Categories: C-C Bond Formation > Nitrogen-containing molecules >
Synthesis of β-Amino Acids and Derivatives
Mannich-rype reactions of secondary amines, aldehydes and ketene silyl acetals were efficiently promoted by catalytic amounts of diarylborinic acid esters, affording β-amino esters selectively with no formation of the corresponding β-hydroxy esters.
Y. Tanaka, T. Hasui, M. Suginome, Synlett, 2008, 1239-1241.
Aminoboranes are highly efficient and mild iminium ion generators in the Mannich-type aminative coupling of aldehydes with silyl ketene acetals. The use of diisopropylaminoboranes enables a three-component Mannich reaction of free secondary amines with aldehydes and silyl ketene acetals.
M. Suginome, L. Uehlin, M. Murakami, J. Am. Chem. Soc., 2004, 126, 13196-13197.
An indium triiodide catalyzed deoxygenative functionalization of N-sulfonyl amides with silyl cyanide or silyl enolates in the presence of hydrosilanes gives α-cyanoamines and β-aminocarboxyl compounds, respectively.
Y. Inamoto, Y. Kaga, Y. Nishimoto, M. Yasuda, A. Baba, Org. Lett., 2013, 15, 3448-3451.
A preparation of highly substituted β-amino acids involves a Vilsmeier-Haack reaction with nonaromatic carbon nucleophiles. The reaction enabled the synthesis of several β2,2,3-amino esters, such as derivatives of homoproline, homoalanine, and homopipecolinic esters.
A. Roamens, G. Bélanger, Org. Lett., 2015, 17, 322-325.
A highly efficient Mukaiyama aldol reaction is catalyzed by sodium phenoxide-phosphine oxides as simple homogeneous Lewis base catalysts, which minimized competing retro-aldol reaction. Various aromatic ketones and aldimines, aldol and Mannich-type products with an α-quaternary carbon center were obtained in good to excellent yields.
M. Hatano, E. Takagi, K. Ishihara, Org. Lett., 2007, 9, 4527-4530.
The Hf(OTf)4-catalyzed Mannich-type reaction of an enol silyl ether or a ketene silyl acetal with an N,O-acetal allows the preparation of amino acid derivatives. In particular, use of the N,O-acetal having a bis(trimethylsilyl)amino group directly produced N-unprotected aspartic acid derivatives after a standard aqueous workup.
N. Sakai, A. Sato, T. Konakahara, Synlett, 2009, 1449-1452.
Catalytic Silicon-Mediated Carbon-Carbon Bond-Forming Reactions of Unactivated Amides
S. Kobayashi, H. Kiyohara, M. Yamaguchi, J. Am. Chem. Soc., 2011, 133, 708-711.
Kowalski Ester Homologation. Application to the Synthesis of β-Amino Esters
D. Gray, C. Concellón, T. Gallagher, J. Org. Chem., 2004, 69, 4849-4851.
Addition of in situ generated samarium acetamide and chloroacetamide enolates to aldimines afforded 3-aminoamides and 3-amino-2-chloroamides in high yields. A mechanism is proposed to explain the synthesis and reactivity of samarium enolates of primary amides.
J. M. Concellón, H. Rodríguez-Solla, C. Concellón, C. Simal, N. Alvaredo, Synlett, 2010, 2119-2121.
A copper-catalyzed oxy-aminomethylation reaction of diazo compounds with readily available N,O-acetals provides α-hydroxy-β2-amino acid derivatives with quaternary carbon centers in good yields.
J. Yu, L. Chen, J. Sun, Org. Lett., 2019, 21, 1664-1667.
An enantiopure hydrogen bond donor catalyst enables an enantioselective addition of dialkyl malonates to Boc-derivatized α-amino sulfones in the presence of K2CO3. The diastereomeric salt is similarly applied to additions of nitroalkanes. Precautions to exclude air or moisture are unnecessary.
H. Joshi, S. K. Ghosh, J. A. Gladysz, Synthesis, 2017, 49, 3905-3915.
N-Benzyldiphenylphosphinamides are deprotonated at the NCα position diastereospecifically upon treatment with t-BuLi in diethyl ether at low temperature. Reaction of the anions with various electrophiles and subsequent cleavage of the P-N linkage affords 1,2-amino alcohols and α-, β-, and γ-amino acids.
P. O. Burgos, I. Fernández, M. J. Iglesias, S. García-Granda, F. L. Ortiz, Org. Lett., 2008, 10, 537-540.
A highly efficient general strategy for the synthesis of 2-amino acids by homologation of α-amino acids, involving the Reformatsky reaction with a Mannich-type imminium electrophile is reported.
R. Moumne, S. Lavielle, P. Karoyan, J. Org. Chem., 2006, 71, 3332-3334.
Sonication of diazo ketones derived from Fmoc-protected amino acids in dioxane in the presence of silver benzoate and water results in clean formation of the corresponding β-amino acid derivatives. The degree of racemization was examined using capillary zone electrophoresis. No substantial epimerization occured except for phenylglycine.
A. Müller, C. Vogt, N. Sewald, Synthesis, 1998, 837-841.
The Arndt-Eistert Reaction in Peptide Chemistry: A Facile Access to Homopeptides
J. Podlech, D. Seebach, Angew. Chem. Int. Ed., 1995, 34, 471-472.
A one-pot, three-component reaction between an aromatic aldehyde, an enolizable ketone or a β-keto ester, and a nitrile in the presence of acetyl chloride is accomplished efficiently using cyanuric chloride in an aqueous medium to give the corresponding β-acetamido ketone or ester in high yield.
B. Das, M. Srilatha, B. Veeranjaneyulu, B. R. Rao, Synthesis, 2010, 803-806.
In a highly enantioselective direct Mannich-type reaction of aldimines with dialkyl malonates, an inexpensive Mg(II)-BINOLate salt can activate both aldimines and malonates as a cooperative acid-base catalyst. Various β-aminoesters and α-halo-β-aminoesters could be synthesized in high yields and with high enantioselectivities even in gram-scale.
M. Hatano, T. Horibe, K. Ishihara, Org. Lett., 2010, 12, 3502-3505.
A highly enantioselective Mannich reaction with in situ generation of carbamate-protected imines from stable α-amido sulfones catalyzed by an organic catalyst provides a concise and highly enantioselective route converting aromatic and aliphatic aldehydes into optically active aryl and alkyl β-amino acids.
J. Song, H.-W. Shih, L. Deng, Org. Lett., 2007, 9, 603-606.
Li(I) BINOLate salts as Lewis acid-Brřnsted base catalysts offer high catalytic activity toward 1,3-dicarbonyl compounds such as diketone, ketoester, ketothioester, ketoamide, and ketolactone. Mannich-type reaction of aldimines with 1,3-dicarbonyl compounds proceeded at -78 °C within 1-2 h in the presence of 1−10 mol % catalyst highly enantio- and diastereoselectively.
M. Hatano, T. Horibe, K. Ishihara, J. Am. Chem. Soc., 2010, 132, 56-57.
A base-catalyzed Michael-type addition of sodium diethyl malonate to N-Boc-α-amidoalkyl-p-tolyl sulfones in tetrahydrofuran followed by hydrolysis of the adducts in refluxing 6 M aqueous hydrochloric acid affords β3-amino acid hydrochlorides in high yield and excellent purity.
M. Nejman, A. Śliwińska, A. Zwierzak, Tetrahedron, 2005, 61, 8536-8541.
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.
The intriguing Rh2(OAc)4 and chiral Brřnsted acid cocatalyzed three-component Mannich-type reaction of a diazo compound, a carbamate, and an imine provides rapid and efficient access to both syn- and anti-α-substituted α,β-diamino acid derivatives with a high level control of chemo-, diastereo-, and enantioselectivity.
J. Jiang, H.-D. Xu, J.-B. Xi, B.-Y. Ren, F.-P. Lv, X. Guo, L.-Q. Jiang, Z.-Y. Zhang, W.-H. Hu, J. Am. Chem. Soc., 2011, 133, 8428-8431.
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.
An axially chiral dicarboxylic acid has been applied to a highly enantioselective Mannich reaction of arylaldehyde N-Boc imines and diazo compounds as a new class of chiral hydrogen-bonding catalyst.
T. Hashimoto, K. Maruoka, J. Am. Chem. Soc., 2007, 129, 10054-10055.
A catalytic, asymmetric conjugate addition of carbamates to enoyl systems provides a highly enantioselective two-step access to N-protected β-amino acids.
C. Palomo, M. Oiarbide, R. Halder, M. Kelso, E. Gómez-Bengoa, J. García, J. Am. Chem. Soc., 2004, 126, 9188-9189.