Categories: C-C Bond Formation > Oxygen-, Nitrogen-containing molecules

Substitution of active methylenes

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Recent Literature

F. Stauffer, R. Neier, Org. Lett., 2000, 2, 3535-3537.

A one-pot procedure for the synthesis of 2-alkyl-2-arylcyanoacetates based on a Pd(OAc)₂/dppf-catalyzed enolate arylation followed by in situ alkylation tolerates a diverse range of aryl and heteroaryl bromides, and provides a rapid entry to a wide range of products in very good to yield.
X. Wang, A. Guram, E. Bunel, G.-Q. Cao, J. R. Allen, M. M. Faul, J. Org. Chem., 2008, 73, 1643-1645.

Simple dialkyl malonate esters exhibit limited scope as carbon nucleophiles in the Mitsunobu reaction. In contrast, bis(2,2,2-trifluoroethyl) malonates readily undergo dehydrative alkylation with primary and some secondary alcohols.
J. M. Takacs, Z. Xu, X.-T. Jiang, A. P. Leonov, G. C. Theriot, Org. Lett., 2002, 4, 3843-3845.

AuCl₃/AgOTf catalyzes a highly efficient intermolecular addition of 1,3-diketones to alkenes. A proposed mechanism for the reaction is based on α-C-H activation.
X. Yao, C.-J. Li, J. Am. Chem. Soc., 2004, 126, 6884-6885.

Perchloric acid-catalyzed additions of various β-dicarbonyl compounds to a series of secondary alcohols and alkenes could be conveniently conducted in commercial solvent and gave good yields. Moreover, silica gel-supported HClO₄ could also catalyze the heterogeneous addition for a series of substrates with similar or even higher yields. The supported catalyst could be readily recovered and reused for four runs.
P. N. Liu, L. Dang, Q. W. Wang, S. L. Zhao, F. Xia, Y. J. Ren, X. Q. Gong, J. Q. Chen, J. Org. Chem., 2010, 75, 5019-5020.

Environmentally benign additions of various 1,3-dicarbonyl compounds to alkenes and alcohols in the presence of solid acid catalysts have been described.
K. Motokura, N. Fujita, K. Mori, T. Mizugaki, K. Ebitani, K. Kaneda, Angew. Chem. Int. Ed., 2006, 45, 2605-2609.

K. Motokura, N. Fujita, K. Mori, T. Mizugaki, K. Ebitani, K. Kaneda, Angew. Chem. Int. Ed., 2006, 45, 2605-2609.

A highly enantioselective catalytic alkylation of cyanoacetates was achieved using a chiral phase-transfer catalyst to give α,α-disubstituted α-cyanoacetates which have a chiral quaternary carbon.
K. Nagata, D. Sano, T. Itoh, Synlett, 2007, 547-550.

A recyclable, convenient, and efficient catalytic system allows the C-acylation of 1,3-dicarbonyl compounds and malononitrile with acid chlorides in moderate to excellent yields under mild conditions.
Q. Shen, W. Huang, J. Wang, X. Zhou, Org. Lett., 2007, 9, 4491-4494.

An organocatalytic asymmetric cascade Michael reaction of α,β-unsaturated aldehydes with bromomalonates, efficiently catalyzed by chiral diphenylprolinol TMS ether in the presence of base 2,6-lutidine, gives cyclopropanes in high enantio- and diastereoselectivities. Using NaOAc as base, a spontaneous ring-opening of cyclopropanes leads to (E) α-substituted malonate α,β-unsaturated aldehydes.
H. Xie, L. Zu, H. Li, J. Wang, W. Wang, J. Am. Chem. Soc., 2007, 129, 10886-10894.

Alkylation of the aza-enolate of valerolactim methyl ether with electrophiles affords α-alkyl lactims. Subsequent mild, acidic hydrolysation gives the corresponding α-alkyl-δ-amino esters hydrochloride salts. Neutralisation of these salts with base results in smooth intramolecular cyclisation to afford α-alkyl lactams in excellent yield.
P. J. M. Taylor, S. D. Bull, P. C. Andrews, Synlett, 2006, 1347-1350.

In the presence of PdCl₂(MeCN)₂, CuCl₂, and PEG-400, various alkenyl β-keto esters and amides underwent a selective cyclization to give six-membered carbocycles in good to excellent yields. The PdCl₂(MeCN)₂/CuCl₂/PEG-400 system could be recycled and reused five times without any loss of catalytic activity.
J.-H. Li, Q.-M. Zhu, Y. Liang, D. Yang, J. Org. Chem., 2005, 70, 5347-5349.

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.

β-Ketoesters can directly be transformed to the corresponding α-hydroxymalonic esters, tartronic esters, with molecular oxygen catalyzed by calcium iodide under visible light irradiation from a fluorescent lamp. This convenient tandem oxidation/rearrangement reduces consumption of energy, time, and solvents.
N. Kanai, H. Nakayama, N. Tada, A. Itoh, Org. Lett., 2010, 12, 1948-1951.

An efficient enantioselective catalysis in the Mannich-type reactions of diketones and ketoester equivalents with aldimines was developed using a chiral combined salt of chiral 1,1′-binaphthyl-2,2′-disulfonic acid with 2,6-diarylpyridine, which acted as convenient chiral tailor-made Brønsted acid-base organocatalysts in situ.
M. Hatano, T. Maki, K. Moriyama, M. Arinobe, K. Ishihara, J. Am. Chem. Soc., 2008, 130, 16858-16860.

Achiral and chiral phosphorodiamidic acids were developed as efficient Brønsted acid catalysts for the direct Mannich reaction of N-acyl imines with 1,3-dicarbonyl compounds.
M. Terada, K. Sorimachi, D. Uraguchi, Synlett, 2006, 133-134.

Catalytic asymmetric direct Mannich-type reactions of α-substituted nitroacetates using a new bench-stable homodinuclear Ni₂-Schiff base complex gave Mannich products in high ee, that serve as precursors for anti-α,β-diamino acids with an α-tetrasubstituted carbon stereocenter. The Ni complex was also applicable to direct Mannich-type reactions of malonates and β-keto ester.
Z. Chen, H. Morimoto, S. Matsunaga, M. Shibasaki, J. Am. Chem. Soc., 2008, 130, 2170-2171.

Efficient carbon-carbon bond formation of N-carbobenzyloxy amines with 1,3-dicarbonyl compounds at the α-position of nitrogen was established by a one-pot oxidative Mannich reaction using N-tert-butylbenzenesulfinimidoyl chloride as an oxidant.
J-I. Matsuo, Y. Tanaki, H. Ishibashi, Org. Lett., 2006, 8, 4371-4374.