111408-95-8Relevant academic research and scientific papers
One-Pot Vinylation of Azlactones: Fast Access to Enantioenriched α-Vinyl Quaternary Amino Acids
Serra, Massimo,Bernardi, Eric,Marrubini, Giorgio,Colombo, Lino
, p. 2964 - 2970 (2017)
We report a fast one-pot protocol for the direct vinylation of azlactones [oxazol-5-(4H)-ones] by using as a key step an aldol addition with 2-(phenylselenenyl)acetaldehyde followed by dehydroxyselenation. The acid hydrolysis of the oxazolone ring gave the desired fully deprotected α-vinyl quaternary α-amino acids in almost quantitative yields. An enantioselective variant of the method was also developed by using catalytic chiral bases. The use of Sharpless ligand (DHQD)2PHAL produced the final quaternary amino acids in good overall yields (62–78 %) and with ee values up to 86 %. Scaling up the optimized protocol to gram quantities did not affect the yields and ee values. We also demonstrated that the vinyl moiety installed onto the oxazolone ring can be exploited as a handle for the attachment of aryl groups through a Heck coupling reaction.
Engineering Acyclic Stereocontrol in the Alkylation of Vinylglycine-Derived Dianions: Asymmetric Synthesis of Higher α-Vinyl Amino Acids
Berkowitz, David B.,McFadden, Jill M.,Sloss, Marianne K.
, p. 2907 - 2918 (2007/10/03)
A generalizable synthesis of higher L-α-vinyl amino acids is presented. The strategy pursued here involves the introduction of the amino acid side chain via the alkylation of a chiral, vinylglycine-derived dianionic dienolate, bearing the (-)-8-(β-naphthyl)menthyl (d'Angelo) auxiliary. A model is presented that postulates a favored "exo-entended" conformation for this dienolate, leading to Cα-alkylation at the si face. The model invokes internal amidate chelation to control ester enolate geometry and soft-soft interactions between the polarizable β-naphthyl ring of the auxiliary and the extended π-system of the dienolate to shield the re face. Heats of formation for four conformers of this dianion were calculated for their semiempirical optimized geometries (PM3). The results support the notion that in these vinylglycine-derived dianionic dienolates, "exo" conformations are considerable lower in energy than their "endo" counterparts, with the "exo-entended" conformation being most favorable. In fact, the d'Angelo auxiliary gives a greater degree of acyclic stereocontrol in this system when compared with the (-)-8-phenylmenthyl (Corey) and trans-2-(β-naphthyl)-cyclohexyl auxiliaries, using isobutyl iodide and benzyl bromide as model electrophiles. These dianions are generated from the corresponding dehydrobutyrine esters via sequential deprotonation with LDA and n-BuLi (2 equiv). When alkylations are carried out at -78°C in THF-HMPA, they proceed in 65-81% yields, with both regiocontrol (deconjugative α-alkylation is preferred over γ-alkylation) and a great degree of acyclic stereocontrol [91:9 to ≥98:2 diastereomeric ratios (10 examples)]. The auxiliary may be recovered in high yield (generally 90%) using a modification of Gassman's "anhydrous hydroxide" conditions, in which considerably higher temperatures are employed. Among the side chains introduced directly are those of butyrine, leucine, ornithine, phenylalanine, aspartate, valine, and norvaline. The lysine side chain is elaborated via a 4-step sequence from the alkylation product obtained with 1-chloro-4-iodobutane as electrophile. Importantly, to our knowledge, this work represents the first asymmetric synthesis of L-α-vinyl analogues of m-tyrosine, ornithine, and lysine, known time-dependent inhibitors for amino acid decarboxylases.
Stereoselective Conversions of t-Butyl rac-, (R)-, or (S)-5-Alkylidene-2-t-butyl-3-methyl-4-oxo-1-imidazolidinecarboxylates (Chiral 2,3-Dehydroamino Acid Derivatives) and Preparation of Some Nonproteinogenic Amino Acids
Seebach, Dieter,Buerger, H. Michael,Schickli, Christof P.
, p. 669 - 684 (2007/10/02)
The reactivity of the alkylidene derivatives 1-11 specified in the title and prepared in two operational steps from commercially available Boc-BMI and aldehydes is investigated. - According to high-field 1H-NMR analysis of the crude products, additions of H-H and D-D (catalytic hydrogenation, products 12-20), of R-H (BF3-activated R2CuLi/LiI and protonation, products 21-29), and of Cl2C (CHCl3/NaOH, products 33,34) occur with complete selectivity from the face opposite to the t-butyl group.The doubly unsaturated carbonyl derivative 11 reacts with dibutyl cuprate in the δ position, again with formation of a single diastereomer 32, while trifluoroethylidene-Boc-BMI 3a is reduced to the difluoro analogue 30 by this cuprate. - Li dienolates are generated by deprotonation with LDA of the ethylidene (2a) and butylidene compound 4a; subsequent alkylations (with primary and secondary halides, products 35-41) and hydroxyalkylations (with aldehydes, products 42-44) lead to single products of electrophilic attack in the α carbonyl position (C-5 of the imidazolidinone ring) under kinetic control.On the other hand, reaction of the 2a-derived dienolate with benzaldehyde under equilibrating conditions furnishes the four possible (E/R, E/S, Z/R, and Z/S) γ adducts 45-48. - A combination of methods - 1H- and 13C-NMR spectroscopy, NOE measurements, spectroscopic analogies, chemical correlation (with authentic samples or by spectroscopic or optical comparison), and X-ray analysis (Table 1, Figure 1, Schemes 1 and 2) - is used to assign the product configurations and thus the stereochemical course of the reactions.Some unusual amino acids (50-52, 54, 55) are prepared by hydrolysis of the corresponding imidazolidinones. Key words: Amino acids, dehydro-, chiral/ Amino acids, nonproteinogenic/ Michael additions of cuprates/ a5-Reactivi ty of doubly unsaturated carbonyl compounds/ Kinetic d2-versus thermodynamic d4-reactivity of Li dienolates
