A stereoselective and practical synthesis of (E)-α,β-unsaturated ketones from aldehydes

Article abstract of DOI:10.1002/ejoc.201001182

α,β-Unsaturated ketones can be prepared by reaction of differently substituted β-keto acids and aldehydes. The reaction is carried out under organocatalysis (β-alanine, 0.5 equiv.) and generates the enones with high E selectivity (>95%). This version of the Verley-Doebner modification of the Knoevenagel reaction is a practical alternative to the classic Horner-Wadsworth-Emmons (HWE) reaction without the formation of high molecular weight byproducts. The process makes use of simple reagents and can be applied to large-scale synthesis under conditions compatible with atom-economy principles. Differently substituted aliphatic, aromatic, or heteroaromatic α,β-unsaturated ketones can be prepared. An example of a hydroformylation/Verley-Doebner Knoevenagel telescoped process is also described. The conditions used in the Knoevenagel reaction to prepare conjugated esters under amino acid organocatalysis can be applied also for the synthesis of α,β unsaturatedketones. β-Keto acids are prepared byhydrogenolysis of the corresponding benzyl ester and react easily with aldehydes to give the α,β-unsaturated ketones without formation of high molecular weight byproducts. Copyright

Full text of DOI:10.1002/ejoc.201001182

FULL PAPER
DOI: 10.1002/ejoc.201001182
A Stereoselective and Practical Synthesis of (E)-α,β-Unsaturated Ketones from
Aldehydes
Evita Balducci,[a] Emanuele Attolino,[b] and Maurizio Taddei*[a]
Keywords: Enones / Electrophilic addition / Synthetic methods / Organocatalysis / Hydroformylation
α,β-Unsaturated ketones can be prepared by reaction of dif-
ferently substituted β-keto acids and aldehydes. The reaction
is carried out under organocatalysis (β-alanine, 0.5 equiv.)
and generates the enones with high E selectivity (Ͼ95%).
This version of the Verley–Doebner modification of the Knoe-
venagel reaction is a practical alternative to the classic
Horner–Wadsworth–Emmons (HWE) reaction without the
formation of high molecular weight byproducts. The process
makes use of simple reagents and can be applied to large-
scale synthesis under conditions compatible with atom-econ-
omy principles. Differently substituted aliphatic, aromatic, or
heteroaromatic α,β-unsaturated ketones can be prepared. An
example of a hydroformylation/Verley–Doebner Knoeve-
nagel telescoped process is also described.
tion, from the use of expensive or sensitive reagents that
prevents the scale-up of the process, and from scarce atom
economy. The most stereocontrolled Wittig or HWE reac-
tions produce in fact high molecular weight byproducts.
The Knoevenagel condensation between a β-keto ester and
an aldehyde has also been applied to α,β-unsaturated
ketone syntheses. After the condensation, the ester can be
hydrolyzed and further decarboxylated to give the conju-
gated ketone.[6] However, mixtures of (E) and (Z) products
are often obtained, limiting the application of this poten-
tially useful and simple procedure (Scheme 1).
Introduction
α,β-Unsaturated ketones are important chemicals as in-
termediates or final products with different applications.[1]
Several methods have been described for their preparation
as aldol-type condensation followed by elimination,[2] acyl-
ation reactions,[3] transition-metal-catalyzed reactions,[4]
Wittig, or Horner–Wadsworth–Emmons (HWE) reaction
with alkoxy phosphoranes.[5] Some of these reactions suffer
from being low (E)-stereoselective in the C–C bond forma-
Results and Discussion
Recently, List described a new protocol for the Knoeven-
agel reaction using malonic acid half ester in the presence
of 10% DMAP to transform an aldehyde into the corre-
sponding α,β-unsaturated ester in good yields with excellent
(E)-stereoselectivity.[7] The possibility to apply an analo-
gous approach to the synthesis of α,β-unsaturated ketones
appeared to be useful to access this class of important com-
pounds. In that case, the malonic acid half ester would be
replaced by a β-keto acid that, reacting with an aldehyde,
gives a ketol that is further transformable into the α,β-un-
saturated ketone.
Scheme 1. Standard approaches for the synthesis of α,β unsatu-
The main expected problem would be the low yield in
the β-keto acid preparation due to decarboxylation, as pre-
viously reported.[8] To overcome this drawback, the reaction
of the potassium salt of 2-oxobutanoic acid with aldehydes
has also been described.[9] The condensation occurred in
water in a very precise pH range (between 7.5 and 8.5) in
order to prevent the self condensation of the aldehyde. A
β-ketol is formed and further strong acidification (pH 1)
generates directly the α,β-unsaturated ketone in a tele-
rated ketones.
[a] Dipartimento Farmaco Chimico Tecnologico, Università degli
Studi di Siena,
Via A. Moro 2, 53100 Siena, Italy
Fax: +39-0577-234280
E-mail: taddei.m@unisi.it
[b] Dipharma Francis Srl,
Via Bissone, 2 20021 Baranzate, Milano, Italy
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201001182.
Eur. J. Org. Chem. 2011, 311–318
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
311

E. Balducci, E. Attolino, M. Taddei
FULL PAPER
scoped process. As these conditions seemed to be not suit- lished (use of pyridine as the solvent or as the base in
able for a large-scale application, we decided to investigate DMF)[8] were also employed, but again the decarboxylation
the application of a Knoevenagel-type protocol to the direct of 2 was the only reaction observed (Table 1, Entries 2 and
synthesis of α,β-unsaturated ketones that could be easily 3). Using piperidine in DMF at 40 °C for 12 h, expected
applied to a preparative level. In order to find the best con- product 4 was obtained in 25% yield (Table 1, Entry 4).
ditions, the reaction between p-cyanobenzaldehyde (3) and However, 4 was isolated as a single (E) isomer (as shown
1
3-oxooctanoic acid (2) was investigated (Scheme 2). A prac- by 400 MHz H NMR spectroscopic analysis), prompting
tical approach towards a β-keto acid might be the hydro- us to investigate different reaction conditions to optimize
genolysis of the corresponding β-keto benzyl ester. The syn- the yield. An increase in the amount of acid 2 gave im-
thesis of β-keto benzyl esters has been described although proved yields of compound 4 or 5. In the presence of trieth-
these products have been employed for different pur- ylamine, decarboxylation was exclusively observed (Table 1,
poses.[10] Thus, compound 1, prepared from hexanoic acid Entry 6), and a complex mixture of products was obtained
and malonic acid monobenzyl ester,[10] was hydrogenolyzed using a primary amine (Table 1, Entry 7). The replacement
over Pd/C (10%) to give acid 2 in almost quantitative yield of DMF with toluene gave a further slight improvement
(Scheme 2).
(higher 4/5 ratio; Table 1, Entry 8), whereas the contempo-
rary use of piperidine and acetic acid promoted decarboxyl-
ation (Table 1, Entry 9). The yield of 4 increased to 73%
when the base was replaced by β-alanine (Table 1, En-
tries 10 and 11). The use of amino acids in aldol/Knoevena-
gel reactions is well precedented,[12] and β-alanine has been
employed since 1925[13] in the Verley–Doebner modification
of the Knoevenagel reaction for the synthesis of β-keto es-
ters.[14] However, these conditions have never been applied
to the synthesis of ketones.
A further improvement in the yield of 4 was achieved by
Scheme 2. Preparation of α,β-unsaturated ketone 4.
removing the water that was formed during the reaction.[6]
Simple filtration of the catalyst and evaporation of the In the presence of dry Na2SO4 or 4 Å molecular sieves
solvent gave acid 2 pure enough to be directly used in the (MS), 4 was isolated in 84 and 86% yield, respectively
next step. Moreover, unlike in the previous descriptions,[8] (Table 1, Entries 12 and 13). The amount of β-alanine and
pure product 2 was sufficiently stable to allow wide investi- β-keto acid could also be reduced up to 0.5 and 1.5 equiv.,
gation of its reactivity.[11]
respectively, without observing a reduction in the yield of
At first, conditions similar to those employed by List[7] 4[15] (Table 1, Entries 14 and 15). To speed up the reaction,
were investigated. However, the presence of DMAP gave the use of microwave dielectric heating was also at-
rapid decarboxylation of 2 with formation of large amounts tempted.[16] However, working at 40 °C in toluene (or with-
of ketone 5 (Table 1, Entry 1). The first conditions pub- out solvent), compound 4 was obtained in about 42% yield
Table 1. Optimization of reaction conditions for the synthesis of 4.[a]
Entry
Solvent
Additive
Temperature
[°C]
Time
[h]
Product
(% yield)[b]
1
2
3
4
5
6
7
8
DMF
pyridine
DMF
DMF
DMF
DMF
DMF
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
–
DMAP (0.1 equiv.)
–
pyridine (1 equiv.)
piperidine (0.5 equiv.)
piperidine (0.5 equiv.)[c]
TEA (0.5 equiv.)
r.t.
r.t.
r.t.
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
2
5 (50)
5 (60)
12
12
12
12
2
12
12
12
12
12
12
12
12
12
2
5 (60)
4 (25), 5 (30)
4 (45), 5 (40)
5 (70)
C4H9NH2 (0.5 equiv.)
piperidine (0.5 equiv.)
piperidine/AcOH (0.5 equiv.)
β-alanine (1 equiv.)
–
4 (45), 5 (10)
4 (35), 5 (50)
4 (67)
9
10
11
12
13
14
15
16
17
18
19
20
β-alanine (1 equiv.)[c]
β-alanine (1 equiv.), Na2SO4 (4 equiv.)[c]
β-alanine (1 equiv.), 4 Å MS[c]
β-alanine (0.5 equiv.), 4 Å MS[d]
4 (73)
4 (84)
4 (86)
4 (84)
[d]
β-alanine (0.5 equiv.), Na2SO4
β-alanine (1 equiv.), 4 Å MS, MW
β-alanine (1 equiv.), 4 Å MS, MW
l-alanine (1 equiv.), Na2SO4 (4 equiv.)
l-proline (1 equiv.), Na2SO4 (4 equiv.)
6-aminocaproic acid (1 equiv.), Na2SO4 (4 equiv.)
4 (82)
4 (44)
2
4 (42)
toluene
toluene
toluene
12
12
12
4 (44)
4 (50)
4 (27)
[a] If not differently stated, the reaction was carried out with 2 equiv. of acid 2 with respect to aldehyde 3. [b] Yield of isolated and fully
characterized compound. [c] 3 equiv. of 2 was used. [d] 1.5 equiv. of 2 was used.
312
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Stereoselective Synthesis of (E)-α,β-Unsaturated Ketones from Aldehydes
after 2 h of irradiation (Table 1, Entries 16 and 17). Higher
The previously optimized reaction conditions (toluene,
temperatures promoted decarboxylation. Finally, β-alanine 0.5 equiv. of β-alanine, 1.5 equiv. of β-keto acid, 4 Å MS,
was superior with respect to other amino acids investigated, 40 °C, 12 h) were applied to different aldehydes and β-keto
including 6-aminocaproic acid, which has been described to acids. All the β-keto acids (10–14, Table 2) employed were
give comparable results[13] (Table 1, Entries 18–20).
obtained in good yields by reaction of the corresponding
Table 2. Transformation of carboxylic acids into α,β-unsaturated ketones.
[a] Overall yield starting from the corresponding carboxylic acid. [b] Yield of isolated and fully characterized product. [c] A complex
mixture of products was formed. HPLC–MS analysis showed the presence of the expected ketone in about 10% yield.
Eur. J. Org. Chem. 2011, 311–318
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313

E. Balducci, E. Attolino, M. Taddei
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activated carboxylic acid with magnesium malonate mono-
benzyl ester[11] followed by hydrogenolysis. Aromatic alde-
hydes carrying either electron-withdrawing or electron-do-
nating substituents gave good results (Table 2, Entries 1, 2,
7, 8, 12, 16, and 17) and even heterocyclic aldehydes (such
as pyridine, furan, and indole aldehydes; Table 2, Entries 3,
4, 5, and 13) gave the corresponding α,β-unsaturated
ketones in significant yields. The presence of different func-
tional groups in the fragments originating from the acid or
the aldehyde is also compatible with the process, and α,β-
unsaturated ketones containing unprotected phenols, ni-
triles, carboxylates, and protected amines or alcohols can
be prepared (Table 2, Entries 2, 8, 12, 16–21). Conjugated
dienyl ketones (as compounds 28 and 35 in Table 2) can
also be prepared starting from α,β-unsaturated aldehydes.
The only limit observed was the low reactivity of aromatic
β-keto acids such as 3-oxo-3-phenylpropionic acid (14;
Table 2, Entry 22). However, chalcones (and chalconoids)
produced with this type of acid could be easily obtained
by alkaline condensation of acetophenones.[17] On the other
hand, it is remarkable that the process works well with ali-
phatic β-keto acids and aliphatic aldehydes. Fully aliphatic
α,β-unsaturated ketones are more difficult to obtain
through aldol-type condensation/elimination because of re-
gioselectivity problems in the enolization of the ketone and
the self-condensation of the enolizable aldehyde.[18] Finally,
products 15–35 were all obtained as (E) isomers (400 MHz
NMR spectroscopic analysis, selectivity Ͼ95%).
Scheme 4. Proposed role of β-alanine in the condensation reaction.
reacts with the amino acid to form imine 39a, which is in
equilibrium with the more reactive iminium (zwitter)ion
39b. Reaction of 39b with the β-keto acid gives intermediate
40 at a pH value suitable to keep the carboxylic acid undis-
sociated and ready for decarboxylation. Finally, the forma-
tion of zwitterion 41b promotes the elimination reaction to
form the (E) double bond and to regenerate the catalyst.
The proximity of opposite charges in 39b or 41b and the
possibility of forming intramolecular H bonds in intermedi-
ates 39a, 40, or 41a may explain the efficacy of β-alanine
as the organocatalyst in the reaction.
This modification of the Verley–Doebner Knoevenagel
reaction can be also applied under conditions analogous to
the one-pot hydroformylation/decarboxylative Knoevenagel
reaction sequence recently described by Breit for the
synthesis of β-keto esters.[19] In our case, the telescoped pro-
cess starts with hydroformylation of terminal alkene 36
(Scheme 3) under microwave dielectric heating.[20] After re-
lease of the syngas, β-alanine, 4 Å MS, and acid 2 or 10
were added, and the mixture was stirred at 40 °C for 12 h
to give α,β-unsaturated ketone 33 or 38, respectively, in 52
and 55% overall yield (Scheme 4).
Conclusions
In conclusion, we have developed a friendly protocol to
carry out the Verley–Doebner modification of the Knoev-
enagel reaction with β-keto acids and aldehydes to produce
α,β-unsaturated ketones. The process is based on the
friendly preparation of β-keto acids by hydrogenolysis of
the corresponding benzyl esters, and the reaction conditions
allow significant reduction in the formation of byproducts.
The method can be applied to the large-scale synthesis of
differently substituted aliphatic, aromatic, or heteroaro-
matic α,β-unsaturated ketones.
Experimental Section
General Methods: The reactions were carried out in oven-dried
glassware under a nitrogen atmosphere. Solvents were dried and
purified by conventional methods prior use. Flash column
chromatography was performed with Merck silica gel 60, 0.040–
0.063 mm (230–400 mesh). Merck aluminum-backed plates pre-
coated with silica gel 60 (UV254
) were used for thin-layer
1
chromatography and were visualized by staining with KMnO4. H
NMR and 13C NMR spectra were recorded with a Bruker AC
400 MHz instrument at 400 and at 100 MHz, respectively. Low-
resolution mass spectra were obtained with an Agilent 1100 LC–
MS instrument in positive or negative mode, and HRMS were
conducted at the Institut Fédératif de Recherche at the Louis
Pasteur University, Strasbourg, France. GC–MS analysis was
performed with a Varian-GC by using a CP 8944 column
Scheme 3. Telescoped hydroformylation/Verley–Doebner Knoeven-
agel reaction.
In light of the recent advances in understanding the role
of organocatalysis in condensation reactions,[21] it is pos-
sible to propose a mechanism that may explain the influ-
ence of β-alanine in the process (Scheme 4). The aldehyde (30 mϫ0.250 mmϫ0.39 μm). For MW reactions, a CEM Discover
314 Eur. J. Org. Chem. 2011, 311–318
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Stereoselective Synthesis of (E)-α,β-Unsaturated Ketones from Aldehydes
microwave oven equipped with an 80 or 10-mL tube for reactions
under pressure was employed.
evaporated under reduced pressure at 30 °C. Compound 2 was ob-
tained as a white solid (908 mg, 95% yield). M.p. 69–72 °C. 1H
NMR (400 MHz, CDCl3): δ = 9.39 (br. s, 1 H, COOH), 3.47 (s, 2
H, CH2), 2.53–2.51 (m, 2 H, CH2), 1.59–1.57 (m, 2 H, CH2), 1.28–
1.26 (m, 4 H, CH2), 0.87–0.86 (m, 3 H, CH3) ppm. 13C NMR
(100 MHz, CDCl3): δ = 203.65, 171.39, 47.58, 42.78, 30.66, 22.64,
21.91, 13.77 ppm. MS (ES+): m/z = 181 [M + Na]+. HRMS (ES+):
calcd. for C8H14NaO3 181.0841; found 181.0843.
Benzyl 3-Oxooctanoate (1): Hexanoic acid (3 mL, 23.94 mmol) was
dissolved in dry THF (42 mL) under an atmosphere of N2 and
1,1Ј-carbonyldiimidazole (4.26 g, 26.33 mmol) was added, and the
mixture was stirred at room temperature for 3 h (solution A). In
a separate flask, to a solution of monobenzyl malonate (5.58 g,
28.73 mmol) in dry THF (42 mL) at 0 °C under an atmosphere of
N2 was dropwise added isopropylmagnesium chloride (2 m in THF,
28.73 mL, 57.46 mmol). After 30 min at 0 °C the solution was
heated at 50 °C for 30 min and then cooled again to 0 °C at which
time solution A was added dropwise. The mixture was left to warm
to room temperature and then stirred for 16 h. The mixture was
then quenched with 1 m HCl and extracted with Et2O. The organic
3-Oxo-4-phenylbutanoic Acid (10): White solid: 1.02 g (95% yield),
1
m.p. 58–60 °C. H NMR (400 MHz, CDCl3): δ = 7.82 (br. s, 1 H,
COOH), 7.33–7.18 (m, 5 H, ArH), 3.82 (s, 2 H, CH2), 3.48 (s, 2 H,
CH2) ppm. 13C NMR (100 MHz, CDCl3): δ = 200.84, 171.21,
132.53, 129.11, 128.99, 128.58, 128.26, 127.17, 49.77, 46.68 ppm.
MS (ES+): m/z = 201 [M + Na]+. HRMS (ES+): calcd. for
layer was washed with 1 m HCl (3ϫ50 mL), NaHCO3 (3ϫ50 mL), C10H10NaO3 201.0528; found 201.0530.
and brine, dried with Na2SO4, filtered, and concentrated under re-
3-Oxo-4-phenoxybutanoic Acid (11): White solid: 1.11 g (95%
yield), m.p. 64–66 °C. H NMR (400 MHz, CDCl3): δ = 8.08 (br.
duced pressure The crude was purified by flash chromatography
on silica gel (petroleum ether 40–60 °C/EtOAc, 9:1). Compound 1
(5.04 g, 85%) was obtained as a colorless oil. 1H NMR (400 MHz,
CDCl3): δ = 7.26–7.22 (m, 5 H, ArH), 5.06 (s, 2 H, CH2), 3.35 (s,
2 H, CH2), 2.37 (t, J = 7 Hz, 2 H, CH2), 1.52–1.45 (m, 2 H, CH2),
1.24–1.15 (m, 4 H, CH2), 0.81 (t, J = 7 Hz, 3 H, CH3) ppm. 13C
NMR (100 MHz, CDCl3): δ = 201.73, 166.46, 135.25, 128.02,
127.73, 127.61, 66.26, 48.55, 42.27, 30.65, 22.61, 21.84, 13.89 ppm.
MS (ES+): m/z = 271 [M + Na]+. HRMS (ES+): calcd. for
C15H20NaO3 271.1310; found 271.1307.
1
s, 1 H, COOH), 7.31–7.27 (m, 2 H, ArH), 7.02–6.86 (m, 3 H, ArH),
4.63 (s, 2 H, CH2), 3.68 (s, 2 H, CH2) ppm. 13C NMR (100 MHz,
CDCl3): δ = 200.25, 171.70, 157.88, 129.39, 129.24, 121.75, 114.24,
114.10, 72.02, 45.02 ppm. MS (ES+): m/z = 217 [M + Na]+. HRMS
(ES+): calcd. for C10H10NaO4 217.0477; found 217.0480.
8-Methoxy-3,8-dioxooctanoic Acid (12): White solid: 1.16 g (95%
1
yield), m.p. 44–46 °C. H NMR (400 MHz, CDCl3): δ = 9.65 (br.
s, 1 H, COOH), 3.60 (s, 3 H, CH3), 3.44 (s, 2 H, CH2), 2.55–2.53
(m, 2 H, CH2), 2.28–2.26 (m, 2 H, CH2), 1.58–1.56 (m, 4 H,
CH2) ppm. 13C NMR (100 MHz, CDCl3): δ = 202.73, 173.60,
170.87, 51.20, 47.87, 42.19, 33.23, 23.65, 22.26 ppm. MS (ES+):
m/z = 225 [M + Na]+. HRMS (ES+): calcd. for C9H14NaO5
225.0739; found 225.0736.
Benzyl 3-Oxo-4-phenylbutanoate (6): Colorless oil: 5.06 g (79%
yield). 1H NMR (400 MHz, CDCl3): δ = 7.36–7.18 (m, 10 H, ArH),
5.17 (s, 2 H, CH2), 3.80 (s, 2 H, CH2), 3.51 (s, 2 H, CH2) ppm. 13
C
NMR (100 MHz, CDCl3): δ = 199.78, 166.49, 134.83, 132.75,
129.14, 128:89, 128.45, 128.20, 128.06, 127.97, 126.96, 126.66,
66.75, 49.64, 47.78 ppm. MS (ES+): m/z = 291 [M + Na]+. HRMS
(ES+): calcd. for C17H16NaO3 291.0997; found 291.0995.
4-(tert-Butoxycarbonylamino)-3-oxobutanoic Acid (13): White solid:
1
1.25 g (95% yield), m.p. 94–96 °C. H NMR (400 MHz, CDCl3): δ
= 8.16 (br. s, 1 H, COOH), 5.35 (br. s, 1 H, NH), 4.16 (s, 2 H,
CH2), 3.50 (s, 2 H, CH2), 1.42 (s, 9 H, CH3) ppm. 13C NMR
(100 MHz, CDCl3): δ = 198.73, 169.61, 155.65, 80.06, 50.12, 45.60,
27.84 ppm. MS (ES+): m/z = 240 [M + Na]+. HRMS (ES+): calcd.
for C9H15NNaO5 240.0848; found 240.0845.
Benzyl 3-Oxo-4-phenoxybutanoate (7): White solid: 5.98 g (88%
yield), m.p. 33–35 °C. H NMR (400 MHz, CDCl3): δ = 7.36–7.18
1
(m, 10 H, ArH), 5.17 (s, 2 H, CH2), 3.80 (s, 2 H, CH2), 3.51 (s, 2
H, CH2) ppm. 13C NMR (100 MHz, CDCl3): δ = 199.97, 166.24,
157.02, 134.80, 129.34, 129.24, 128.23, 128.09, 128.00, 121.58,
114.27, 114.15, 72.01, 66.86, 45.67 ppm. MS (ES+): m/z = 307 [M
+ Na]+. HRMS (ES+): calcd. for C17H16NaO4 307.0946; found
307.0949.
3-Oxo-3-phenyl Propanoic Acid: (14) White solid: 1.02 g (77%
1
yield), m.p. 79–80 °C. H NMR (400 MHz, CDCl3): δ = 10.11 (br.
s, 1 H, COOH), 7.59 (m, 2 H, ArH), 7.16 (m, 3 H, ArH), 3.48 (s,
2 H, CH2) ppm. 13C NMR (100 MHz, CDCl3): δ = 199.72, 169.71,
132.88, 129.19, 128.94, 121.35, 52.12 ppm. MS (ES+): m/z = 187
[M + Na]+. HRMS (ES+): calcd. for C9H19NaO3 187.0371; found
187.0375.
1-Benzyl 8-Methyl 3-Oxooctanedioate (8): Colorless oil: 5.17 g
1
(74% yield). H NMR (400 MHz, CDCl3): δ = 7.27–7.24 (m, 5 H,
ArH), 5.07 (s, 2 H, CH2), 3.55 (s, 3 H, CH3), 3.38 (s, 2 H, CH2),
2.44–2.41 (m, 2 H, CH2), 2.20–2.17 (m, 2 H, CH2), 1.51–1.48 (m,
4 H, CH2) ppm. 13C NMR (100 MHz, CDCl3): δ = 201.66, 173.15,
166.52, 134.97, 128.11, 127.87, 126.37, 66.49, 50.95, 48.63, 41.95,
33.15, 23.67, 22.28 ppm. MS (ES+): m/z = 315 [M + Na]+. HRMS
(ES+): calcd. for C16H20NaO5 315.1208; found 315.1205.
Preparation of (E)-4-(3-Oxooct-1-enyl)benzonitrile (4) as a Repre-
sentative Procedure for the Modified Verley–Doebner Knoevenagel
Condensation: Acid 2 (1.09 g, 6.9 mmol), 3 (0.60 g, 4.6 mmol), β-
alanine (0.41 g, 4.6 mmol), 4 Å molecular sieves (0.4 g), and tolu-
ene (6 mL) were placed in a 25-mL vial. After closing the vial with
a rubber septum, the mixture was heated at 40 °C for 12 h under
magnetic stirring. The mixture was diluted with EtOAc (50 mL),
washed with 1 n HCl (3ϫ10 mL) and brine, dried with dry
Na2SO4, filtered, and concentrated under reduced pressure. The
crude was purified by flash chromatography on silica gel (hexane/
EtOAc, 9:1) to give 4 as a white solid (0.88 g, 84% yield). M.p. 80–
81 °C. 1H NMR (400 MHz, CDCl3):[22] δ = 7.64–7.60 (m, 4 H,
ArH), 7.47 (d, J = 16 Hz, 1 H, CH=), 6.76 (d, J = 16 Hz, 1 H,
CH=), 2.62 (t, J = 7 Hz, 2 H, CH2), 1.65–1.62 (m, 2 H, CH2),
1.30–1.27 (m, 4 H, CH2), 0.87–0.84 (m, 3 H, CH3) ppm. 13C NMR
(100 MHz, CDCl3): δ = 199.47, 139.23, 139.08, 138.60, 132.19,
128.56, 128.19, 117.91, 112.94, 40.97, 30.98, 23.36, 22.02,
Benzyl 4-(tert-Butoxycarbonylamino)-3-oxobutanoate (9): Colorless
1
oil: 5.43 g (74% yield). H NMR (400 MHz, CDCl3): δ = 7.33 (s,
5 H, ArH), 5.14 (s, 2 H, CH2), 4.07 (s, 2 H, CH2), 3.50 (s, 2 H,
CH2), 1.41 (s, 9 H, CH3) ppm. 13C NMR (100 MHz, CDCl3): δ =
198.16, 166.02, 155.19, 134.66, 128.23, 128.13, 127.96, 79.78, 66.95,
50.18, 46.01, 27.85 ppm. MS (ES+): m/z = 330 [M + Na]+. HRMS
(ES+): calcd. for C16H21NNaO5 330.1317; found 330.1319.
Preparation of 3-Oxooctanoic Acid (2) as a Representative Pro-
cedure for Hydrogenolysis: A solution of 1 (1.5 g, 6.05 mmol) in
EtOAc (30 mL) was stirred with 10% Pd/C (320 mg, 0.30 mmol)
under an atmosphere of hydrogen (1 atm) at room temperature for
1 h. The mixture was filtered through Celite, and the solvent was
Eur. J. Org. Chem. 2011, 311–318
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
315

E. Balducci, E. Attolino, M. Taddei
FULL PAPER
13.40 ppm. MS (ES+): m/z (%) = 250 [M + Na]+. HRMS (ES+):
calcd. for C15H17NNaO 250.1208; found 250.1210.
= 16 Hz, 1 H, CH=), 7.51–7.49 (m, 2 H, ArH), 7.37–7.25 (m, 8 H,
ArH), 6.75 (d, J = 16 Hz, 1 H, CH=), 3.93 (s, 2 H, CH2) ppm. 13
C
NMR (100 MHz, CDCl3): δ = 196.87, 142.99, 134.04, 130.16,
129.09, 128.52, 128.37, 127.97, 126.59, 124.81, 47.99 ppm. MS
(ES+): m/z = 245 [M + Na]+. HRMS (ES+): calcd. for C16H14NaO
245.0942; found 245.0945.
(E)-1-(4-Methoxyphenyl)oct-1-en-3-one (15): Colorless oil: 59 mg
(55% yield). H NMR (400 MHz, CDCl3): δ = 7.51–7.47 (m, 3 H,
1
CH=, ArH), 6.89 (d, J = 8 Hz, 2 H, ArH), 6.60 (d, J = 16 Hz, 1
H, CH=), 3.82 (s, 3 H, CH3), 2.61 (t, J = 7 Hz, 2 H, CH2), 1.69–
1.63 (m, 2 H, CH2), 1.33–1.31 (m, 4 H, CH2), 0.90–0.87 (m, 3 H,
CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 200.30, 161.10,
141.66, 135.61, 129.50, 123.74, 113.98, 54.96, 40.40, 31.13, 23.80,
22.07, 13.51 ppm. MS (ES+): m/z = 255 [M + Na]+. HRMS (ES+):
calcd. for C15H20NaO2 255.1361; found 255.1364.
(E)-4-(3-Oxo-4-phenylbut-1-enyl)benzonitrile (22): White solid:
90 mg (79% yield), m.p. 106–108 °C. 1H NMR (400 MHz, CDCl3):
δ = 7.63–7.54 (m, 5 H, ArH, CH=), 7.35–7.23 (m, 5 H, ArH), 6.81
(d, J = 16 Hz, 1 H, CH=), 3.92 (s, 2 H, CH2) ppm. 13C NMR
(100 MHz, CDCl3): δ = 196.18, 140.24, 138.35, 133.41, 132.19,
129.07, 128.49, 128.24, 127.43, 126.82, 117.90, 113.10, 48.40 ppm.
MS (ES+): m/z = 270 [M + Na]+. HRMS (ES+): calcd. for
C17H13NNaO 270.0895; found 270.0897.
(E)-1-(4-Hydroxyphenyl)oct-1-en-3-one (16): White solid: 70 mg
(70% yield), m.p. 112–113 °C. 1H NMR (400 MHz, CDCl3): δ =
7.50 (d, J = 16 Hz, 1 H, CH=), 7.43 (d, J = 8 Hz, 2 H, ArH), 6.86
(d, J = 8 Hz, 2 H, ArH), 6.60 (d, J = 16 Hz, 1 H, CH=), 6.46 (br.
s, 1 H, OH), 2.63 (t, J = 7 Hz, 2 H, CH2), 1.68–1.64 (m, 2 H, CH2),
1.33–1.30 (m, 4 H, CH2), 0.89–0.86 (m, 3 H, CH3) ppm. 13C NMR
(100 MHz, CDCl3): δ = 201.35, 157.98, 142.50, 129.86, 126.56,
123.34, 115.64, 40.32, 31.10, 23.91, 22.04, 13.49 ppm. MS (ES+):
m/z = 241 [M + Na]+. HRMS (ES+): calcd. for C14H18NaO2
241.1204; found 241.1202.
(E)-4-(4-Methoxyphenyl)-1-phenylbut-3-en-2-one (23): White solid:
88 mg (76% yield), m.p. 93–95 °C. 1H NMR (400 MHz, CDCl3): δ
= 7.58 (d, J = 16 Hz, 1 H), 7.44 (d, J = 8 Hz, 2 H), 7.34–7.23 (m,
5 H), 6.87 (d, J = 8 Hz, 2 H), 6.65 (d, J = 16 Hz, 1 H), 3.90 (s, 2
H), 3.80 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 196.86,
161.27, 142.79, 134.34, 129.72, 129.07, 128.32, 126.69, 126.49,
122.63, 113.99, 54.97, 47.88 ppm. MS (ES+): m/z
= 275
[M + Na]+. HRMS (ES+): calcd. for C17H16NaO2 275.1048; found
275.1045.
(E)-1-(Pyridin-3-yl)oct-1-en-3-one (17): Light-yellow oil: 70 mg
1
(75% yield). H NMR (400 MHz, CDCl3): δ = 8.73 (s, 1 H, ArH),
8.57 (s, 1 H, ArH), 7.82 (d, J = 8 Hz, 1 H, ArH), 7.49 (d, J =
16 Hz, 1 H, CH=), 7.31–7.28 (m, 1 H, ArH), 6.76 (d, J = 16 Hz, 1
H, CH=), 2.63 (t, J = 7 Hz, 2 H, CH2), 1.68–1.63 (m, 2 H, CH2),
1.32–1.30 (m, 4 H, CH2), 0.89–0.85 (m, 3 H, CH3) ppm. 13C NMR
(100 MHz, CDCl3): δ = 199.52, 150.53, 149.41, 137.93, 133.88,
130.03, 127.51, 123.34, 40.74, 31.01, 23.43, 22.03, 13.47 ppm. MS
(E)-1-Phenylhept-3-en-2-one (24): Colorless oil: 44 mg (51% yield).
1H NMR (400 MHz, CDCl3): δ = 7.32–7.18 (m, 5 H, ArH), 6.89
(dt, J = 6, 16 Hz, 1 H, CH=), 6.12 (d, J = 16 Hz, 1 H, CH=), 3.80
(s, 2 H, CH2), 2.15 (q, J = 6 Hz, 2 H, CH2), 1.49–1.42 (m, 2 H,
CH2), 0.89 (t, J = 7 Hz, 3 H, CH3) ppm. 13C NMR (100 MHz,
CDCl3): δ = 197.12, 147.97, 129.00, 128.22, 126.41, 122.51, 47.14,
34.05, 20.89, 13.22 ppm. MS (ES+): m/z = 211 [M + Na]+. HRMS
(ES+): calcd. for C13H16NaO 211.1099; found 211.1096.
(ES+): m/z
C13H17NNaO 226.1208; found 226.1211.
= 226 [M +
Na]+. HRMS (ES+): calcd. for
(E)-1-(Furan-2-yl)oct-1-en-3-one (18): Light-yellow solid: 75 mg
(85% yield), m.p. 36–38 °C. 1H NMR (400 MHz, CDCl3): δ = 7.42
(s, 1 H, ArH), 7.25 (d, J = 16 Hz, 1 H, CH=), 6.60–6.56 (m, 2 H,
ArH, CH=), 6.42–6.41 (m, 1 H, ArH), 2.52 (t, J = 7 Hz, 2 H, CH2),
1.63–1.56 (m, 2 H, CH2), 1.28–1.25 (m, 4 H, CH2), 0.84 (t, J =
6 Hz, 3 H, CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 199.66,
150.71, 144.32, 127.96, 122.98, 114.98, 112.02, 40.92, 31.03, 23.64,
22.02, 13.45 ppm. MS (ES+): m/z = 215 [M + Na]+. HRMS (ES+):
calcd. for C12H16NaO2 215.1048; found 215.1045.
(E)-1,6-Diphenylhex-3-en-2-one (25): Colorless oil: 73 mg (63%
yield). 1H NMR (400 MHz, CDCl3): δ = 7.32–7.11 (m, 10 H, ArH),
6.91 (dt, J = 6, 16 Hz, 1 H, CH=), 6.13 (d, J = 16 Hz, 1 H, CH=),
3.78 (s, 2 H, CH2), 2.75 (t, J = 7 Hz, 2 H, CH2), 2.50 (q, J = 7 Hz,
2 H, CH2) ppm. 13C NMR (100 MHz, CDCl3): δ = 196.75, 146.52,
140.20, 134.17, 129.48, 128.95, 128.21, 128.03, 127.87, 127.25,
126.39, 125.75, 47.19, 33.95, 33.58 ppm. MS (ES+): m/z = 273 [M
+ Na]+. HRMS (ES+): calcd. for C18H18NaO 273.1255; found
273.1258.
(E)-1-(1H-Indol-5-yl)oct-1-en-3-one (19): White solid: 76 mg (69%
yield), m.p. 123–125 °C. 1H NMR (400 MHz, CDCl3): δ = 8.37 (br.
s, 1 H, NH), 7.81 (s, 1 H, ArH), 7.69 (d, J = 16 Hz, 1 H, CH=),
7.44–7.36 (m, 2 H, ArH), 7.23–7.21 (m, 1 H, ArH), 6.72 (d, J =
16 Hz, 1 H, CH=), 6.57 (s, 1 H, ArH), 2.65 (t, J = 7 Hz, 2 H, CH2),
1.70–1.67 (m, 2 H, CH2), 1.35–1.33 (m, 4 H, CH2), 0.91–088 (m, 3
H, CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 200.66, 144.04,
136.72, 127.83, 126.24, 125.05, 123.36, 122.26, 121.34, 111.22,
103.08, 40.33, 31.17, 23.94, 22.09, 13.53 ppm. MS (ES+): m/z = 264
[M + Na]+. HRMS (ES+): calcd. for C16H19NNaO 264.1364;
found 264.1361.
(E)-4-(3-Oxo-4-phenoxybut-1-enyl)benzonitrile (26): White solid:
91 mg (75% yield), m.p. 108–110 °C. 1H NMR (400 MHz, CDCl3):
δ = 7.71 (d, J = 16 Hz, 1 H, CH=), 7.67–7.61 (m, 4 H, ArH), 7.29
(t, J = 7 Hz, 2 H, ArH), 7.14 (d, J = 16 Hz, 1 H, CH=), 6.99 (t, J
= 7 Hz, 1 H, ArH), 6.91 (d, J = 8 Hz, 2 H, ArH), 4.75 (s, 2 H,
CH2) ppm. 13C NMR (100 MHz, CDCl3): δ = 195.34, 157.31,
141.41, 138.16, 132.25, 129.34, 128.46, 123.44, 121.53, 117.83,
114.23, 113.47, 72.15 ppm. MS (ES+): m/z = 286 [M + Na]+.
HRMS (ES+): calcd. for C17H13NNaO2 286.0844; found 286.0847.
(E)-4-(Furan-2-yl)-1-phenoxybut-3-en-2-one (27): Light-yellow oil:
89 mg (85% yield). 1H NMR (400 MHz, CDCl3): δ = 7.54–7.48
(m, 1 H, ArH), 7.30–7.25 (m, 2 H, ArH, CH=), 6.99–6.85 (m, 5 H,
ArH), 6.70–6.69 (m, 1 H, CH=), 6.47–6.46 (m, 1 H, ArH), 4.70 (s,
2 H, CH2) ppm. 13C NMR (100 MHz, CDCl3): δ = 195.23, 157.58,
145.00, 129.84, 129.23, 121.24, 117.91, 116.66, 114.29, 114.11,
112.35, 72.09 ppm. MS (ES+): m/z = 251 [M + Na]+. HRMS
(ES+): calcd. for C14H12NaO3 251.0684; found 251.0681.
(E)-1-Phenyldec-3-en-5-one (20): Colorless oil: 76 mg (72% yield).
1H NMR (400 MHz, CDCl3): δ = 7.29–7.15 (m, 5 H, ArH), 6.84–
6.78 (m, 1 H, CH=), 6.08 (d, J = 16 Hz, 1 H, CH=), 2.78–2.75 (m,
2 H, CH2), 2.54–2.46 (m, 4 H, CH2), 1.59–1.56 (m, 2 H, CH2),
1.31–1.27 (m, 4 H, CH2), 0.89–086 (m, 3 H, CH3) ppm. 13C NMR
(100 MHz, CDCl3): δ = 200.37, 145.33, 140.32, 130.35, 128.05,
127.91, 125.76, 39.72, 34.04, 33.67, 31.05, 23.57, 22.03, 13.49 ppm.
MS (ES+): m/z = 253 [M + Na]+. HRMS (ES+): calcd. for
C16H22NaO 253.1568; found 253.1566.
(3E,5E)-1-Phenoxy-6-phenylhexa-3,5-dien-2-one (28): Yellow oil:
80 mg (66% yield). 1H NMR (400 MHz, CDCl3): δ = 7.57–7.27
(m, 8 H, ArH, CH=), 7.01–6.87 (m, 5 H, ArH, CH=), 6.61 (d, J =
(E)-1,4-Diphenylbut-3-en-2-one (21): White solid: 82 mg (80%
1
yield), m.p. 64–65 °C. H NMR (400 MHz, CDCl3): δ = 7.62 (d, J 16 Hz, 1 H, CH=), 4.70 (s, 2 H, CH2) ppm. 13C NMR (100 MHz,
316
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 311–318

Stereoselective Synthesis of (E)-α,β-Unsaturated Ketones from Aldehydes
CDCl3): δ = 195.70, 158.21, 144.06, 142.59, 135.48, 129.26, 129.05, 7.48–7.31 (m, 6 H, ArH, CH=), 6.99–6.86 (m, 2 H, CH=), 6.27 (d,
128.46, 126.99, 126.22, 123.95, 121.25, 114.26, 71.93 ppm. MS
J = 16 Hz, 1 H, CH=), 5.39 (br. s, 1 H, NH), 4.23–4.22 (m, 2 H,
CH2), 1.44 (s, 9 H, CH3) ppm. 13C NMR (100 MHz, CDCl3): δ =
193.77, 153.83, 143.47, 142.21, 135.21, 129.06, 128.46, 126.97,
125.85, 48.63, 27.92 ppm. MS (ES+): m/z = 310 [M + Na]+. HRMS
(ES+): calcd. for C17H21NNaO3 310.1419; found 310.1416.
(ES+): m/z 287 [M
=
+
Na]+. HRMS (ES+): calcd. for
C18H16NaO2 287.1048; found 287.1045.
(E)-1-Phenoxy-6-phenylhex-3-en-2-one (29): Colorless oil: 84 mg
1
(69% yield). H NMR (400 MHz, CDCl3): δ = 7.31–6.96 (m, 9 H,
ArH, CH=), 6.87 (d, J = 8 Hz, 2 H, ArH), 6.41 (d, J = 16 Hz, 1 Preparation of (E)-Hexadec-7-en-6-one (37) as a Representative Pro-
H, CH=), 4.66 (s, 2 H, CH2), 2.78 (t, J = 7 Hz, 2 H, CH2), 2.58– cedure for Telescoped Hydroformylation/Verley–Doebner Knoevena-
2.53 (m, 2 H, CH2) ppm. 13C NMR (100 MHz, CDCl3): δ = 195.16, gel Reaction: 1-Octene (74 μL, 0.46 mmol) was dissolved in toluene
157.53, 148.09, 140.14, 129.21, 128.11;127.92, 125.85, 125.59,
121.23, 114.27, 114.13, 71.60, 33.95, 33.82 ppm. MS (ES+): m/z =
289 [M + Na]+. HRMS (ES+): calcd. for C18H18NaO2 289.1204;
found 289.1201.
(0.6 mL) followed by (Ph3P)3Rh(CO)H (9 mg, 0.01 mmol) and
xantphos (23 mg, 0.04 mmol). The yellow solution obtained was
submitted to pressurized syngas (CO/H2, 1:1) at 120 psi and heated
for 30 min at 110 °C by microwave irradiation at 250 W (value pre-
viously settled on the microwave oven). The vessel was cooled, and
the internal gas was released. Compound 2 (109 mg, 0.69 mmol),
β-alanine (41 mg, 0.46 mmol), and 4 Å MS were added, and the
reaction mixture was stirred at 40 °C for 12 h. The mixture was
diluted with EtOAc and washed with 1 n HCl (3ϫ) and brine, dried
with Na2SO4, filtered, and concentrated under reduced pressure.
The crude was purified by flash chromatography on silica gel (pe-
troleum ether 40–60 °C/EtOAc, 97:3). A colorless oil was obtained
(E)-Methyl 8-(4-Cyanophenyl)-6-oxooct-7-enoate (30): White solid:
91 mg (73% yield), m.p. 97–99 °C. 1H NMR (400 MHz, CDCl3): δ
= 7.64–7.57 (m, 4 H, ArH), 7.47 (d, J = 16 Hz, 1 H, CH=), 6.74
(d, J = 16 Hz, 1 H, CH=), 3.61 (s, 3 H, CH3), 2.67–2.64 (m, 2 H,
CH2), 2.32–2.29 (m, 2 H, CH2), 1.66–1.64 (m, 4 H, CH2) ppm. 13
C
NMR (100 MHz, CDCl3): δ = 198.72, 173.32, 139.38, 138.48,
132.20, 128.39;128.13, 117.88, 113.01, 51.09, 40.44, 33.33, 24.00,
22.96 ppm. MS (ES+): m/z = 294 [M + Na]+. HRMS (ES+): calcd.
for C16H17NNaO3 294.1106; found 294,1109.
1
(56 mg, 52% yield). H NMR (400 MHz, CDCl3): δ = 6.79 (dt, J
= 6, 16 Hz, 1 H, CH=), 6.05 (d, J = 16 Hz, 1 H, CH=), 2.49 (t, J
= 7 Hz, 2 H, CH2), 2.17 (q, J = 7 Hz, 2 H, CH2), 1.60–1.56 (m, 2
H, CH2), 1.45–1.41 (m, 2 H, CH2), 1.29–1.24 (m, 14 H), 0.88–0.85
(m, 6 H, CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 200.57,
146.88, 129.88, 39.64, 32.01, 31.39, 31.08, 28.91, 28.74, 27.69,
23.62, 22.20, 22.04, 13.63, 13.48 ppm. MS (ES+): m/z = 261 [M +
Na]+. HRMS (ES+): calcd. for C16H30NaO 261.2194; found
261.2197.
(E)-Methyl 8-(4-Methoxyphenyl)-6-oxooct-7-enoate (31): White so-
lid: 100 mg (79% yield), m.p. 53–55 °C. 1H NMR (400 MHz,
CDCl3): δ = 7.45–7.40 (m, 3 H, ArH, CH=), 6.82 (d, J = 8 Hz, 2
H, ArH), 6.53 (d, J = 16 Hz, 1 H, CH=), 3.75 (s, 3 H, CH3), 3.58
(s, 3 H, CH3), 2.59–2.56 (m, 2 H, CH2), 2.29–2.26 (m, 2 H, CH2),
1.63–1.61 (m, 4 H, CH2) ppm. 13C NMR (100 MHz, CDCl3): δ =
199.32, 173.36, 161.11, 141.80, 129.49, 126.68, 123.49, 113.94,
54.88, 50.99, 39.76, 33.38, 24.12, 23.31 ppm. MS (ES+): m/z = 299
[M + Na]+. HRMS (ES+): calcd. for C16H20NaO4 299.1259; found
299.1262.
(E)-1-Phenyldodec-3-en-2-one (38): Colorless oil: 63 mg, 55% yield.
1H NMR (400 MHz, CDCl3): δ = 7.32–7.18 (m, 5 H, ArH), 6.89
(dt, J = 6, 16 Hz, 1 H, CH=), 6.11 (d, J = 16 Hz, 1 H, CH=), 3.80
(s, 2 H, CH2), 2.17 (q, J = 8 Hz, 2 H, CH2), 1.35–1.23 (m, 12 H,
CH2), 0.88–0.84 (m, 3 H, CH3) ppm. 13C NMR (100 MHz,
CDCl3): δ = 197.18, 148.32, 135.20, 128.99, 128.22, 126.40, 47.12,
32.06, 31.38, 28.88, 28.72, 27.61, 22.21, 13.64 ppm. MS (ES+): m/z
= 281 [M + Na]+. HRMS (ES+): calcd. for C18H26NaO 281.1881;
found 281.1884.
(E)-Methyl 6-Oxo-10-phenyldec-7-enoate (32): Colorless oil: 76 mg
1
(60% yield). H NMR (400 MHz, CDCl3): δ = 7.28–7.13 (m, 5 H,
ArH), 6.80 (dt, J = 6, 16 Hz, 1 H, CH=), 6.06 (d, J = 16 Hz, 1 H,
CH=), 3.63 (s, 3 H, CH3), 2.75 (t, J = 7 Hz, 2 H, CH2), 2.53–
2.48 (m, 4 H, CH2), 2.31–2.27 (m, 2 H, CH2), 1.62–1.58 (m, 4 H,
CH2) ppm. 13C NMR (100 MHz, CDCl3): δ = 199.54, 173.41,
145.61, 140.25, 130.24, 128.06, 127.89, 125.77, 51.06, 39.16, 33.99,
33.65, 33.39, 24.07, 23.12 ppm. MS (ES+): m/z = 297 [M + Na]+.
HRMS (ES+): calcd. for C17H22NaO3 297.1467; found 297.1465.
Supporting Information (see footnote on the first page of this arti-
1
cle): H and 13C NMR spectra of compounds.
(E)-tert-Butyl 2-Oxohept-3-enylcarbamate (33): Colorless oil: 54 mg
(52% yield). 1H NMR (400 MHz, CDCl3): δ = 6.91 (dt, J = 6,
16 Hz, 1 H, CH=), 6.09 (d, J = 16 Hz, 1 H, CH=), 5.34 (br. s, 1
H, NH), 4.17–4.16 (m, 2 H, CH2), 2.21–2.13 (m, 2 H, CH2), 1.49–
1.42 (m, 11 H, CH3, CH2), 0.93–0.89 (m, 3 H, CH3) ppm. 13C
NMR (100 MHz, CDCl3): δ = 194.02, 155.31, 148.65, 127.10,
79.27, 47.96, 34.19, 27.92, 20.78, 13.21 ppm. MS (ES+): m/z = 250
[M + Na]+. HRMS (ES+): calcd. for C12H21NNaO3 250.1419;
found 250.1415.
Acknowledgments
This work was financially supported by Dipharma Francis Srl (Ba-
ranzate di Bollate, Milano, Italy).
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Hershberger, A. R. Pinhas, Organometallics 1995, 14, 5426–
5429.
(E)-tert-Butyl 2-Oxo-6-phenylhex-3-enylcarbamate (34): Colorless
oil: 93 mg (70% yield). 1H NMR (400 MHz, CDCl3): δ = 7.28–7.13
(m, 5 H, ArH), 6.93 (dt, J = 6, 16 Hz, 1 H, CH=), 6.10 (d, J =
16 Hz, 1 H, CH=), 5.35 (br. s, 1 H, NH), 4.14–4.13 (m, 2 H, CH2),
2.76 (t, J = 7 Hz, 2 H, CH2), 2.56–2.51 (m, 2 H, CH2), 1.43 (s, 9
H, CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 193.87, 155.27,
147.36, 139.97, 128.13, 127.87, 127.38, 125.88, 79.32, 48.02, 33.80,
27.91 ppm. MS (ES+): m/z = 312 [M + Na]+. HRMS (ES+): calcd.
for C17H23NNaO3 312.1576; found 312.1579.
tert-Butyl (3E,5E)-2-Oxo-6-phenylhexa-3,5-dienylcarbamate (35):
Yellow oil: 77 mg (58% yield). 1H NMR (400 MHz, CDCl3): δ =
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Received: August 23, 2010
Published Online: November 15, 2010
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