Synthesis of unsaturated esters, amides and carboxylic acids

Related: α,β-unsaturated compounds
(C-C Coupling)

Recent Literature

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.