), 147.02
2
(@C), 170.93 (d, JCP = 3.3, COOH), 214.21 (CO). Anal.
Calcd for C17H29O6P: C, 56.66; H, 8.11. Found: C, 56.73;
H, 8.01.
4.2.2. 2-(Diethoxyphosphoryl)-3-(4-isopropenyl-1-methyl-2-
oxocyclohexyl)propanoic acids 13 and 4. (2.88 g, 80%
yield); diastereoisomeric ratio 6:1, colorless oil; IR (film)
3090, 1762, 1690, 1265 cmꢀ1. Anal. Calcd for C17H29O6
P: C, 56.66; H, 8.11. Found: C, 56.73; H, 8.01.
1
Compound 13. 31P NMR (CDCl3): d = 24.95; H NMR
Figure 3. The molecular structure of 11 as published in Ref. 14.
Displacement ellipsoids are drawn at the 50% probability level. H atoms
are represented by circles of an arbitrary radius.
3
(CDCl3): d = 1.15 (s, 3H, CH3), 1.35 (t, 6H, JHH = 7.0,
2 · CH3CH2OP), 1.59–1.97 (m, 4H, 2 · CH2), 1.73 (s,
3H, CH3C@), 2.07–2.50 (m, 5H, 2 · CH2, CH), 3.03
bicyclic d-valerolactones bearing chiral quaternary stereo-
genic centers.
3
3
2
(ddd, 1H, JHH = 9.0, JHH = 15.0, JHP = 26.5, CHP),
4.10–4.28 (m, 4H, 2 · CH2OP), 4.70 (s, 1H, @CH), 4.76
(s, 1H, @CH); 13C NMR (CDCl3): d 16.00 (d, JCP = 3.8,
3
4. Experimental
4.1. General
2 · CH3CH2OP), 20.41 (CH3), 21.02 (CH3), 25.55 (CH2),
2
33.94 (d, JCP = 4.4, CH2), 35.30 (CH2), 41.45 (d,
1JCP = 125.6, CHP), 42.71 (CH2), 45.51 (CH), 47.85 (d,
3JCP = 13.0, C), 62.88 (d, JCP = 6.4, CH2OP), 63.30 (d,
2
2JCP2 = 6.4, CH2OP), 110.05 (=CH2), 146.08 (=C), 171.77
(d, JCP = 3.1, COOH), 215.62 (CO).
NMR spectra were recorded on a Bruker DPX 250 instru-
1
ment at 250.13 MHz for H and 62.9 MHz for 13C and
101.3 MHz for 31P NMR, respectively, using tetramethyl-
silane as an internal standard and 85% H3PO4 as an exter-
nal standard. The multiplicities of carbons were determined
by DEPT experiments. IR spectra were measured on Spe-
cord M80 (Zeiss) instrument. Elemental analyses were per-
formed on Perkin–Elmer PE 2400 analyzer. Melting points
were determined in open capillaries and are uncorrected.
Dicyclohexylammonium 2-(diethoxyphosphoryl)acrylate 1
was prepared according to the literature procedure.15
4.3. General procedure for the preparation of phosphono-
lactones 5, 10, 14, and 18
To a stirred solution of 4 (2.88 g, 0.008 mol) in methanol
(50 ml) was added KBH4 (0.86 g, 0.016 mol). Stirring was
continued for 24 h at room temperature. The resulting mix-
ture was neutralized to pH ꢂ 3 with 5% HCl. The solvent
was evaporated and the residue was diluted with water
(20 ml) and extracted with chloroform (3 · 20 ml). The
organic layer was dried (MgSO4) and evaporated. The oily
residue was purified by column chromatography on silica
gel using ethyl acetate/hexane (3:1) as eluent to give pure
lactone 5.
4.2. General procedure for the preparation of phosphonoal-
kanoic acids 4, 9, 13, and 17
A mixture of acrylate 1 (3.89 g, 0.01 mol) and enamine 3, 8,
12, or 16 (0.011 mol) in benzene (50 ml) was stirred at room
temperature for 48 h. After the reaction was completed (31P
NMR) the solvent was evaporated and the residue was sub-
jected to ion-exchange chromatography performed on a
glass column packed with Dowex 50W using H2O/acetone,
1:1 as eluent. The eluent was evaporated to give the acid as
a colorless oil.
4.3.1. Diethyl (7-isopropenyl-4a-methyl-2-oxo-octahydro-
2H-chromen-3-yl)phosphonate 5. (2.48 g, 90% yield);
colorless oil; IR (film) 3093, 1787, 1279, 1190 cmꢀ1 31P
;
NMR (CDCl3): d = 23.30; 1H NMR (CDCl3): d = 1.11
3
(s, 3H, CH3), 1.31 (t, 3H, JHH = 7.1, CH3CH2OP), 1.34
3
(t, 3H, JHH = 7.1, CH3CH2OP), 1.43–1.60 (m, 6H,
3 · CH2), 1.65 (s, 3H, CH3), 1.81–2.15 (m, 2H, CH,
2
3
4.2.1. 2-(Diethoxyphosphoryl)-3-(4-isopropenyl-1-methyl-2-
oxocyclohexyl)propanoic acid 4. (3.06 g, 85% yield); white
solid, mp = 104–106 ꢁC; IR (film) 3090, 1762, 1690,
CHCHP), 2.58 (dt, 1H, JHH = 3JHH = 11.5, JHP = 14.5,
3
3
CHCHP), 3.20 (ddd, 1H, JHH = 9.0, JHH = 11.5,
2JHP = 28.6, CHP), 4.10–4.28 (m, 1H, CHO), 4.18 (q,
2H, 3JHH = 3JHP = 7.1, CH2OP), 4.20 (q, 2H,
3JHH = 3JHP = 7.1, CH2OP), 4.73 (s, 2H, @CH2); 13C
1265 cmꢀ1
;
31P NMR (CDCl3): d = 23.82; 1H NMR
3
(CDCl3): d = 0.99 (s, 3H, CH3), 1.32 (t, 3H, JHH = 7.0,
3
3
CH3CH2OP), 1.34 (t, 3H, JHH = 7.0, CH3CH2OP), 1.48–
NMR (CDCl3): d = 16.11 (d, JCP = 5.6, CH3CH2OP),
3
1.91 (m, 4H, 2 · CH2), 1.74 (s, 3H, CH3C@), 2.08–2.65
16.21 (d, JCP = 5.6, CH3CH2OP), 20.71 (CH3), 25.11
3
2
(m, 5H, 2 · CH2, CH), 2.82 (ddd, 1H, JHH = 2.7,
(CH3), 25.61 (CH2), 26.91 (d, JCP = 3.8, CH2), 31.50 (d,
1
3JHH = 7.5, 2JHP = 25.5, CHP), 4.14 (q, 3JHH
=
3JCP = 5.0, C), 34.43 (CH2), 37.11 (d, JCP = 140.5,
2
3JHP = 7.2, CH2OP), 4.20 (q , 3JHH = 3JHP = 7.2, CH2OP),
CHP), 37.25 (CH2), 43.60 (CH@), 62.61 (d, JCP = 6.9,

H. Krawczyk et al. / Tetrahedron: Asymmetry 18 (2007) 2712–2718
2717
2
CH2OP), 63.31 (d, JCP = 6.9, CH2OP), 86.32 (CHO),
tals, mp = 80–82 ꢁC; IR (film) 3089, 1780, 1610,
1180 cmꢀ1 1H NMR (CDCl3): d = 0.95 (s, 3H, CH3),
109.45 (CH2@), 147.62 (C@), 165.21 (COO). Anal. Calcd
for C17H29O5P: C, 59.29; H, 8.49. Found: C, 59.07; H, 8.61.
;
1.20–1.60 (m, 5H, 2 · CH2, CH), 1.90–2.11 (m, 2H,
CH2), 2.17 (s, 3H, CH3), 2.36 (dd, 1H, 4J = 2.5,
2J = 15.5, CH), 2.50 (d, 1H, 2J = 15.5, CH), 4.12 (dd,
4.3.2. Diethyl (7-isopropenyl-4a-methyl-2-oxo-octahydro-
2H-chromen-3-yl)phosphonates 14 and 5. (2.34 g, 85%
yield); diastereoisomeric ratio 6:1, colorless oil; IR (film)
3093, 1787, 1279, 1190 cmꢀ1. Anal. Calcd for C17H29O5P:
C, 59.29; H, 8.49. Found: C, 59.07; H, 8.61.
4
3
1H, J = 2.5, J = 10.0, CHO), 4.75 (s, 2H, @CH2), 5.58
(t, 1H, 4J = 2J = 2.5, @CH), 6.50 (t, 1H, 2J = 4J = 2.5,
@CH); 13C NMR (CDCl3): d = 15.32 (CH3), 20.82
(CH3), 25.93 (CH2), 31.79 (CH2), 33.59 (C), 36.94 (CH2),
43.26 (CH–C@), 43.83 (CH2), 83.83 (CHO), 108.96
(CH2@), 129.43 (CH2@), 133.46 (C@), 147.97 (C@),
165.61 (COO). Anal. Calcd for C14H20O2: C, 76.33; H,
9.15. Found: C, 76.45; H, 9.03.
Compound 14. 31P NMR (CDCl3): d = 23.46; H NMR
(CDCl3): d = 0.95 (s, 3H, CH3), 1.35 (t, 6H, JHH = 7.1,
1
3
2 · CH3CH2OP), 1.43–1.60 (m, 6H, 3 · CH2), 1.74 (s,
3H, CH3), 1.80–2.20 (m, 3H, CH, CH2), 3.24 (dt, 1H,
25
3JHH = 9.0, JHP = 28.5, CHP), 4.05–4.44 (m, 5H, CHO,
Compound 15. ½aꢃD ¼ þ116:15 (c 0.39, MeOH).
2
2 · CH2OP), 4.73 (s, 1H, @CH), 4.75 (s, 1H, @CH); 13C
25
3
NMR (CDCl3): d 14.05 (CH3), 14.91 (d, JCP = 5.0,
Compound 19. ½aꢃD ¼ ꢀ117:5 (c 0.56, MeOH).
3
CH3CH2OP), 15.15 (d, JCP = 5.0, CH3CH2OP), 19.51
3
(CH3@), 24.41 (CH2), 30.51 (CH2), 31.95 (d, JCP = 7.0,
4.5. X-ray single crystal structure analysis for 4
2
C), 35.72 (d, JCP = 4.3, CH2), 36.03 (CH2), 37.41 (d,
1JCP = 133.5, CHP), 41.72 (CH–C@), 61.41 (d,
Formula: C17H29O6P, Mw = 360.37, colorless crystal
2JCP = 6.5, CH2OP), 62.44 (d, JCP = 6.5, CH2OP), 82.11
2
0.40 · 0.15 · 0.10 mm, a = 10.6509(14), b = 6.9574(8),
3
˚
˚
(CHO), 108.15 (CH2@), 146.62 (C@), 165.21 (d,
c = 13.6821(16) A, V = 1010.8(2) (2) A , b = 94.456(7)ꢁ
2JCP = 5.0, COO).
q
calcd = 1.18 g cmꢀ3, l = 14.35 cmꢀ1, semi-empirical abs-
orption correction based on multiple scanned equivalent
reflections16 (0.727 < T < 0.870), Z = 2, crystal system:
monoclinic, space group: P21, k = 1.54178 A, T = 293 K,
4.4. General procedure for the preparation of methylene-
lactones 6, 11, 15, and 19
˚
x scans, 11,625 reflections collected ( h, k, l), 2hmax
=
To a stirred solution of a-phosphonolactone 5 (2.06 g,
0.0060 mol) in diethyl ether (50 ml), potassium t-butoxide
(0.74 g, 0.0066 mol) was added and the resulting mixture
was stirred for 15 min at room temperature. Then satd
NaCl solution (20 ml) was added and the mixture was
extracted with diethyl ether (3 · 10 ml). The organic layer
was dried (MgSO4) and evaporated. The oily residue was
purified by column chromatography on silica gel using
ethyl acetate/hexane (1:5) as eluent to give lactone 6.
141.84ꢁ, 3680 unique reflections (Rint = 0.0180) and 3384
observed reflections [I P 2r(I)], 232 refined parameters,
refinement on F2, Rall = 0.0611, wR (F2) = 0.1845, max
(min) residual electron density Dqmax = 0.34 (Dqmin
=
ꢀ3
ꢀ0.25) e A , Flack parameter17 calculated with 1576 Fri-
edel pairs g = 0.00(3), all hydrogen atoms refined as riding
on their parent atoms. X-ray data were collected with Bru-
ker SMART APEX CCD area detector diffractometer. Com-
puter programs used: data collection SMART APEX,18 data
reduction SAINT-PLUS,19 absorption correction SADABS,20
structure solution, refinement, and molecular graphics
SHELXTL.21 Crystallographic data (excluding structure fac-
tors) for the structure reported herein have been deposited
with the Cambridge Crystallographic Data Centre as sup-
plementary publication CCDC 662749. Copies of the data
can be obtained free of charge on application to The Direc-
tor, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK.
Any request should be accompanied by a full literature
citation.
˚
4.4.1. (4aS,7S,8aS)- and (4aR,7R,8aR)-7-Isopropenyl-4a-
methyl-3-methyleneoctahydrochromen-2-ones
(1.12 g, 85% yield); white crystals, mp = 55–57 ꢁC; IR
(film) 3089, 1780, 1610, 1180 cmꢀ1 1H NMR (CDCl3):
6
and 11.
;
d = 1.11 (s, 3H, CH3), 1.34–1.52 (m, 3H, CH2, CH), 1.73
(s, 3H, CH3), 1.59–1.75 (m, 2H, CH2), 1.95 (dt, 1H,
4J = 2.5, 2J = 13.7, CH), 2.04–2.18 (m, 2H, CH2), 3.01
(dd, 1H, 4J = 2.5, 2J = 13.7, CH), 4.12 (ddd, 1H,
2
2
4J = 2.5, J = 4.2, J = 12.2, CHO), 4.71 (s, 1H, @CH),
4.74 (s, 1H, @CH), 5.57 (dt, 1H, 2J = 1.5, 4J = 2.5,
@CH), 6.51 (dt, 1H, J = 1.5, J = 2.5, @CH); 13C NMR
(CDCl3): d = 20.56 (CH3), 25.69 (CH2), 25.58 (CH3),
32.11 (C), 32.91 (CH2), 34.46 (CH2), 36.62 (CH2), 43.13
(CH–C@), 85.21 (CHO), 108.91 (CH2@), 129.12 (CH2@),
132.52 (C@), 147.45 (C@), 164.20 (COO). Anal. Calcd
for C14H20O2: C, 76.33; H, 9.15. Found: C, 76.45; H, 9.03.
2
4
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