Asymmetric Nucleophilic Acylation via Metalated Chiral Amino Cyanides: Enantioselective Synthesis of 3‐Substituted 4‐Oxoesters by Asymmetric Michael Addition

Enders, Dieter; Gerdes, Peter; Kipphardt, Helmut

doi:10.1002/anie.199001791

Cited by 38 publications

(10 citation statements)

References 46 publications

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“…Data for methyl ( S )-2-methyl-4-oxopentanoate: 1 H NMR (CDCl 3 ) δ 1.43 (d, J = 7.26 Hz, 3H, CH CH 3 ), 2.22 (s, 3H, C(O) CH 3 ), 2.30 (dd, J = 16.83, 5.61 Hz, 1H, C H H), 2.77 (dd, J = 16.83, 8.58 Hz, 1H, CH H ), 2.95−3.06 (m, 1H, C H CH 3 ), 3.66 (s, 3H, COO CH 3 ). The absolute configuration was determined to be S by comparison of the optical rotation value with the literature data …”

Section: Methodsmentioning

confidence: 99%

Mechanistic Aspects of the Alternating Copolymerization of Propene with Carbon Monoxide Catalyzed by Pd(II) Complexes of Unsymmetrical Phosphine−Phosphite Ligands

et al. 1997

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The reaction steps responsible for the highly enantioselective asymmetric copolymerization of propene with carbon monoxide catalyzed by a cationic Pd(II) complex bearing an unsymmetrical chiral bidentate phosphine−phosphite, (R,S)-BINAPHOS [(R,S)-2-(diphenylphosphino)-1,1‘-binaphthalen-2‘-yl 1,1‘-binaphthalene-2,2‘-diyl phosphite = L1], have been studied. Stepwise identification and characterization were carried out for catalyst precursors (SP-4-2)- and (SP-4-3)-Pd(CH3)Cl(L1) (1a and 1b) and (SP-4-3)-[Pd(CH3)(CH3CN)(L1)]·X1 (X1 = B{3,5-(CF3)2C6H3}4) (2), and complexes related to the reaction steps, (SP-4-3)-[Pd(COCH3)(CH3CN)(L1)]·X1 (3), (SP-4-3)- and (SP-4-4)-[Pd{CH2CH(CH3)COCH3}(L1)]·X1 (4a and 4b), (SP-4-3)-[Pd{COCH2CH(CH3)COCH3}(CH3CN)(L1)]·X1 (5), and (SP-4-3)-[Pd{CH2CH(CH3)COCH2CH(CH3)COCH3}(L1)]·X1 (6). An X-ray structure of alkyl complex 4a has been obtained. Studies on [Pt(CH3)2(L1)] (8) reveal that the methyl group is more stabilized at a position trans to the phosphine than at the cis position. This is consistent with the structures of 1−6 in which all carbon substituents are trans to the phosphine moiety in their major forms. On the basis of analogous studies using platinum complexes, an isomerization from (SP-4-3)-[Pd(CH3)(CO)(L1)]·X1 (13a) to the (SP-4-4) isomer (13b) is suggested to occur for the CO-insertion process 2 → 3, which results in the activation of the methyl group for the migration to the coordinated CO. Rapid equilibrium was observed between the two isomers 4a and 4b during the CO insertion process to give 5. Theoretical studies have been carried out on the transformation of 3 to 4a and 4b. The B3LYP and MPn calculations indicated that the alkene insertion into the Pd−acyl bond trans to a phosphine is more favorable than that into the Pd−acyl bond trans to a phosphite. The MM3 calculations demonstrated that one specific transition structure is more favorable than the other possible transition structures for the transformation of (SP-4-4)-[Pd(COCH3)(propene)(L1)]·X1 (14b) to 4b. The difference originates from the steric effects of the BINAPHOS ligand, and the results account for high enantio- and regioselectivities experimentally observed. The two key steps, propene insertion into 3 and CO insertion into 4, were monitored by 1H NMR spectroscopy. The activation energies for these two steps were estimated to be 19.0−19.6 kcal/mol at −20 to 0 °C, their difference being insignificant. The living nature of the copolymerization was proved. Some related chiral ligands were examined for the copolymerization. Copolymerization of other olefins with CO was also investigated.

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Section: Methodsmentioning

confidence: 99%

Mechanistic Aspects of the Alternating Copolymerization of Propene with Carbon Monoxide Catalyzed by Pd(II) Complexes of Unsymmetrical Phosphine−Phosphite Ligands

et al. 1997

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“…In the 1990's, the Enders group employed Strecker products derived from the N-methyl analogue of 1 as chiral acyl anion equivalents for diastereoselective 1,4-additions to α,β-unsaturated carbonyl compounds. [45][46][47] The reaction of the hydrochloride salt of 1 with benzaldehyde (2a) and 2-napththaldehyde (2b) in the presence of KCN furnished the aminonitriles 3a and 3b as single diastereomers after crystallization from the reaction medium in 82% and 67% yield, respectively. Their deprotonation with potassium bis(trimethylsilyl)amide (KHMDS) in THF at -78 °C furnished the corresponding potassium keteneiminates which were α-alkylated with various alkyl and benzyl halides to the α-quaternary aminonitriles 4 (Scheme 1).…”

Section: Page 2 Of 24 Acs Paragon Plus Environmentmentioning

confidence: 99%

“…Optical rotations were measured at 546 nm and 576 nm and were extrapolated to 589 nm using the Drude equation. Melting points were measured on an electrothermal apparatus with a digital thermometer.General procedure for the synthesis of aminonitriles 3.The title compounds were prepared according to a modification of a protocol by Enders et al45 (4S,5S)-(+)-5-Amino-2,2-dimethyl-4-phenyl-1,3-dioxane (1) was dissolved in methanol/water 1:1 and was acidified with hydrochloric acid (1 M) to pH 5. Under cooling (ice bath), the respective aldehyde and KCN were added and the mixture was stirred until TLC indicated complete conversion.…”

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confidence: 99%

Enantioselective Synthesis of α-Quaternary Amino Acids by Alkylation of Deprotonated α-Aminonitriles

2015

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A series of α-quaternary arylglycines were prepared in high optical purity (up to 98% ee) by α-alkylation of deprotonated α-aminonitriles derived by the Strecker reaction from (4S,5S)-5-amino-2,2-dimethyl-4-phenyl-1,3-dioxane. The procedure includes only chromatographic purification of the final products and is devoid of chromatography or crystallization operations on intermediates to raise the optical purity.

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“…A slightly more complex but only monofunctional N-auxiliary was developed by Enders, who employed lithiated a-aminonitriles derived from (S,S)-2,2-dimethyl-5-Nmethylamino-4-phenyl-1,3-dioxane as chiral acyl anion equivalents (Scheme 38). [209][210][211][212] The auxiliary is the Nmethyl derivative of the amine used by Weinges for the preparation of chiral a-amino acids in an asymmetric Strecker reaction. 8,213 The latter compound is formed as a side product in an industrial synthesis of the antibiotic chloramphenicol.…”

Section: Scheme 37 Husson's Asymmetric Synthesis Of Ferrugininementioning

confidence: 99%

The Chemistry of Deprotonated α-Aminonitriles

Opatz¹

2009

Synthesis

105

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This review highlights various aspects of the chemistry of the anions of a-aminonitriles. Their structural features and their characteristic reactivity are discussed, along with various methods for their preparation. Special emphasis is given to synthetic applications of deprotonated a-aminonitriles which have been used as valuable and readily accessible synthetic equivalents of acyl anions and a-aminocarbanions.

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Asymmetric Nucleophilic Acylation via Metalated Chiral Amino Cyanides: Enantioselective Synthesis of 3‐Substituted 4‐Oxoesters by Asymmetric Michael Addition

Cited by 38 publications

References 46 publications

Mechanistic Aspects of the Alternating Copolymerization of Propene with Carbon Monoxide Catalyzed by Pd(II) Complexes of Unsymmetrical Phosphine−Phosphite Ligands

Mechanistic Aspects of the Alternating Copolymerization of Propene with Carbon Monoxide Catalyzed by Pd(II) Complexes of Unsymmetrical Phosphine−Phosphite Ligands

Enantioselective Synthesis of α-Quaternary Amino Acids by Alkylation of Deprotonated α-Aminonitriles

The Chemistry of Deprotonated α-Aminonitriles

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