Categories: C=C Bond Formation >
Synthesis of unsaturated esters, amides and carboxylic acids
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α,β-unsaturated compounds (C-C Coupling) |
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Activation of the silicon-carbon bond of α-trimethylsilylethylacetate in the
presence of P(i-PrNCH2CH2)3N as catalyst
allows an efficient synthesis of β-hydroxyesters and α,β-unsaturated esters.
Selectivity for either of these two products can be achieved simply by altering
the catalyst loading and reaction temperature.
K. Wadhwa, J. G. Verkade, J. Org. Chem., 2009,
74, 4368-4371.

Copper iodide is an effective cocatalyst for the olefin cross-metathesis
reaction. It has both a catalyst stabilizing effect due to iodide ion, as well
as copper(I)-based phosphine-scavenging properties. A variety of Michael
acceptors and olefinic partners can be cross-coupled under mild conditions in
diethyl ether and in water using the new surfactant TPGS-750-M.
K. Voigtritter, S. Ghorai, B. H. Lipshutz, J. Org. Chem., 2011,
76, 4697-4702.

A bifunctional polystyrene bearing both DMAP and piperidine groups is an
effective organocatalyst for decarboxylative Doebner-Knoevenagel reactions of
arylaldehydes and monoethyl malonate to give E-cinnamates in high yields.
A synergistic effect obtained by co-locating the two different catalytic amine
groups on the same polymer backbone has been detected.
J. Lu, P. H. Toy, Synlett, 2011,
1723-1726.

A very simple one-pot process involving a cross-metathesis between acryloyl
chloride and a terminal olefin followed by the addition of a nucleophile allows
the synthesis of various functionalized α,β-unsaturated carbonyl compounds in
good yield.
L. Ferrié, S. Bouzbouz, J. Cossy, Org. Lett., 2009,
11, 5446-5448.

Phosphine and amine functionalized polystyrene was used in one-pot Wittig
reactions with an aldehyde and either an α-halo-ester, -ketone, or -amide. Due
to the heterogeneous nature of the polymer, the desired alkene product of these
reactions could be isolated in excellent yield in essentially pure form after
only filtration and solvent removal.
P. S.-W. Leung, Y. Teng, P. H. Toy, Org. Lett., 2010,
12, 4996-4999.

A simple protocol for a highly E-selective
Wadsworth-Emmons reaction via deprotonation of alkyl diethylphosphonoacetates
with MeMgBr allows the conversion of a range of straight-chain and branched aliphatic, substituted aromatic,
and base-sensitive aldehydes.
T. D. W. Claridge, S. G. Davies, J. A. Lee, R. L. Nicholson, P. M. Roberts, A.
J. Russel, A. D. Smith, S. M. Toms, Org. Lett., 2008,
10, 5437-5440.

Water is an effective medium for the Wittig reaction over a wide range of
stabilized ylides and aldehydes including especially substrates with large
hydrophobic entities. Despite sometimes poor solubility of the reactants, good
yields and high E-selectivities are achieved, and the rate of the
reactions in water is unexpectedly accelerated.
A. El-Batta, C. Jiang, W. Zhao, R. Anness, A. L. Cooksy, M. Bergdahl, J. Org. Chem., 2007,
72, 5244-5259.

A. El-Batta, C. Jiang, W. Zhao, R. Anness, A. L. Cooksy, M. Bergdahl, J. Org. Chem., 2007,
72, 5244-5259.

A mild and efficient one-pot Wittig reaction performed in both water and
sodium dodecyl sulfate (SDS)-water solution in open atmosphere allowed the
synthesis of various α,β-unsaturated esters in good yields.
F. Orsini, G. Sello, T. Fumagalli, Synlett, 2006,
1717-1718.

Optimized conditions for the Wittig reaction of aldehydes with ethyl
tribromoacetate and triphenylphosphine allowed the synthesis of α-bromoacrylates
with high selectivity. A simple and efficient one-pot procedure was developed
for the preparation of various conjugated acetylenic carboxylates in good yields.
J.-G. Kim, D. H. Kang, D. O. Jang, Synlett, 2008,
443-447.

Ethyl (benzothiazol-2-ylsulfonyl)acetate engaged in the modified Julia
olefination with aldehydes under mild reaction conditions to yield α,β-unsaturated esters.
Aryl aldehydes and aliphatic aldehydes possessing significant chain
branching elements gave trans alkene products with
high stereoselectivity, while straight chain aliphatic
aldehydes gave cis products preferentially.
P. R. Blakemore, D. K. H. Ho, W. M. Nap, Org. Biomol. Chem., 2005, 3, 1365-1368.

gem-Dibromomethylarenes: A Convenient Substitute for Noncommercial Aldehydes
in the Knoevenagel−Doebner Reaction for the Synthesis of α,β-Unsaturated
Carboxylic Acids
J. K. Augustine, Y. A. Naik, A. B. Mandal, N. Chowdappa, V. B. Praveen, J. Org. Chem., 2007,
72, 9854-9856.

A complete E-selective synthesis of α,β-unsaturated amides through a
sequential reaction of a range of dichloroamides with a variety of aldehydes is
promoted by Rieke manganese (Mn*). The unsaturated amides obtained are readily
and efficiently transformed into α,β-unsaturated ketones, aldehydes, or
carboxylic acids.
J. M. Concellón, H. Rodríquez-Solla, P. Díaz, J. Org. Chem., 2007,
72, 7974-7979.

A generally applicable, sequential reaction of dichloroesters with various
aldehydes is promoted by active manganese to give α,β-unsaturated esters with
complete control of stereoselectivity. The C-C double bond can be di- or
trisubstituted. A mechanism based on a successive aldol-type reaction/-elimination
is proposed.
J. M. Concellón, H. Rodríquez-Solla, P. Díaz, R. Llaona, J. Org. Chem., 2007,
72, 4396-4400.

The stereoselective
reaction of different aldehydes and ethyl dibromoacetate promoted by SmI2 or
CrCl2 gives
(E)-α,β-unsaturated esters by an an aldol-type
reaction and a subsequent β-elimination reaction.
J. M. Concellon, C. Concellon, C. Mejica, J. Org. Chem., 2005, 70, 6111-6113.

A mild protocol for the Horner-Wadsworth-Emmons reaction of diprotic
phosphonates makes use of a zinc triflate promoter in the presence of mild
tertiary amine bases to produce α,β-unsaturated carboxylic acids and amides.
D. J. Schauer, P. Helquist, Synthesis, 2006, 3654-3660.

D. J. Schauer, P. Helquist, Synthesis, 2006, 3654-3660.

The stereoselective reaction of different aldehydes and dibromoacetic acid
promoted by SmI2 gives (E)-α,β-unsaturated
carboxylic acids. The mechanism is discussed.
J. M. Concellon, C. Concellon, J. Org. Chem., 2006, 71, 1728-1731.

A domino oxidation of primary alcohols gives α,β-unsaturated compounds using the
combination of PCC-NaOAc and stabilized Wittig reagents.
J. Shet, V. Desai, S. Tilve, Synthesis,
2004,
1859-1863.

The reaction of alkyl-substituted sec-ethoxyalkynyl acetates with water
catalyzed by Hg(OTf)2 afforded α,β-unsaturated esters in excellent
yield with high catalytic turnover under very mild reaction conditions with
virtually complete E-selectivity.
M. Nishizawa, H. Hirakawa, Y. Nakagawa, H. Yamamoto, K. Namba, H. Imagawa, Org. Lett., 2007,
9, 5577-5580.

Efficient and stereoselective rearrangement catalyzed by only one mole-percent
gold(I) chloride/silver(I) trifluoromethanesulfonate of Baylis-Hillman acetates
afforded 2-(acetoxymethyl)alk-2-enoates under mild reaction conditions in very
good yields with 100% E-selectivity.Cyclohex-2-enone derived
Baylis-Hillman acetates gave 2-alkylidenecyclohex-3-enones by elimination of
acetic acid.
Y. Liu, D. Mao, J. Qian, S. Lou, Z. Xu, Y. Zhang, Synthesis, 2009,
1170-1174.

Zinc-promoted reduction of 2-(bromomethyl)alkenoates derived from Baylis-Hillman adducts gave (E)-2-methylacrylates in good yield and high
stereoselectivity. Synthesis of the male ant pheromone (E)-2,4-dimethyl-2-hexenoic
acid was performed using this simple methodology.
L. Fernandes, A. J. Bortoluzzi, M. M. Sa, Tetrahedron, 2004,
60, 9983-9989.

Stereoselective β-elimination of diastereomeric mixtures of
2-bromo-3-hydroxyesters is achieved by using unactivated manganese and
trimethylsilyl chloride, to yield (E)-α,β-unsaturated esters with total
diastereoselectivity.
J. M. Concellón, H. Rodríguez-Solla, V. del Amo, Synlett,
2006, 315-317.

Dimethyl sulfoxide efficiently causes the reductive elimination of 3-aryl
2,3-dibromopropanoates to cinnamates with good yield. For most substrates
debromination is the major pathway, whereas dehydrobromination is a competing
pathway with thiophene derivatives. 1H NMR, 81Br NMR, and
MS indicated the formation of brominated-DMSO, MeBr, and HBr as byproducts.
W. Li, J. Li, M. Lin, S. Wacharasindhu, K. Tabei, T. S. Mansour, J. Org. Chem., 2007,
72, 6016-6021.

(E)-α-Ethynyl-α,β-unsaturated esters were prepared in good yields from
allenyl acetates by treatment with 10 mol % DABCO in DMF at room temperature.
Y. Choe, P. H. Lee, Org. Lett., 2009,
11, 1445-1448.

α,β-Dihalopropanoate derivatives undergo efficient, selective
dehydrohalogenation to form α-haloacrylate analogues in the presence of DMSO. A
variety of α-halo Michael acceptors were prepared in dimethyl sulfoxide under
mild, base-free conditions, including the preparation of α-bromoacrolein and
α-chloro- and bromoacrylonitriles.
W. Li, J. Li, Z.-K. Wan, J. Wu, W. Massefski, Org. Lett., 2007,
9, 4607-4610.

Deprotonation of a 64:36 mixture of ethyl bromo(diphenylphosphono)acetate and
ethyl dibromo(diphenylphosphono)acetate using NaH as base at 0 °C and subsequent
reaction with various aldehydes provided unsaturated α-bromoesters in good
yields and high E-selectivities.
T. Olpp, R. Brückner, Synthesis,
2004, 2135-2152.

A zinc carbenoid-mediated chain extension of β-dicarbonyl compounds
provides access to α,β-unsaturated-γ-keto esters and amides with complete E selectivity
via an intermediate
zinc enolate, which is treated sequentially with iodine and DBU.
M. D. Ronsheim, C. K Zercher, J. Org. Chem., 2003, 68,
4535-4538.

Among the reported examples of new reactivity of the hypervalent iodine
reagent DMP (Dess-Martin periodinane) are the one-step oxidation of
secondary amides to imides and N-acyl vinylogous carbamates or ureas
and the direct oxidation of benzylic and related primary amines to the
corresponding nitriles.
K. C. Nicolaou, C. J. N. Mathison, Angew. Chem. Int. Ed., 2005,
44, 5992-5997.

In the presence of ruthenium-based olefin metathesis catalysts and
triphenylphosphine, α,β-unsaturated aldehydes can be olefinated with
diazoacetates. A tandem transformation of
terminal olefins to 1,3-dienoic olefins in a single operation based on olefin
cross-metathesis and Wittig olefination has been developed.
R. P. Murelli, M. L. Snapper, Org. Lett., 2007,
9, 1749-1752.

An expeditious synthesis of α-substituted tert-butyl acrylates from
commercially available aldehydes and Meldrum's acid includes a telescoped
condensation-reduction sequence to afford 5-monosubstituted Meldrum's acid
derivatives followed by a Mannich-type reaction triggered by a rapid
cycloreversion of the dioxinone ring on heating with tert-butyl alcohol.
C. G. Frost, S. D. Penrose, R. Gleave, Synthesis, 2009,
627-635.
