New results on the triplet photoreactivity of β,γ-unsaturated aldehydes: Diastereoselective synthesis of cyclopropanecarbaldehydes

Article abstract of DOI:10.1055/s-2001-15059

A comparative study on the triplet photoreactivity of a series of β,γ-unsaturated aldehydes and methyl ketones has been carried out. Aldehydes 14 and 20 were found to undergo the oxa-di-π-methane rearrangement yielding the corresponding cyclopropane carbaldehydes 15 and 21 diastereoselectively. Decarbonylations and 1,3-carbonyl migrations have been observed in some cases, although these reactions do not take place via a Norrish Type I mechanism.

Full text of DOI:10.1055/s-2001-15059

PAPER
1149
New Results on the Triplet Photoreactivity of , -Unsaturated Aldehydes:
Diastereoselective Synthesis of Cyclopropanecarbaldehydes
D
iastereoselective
i
Synthe
e
sis of Cycl
g
opropanecar
b
o
aldehydes Armesto,* Maria J. Ortiz,* Antonia R. Agarrabeitia, Santiago Aparicio-Lara
Departamento de Quimica Organica I, Facultad de Ciencias Quimicas, Universidad Complutense, 28040-Madrid, Spain
Fax +34(91)3944103; E-mail: darmesto@eucmos.sim.ucm.es
Received 1 February 2001; revised 29 March 2001
Dedicated with admiration to Professor Howard E. Zimmerman on the occasion of his 75th birthday
cases previously probed,1e undergo exclusive photodecar-
bonylation.
Abstract: A comparative study on the triplet photoreactivity of a
series of , -unsaturated aldehydes and methyl ketones has been
carried out. Aldehydes 14 and 20 were found to undergo the oxa-di-
-methane rearrangement yielding the corresponding cyclopropane
carbaldehydes 15 and 21 diastereoselectively. Decarbonylations
and 1,3-carbonyl migrations have been observed in some cases, al-
though these reactions do not take place via a Norrish Type I mech-
anism.
In this publication, we describe an extension of our studies
on the photoreactivity of , -unsaturated aldehydes. The
current effort was aimed at determining the efficacy of our
proposal about the factors governing ODPM reactivity of
these substances and establishing the scope of the process.
In a previous study Schaffner and his co-workers 5 report-
ed that aldehyde 1 does not undergo ODPM photorear-
rangement but rather on irradiation a decarbonylation to
produce the alkenes 2a and 2b. If the proposals presented
above are correct, it should be possible to transform 1 into
a ODPM reactive substrate by introducing a substituent
which would enable efficient triplet energy transfer to the
C–C double bond and lead to stabilization of the biradical
intermediates in the ODPM pathway. With this idea in
mind, we prepared aldehyde 3, a phenyl-substituted ana-
log of 1. Unfortunately, all synthetic attempts yielded an
inseparable mixture of 3 and its endocyclic double bond
isomer 4. Nevertheless, a 1:1 mixture of 3 and 4 was irra-
diated using acetophenone as sensitizer. In spite of the
Keywords: , -unsaturated carbonyl compounds, oxa-di- -meth-
ane rearrangement, decarbonylation, cyclopropanecarbaldehydes,
1,3-formyl migration.
The photochemical reactivity of , -unsaturated carbonyl
compounds has been the subject of extensive studies.1 The
results obtained from these efforts, conducted over a thirty
year period, show that, in general, direct irradiation of , -
unsaturated ketones yields products resulting from 1,3-
acyl migration, while triplet-sensitized reactions of these
compounds afford cyclopropyl ketones by oxa-di- -meth-
ane rearrangement (ODPM) pathways.1 In addition, the
results of numerous studies suggest that , -unsaturated
aldehydes undergo only decarbonylation to form alkenes
both on direct and sensitized irradiation.1a,b,d,e There are
only two examples of the occurrence of ODPM rearrange-
ments on triplet sensitized irradiation of , -unsaturated
aldehydes. One is found in a report by Schaffner et al. in
19662 and the other by Zimmerman and Cassel in 1989.3
1
complexity of the photomixture, H NMR analysis sug-
gested that the bicyclic aldehyde 5, the product of ODPM
rearrangement of the aldehyde 3, was present in the crude
photolysate (Figure).
In order to avoid synthetic problems, we prepared alde-
hyde 6, a substrate in which isomerization of the C–C
double bond to the endocyclic position is less likely. Con-
trary to our expectations, irradiation of 6, by using m-
methoxyacetophenone as sensitizer, led to formation of
the diene 7 (38%), the product of photodecarbonylation.
No ODPM product was formed in this process. The for-
mation of 7 is reminiscent of a Norrish Type I process.
However, in this case, homolytic bond fission does not oc-
cur in the carbonyl n- * excited state, as is the case in nor-
mal Norrish Type I reactions.1a–c In addition, irradiation of
the corresponding methyl ketone 9, under the same condi-
tions as used for 6, afforded the product of 1,3-acyl migra-
tion, 10 (24%) (Figure). Again, no ODPM product was
formed.
The combined results have led to a consensus opinion that
, -unsaturated aldehydes lack ODPM photoreactivi-
ty.1b,d Contrary to this common belief are our recent obser-
vations of efficient triplet ODPM rearrangement
reactivity in members of a series of acyclic and cyclic , -
unsaturated aldehydes.4 Based on these results, we pro-
posed that , -unsaturated aldehydes do indeed undergo
efficient triplet ODPM rearrangement when the following
criteria are met. First, the triplet energy of the sensitizer
must be efficiently transferred to the , -double bond in
order to generate a T1( - *) excited state of the substrate.
Second, the biradical intermediates in the non-concerted
ODPM pathway must be stabilized by conjugation with
phenyl or vinyl groups.4b , -Unsaturated aldehydes that
do not meet these two requirements, like in most of the
As far as we are aware, these observations are the first
which show that the well known Norrish Type I reactions
of , -unsaturated carbonyl compounds can take place by
excitation of the alkene moiety rather than the carbonyl
group. The reason for this unusual reactivity may be that
the T1 ( - *) excited states of 6 and 9 possess sufficient
Synthesis 2001, No. 8, 18 06 2001. Article Identifier:
1437-210X,E;2001,0,08,1149,1158,ftx,en;C01001SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

1150
D. Armesto et al.
PAPER
is not an ODPM substrate.6 The corresponding aldehyde
14a, which has the same substitution pattern as 13a, ac-
cording to our postulates, should undergo the ODPM re-
arrangement. In order to test this proposal, aldehydes 14a
and 14b were synthesized by a modification of the proce-
dure used to prepare 13a. m-Methoxyacetophenone trip-
let-sensitized irradiation (1 h) of 14a leads to generation
of the spirocyclic derivative 15a (36%), as the trans-dias-
tereoisomer, along with a mixture of starting material and
16, a compound resulting from 1,3-formyl migration
(Scheme 1). Irradiation (2 h) of the diphenyl analog 14b,
under the same conditions used for 14a gives rise to the
ODPM product 15b (24%), the alkene 17 (5%) and recov-
ered starting material (53%) (Scheme 1). The formation
of the alkene 17 in the irradiation of 14b might be due to
the stabilization of the radical resulting from homolytic
fission of the bond between the formyl group and the -
carbon, similarly to the reaction observed for compound
6. In contrast, the methyl ketone derivative 13b does not
undergo the ODPM rearrangement; sensitized irradiation
(17 h) of this substance provides recovered starting mate-
rial (71%) and a complex mixture of products. These ad-
ditional examples add further support to the proposal that
, -unsaturated aldehydes are more prone to undergo the
ODPM rearrangement than the corresponding methyl ke-
tones.
CHO
1
2a
2b
Ph
CHO
CHO
OHC
Ph
Ph
Ph
Ph
3
4
5
CHO
Ph
Ph
Ph
Ph
8
6
7
O
O
Ph
Ph
Ph
Ph
10
9
CHO
O
O
Ph
Ph
Ph
Ph
Ph
R
13a: R = H
13b: R = Ph
11
12
hν
R2
Ph
CHO
19a: R1 = H; R2 = iPr
R
CHO
H
Ph
Ph
Ph
19b: R1 = Ph; R2 = iPr
19c: R1 = H; R2 = Et
19d: R1 = Ph; R2 = Et
Ph
Sens.
Ph
R
CHO
Ph
O
O
Ph
Ph
14a: R = H
14b: R = Ph
1 h
2 h
15a (36%)
15b (24%)
16 (13%)
------
R1
------
17 (5%)
18
19
Scheme 1
Figure Structures of compounds 1–13, 18 and 19
The large number of studies carried out in the di- -meth-
ane area have established that disubstitution at the central
carbon of 1,4-diene substrates is an important structural
requirement for efficient rearrangement.1 In fact, there are
only two examples in which , -unsaturated ketones (187
and 19a6), monosubstituted at -position, undergo the
ODPM rearrangement. The reactivity observed in these
two substrates was attributed to the bulk of the substituent
at C-2 that compensates for the absence of disubstitution
at that -position.1e In an attempt to establish the limits for
ODPM reactivity of , -unsaturated aldehydes, we have
extended our studies to a series of , -unsaturated alde-
hydes 20, which are monosubstituted at C-2. Triplet-sen-
sitized irradiation of 20 leads to formation of the
energy to promote the homolytic bond fission at the allylic
position to form the stabilized pentadienyl radical 8. As a
result photodecarbonylation competes favorably with the
ODPM rearrangement.
These unexpected results suggest a modification of the
conclusions reached in our earlier studies. Specifically,
the observations indicate that in order to detect ODPM
photoreactivity in , -unsaturated aldehydes, substituents
should be present to stabilize intermediate biradicals in
the rearrangement pathway, but not to enhance alternative
reactions, such as allylic homolytic cleavage. Further
studies will be necessary to confirm this hypothesis and to
determine the scope of these new reactions.
corresponding
cyclopropanecarbaldehydes
21
Another intriguing observation made in our preliminary
investigation is that , -unsaturated aldehyde 11 under-
goes photoinduced ODPM rearrangement while the anal-
ogous methyl ketone 12 does not react in this manner.4b
This result suggests that other aldehydes with substitution
patterns similar to those found in ODPM unreactive ke-
tones might participate in this photorearrangement pro-
cess. Previous studies have shown that methyl ketone 13a
(Scheme 2). The diphenyl-substituted aldehydes 20b and
20d yielded, in addition to the ODPM products, the corre-
sponding alkenes 22a and 22b, resulting from photodecar-
bonylation. The formation of these alkenes is probably
due to stabilization of the radical, formed by allylic cleav-
age, by diphenyl-conjugation.
Synthesis 2001, No. 8, 1149–1158 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Diastereoselective Synthesis of Cyclopropanecarbaldehydes
1151
ered starting material. Prolonged irradiation of 19b and
19d under these conditions afforded a complex mixture of
highly polar materials (ca 20%) along with recovered
starting material (ca 80%). These results confirm the pos-
tulate that , -unsaturated aldehydes are better substrates
for ODPM rearrangement. In this regard, there are ques-
tions that still remain to be answered. For instance, it is
surprising that ketone 19a is reported to be ODPM reac-
tive while ketones 19b–d do not undergo this rearrange-
ment reaction.
R2
R2
Ph
H
R2
CHO
R1
Ph
CHO
H
hν
Ph
R1
Sens.
Ph
20a: R1 = H; R2 = iPr
20b: R1 = Ph; R2 = iPr
20c: R1 = H; R2 = Et
20d: R1 = Ph; R2 = Et
------
40 min
21a (21%)
21b (23%)
21c (22%)
21d (24%)
22a (9%)
------
2.5 h
7.0 h
7.0 h
22b (25%)
Scheme 2
In summary, our current studies have provided the first
examples of reactions, similar to the well know Norrish
Type I process, which take place in the triplet excited state
of , -unsaturated carbonyl compounds by excitation of
the C–C double bond instead of the carbonyl group. In ad-
dition, a comparison of the photochemical reactivity of
, -unsaturated aldehydes and corresponding methyl ke-
tones has shown that the ketones do not undergo the
ODPM rearrangement while the corresponding aldehydes
are reactive by this pathway. The results contrast with
firmly established, but apparently incorrect, ideas about
the reactivity of compounds in these families. Finally,
ODPM rearrangement of mono-C-2 substituted aldehydes
is surprising since there are only two precedents of ke-
tones with this type of substitution that undergo this pho-
toreaction. Furthermore, the photoreactions of these
substances are stereoselective, yielding only one of the
possible diastereoisomeric cyclopropanecarbaldehyde
products. When combined, the results of the current effort
broaden the synthetic potential of the ODPM rearrange-
ment.
ODPM rearrangement of aldehydes 20 is stereoselective,
yielding only one diastereoisomer of 21. Stereochemical
assignment to 21 was made by use of conventional spec-
troscopic methods in conjunction with comparisons to re-
lated compounds.4 Specifically, in the 1H NMR spectra of
21c, the aldehydic hydrogen resonates as a doublet at
= 9.35 (J = 4.8 Hz), while cyclopropane H-1 appears at
= 2.19 as a quadruplet (J = 5.0 Hz). These data are con-
sistent with a trans arrangement for these hydrogens. The
appearance of cyclopropane hydrogen next to the phenyl
at = 2.94 as a doublet of doublets (J = 9.6, 5.1 Hz) sug-
gests a cis arrangement between this hydrogen and the cy-
clopropane hydrogen next to the ethyl group and trans
with respect to the hydrogen at C-1. These relative stere-
ochemical assignments were confirmed by NOE experi-
ments. Thus, irradiation at = 2.94 results in the
disappearance of the signal at = 2.19 and the enhance-
ment (6%) of the signal at = 1.80 corresponding to the
cyclopropane hydrogen next to the ethyl group. Further-
more, the signals at = 2.94 and 1.80 disappear on irradi-
ation of the signal at = 2.19. These data permitted the
assignment of 21c as the 1R,2S,3R/1S,2R,3S diastereoiso-
mer. The ODPM rearrangement of 20a occurs with the
Melting points were determined in open capillaries and are uncor-
rected. IR spectra were recorded on a Perkin Elmer 781 spectrome-
same stereoselectivity, yielding the cyclopropylaldehyde ter. NMR spectra were recorded on a Varian VXR-300S (1H, 300
MHz; 13C, 75 MHz), a Bruker AC-250F (1H, 250 MHz; 13C, 62
21a as the 1R,2S,3R/1S,2R,3S diastereoisomer. Alde-
hydes 20b and 20d afford the cyclopropanes 21b and 21d
in which the formyl group and the alkyl group are trans to
MHz) or a Bruker AC-200 (1H, 200 MHz; 13C, 50 MHz) spectro-
meter in CDCl3 solution. J values are given in Hertz. Chemical
shifts ( ) are expressed in ppm downfield from internal TMS. Mass
each other. A similar diastereoselectivity has been ob-
spectra were recorded on a HP 5989 A spectrometer. UV/visible
served for ODPM rearrangements of other aldehydes.4
spectra were recorded on a Perkin Elmer Lambda 3B in CH2Cl2 so-
lutions. Column chromatography was performed using silica gel 60
(40–63 mm) from Merck. Commercially available starting materi-
als and reagents were purchased from Aldrich.
Aldehyde 20b3 and ketones 13a8 and 19a8 were synthesized by the
The ODPM reactivity of aldehydes 20 is surprising since,
as mentioned before, the only two ODPM reactive acyclic
, -unsaturated mono-C-2 substituted ketones are com-
pounds 18 and 19a, each containing bulky substituents at
methods previously described.
C-2. However, the observations made with 20c and 20d,
each having ethyl groups at C-2, clearly demonstrates that
, -Unsaturated Aldehydes 14, 20a, 20c, 20d; General
the bulk of the C-2 substituent is not an important feature
in determining the ODPM reactivity of , -unsaturated al-
dehydes. However, it should be noted that the isopropyl
substituted aldehydes 20a and 20b do react more effi-
ciently, in qualitative terms, than 20c and 20d.
Procedures
These aldehydes were synthesized from the corresponding carbox-
ylic acids by a procedure consisting of esterification, -alkylation,
reduction and oxidation, according to the following general proce-
dures. When describing the experimental procedure below for indi-
vidual products, a further reference to the general procedure is not
always necessarily given.
Substrates 19b–d were synthesized in order to determine
whether the aldehydes 20 are more reactive towards the
ODPM than the corresponding methyl ketones (Figure).
Compound (E)-19c does not undergo the ODPM rear-
rangement. Irradiation of this ketone under the same con-
ditions used for 20 affords the corresponding
diastereoisomer (Z)-19c in 50% yield and 25% of recov-
Esterification of , -Unsaturated Acids: To a solution of , -unsat-
urated acid in anhyd CH2Cl2 was added anhyd MeOH and a few
drops of H2SO4. The resulting mixture was refluxed for different
times (for specific cases, see below). The organic layer was washed
with H2O, sat. aq NaHCO3 solution, H2O, dried (MgSO4), filtered
and evaporated to dryness. The , -unsaturated esters were purified
Synthesis 2001, No. 8, 1149–1158 ISSN 0039-7881 © Thieme Stuttgart · New York

1152
D. Armesto et al.
PAPER
by flash chromatography on silica gel using hexane–Et2O (8:2) as
eluent.
centrated to dryness. Flash chromatography using hexane–Et2O
(9:1) yielded ethyl (E)-2-(3,3-diphenylprop-2-enylidene)-1-methyl-
cyclopentanecarboxylate (1.4 g, 79%) as an oil.
-Alkylation of , -Unsaturated Esters: To a solution of i-Pr2NH in
anhyd THF at –78°C under argon was added BuLi (1.6 M in hex-
ane) dropwise. The mixture was stirred for 1 h, and then a solution
of the corresponding , -unsaturated ester (for specific cases, see
below) in anhyd THF was added dropwise over 1 h. The resulting
solution was stirred for an additional 10 min at –78°C, and then the
corresponding halogen derivative was added dropwise. The solu-
tion was stirred for 18 h at r.t. before quenching with 5% aq NH4Cl
solution. The organic layer was washed with 5% aq HCl and H2O,
dried (MgSO4), filtered and evaporated to dryness. The alkylated
, -unsaturated esters were purified by flash chromatography on
silica gel using hexane–Et2O as eluent.
IR (neat): = 1724 cm–1.
1H NMR (200 MHz): = 1.14 (t, 3 H, J = 7.1 Hz, CH3), 1.25 (s, 3 H,
CH3), 1.49–1.58 (m, 1 H, CH2), 1.71–1.97 (m, 2 H, CH2), 2.35 (dt,
1 H, J = 12.1, 6.8 Hz, CH2), 2.65 (t, 2 H, J = 6.2 Hz, CH2), 4.05 (q,
2 H, J = 7.1 Hz, OCH2), 6.12 (dt, 1 H, J = 11.4, 2.5 Hz, CH=C), 6.71
(d, 1 H, J = 11.4 Hz, CH=C), 7.11–7.43 (m, 10 H, ArH).
13C NMR (50 MHz): = 14.2 (CH3), 23.9 (CH2), 24.7 (CH3), 30.5
(CH2), 38.7 (CH2), 53.3 (quat. C), 60.7 (OCH2), 120.4–143.0 (C=C
and Ar-C), 151.9 (CO2).
MS: m/z (%) = 346 (M+, 61), 273 (100), 191 (23), 167 (14), 91 (25).
Reduction of Esters: A solution of the corresponding ester (for spe-
cific cases, see below) in anhyd Et2O was added slowly at 0°C to a
suspension of LiAlH4 in Et2O. The resulting mixture was stirred at
r.t. for 1 h. The residual LiAlH4 was decomposed by addition of
H2O. The mixture was filtered and washed with Et2O. The organic
layer was dried (MgSO4), filtered and evaporated to dryness. The al-
cohol was purified by flash chromatography on silica gel.
The above ester (1.4 g, 4 mmol) was reduced with LiAlH4 (0.2 g,
4.8 mmol). Chromatography using hexane–Et2O (8:2) yielded 1.1 g
(89%) of (E)-2-(3,3-diphenylprop-2-enylidene)-1-hydroxymethyl-
1-methylcyclopentane as a yellow oil.
IR (neat): = 3500–3200 cm–1.
1H NMR (200 MHz): = 0.99 (s, 3 H, CH3), 1.32 (t, 1 H, J = 6.6,
OH), 1.43–1.54 (m, 1 H, CH2), 1.61–1.82 (m, 2 H, CH2), 1.82–1.93
(m, 1 H, CH2), 2.51–2.69 (m, 2 H, CH2), 3.29–3.36 (m, 2 H,
CH2OH), 5.94 (dt, 1 H, J = 11.3, 2.4 Hz, CH=C), 6.74 (d, 1 H,
J = 11.3 Hz, CH=C), 7.17–7.43 (m, 10 H, ArH).
13C NMR (50 MHz): = 22.8 (CH2), 23.7 (CH3), 31.0 (CH2), 36.9
(CH2), 48.6 (quat. C), 69.3 (CH2OH), 119.1, 125.6–130.7, 140.1,
140.8, 143.1, 153.7 (C=C and Ar-C).
Oxidation of Alcohols to Aldehydes: A solution of the correspond-
ing , -unsaturated alcohols and PCC were allowed to react in
CH2Cl2 at r.t. for different times (for specific cases, see below). The
reaction mixture was filtered through silica gel and the solvent
evaporated to give the desired aldehyde. The products were purified
by flash chromatography on silica gel.
, -Unsaturated Methyl Ketones 13b, 19b–d; General
Procedures
MS: m/z (%) = 304 (M+, 35), 273 (100), 191 (22), 167 (12), 91 (25).
(E)-2-(3,3-Diphenylprop-2-enylindene)-1-hydroxymethyl-1-meth-
ylcyclopentane (1.1 g, 3.6 mmol) was oxidized with PCC (1.7 g, 8.8
mmol) by stirring for 1 h. Chromatography using hexane–EtOAc
(9:1) yielded 540 mg (50%) of 6 as an oil.
These ketones were synthesized from , -unsaturated aldehydes by
reaction with MeMgI followed by oxidation of the corresponding
alcohols. When describing the experimental procedure below for in-
dividual products, a further reference to the general procedure is not
always necessarily given.
IR (neat): = 1718 cm–1.
1H NMR (200 MHz): = 1.14 (s, 3 H, CH3), 1.42–1.60 (m, 1 H,
CH2), 1.75–1.89 (m, 2 H, CH2), 2.19 (app dt, 1 H, J = 12.7, 6.6 Hz,
CH2), 2.61 (dq, 2 H, J = 7.4, 2.5 Hz, CH2), 5.98 (dt, 1 H, J = 11.3,
2.5 Hz, CH=C), 6.72 (d, 1 H, J = 11.3 Hz, CH=C), 7.12–7.41 (m,
10 H, ArH), 9.23 (s, 1 H, CHO).
13C NMR (50 MHz): = 20.6 (CH3), 23.6 (CH2), 31.6 (CH2), 34.8
(CH2), 58.3 (quat. C), 122.5–148.6 (C=C and Ar-C), 200.5 (CHO).
, -Unsaturated Alcohols: To a solution of MeMgI in anhyd Et2O
under argon was added dropwise a solution of aldehyde (for specific
cases, see below) in anhyd Et2O. After refluxing for 1 h, the solution
was cooled to 0°C, quenched with sat. aq NH4Cl solution. The mix-
ture was extracted with Et2O and the organic layer was washed with
H2O, dried (MgSO4), filtered and concentrated to dryness. The al-
cohols were purified by flash chromatography on silica gel.
Oxidation of Alcohols to Ketones: To a solution of the alcohol (for
specific cases, see below) in Et2O was added dropwise a solution of
K2Cr2O7, H2SO4 and H2O (the temperature was maintained below
25°C). After the addition was complete, the solution was stirred at
r.t. for different times (for specific cases, see below). Et2O was add-
ed, the organics layers were separated, washed with H2O, sat. aq
NaHCO3 solution and H2O, dried (MgSO4), filtered and evaporated
under reduced pressure to give, after purification by flash chroma-
tography on silica gel, the corresponding , -unsaturated ketones.
MS: m/z (%) = 273 (M+ – 29, 2), 228 (27), 197 (100), 169 (24), 155
(24), 141 (28), 117 (19), 91 (42).
UV (CH2Cl2): max = 245 nm ( = 34040).
Anal. Calcd for C22H22O: C, 87.42; H, 7.28. Found: C, 87.22; H,
7.20.
(E)-1-Acetyl-2-(3,3-diphenylprop-2-enylidene)-1-methylcyclo-
pentane (9)
This compound was synthesized in three steps from (E)-ethyl
2-(3,3-diphenylprop-2-enylidene)-1-methylcyclopentanecarboxyl-
ate, obtained previously in the synthesis of aldehyde 6. A solution
of KOH (0.23 g, 0.2 mmol) and (E)-ethyl 2-(3,3-diphenylprop-2-
enylidene)-1-methylcyclopentanecarboxylate (0.5 g, 1.4 mmol) in
absolute EtOH (18 mL) was refluxed for 24 h. The solvent was
evaporated to dryness and the crude product was dissolved in H2O.
The solution was washed with Et2O and the aqueous layer was acid-
ified with a 20% HCl and extracted with Et2O. The organic layers
were dried (MgSO4), filtered and concentrated to dryness. Flash
chromatography using hexane–Et2O (7:3) yielded (E)-2-(3,3-diphe-
nylprop-2-enylidene)-1-methylcyclopentanecarboxylic acid (240
mg, 54%) as a white solid; mp 137–138°C (hexane).
(E)-2-(3,3-Diphenylprop-2-enylidene)-1-methylcyclopentane
Carbaldehyde (6)
This compound was synthesized in three steps from ethyl 2-formyl-
methylidene-1-methylcyclopentanecarboxylate, obtained by the
method previously described for the corresponding methyl ester.9
To a stirred solution of diethyl diphenylmethylphosphonate10 (2.5 g,
8.2 mmol) in anhyd DME (10 mL) under argon and at 0°C was add-
ed BuLi (3.3 mL, 2.5 M in hexane). The resulting solution was
stirred for 1 h at 0°C, and ethyl 2-formylmethylidene-1-methylcy-
clopentanecarboxylate (1 g, 5.1 mmol) in DME (10 mL) was added.
The reaction mixture was stirred at 0°C for 3 h before quenching
with sat. aq NH4Cl solution and extracted with Et2O. The organic
layer was washed with brine, H2O, dried (MgSO4), filtered and con-
IR (KBr): = 3500–2500, 1690 cm–1.
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PAPER
Diastereoselective Synthesis of Cyclopropanecarbaldehydes
1153
1H NMR (300 MHz): = 1.28 (s, 3 H, CH3), 1.53–2.01 (m, 3 H, 2
CH2), 2.36 (dt, 1 H, J = 12.4, 6.2 Hz, CH2), 2.63 (app dt 2 H, J = 7.2,
2.4 Hz, CH2), 6.19 (dt, 1 H, J = 11.3, 2.4 Hz, CH=C), 6.69 (d, 1 H,
J = 11.3 Hz, CH=C), 7.17–7.38 (m, 10 H, ArH).
13C NMR (75 MHz): = 23.8 (CH2), 24.1 (CH3), 30.3 (CH2), 38.7
(CH2), 52.9 (quat. C), 121.0, 125.3–130.7, 139.5, 141.9, 143.0,
150.7 (C=C and Ar-C), 182.9 (CO2).
MS: m/z (%) = 230 (M+, 2), 171 (15), 129 (19), 117 (16), 91 (25), 71
(47), 57 (100).
(E)-Methyl 1-(2-phenylvinyl)-1-cyclopentanecarboxylate (0.6 g,
2.61 mmol) was reduced with LiAlH4 (0.1 g, 2.61 mmol). Chroma-
tography using hexane–Et2O (8:2) yielded 0.39 g (73%) of (E)-1-
hydroxymethyl-1-(2-phenylvinyl)cyclopentane as a yellow oil.
IR (neat): = 3620, 3450 cm–1.
MS: m/z (%) = 318 (M+ 81), 273 (100), 218 (10), 191 (31), 165 (26),
1H NMR (250 MHz): = 1.60–1.76 (m, 9 H, 4 CH2 and OH), 3.48
(br s, 2 H, CH2OH), 6.24 (AB system, 2 H, J = 16.3 Hz, CH=CH),
7.17–7.39 (m, 5 H, ArH).
13C NMR (75 MHz): = 24.4 (2 CH2), 34.3 (2 CH2), 51.3 (quat. C),
69.0 (CH2OH), 126.2–129.0, 136.1 (C=C and Ar-C).
MS: m/z (%) = 202 (M+, 7), 171 (80), 129 (75), 115 (27), 91 (100),
77 (22).
,
91 (43), 81 (9), 77 (10), 55 (5).
A solution of (E)-2-(3,3-diphenylprop-2-enylidene)-1-methylcy-
clopentanecarboxylic acid (0.24 g, 0.7 mmol) and SOCl2 (1 mL)
was heated at reflux for 20 min. Removal of the residual SOCl2 un-
der reduced pressure yielded (E)-2-(3,3-diphenylprop-2-
enylidene)-1-methylcyclopentanecarbonyl chloride (253 mg, 99%)
as an oil, which was used without further purification.
IR (neat): = 1787 cm–1.
(E)-1-Hydroxymethyl-1-(2-phenylvinyl)cyclopentane (0.386 g,
1.91 mmol) was oxidized with PCC (1.03 g, 4.78 mmol) by stirring
for 3 h. Chromatography using hexane–Et2O (9:1), yielded 0.3 g
(78%) of aldehyde (E)-14a as an oil.
1H NMR (300 MHz): = 1.36 (s, 3 H, CH3), 1.59–2.01 (m, 3 H, 2
CH2), 2.43–2.58 (m, 1 H, CH2), 2.62–2.79 (m, 2 H, CH2), 6.14 (dt,
1 H, J = 11.4, 2.7 Hz, CH=C), 6.70 (d, 1 H, J = 11.4 Hz, CH=CPh2),
7.20–7.42 (m, 10 H, ArH).
IR (neat): = 1730 cm–1.
1H NMR (250 MHz): = 1.59–1.74 (m, 6 H, 3 CH2), 2.16–2.35 (m,
2 H, CH2), 6.30 (AB system, 2 H, J = 16.4 Hz, CH=CH), 7.15–7.50
(m, 5 H, ArH), 9.46 (s, 1 H, CHO).
13C NMR (62 MHz): = 24.6 (2 CH2), 32.8 (2 CH2), 61.2 (quat. C),
126.3–131.4, 136.8 (C=C and Ar-C), 201.3 (CHO).
MS: m/z (%) = 201 (M+ + 1, 11), 171 (66), 141 (28), 128 (51), 105
(100), 91 (99), 77 (53), 55 (30).
To a stirred suspension of CuI (171 mg, 0.9 mmol) in anhyd Et2O
(15 mL) under argon and at –40°C was added MeLi (1 mL, 1.5 M
in Et2O). The mixture was stirred for 30 min, and (E)-2-(3,3-diphe-
nylprop-2-enylidene)-1-methylcyclopentanecarbonyl chloride (253
mg, 0.75 mmol) in Et2O (5 mL) was added. The reaction was kept
at –40°C for 30 min, allowed to warm at 0°C, and stirred for 30 min
before being quenched with a sat. aq NH4Cl solution and extracted
with Et2O. The combined organic phases were dried, filtered, and
concentrated to dryness. Flash chromatography using hexane–Et2O
(9:1) afforded the ketone 9 (210 mg, 89%) as an oil.
UV (CH2Cl2): max = 256 nm ( = 17200).
1-(2,2-Diphenylvinyl)-1-cyclopentanecarbaldehyde (14b)
4,4-Diphenylbut-3-enoic acid11 (2 g, 8.4 mmol) was esterified with
MeOH (1 mL, 25 mmol) in the presence of H2SO4 (5 drops) by re-
fluxing for 2.5 h to afford methyl 4,4-diphenylbut-3-enoate as a yel-
low oil; yield: 1.53 g (72%).
IR (neat): = 1787 cm–1.
1H NMR (300 MHz): = 1.12 (s, 3 H, CH3), 1.47–1.54 (m, 1 H,
CH2), 1.73–1.90 (m, 2 H, CH2), 2.06 (s, 3 H, CH3CO), 2.12–2.58
(dt, 1 H, J = 11.7, 7.7 Hz, CH2), 2.50–2.93 (m, 2 H, CH2), 5,90 (dt,
1 H, J = 11.2, 2.5 Hz, CH=C), 6.72 (d, 1 H, J = 11.2 Hz, CH=C),
7.15–7.38 (m, 10 H, ArH).
13C NMR (75 MHz): = 23.3 (CH3), 23.7 (CH2), 25.6 (CH3), 30.7
(CH2), 37.8 (CH2), 60.2 (quat. C), 121.2, 125.2, 130.5, 139.6, 141.8,
142.7, 151.5 (C=C and Ar-C), 210.2 (CO).
IR (neat): = 1750 cm–1.
1H NMR (300 MHz): = 3.16 (d, 2 H, J = 7.5 Hz, CH2), 3.67 (s, 3
H, OCH3), 6.25 (t, 1 H, J = 7.5 Hz, CH=C), 7.16–7.37 (m, 10 H,
ArH).
13C NMR (75 MHz): = 33.2 (CH2), 51.9 (CH3), 120.2–144.8
(C=C and Ar-C), 172.3 (CO2).
MS: m/z (%) = 316 (M+, 9), 273 (100), 191 (23), 165 (15), 91 (29),
77 (6), 55 (6).
i-Pr2NH (1.2 mL, 8.9 mmol), BuLi (5.5 mL, 1.6 M in hexane), me-
thyl 4,4-diphenylbut-3-enoate (1.5 g, 5.95 mmol) and 1,4-dibro-
mobutane (0.7 mL, 5.95 mmol) were used for the -alkylation
reaction. Chromatography using hexane–Et2O (85:15) yielded 2.15
g (94%) of methyl 2-(4-bromobutyl)-4,4-diphenylbut-3-enoate as a
yellow oil.
1H NMR (300 MHz): = 1.21–1.80 (m, 6 H, 3 CH2), 3.15–3.25 (m,
1 H, CH), 3.31 (q, 2 H, J = 6.7 Hz, CH2Br), 3.70 (s, 3 H, OCH3),
6.10 (d, 1 H, J = 10.5 Hz, CH=C), 7.21–7.40 (m, 10 H, ArH).
UV (CH2Cl2): max = 310 nm ( = 60189).
Anal. Calcd for C23
7.43.
: C, 87.34; H, 7.59. Found: C, 87.20; H,
24
(E)-1-(2-Phenylvinyl)-1-cyclopentanecarbaldehyde (14a)
trans-Styrylacetic acid (5 g, 30.9 mmol), MeOH (3 mL, 92.5 mmol)
and H2SO4 (5 drops) were refluxed for 24 h to afford (E)-methyl 4-
phenylbut-3-enoate;8 yield: 4.83 g (89%).
i-Pr2NH (1.7 mL, 12.75 mmol), BuLi (8 mL, 1.6 M in hexane), (E)-
methyl 4-phenylbut-3-enoate (1.5 g, 8.5 mmol), and 1,4-dibromo-
butane (1 mL, 8.5 mmol) were used for the -alkylation reaction.
Chromatography using hexane–Et2O (85:15) gave (E)-methyl 1-(2-
phenylvinyl)-1-cyclopentanecarboxylate as a yellow oil; yield: 0.79
g (40%).
The cyclization to the cyclopropane derivative was carrried out as
follows: To a solution of i-Pr2NH (0.9 mL, 6.11 mmol) in anhyd
DME (25 mL) at –78°C under argon was added dropwise BuLi (3.8
mL, 1.6 M in hexane). After the mixture was stirred for 20 min, a
solution of methyl 2-(4-bromobutyl)-4,4-diphenylbut-3-enoate
(2.15 g, 5.5 mmol) in anhyd DME (15 mL) was added dropwise
over 30 min. The resulting solution was stirred for 2 h at 0°C and
16 h at r.t. before quenching with 10% aq HCl. The organic layer
was washed with 5% aq HCl and H2O, dried (MgSO4), filtered and
evaporated to dryness. Flash chromatography on silica gel using
hexane–EtOAc (95:5) yielded 1.62 g (96%) of methyl 1-(2,2-diphe-
nylvinyl)-1-cyclopentanecarboxylate as a yellow oil.
IR (neat): = 1740 cm–1.
1H NMR (300 MHz): = 1.61–1.75 (m, 4 H, 2 CH2), 1.80–1.88 (m,
2 H, CH2), 2.21–2.32 (m, 2 H, CH2), 3.70 (s, 3 H, OCH3), 6.40 (AB
system, 2 H, J = 16.2 Hz, CH=CH), 7.19–7.39 (m, 5 H, ArH).
13C NMR (62 MHz): = 24.0 (2 CH2), 35.8 (2 CH2), 52.3 (OCH3),
56.5 (quat. C), 126.4–137.0 (C=C and Ar-C), 176.5 (CO2).
Synthesis 2001, No. 8, 1149–1158 ISSN 0039-7881 © Thieme Stuttgart · New York

1154
D. Armesto et al.
PAPER
IR (neat): = 1735 cm–1.
1H NMR (250 MHz): = 1.21–1.72 (m, 7 H, 4 CH2), 2.00 (s, 3 H,
CH3CO), 2.00–2.13 (m, 1 H, CH2), 6.20 (s, 1 H, CH=C), 6.95–7.25
(m, 10 H, ArH).
13C NMR (62 MHz): = 25.0 (2 CH2), 26.9 (CH3), 37.8 (2 CH2),
62.1 (quat. C), 126.4–134.5, 139.2, 143.3, 145.3 (C=C and Ar-C),
208.7 (CO).
1H NMR (250 MHz): = 1.58–1.69 (m, 6 H, 3 CH2), 2.21–2.26 (m,
2 H, CH2), 3.36 (s, 3 H, OCH3), 6.16 (s, 1 H, CH=C), 7.09–7.33 (m,
10 H, ArH).
13C NMR (62 MHz): = 24.5 (2 CH2), 39.1 (2 CH2), 51.7 (OCH3),
55.4 (quat. C), 127.3–134, 139.5, 142.0, 143.3 (C=C and Ar-C),
176.3 (CO2).
MS: m/z (%) = 247 (M+ – 43, 58), 205 (14), 178 (11), 167 (30), 165
(30), 112 (64), 91 (100), 77 (15), 71 (19), 51 (17).
MS: m/z (%) = 306 (M+, 22), 247 (100), 205 (27), 169 (36), 141
(24), 117 (60), 91 (85), 77 (18), 51 (14).
UV (CH2Cl2): max = 253 nm ( = 10350).
Methyl 1-(2,2-diphenylvinyl)-1-cyclopentanecarboxylate (0.47 g,
1.5 mmol) was reduced with LiAlH4 (63 mg, 1.65 mmol). Chroma-
tography using hexane–EtOAc (8:2) yielded 0.31 g (75%) of 1-
(2,2-diphenylvinyl)-1-hydroxymethylcyclopentane as a yellow oil.
(E)-2-Isopropyl-4-phenylbut-3-enal (20a)
i-Pr2NH (0.8 mL, 6.1 mmol), BuLi (3.8 mL, 1.6 M in hexane), (E)-
methyl 4-phenylbut-3-enoate8 (0.789 g, 4.48 mmol), and i-PrI (0.9
mL, 8.96 mmol) were used for the -alkylation. Chromatography
using hexane–Et2O (96:4) yielded 0.345 g (35%) of (E)-methyl 2-
isopropyl-4-phenylbut-3-enoate as a yellow oil.
IR (neat): = 3360 cm–1.
1H NMR (300 MHz): = 1.54–1.59 (m, 9 H, 4 CH2 and OH), 3.27
(br s, 2 H, CH2OH), 6.13 (s, 1 H, CH=C), 7.19–7.36 (m, 10 H,
ArH).
13C NMR (75 MHz): = 24.2 (2 CH2), 36.5 (2 CH2), 51.2 (quat. C),
68.4 (CH2OH), 126.8–129.8, 135.9, 140.3, 141.9, 143.6, (C=C and
Ar-C).
IR (neat): = 1730 cm–1.
1H NMR (300 MHz): = 0.93 (d, 3 H, J = 6.9 Hz, CH3), 0.96 (d, 3
H, J = 6.9 Hz, CH3), 2.04–2.17 [m, 1 H, CH(CH3)2], 2.86 (t, 1 H,
J = 9.6 Hz, CH), 3.69 (s, 3 H, OCH3), 6.22 (dd, 1 H, J = 15.8, 9.6 Hz,
PhCH=CH), 6.45 (d, 1 H, J = 15.8 Hz, PhCH=CH), 7.20–7.41 (m,
5 H, ArH).
MS: m/z (%) = 278 (M+, 5), 247 (100), 205 (22), 169 (37), 141 (24),
13C NMR (62 MHz): = 19.7 (CH3), 20.6 (CH3), 31.1 [CH(CH3)2],
51.5 (CH), 57.2 (OCH3), 126.1–128.3, 132.8, 136.6 (C=C and Ar-
C), 174 (CO2).
MS: m/z (%) = 218 (M+, 15), 159 (30), 144 (30), 128 (24), 115
(100), 91 (63), 71 (36), 57 (76).
117 (60), 91 (92), 77 (20), 55 (25).
Oxidation of 1-(2,2-diphenylvinyl)-1-hydroxymethylcyclopentane
(0.33 g, 1.19 mmol) was carried out with PCC (0.64 g, 2.96 mmol)
by stirring for 1 h. Chromatography using hexane–EtOAc (8:2)
yielded 0.26 g (80%) of aldehyde 14b as an oil.
IR (neat): = 1730 cm–1.
(E)-Methyl 2-isopropyl-4-phenylbut-3-enoate (1 g, 4.6 mmol) was
reduced with LiAlH4 (0.175 g, 4.6 mmol). Chromatography using
hexane–Et2O (8:2) yielded 0.62 g (71%) of (E)-2-isopropyl-4-phe-
nylbut-3-en-1-ol as a yellow oil.
1H NMR (250 MHz): = 1.20–1.35 (m, 2 H, CH2), 1.50–1.75 (m, 4
H, 2 CH2), 1.95–2.15 (m, 2 H, CH2), 6.10 (s, 1 H, CH=C), 7.10–
7.41 (m, 10 H, ArH), 9.20 (s, 1 H, CHO).
IR (neat): = 3350 cm–1.
13C NMR (62 MHz): = 25.2 (2 CH2), 35.7 (2 CH2), 60.4 (quat. C),
1H NMR (250 MHz): = 0.91 (d, 3 H, J = 6.8 Hz, CH3), 0.95 (d, 3
H, J = 6.8 Hz, CH3), 1.60 (br s, 1 H, OH), 1.73–1.83 [m, 1 H,
CH(CH3)2], 2.12–2.24 (m, 1 H, CH), 3.50 (dd, 1 H, J = 10.5, 8.8 Hz,
CHHOH), 3.71 (dd, 1 H, J = 10.5, 4.9 Hz, CHHOH), 6.01 (dd, 1 H,
J = 15.9, 9.5 Hz, PhCH=CH), 6.50 (d, 1 H, J = 15.9 Hz,
PhCH=CH), 7.30–7.40 (m, 5 H, ArH).
13C NMR (62 MHz): = 19.8 (CH3), 21.0 (CH3), 29.2 [CH(CH3)2],
53.1 (CH), 64.3 (CH2OH), 126.3–129.8, 133.6, 137.2 (C=C and Ar-
C).
127.3–132.5, 139.4, 142.4, 144.1 (C=C and Ar-C), 199.5 (CHO).
MS: m/z (%) = 276 (M+, 2), 259 (10), 247 (3), 207 (6), 171 (36), 141
(18), 129 (44), 91 (100), 77 (58), 55 (60).
UV (CH2Cl2): max = 252 nm ( = 41800).
1-Acetyl-1-(2,2-diphenylvinyl)cyclopentane (13b)
Mg (72 mg, 2.94 mmol), MeI (0.2 mL, 2.83 mmol) and aldehyde
14b (0.263 g, 0.96 mmol) were used for the preparation of the , -
unsaturated alcohol. Chromatography using hexane–Et2O (8:2)
yielded 90 mg (30%) of 1-(2,2-diphenylvinyl)-1-(1-hydroxyeth-
yl)cyclopentane as a yellow oil.
MS: m/z (%) = 190 (M+, 8), 172 (5), 159 (23), 129 (56), 117 (55),
115 (30), 91 (100), 71 (38), 57 (80).
IR (neat): = 3350 cm–1.
(E)-2-Isopropyl-4-phenylbut-3-en-1-ol (0.62 g, 3.26 mmol) was ox-
idized with PCC (1.76 g, 8.15 mmol) by stirring for 80 min. Chro-
matography using hexane–Et2O (95:5) yielded 0.29 g (46%) of
aldehyde (E)-20a as an oil.
1H NMR (250 MHz): = 1.22 (d, 3 H, J = 6.4 Hz, CH3), 1.41–2.70
(m, 8 H, 4 CH2), 3.51 (br s, 1 H, OH), 3.70 (q, 1 H, J = 6.4 Hz,
CHOH), 6.11 (s, 1 H, CH=C), 7.12–7.41 (m, 10 H, ArH).
IR (neat): = 1720 cm–1.
13C NMR (62 MHz): = 19.7 (CH3), 24.5 (CH2), 24.7 (CH2), 35.0
(CH2), 35.4 (CH2), 54.9 (quat. C), 74.0 (CHOH), 126.1–129.9,
135.6, 140.6, 142.0, 144.4 (C=C and Ar-C).
MS: m/z (%) = 247 (M+ – 45, 60), 205 (14), 167 (34), 112 (65), 91
(100), 71 (19).
1H NMR (300 MHz): = 0.96 (d, 3 H, J = 6.9 Hz, CH3), 1.00 (d, 3
H, J = 6.9 Hz, CH3), 2.18–2.38 [m, 1 H, CH(CH3)2], 2.85–2.91 (m,
1 H, CH), 6.15 (dd, 1 H, J = 16.0, 9.1 Hz, PhCH=CH), 6.51 (d, 1 H,
J = 16.0 Hz, PhCH=CH), 7.21–7.41 (m, 5 H, ArH), 9.60 (d, 1 H,
J =2.7 Hz, CHO).
13C NMR (62 MHz): = 19.6 (CH3), 20.9 (CH3), 31.7 [CH(CH3)2],
63.6 (CH), 123.3, 126.4–128.7, 135.2, 136.8 (C=C and Ar-C),
201.8 (CHO).
1-(2,2-Diphenylvinyl)-1-(1-hydroxyethyl)cyclopentane (90 mg, 0.3
mmol) was oxidized with K2Cr2O7 (90 mg, 0.3 mmol) in H2SO4 (2
mL) and H2O (4 mL) by stirring for 5 min at r.t. Chromatography
using hexane–Et2O (9:1) yielded 57 mg (65%) of ketone 13b as an
oil.
MS: m/z (%) = 188 (M+, 4), 159 (18), 131 (24), 105 (100), 91 (46),
77 (48), 51 (2).
IR (neat): = 1705 cm–1.
UV (CH2Cl2): max = 255 nm ( = 16250).
Synthesis 2001, No. 8, 1149–1158 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Diastereoselective Synthesis of Cyclopropanecarbaldehydes
1155
(E)-2-Ethyl-4-phenylbut-3-enal (20c)
13C NMR (62 MHz): = 11.6 (CH3), 26.5 (CH2), 47.5 (CH), 51.8
(OCH3), 126.6–129.8, 139.4, 141.9, 144.1 (C=C and Ar-C), 174.8
(CO2).
MS: m/z (%) = 280 (M+, 21), 221 (55), 191 (37), 179 (4), 143 (31),
91 (100), 77 (11), 51 (12).
i-Pr2NH (2.3 mL, 16.5 mmol), BuLi (10.3 mL, 1.6 M in hexane),
(E)-methyl 4-phenylbut-3-enoate8 (2.9 g, 16.5 mmol), and EtI (1
mL, 11.4 mmol) were used for the -alkylation. Chromatography
using hexane–Et2O (99:1) yielded 1.42g (42%) of (E)-methyl 2-eth-
yl-4-phenylbut-3-enoate as a yellow oil.
According to the general procedure for reduction, methyl 2-ethyl-
4,4-diphenylbut-3-enoate (0.762 g, 2.72 mmol) and LiAlH4 (0.114
g, 2.99 mmol) were used. Chromatography using hexane–Et2O
(8:2) gave 0.493 g (72%) of 2-ethyl-4,4-diphenylbut-3-en-1-ol as a
yellow oil.
IR (neat): = 1740 cm–1.
1H NMR (300 MHz): = 0.94 (t, 3 H, J = 7.4 Hz, CH3), 1.60–1.75
(m, 1 H, CH2), 1.82–1.96 (m, 1 H, CH2), 3.05–3.17 (m, 1 H, CH),
3.70 (s, 3 H, OCH3), 6.22 (dd, 1 H, J = 15.9, 8.9 Hz, PhCH=CH),
6.44 (d, 1 H, J = 15.9 Hz, PhCH=CH), 7.30–7.38 (m, 5 H, ArH).
13C NMR (62 MHz): = 11.8 (CH3), 26.0 (CH2), 51.3 (CH), 51.9
(OCH3), 126.4–128.8, 132.4, 136.9 (C=C and Ar-C), 174.7 (CO2).
IR (neat): = 3620, 3450 cm–1.
1H NMR (250 MHz): = 0.88 (t, 3 H, J = 7.4 Hz, CH3), 1.32–1.36
(m, 2 H, CH2 and OH), 1.53–1.57 (m, 1 H, CH2), 2.39–2.43 (m, 1
H, CH), 3.47–3.51 (m, 2 H, CH2OH), 5.85 (d, 1 H, J = 10.5 Hz,
CH=C), 7.19–7.38 (m, 10 H, ArH).
MS: m/z (%) = 145 (M+ – 59, 100), 130 (22), 115 (45), 103 (14), 91
(96), 77 (37), 51 (41).
(E)-Methyl 2-ethyl-4-phenylbut-3-enoate (0.74 g, 3.6 mmol) was
reduced with LiAlH4 (0.15 g, 4 mmol). Chromatography using hex-
ane–Et2O (8:2) yielded 0.46 g (71%) of (E)-2-ethyl-4-phenylbut-3-
en-1-ol as a yellow oil.
13C NMR (62 MHz): = 11.7 (CH3), 24.7 (CH2), 43.9 (CH), 66.6
(CH2OH), 127.0–130.7, 140.0, 142.0, 145.0 (C=C and Ar-C).
MS: m/z (%) = 252 (M+, 7), 221 (52), 205 (8), 192 (4), 165 (11), 115
(16), 91 (100), 77 (13), 51 (89).
IR (neat): = 3350 cm–1.
2-Ethyl-4,4-diphenylbut-3-en-1-ol (0.4 g, 1.59 mmol) was oxidized
with PCC (0.85 g, 3.97 mmol) by stirring for 75 min. Chromatogra-
phy using hexane–Et2O (98:2) yielded 0.37 g (93%) of aldehyde
20d as an oil.
1H NMR (250 MHz): = 0.94 (t, 3 H, J = 7.5 Hz, CH3), 1.36–1.42
(m, 1 H, CH2), 1.51–1.58 (m, 1 H, CH2), 1.91 (br s, 1 H, OH), 2.28–
2.32 (m, 1 H, CH), 3.50 (dd, 1 H, J = 10.6, 8.0 Hz, CHHOH), 3.61
(dd, 1 H, J = 10.6, 5.3 Hz, CHHOH), 5.90 (dd, 1 H, J = 15.9, 8.9 Hz,
PhCH=CH), 6.51 (d, 1 H, J = 15.9 Hz, PhCH=CH), 7.20–7.41 (m,
5 H, ArH).
13C NMR (75 MHz): = 11.6 (CH3), 23.9 (CH2), 48.0 (CH), 65.7
(CH2OH), 126.0–128.4, 131.2, 132.4, 137.0 (C=C and Ar-C).
MS: m/z (%) = 176 (M+, 10), 145 (61), 130 (9), 117 (30), 105 (26),
91 (78), 71 (44), 57 (100).
IR (neat): = 1730 cm–1.
1H NMR (250 MHz): = 0.90 (t, 3 H, J = 7.5 Hz, CH3), 1.52–1.70
(m, 1 H, CH2), 1.75–1.95 (m, 1 H, CH2), 3.09–3.18 (m, 1 H, CH),
5.91 (d, J =10.2 Hz, CH=C), 7.20–7.40 (m, 10 H, ArH), 9.60 (d, 1
H, J = 1.8 Hz, CHO).
13C NMR (62 MHz): = 11.5 (CH3), 22.9 (CH2), 55.0 (quat. C),
123.8–132.5, 139.5, 141.7, 146.8 (C=C, Ar-C), 201.6 (CHO).
(E)-2-Ethyl-4-phenylbut-3-en-1-ol (0.66 g, 3.74 mmol) was oxi-
dized with PCC (2 g, 9.3 mmol) were stirred for 50 min. Chroma-
tography using hexane–Et2O (95:5) yielded 0.52 g (80%) of
aldehyde (E)-20c as an oil.
MS: m/z (%) = 250 (M+, 4), 221 (28), 205 (6), 143 (29), 105 (36), 91
(100), 77 (20), 51 (17).
UV (CH2Cl2): max = 255 nm ( = 14950).
IR (neat): = 1730 cm–1.
3-Isopropyl-5,5-diphenylpent-4-en-2-one (19b)
1H NMR (250 MHz): = 0.97 (dt, 3 H, J = 7.5, 1.8 Hz, CH3), 1.57–
1.68 (m, 1 H, CH2), 1.89–2.01 (m, 1 H, CH2), 2.98–3.05 (m, 1 H,
CH), 6.10 (dd, 1 H, J = 15.8, 8.7 Hz, PhCH=CH), 6.52 (d, 1 H,
J = 15.8 Hz, PhCH=CH), 7.20–7.37 (m, 5 H, ArH), 9.63 (d, 1 H,
J = 1.8 Hz, CHO).
Mg (0.13 g, 5.4 mmol), MeI (0.3 mL, 5.2 mmol) and aldehyde 20b
(0.47 g, 1.77 mmol) were reacted to form the alcohol. Chromatog-
raphy using hexane–Et2O (8:2) yielded 414 mg (83%) of 3-isopro-
pyl-5,5-diphenylpent-4-en-2-ol as a 2:1 mixture of diastereo-
isomers A and B.
13C NMR (75 MHz): = 11.6 (CH3), 22.3 (CH2), 58.1 (CH), 124.6–
IR (neat): = 3600, 3450 cm–1.
128.7, 134.6 (C=C and Ar-C), 201.5 (CHO).
MS: m/z (%) = 174 (M+, 19), 173 (33), 145 (100), 105 (35), 91 (79),
77 (44), 65 (23), 57 (62).
1H NMR (250 MHz): = 0.85 (d, 1 H, J = 5.5 Hz, CH3, isomer B),
0.87 (d, 2 H, J = 5.5 Hz, CH3, isomer A), 0.94 (d, 2 H, J = 5.5 Hz,
CH3, isomer A), 0.96 (d, 1 H, J = 5.5 Hz, CH3, isomer B), 1.15 (d, 2
H, J = 6.0 Hz, CH3CHOH, isomer A), 1.21 (d, 1 H, J = 6.9 Hz,
CH3CHOH, isomer B), 1.80–2.00 [m, 0.66 H, CH(CH3)2, isomer
A], 2.19–2.23 [m, 0.33 H, CH(CH3)2, isomer B], 3.46–3.50 (m, 1 H,
CH), 3.80–4.00 (m, 1 H, CHOH), 5.90 (d, 0.33 H, J =11.0 Hz,
CH=C, isomer B), 6.08 (d, 0.66 H, J = 11.0 Hz, CH=C, isomer A),
7.21–7.40 (m, 10 H, ArH).
13C NMR (62 MHz): = 18.9, 19.5, 21.1, 21.5, 21.6, 21.8 (3 CH3),
29.0 [CH(CH3)2, isomer B], 29.4 [CH(CH3)2, isomer A], 52.1 (CH,
isomer B), 52.3 (CH, isomer A), 68.6 (CHOH, isomer A), 68.8
(CHOH, isomer B), 125.9–130.2, 140.3, 145.4 (C=C and Ar-C).
UV (CH2Cl2): max = 254 nm ( = 11000).
2-Ethyl-4,4-diphenylbut-3-enal (20d)
This compound was synthesized from methyl 4,4-diphenylbut-3-
enoate obtained in the synthesis of aldehyde 14b. According to the
general procedure for alkylation, i-Pr2NH (0.8 mL, 5.95 mmol),
BuLi (3.7 mL, 1.6 M in hexane), methyl 4,4-diphenylbut-3-enoate
(1.5 g, 5.95 mmol), and EtI (0.5 mL, 5.95 mmol) were used. Chro-
matography using hexane–Et2O (9:1) yielded 1.1 g (66%) of methyl
2-ethyl-4,4-diphenylbut-3-enoate as a yellow oil.
IR (neat): = 1720 cm–1.
MS: m/z (%) = 235 (M+ – 45, 82), 192 (18), 179 (6), 165 (24), 105
(74), 91 (100), 51 (20).
1H NMR (300 MHz): = 0.84 (t, 3 H, J = 7.5 Hz, CH3), 1.55–1.61
(m, 1 H, CH2), 1.78–1.82 (m, 1 H, CH2), 3.15–3.21 (m, 1 H, CH),
3.78 (s, 3 H, OCH3), 6.10 (d, 1 H, J = 10.2 Hz, CH=C), 7.17–7.39
(m, 10 H, ArH).
3-Isopropyl-5,5-diphenylpent-4-en-2-ol (0.41 g, 1.48 mmol) was
oxidized with K2Cr2O7 (0.43 g, 1.47 mmol) in H2SO4 (4 mL) and
H2O (8 mL) by stirring for 1 h. Chromatography using hexane–Et2O
(8:2) afforded 262 mg (64%) of ketone 19b as an oil.
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IR (neat): = 1720 cm–1.
1.5 H, J = 6.3 Hz, CH3CHOH), 1.33–1.37 (m, 1 H, CH2), 1.50–1.70
(m, 1 H, CH2), 2.10–2.30 (m, 1 H, CH), 3.73–3.77 (m, 1 H, CHOH),
5.88 (d, 0.5 H, J = 10.8 Hz, CH=C), 5.91 (d, 0.5 H, J = 10.5 Hz,
CH=C), 7.18–7.36 (m, 10 H, ArH).
13C NMR (62 MHz): = 12.1 (CH3), 12.3 (CH3), 21.0 (CH3CHOH),
21.2 (CH3CHOH), 24.6 (CH2), 24.7 (CH2), 48.3 (CH), 48.5 (CH),
70.6 (CHOH), 71.2 (CHOH), 126.0–131.0, 140.4, 144.9 (C=C and
Ar-C).
1H NMR (300 MHz): = 0.83 (d, 3 H, J = 6.6 Hz, CH3), 0.93 (d, 3
H, J = 6.6 Hz, CH3), 2.07 (s, 3 H, CH3CO), 2.08–2.13 [m, 1 H,
CH(CH3)2], 3.01 (app t, 1 H, J = 7.0 Hz, CH), 6.02 (d, 1 H, J = 10.8
Hz, CH=C), 7.14–7.41 (m, 10 H, ArH).
13C NMR (62 MHz): = 20.3 (CH3), 21.0 (CH3), 30.1 [CH(CH3)2],
31.0 (CH3CO), 61.1 (CH), 125.9–132.5, 139.7, 141.9, 145.1 (C=C
and Ar-C), 209.9 (CO).
MS: m/z (%) = 278 (M+, 4), 235 (82), 219 (6), 205 (9), 193 (17), 179
(6), 157 (31), 129 (13), 115 (34), 105 (75), 91 (100), 77 (31), 51
(20).
MS: m/z (%) = 266 (M+, 6), 221 (64), 191 (18), 143 (34), 105 (66),
91 (100), 57 (24).
3-Ethyl-5,5-diphenylpent-4-en-2-ol (0.16 g, 0.6 mmol) was oxi-
dized with K2Cr2O7 (0.2 g, 0.6 mmol) in H2SO4 (2 mL) and H2O (4
mL) by stirring for 1 h. Chromatography using hexane–Et2O (8:2)
yielded 100 mg (62%) of ketone 19d as an oil.
UV (CH2Cl2): max = 254 nm ( = 13600).
(E)-3-Ethyl-5-phenylpent-4-en-2-one (19c)
According to general procedure, Mg (0.18 g, 7.4 mmol), MeI (0.5
mL, 7.4 mmol) and aldehyde (E)-20c (0.43 g, 2.47 mmol) were re-
acted to give the alcohol. Chromatography using hexane–EtOAc
(85:15) gave 290 mg (62%) of (E)-3-ethyl-5-phenylpent-4-en-2-ol
as a 3:2 mixture of diastereoisomers A and B.
IR (neat): = 1710 cm–1.
1H NMR (250 MHz): = 0.87 (t, 3 H, J = 7.5 Hz, CH3), 1.50–1.67
(m, 1 H, CH2), 1.71–1.87 (m, 1 H, CH2), 2.08 (s, 3 H, CH3CO),
3.15–3.25 (m, 1 H, CH), 5.97 (d, 1 H, J = 10.8 Hz, CH=C), 7.16–
7.61 (m, 10 H, ArH).
13C NMR (62 MHz): = 11.8 (CH3), 25.2 (CH2), 29.4 (CH3CO),
55.4 (CH), 127.0–132.5, 139.7, 141.8, 144.9 (C=C and Ar-C),
209.7 (CO).
IR (neat): = 3400 cm–1.
1H NMR (250 MHz): = 0.91 (m, 3 H, CH3), 1.16 (d, 1.2 H, J = 6.3
Hz, CH3CHOH, isomer B), 1.21 (d, 1.8 H, J = 6.3 Hz, CH3CHOH,
isomer A), 1.29–1.42 (m, 1 H, CH2), 1.57–1.80 (m, 1 H, CH2), 1.95–
2.34 (m, 1 H, CH), 3.70–3.76 (m, 1 H, CHOH), 6.00 (dd, 0.4 H,
J = 15.9, 21.6 Hz, PhCH=CH, isomer B), 6.01 (dd, 0.6 H, J = 15.6,
3.0 Hz, PhCH=CH, isomer A), 6.44 (d, 0.4 H, J = 15.9 Hz,
PhCH=CH, isomer B), 6.46 (d, 0.6 H, J = 15.6 Hz, PhCH=CH, iso-
mer A), 7.24–7.39 (m, 5 H, ArH).
MS: m/z (%) = 264 (M+, 3), 221 (66), 206 (2), 191 (18), 165 (27),
143 (34), 128 (21), 105 (66), 91 (100), 77 (39), 51 (24).
UV (CH2Cl2): max = 253 nm ( = 14350).
Preparative Photolyses; General Procedure
The photolyses were carried out in a quartz immersion well appara-
tus with a Pyrex filter and a 400 W medium pressure Hg arc lamp.
Solutions of the compound to be photolyzed and the sensitizer (ac-
etophenone or m-methoxyacetophenone) in anhyd CH2Cl2 (450
mL) were purged for 1 h with argon and irradiated under a positive
pressure of argon. After completion of the irradiation, the solvent
was evaporated under reduced pressure and the sensitizer was re-
moved by vacuum distillation (acetophenone at 30°C/0.3 Torr, m-
methoxyacetophenone at 50°C/0.3 Torr). The products were sepa-
rated by flash chromatography on silica gel.
13C NMR (62 MHz): = 12.2 (CH3), 20.4 (CH3CHOH, isomer B),
20.9 (CH3CHOH, isomer A), 24.0 (CH2, isomer B), 24.1 (CH2, iso-
mer A), 53.0 (CH, isomer B), 53.5 (CH, isomer A), 70.2 (CHOH,
isomer A), 70.5 (CHOH, isomer B), 125.5–132.2, 132.9, 137.4,
133.5, 136.6, 137.3 (C=C and Ar-C).
MS: m/z (%) = 190 (M+, 4), 145 (54), 105 (84), 117 (80), 57 (94), 77
(37), 91 (100).
Oxidation of (E)-3-ethyl-5-phenylpent-4-en-2-ol (0.25 g, 1.3
mmol) was carried out with K2Cr2O7 (0.38 g, 1.3 mmol) in H2SO4
(4 mL) and H2O (8 mL) by stirring for 50 min. Chromatography us-
ing hexane–Et2O (8:2) furnished 130 mg (53%) of ketone (E)-19c
as an oil.
Irradiation of 6
Compound 6 (200 mg, 0.7 mmol) and m-methoxyacetophenone
(2.16 g, 14 mmol) were irradiated for 20 min. Chromatography us-
ing hexane–Et2O (95:5) as eluent gave 70 mg (38%) of 7 as a yellow
oil and 77 mg (39%) of 6. Further elution with Et2O afforded 53 mg
of a highly polar material.
IR (neat): = 1710 cm–1.
1H NMR (300 MHz): = 0.91 (dt, 3 H, J = 7.5, 1.2 Hz, CH3), 1.55–
1.62 (m, 1 H, CH2), 1.80–1.90 (m, 1 H, CH2), 2.18 (s, 3 H, CH3CO),
3.16 (app q, 1 H, J = 8.2 Hz, CH), 6.10 (dd, 1 H, J = 15.9, 9.6 Hz,
PhCH=CH), 6.50 (d, 1 H, J = 15.9 Hz, PhCH=CH), 7.15–7.39 (m,
5 H, ArH).
13C NMR (62 MHz): = 11.8 (CH3), 24.5 (CH3CO), 28.9 (CH2),
59.4 (CH), 126.1–129.0, 133.3, 136.9 (C=C and Ar-C), 209.5 (CO).
IR (neat): = 1635, 1596 cm–1.
1H NMR (300 MHz): = 0.97 (d, 3 H, J = 6.8 Hz, CH3), 1.74–1.97
(m, 2 H, CH2), 2.20–2.60 (m, 5 H, 2 CH2 and CH), 5.97 (dt, 1 H,
J = 11.5, 2.4 Hz, CH=C), 6.76 (d, 1 H, J = 11.5 Hz, CH=CPh2),
7.16–7.41 (m, 10 H, ArH).
13C NMR (75 MHz): = 18.9 (CH3), 24.1 (CH2), 30.0 (CH2), 35.2
(CH2), 39.8 (CH), 117.8, 126.0–130.6, 140.2, 145.0, 154.9 (C=C
and Ar-C).
MS m/z (%) = 187 (M+ – 1, 5), 145 (17), 129 (16), 105 (100), 91
(43), 77 (80), 51 (51).
UV (CH2Cl2): max = 251 nm ( = 13100).
MS: m/z (%) = 274 (M+, 100), 197 (40), 192 (43), 91 (53), 77 (32),
55 (21).
3-Ethyl-5,5-diphenylpent-4-en-2-one (19d)
Mg (0.1 g, 4.4 mmol), MeI (0.3 mL, 4.4 mmol) and aldehyde 20d
(0.37 g, 1.48 mmol) were reacted to form the alcohol. Chromatog-
raphy using hexane–Et2O (8:2) yielded 350 mg (89%) of 3-ethyl-
5,5-diphenylpent-4-en-2-ol as a 1:1 mixture of diastereoisomers A
and B.
IR (neat): = 3350 cm–1.
1H NMR (250 MHz): = 0.87 (t, 1.5 H, J = 7.5 Hz, CH3), 0.88 (t, 1.5
H, J = 7.5 Hz, CH3), 1.15 (d, 1.5 H, J = 6.3 Hz, CH3CHOH), 1.18 (d,
Anal. Calcd for C21H22: C, 91.97; H, 8.03. Found: C, 91.85; H, 8.00.
Irradiation of 9
Compound 9 (177 mg, 0.6 mmol) and m-methoxyacetophenone (2.9
g, 19 mmol) were irradiated for 3 h. Chromatography using hexane–
Et2O (95:5) as eluent gave 43 mg (24%) of 10 as a yellow oil and
88 mg (50%) of 9. Further elution with Et2O afforded 28 mg of a
highly polar material.
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PAPER
Diastereoselective Synthesis of Cyclopropanecarbaldehydes
1157
IR (neat): = 1710, 1596 cm–1.
hyde 20a, as a 1:1 mixture of Z:E-isomers; yellow oil. An amount
of 61 mg (21%) of the yellow oil was identified as the 1R,2S,3R/
1S,2R,3S diastereoisomer of cyclopropanecarbaldehyde 21a. Fur-
ther elution with Et2O afforded 14 mg of a highly polar material.
1H NMR (300 MHz): = 1.43 (br s, 3 H, CH3), 1.64–1.82 (m, 2 H,
CH2), 2.00 (s, 3 H, CH3CO), 2.12–2.34 (m, 4 H, 2 CH2), 4.20 (d,
1 H, J = 9.7 Hz, CH), 6.49 (d, 1 H, J = 9.7 Hz, CH=C), 7.02–7.41
(m, 10 H, ArH).
13C NMR (75 MHz): = 14.0 (CH3), 21.7 (CH2), 28.5 (CH3CO),
33.0 (CH2), 38.3 (CH2), 53.7 (CH), 122.0–143.0 (C=C and Ar-C),
207.1 (CO).
1H NMR (300 MHz): = 0.92 (d, 1.5 H, J = 6.6 Hz, CH3, E-isomer),
0.94 (d, 1.5 H, J = 6.6 Hz, CH3, E-isomer), 0.96 (d, 1.5 H, J = 6.6 Hz,
CH3, Z-isomer), 1.01 (d, 1.5 H, J = 6.6 Hz, CH3, Z-isomer), 2.40–
2.60 [m, 0.5 H, CH(CH3)2, E-isomer], 2.65–2.75 [m, 0.5 H,
CH(CH3)2, Z-isomer), 2.90–2.98 (m, 0.5 H, CH, E-isomer), 3.20–
3.30 (m, 0.5 H, CH, Z-isomer), 5.60 (t, 0.5 H, J = 11.7 Hz,
PhCH=CH, Z-isomer), 6.17 (dd, 0.5 H, J = 16.0, 9.3 Hz,
PhCH=CH, E-isomer), 6.50 (d, 0.5 H, J = 16.0 Hz, PhCH=CH, E-
isomer), 6.80 (d, 0.5 H, J = 11.4 Hz, PhCH=CH, Z-isomer), 7.01–
7.40 (m, 5 H, ArH), 9.55 (s, 1 H, CHO, Z-isomer), 9.60 (s, 1 H,
CHO, E-isomer).
MS: m/z (%) = 273 (M+ – 43, 100), 191 (26), 165 (19), 91 (32), 77
(8), 55 (5).
Irradiation of (E)-14a
Compound (E)-14a (300 mg, 1.5 mmol) and m-methoxyacetophe-
none (2.16 g, 14.4 mmol) were irradiated for 1 h. Chromatography
using pentane–Et2O (85:15) as eluent gave 161 mg (51%) of an in-
separable mixture of 14a (as a 2:1 mixture of Z:E-isomers) and al-
dehyde 16 in a 3:1 ratio and 109 mg (36%) of trans-
cyclopropanecarbaldehyde (15a) as a yellow oil. Further elution
with Et2O afforded 27 mg of a highly polar material.
21a
IR (neat): = 1690 cm–1.
1H NMR (300 MHz): = 0.82 (d, 3 H, J = 6.3 Hz, CH3), 1.02 (d, 3
H, J = 6.3 Hz, CH3), 1.15–1.25 [m, 1 H, CH(CH3)2], 1.60–1.70 (m,
1 H, CH), 2.30 (q, 1 H, J = 5.1 Hz, CHCHO), 2.95 (dd, 1 H, J = 9.5,
5.1 Hz, CHPh), 7.20–7.40 (m, 5 H, ArH), 9.34 (d, 1 H, J = 5.1 Hz,
CHO).
13C NMR (75 MHz): = 21.4 (CH3), 22.6 (CH3), 24.1 [CH(CH3)2],
26.6 (CH), 32.7 (CHPh), 38.4 (CHCHO), 126.4–128.4, 135.1,
135.6 (Ar-C), 200.6 (CHO).
16 and 14a
1H NMR (300 MHz): = 1.50–1.74 (m, 8 H, 4 CH2), 2.12–2.34 (m,
4 H, 4 CH2), 4.29 (d, 0.25 H, J = 7.5 Hz, CH=C, 16), 5.70 (br s, 0.25
H, PhCH, 16), 5.71 (d, 0.5 H, J = 12 Hz, PhCH=CH, Z-isomer),
6.30 (AB system, 0.5 H, J = 16.5 Hz, PhCH=CH, E-isomer), 6.65
(d, 0.5 H, J = 12.0 Hz, PhCH=CH, Z-isomer), 7.00–7.40 (m, 5 H,
ArH), 9.26 (s, 0.5 H, CHO, Z-isomer), 9.46 (s, 0.25 H, CHO, E-iso-
mer), 9.57 (d, 0.25 H, J = 2.7 Hz, CHO, 16).
Anal. Calcd for C13H16O2 (acid): C, 76.47; H, 7.84. Found: C, 76.35;
H, 7.80.12
15a
Irradiation of 20b
IR (neat): = 1710 cm–1.
Compound 20b (300 mg, 1.14 mmol) and m-methoxyacetophenone
(5.65 g, 37.4 mmol) were irradiated for 2.5 h. Chromatography us-
ing pentane–Et2O (95:5) as eluent afforded 23 mg (9%) of 22a14 as
a yellow oil, 137 mg (46%) of starting material (20b) and 69 mg
(23%) of trans-cyclopropanecarbaldehyde 21b as an oil. Further
elution with Et2O afforded 66 mg of a highly polar material.
1H NMR (300 MHz): = 1.43–1.75 (m, 6 H, 3 CH2), 1.90–1.94 (m,
2 H, CH2), 2.37 (app t, 1 H, J = 5.4 Hz, CHCHO), 2.95 (d, 1 H,
J = 5.4 Hz, PhCH), 7.10–7.30 (m, 5 H, ArH), 9.43 (d, 1 H, J = 5.7
Hz, CHO).
13C NMR (62 MHz): = 25.0 (CH2), 26.0 (CH2), 31.0 (CH2), 32.9
(CH2), 39.0 (CH), 41.0 (CH), 126.5, 127.9, 128.2, 136.6 (Ar-C),
200.7 (CHO).
IR (neat): = 1700 cm–1.
1H NMR (300 MHz): = 0.97 (d, 3 H, J = 5.7 Hz, CH3), 1.21 (d, 3
H, J = 5.7 Hz, CH3), 1.50–1.70 [m, 1 H, CH(CH3)2], 2.20–2.30 (m,
1 H, CH), 2.42–2.58 (m, 1 H, CHCHO), 7.19–7.34 (m, 10 H, ArH),
8.57 (d, 1 H, J = 6.6 Hz, CHO).
Anal. Calcd for C14H16O2 (acid): C, 77.78; H, 7.41. Found: C, 77.68;
H, 7.30.12
Irradiation of 14b
13C NMR (75 MHz): = 21.8 (CH3), 22.2 (CH3), 27.6 (CH), 30.3
(CH), 39.6 (CH), 47.8 (quat. C), 126.6–130.9, 140.7, 141.8 (Ar-C),
201.1 (CO).
Compound 14b (261 mg, 0.94 mmol) and m-methoxyacetophenone
(2 g, 13.3 mmol) were irradiated for 2 h. Chromatography using
pentane–Et2O (8:2) as eluent gave 12 mg (5%) of 1713 as a yellow
oil, 138 mg (53%) of 14b, and 62 mg (24%) of 15b as a yellow oil.
Further elution with Et2O afforded 39 mg of a highly polar material.
Anal. Calcd for C19H20O2 (acid): C, 81.43; H, 7.14. Found: C, 81.36;
H, 7.07.12
IR (neat): = 1715 cm–1.
Irradiation of (E)-20c
1H NMR (300 MHz): = 1.69–1.84 (m, 8 H, 4 CH2), 2.48 (d, 1 H,
J = 7.2 Hz, CHCHO), 7.20–7.80 (m, 10 H, ArH), 9.02 (d, 1 H,
J = 7.2 Hz, CHO).
13C NMR (75 MHz): = 24.0 (CH2), 25.8 (CH2), 29.4 (CH2), 34.3
(CH2), 43.7 (CH), 43.9 (quat. C), 50.6 (CPh2), 126.4–130.2, 139.2,
139.6, 142.2, 143.0 (Ar-C), 202.4 (CHO).
Compound (E)-20c (520 mg, 3 mmol) and acetophenone (3 g, 25
mmol) were irradiated for 7 h. Chromatography using pentane–
Et2O (98:2) as eluent gave 295 mg (57%) of (Z)-20c as a yellow oil.
An amount of 115 mg (22%) of a yellow oil was identified as the
1R,2S,3R/1S,2R,3S diastereoisomer of cyclopropanecarbaldehyde
21c. Further elution with Et2O afforded 99 mg of a highly polar ma-
terial.
MS: m/z (%) = 247 (M+ – 29, 6), 171 (26), 129 (4), 105 (100), 91
(14), 77 (64), 51 (31).
(Z)-20c
1H NMR (300 MHz): = 0.90 (t, 3 H, J = 7.2 Hz, CH3), 1.61 (m, 1
H, CH2), 1.85 (m, 1 H, CH2), 3.40 (m, 1 H, CH), 5.50 (app t, 1 H,
J = 11.4 Hz, PhCH=CH), 6.81 (d, 1 H, J = 11.4 Hz, PhCH=CH),
7.25–7.40 (m, 5 H, ArH), 9.60 (d, 1 H, J = 2.7 Hz, CHO).
Anal. Calcd for C20H20O2 (acid): C, 82.19; H, 6.85. Found: C, 82.10;
H, 6.75.12
Irradiation of (E)-20a
Compound (E)-20a (285 mg, 1.5 mmol) and m-methoxyacetophe-
none (1.3 g, 8.7 mmol) were irradiated for 40 min. Chromatography
using pentane–Et2O (95:5) as eluent gave 199 mg (21%) of alde-
21c
IR (neat): = 1690 cm–1.
Synthesis 2001, No. 8, 1149–1158 ISSN 0039-7881 © Thieme Stuttgart · New York

1158
D. Armesto et al.
PAPER
1H NMR (300 MHz): = 0.80 (t, 3 H, J = 7.5 Hz, CH3), 1.00–1.20
(m, 1 H, CH2), 1.21–1.41 (m, 1 H, CH2), 1.70–1.90 (m, 1 H, CHEt),
2.19 (q, 1 H, J = 5.0 Hz, CHCHO), 2.94 (dd, 1 H, J = 9.6, 5.1 Hz,
CHPh), 7.20–7.41 (m, 5 H, ArH), 9.35 (d, 1 H, J = 4.8 Hz, CHO).
13C NMR (62 MHz): = 13.4 (CH3), 20.8 (CH2), 31.3 (CHEt), 31.9
(CHPh), 35.5 (CHCHO), 126.9, 128.4, 129.0, 135.6 (Ar-C), 200.6
(CHO).
Irradiation of 19d
Compound 19d (40 mg, 0.15 mmol) and m-methoxyacetophenone
(215 mg, 1.43 mmol) were irradiated for 31 h. Chromatography us-
ing hexane–Et2O (9:1) as eluent gave 30 mg (75%) of recovered
starting material. Further elution with Et2O afforded 9 mg of a high-
ly polar material.
MS: m/z (%) = 173 (M+ – 1, 12), 145 (26), 129 (4), 105 (100), 91
(18), 77 (64), 51 (28).
Acknowledgments
S. A-L. thanks the Ministerio de Educacion y Ciencia for a postgra-
duate fellowship. We thank the Direccion General de Investigacion
Cientifica y Tecnica (grant no. PB 97/0235) for financial support.
We acknowledge the support provided by the Centro de Resonancia
Magnetica, the Centro de Microanalisis and the Servicio de Espec-
trometria de Masas of the Universidad Complutense.
Anal. Calcd for C12H14O2 (acid): C, 75.78; H, 7.37. Found: C, 75.57;
H, 7.20.12
Irradiation of 20d
Compound 20d (300 mg, 1.2 mmol) and m-methoxyacetophenone
(1 g, 6.7 mmol) were irradiated for 7 h. Chromatography using pen-
tane–Et2O (95:5) as eluent gave 66 mg (25%) of 22b15 as a yellow
oil, 120 mg (40%) of 20d and 72 mg (24%) of trans-cycloprop-
anecarbaldehyde (21d) as a yellow oil. Further elution with Et2O af-
forded 18 mg of a highly polar material.
References
(1) For reviews see: (a) Dauben, G. W.; Lodder, G.; Ipaktschi,
J. Top. Curr. Chem. 1975, 54, 73. (b) Houk, K. N. Chem.
Rev. 1976, 76, 1. (c) Schuster, D. I. Rearrangements in
Ground and Excited States, Vol. 3; deMayo, P., Ed.;
Academic Press: New York, 1980, 167. (d) Demuth, M.
Org. Photochem., Vol.11; Padwa, A., Ed.; Marcel Dekker:
New York, 1991, 37. (e) Zimmerman, H. E.; Armesto, D.
Chem. Rev. 1996, 96, 3065.
(2) (a) Poel, D. E.; Wehrli, H.; Schaffner, K.; Jeger, O. Chimia
1966, 20, 110. (b) Pfenninger, E.; Poel, D. E.; Berse, C.;
Wehrli, H.; Schaffner, K.; Jeger, O. Helv. Chim. Acta 1968,
51, 772.
(3) Zimmerman, H. E.; Cassel, J. M. J. Org. Chem. 1989, 54,
3800.
(4) (a) Armesto, D.; Ortiz, M. J.; Romano, S. Tetrahedron Lett.
1995, 36, 965. (b) Armesto, D.; Ortiz, M. J.; Romano, S.;
Agarrabeitia, A. R.; Gallego, M. G.; Ramos, A. J. Org.
Chem. 1996, 61, 1459.
(5) Baggiolini, E.; Hamlow, H. P.; Schaffner, K. J. Am. Chem.
Soc. 1970, 92, 4906.
(6) van der Weerdt, A. J. A.; Cerfontain, H. Recl. Trav. Chim.
Pays-Bas 1977, 96, 247.
(7) Tenney, L. P.; Boykin, D. W. Jr.; Lutz, R. E. J. Am. Chem.
Soc. 1966, 88, 1835.
(8) van der Weerdt, A. J. A.; Cerfontain, H. Tetrahedron 1981,
37, 2121.
IR (neat): = 1690 cm–1.
1H NMR (300 MHz): = 0.91 (t, 3 H, J = 7.5 Hz, CH3), 1.70–190
(m, 2 H, CH2), 2.38 (t, 1 H, J = 6.0 Hz, CHEt), 2.47 (q, 1 H, J = 6.0
Hz, CHCHO), 7.18–7.82 (m, 10 H, ArH), 8.60 (d, 1 H, J = 6.6 Hz,
CHO).
13C NMR (75 MHz): = 13.4 (CH3), 22.5 (CH2), 33.1 (CHEt), 40.7
(CHCHO), 46.9 (quat. C), 126.4–129.9, 132.0, 137.6, 140.6 (ArH),
201.1 (CHO).
MS: m/z (%) = 250 (M+, 4), 221 (12), 173 (14), 143 (18), 129 (4),
105 (100), 77 (64), 51 (26).
Anal. Calcd for C18H18O2 (acid): C, 81.20; H, 6.76. Found: C, 81.00;
H, 6.86.12
Irradiation of 13b
Compound 13b (50 mg, 0.17 mmol) and m-methoxyacetophenone
(0.5 g, 3.3 mmol) were irradiated for 17 h. Chromatography using
hexane–Et2O (9:1) as eluent gave 36 mg (71%) of recovered start-
ing material. Further elution with Et2O afforded 14 mg of a highly
polar material.
Irradiation of 19b
Compound 19b (216 mg, 0.78 mmol) and m-methoxyacetophenone
(1 g, 6.6 mmol) were irradiated for 12 h. Chromatography using
hexane–Et2O (9.1) as eluent gave 180 mg (83%) of recovered start-
ing material. Further elution with Et2O afforded 35 mg of highly po-
lar material.
(9) Dauben, W. G.; Warshawsky, A. M. J. Org. Chem. 1990, 55,
3075.
(10) Zimmerman, H. E.; Khun, R. T. Tetrahedron 1978, 34,
1775.
(11) Johnson, W. S.; Petersen, J. W.; Schneider, W. P. J. Am.
Chem. Soc. 1947, 69, 74.
(12) Aldehydes 15a–b and 21a–d undergo spontaneous oxidation
in the presence of atmospheric oxygen. The combustion
analyses quoted correspond to the carboxylic acids resulting
from oxidation.
(13) Stetter, H.; Kiehs, K. Chem.Ber. 1965, 98, 1181.
(14) Schorigin, P. Ber. Dtsch. Chem. Ges. 1907, 41, 2711.
(15) Serijan, K. T.; Wise, H. P. J. Am. Chem. Soc. 1951, 73, 5191.
Irradiation of (E)-19c
Compound (E)-19c (40 mg, 0.21 mmol) and m-methoxyacetophe-
none (296 mg, 2 mmol) were irradiated for 30 h. Chromatography
using hexane–Et2O (9:1) as eluent gave 20 mg (50%) of (Z)-19c and
10 mg (25%) of recovered starting material. Further elution with
Et2O afforded 9 mg of a highly polar material.
1H NMR (300 MHz): = 0.87 (t, 3 H, J = 7.5 Hz, CH3), 1.55–1.62
(m, 1 H, CH2), 1.76–1.80 (m, 1 H, CH2), 2.15 (s, 3 H, CH3CO),
3.50–3.61 (m, 1 H, CH), 5.56 (app t, 1 H, J = 10.8 Hz, PhCH=CH),
6.66 (d, 1 H, J = 10.8 Hz, PhCH=CH), 7.24–7.36 (m, 5 H, ArH).
Synthesis 2001, No. 8, 1149–1158 ISSN 0039-7881 © Thieme Stuttgart · New York