An expedient route to the tetrazole analogues of alpha-amino acids

[reaction: see text] Convenient conditions are described for the transformation of alpha-aminonitriles to the tetrazole analogues of alpha-amino acids. Refluxing the starting material in water/2-propanol at 80 degrees C with sodium azide and catalytic zinc bromide affords the tetrazole product in yields generally exceeding 90%.     

A general,highly enantioselective method for the synthesis of D and L alpha-amino acids and allylic amines

Catalytic and enantioselective synthesis of amino acids is a subject of intense interest in the field of asymmetric catalysis. Traditionally, researchers have concentrated their efforts largely on the design and discovery of enantiopure catalysts for the Strecker reaction, alkylation of tert-butyl gylcinate-benzophenone, electrophilic amination of carbonyl compounds, and hydrogenation of N-acyl-aminoacrylic acid; however, the scope of these reactions is limited. In this paper, we report on a different approach to amino acids based on an expeditious route to enantiopure allylic amines. A highly enantioselective and catalytic vinylation of aldehydes leads to allylic alcohols that are then transformed to the allylic amines via Overman's [3,3]-sigmatropic rearrangement of imidates. Oxidative cleavage of the allylic amines furnishes the amino acids in good yields and excellent ee's. The scope and utility of this method are demonstrated by the synthesis of challenging allylic amines and their subsequent transformation to valuable nonproteinogenic amino acids, including both D and L configured (1-adamantyl)glycine.     

A new method for the synthesis of chiral beta-branched alpha-amino acids

A new method for the synthesis of chiral beta-branched alpha-amino acids based on a copper-mediated directed allylic substitution reaction with Grignard reagents is reported. This is the first case in which a delta-stereogenic center is controlling the diastereoselectivity of an o-DPPB-directed allylic substitution. Depending on the alkene geometry of the starting material either diastereomer, anti or syn, is accessible with good levels of acyclic stereocontrol.     

Asymmetric allylboration of alpha,beta-enals as a surrogate for the enantioselective synthesis of allylic amines and alpha-amino acids

[reaction: see text] Optically pure allylic amines have been synthesized from alpha,beta-unsaturated aldehydes via allylboration with (-)-B-allyldiisopinocampheylborane, followed by Overman rearrangement. By incorporating crotyl and alkoxyallylboration, functionalization at delta-position was readily accomplished. By applying this methodology, the synthesis of several chiral alpha-amino acids has been achieved.     

An expedient synthesis of salviadione

An expedient synthesis of the alkaloid salviadione, the only to date isolated naturally occurring 1H-benzo[def]carbazole is described. The key step in the synthesis is a palladium-catalyzed, carbon monoxide-mediated reductive N-heterocyclization of a nitroarene with an adjacent alkene.     

An expedient synthesis of homophthalimides

The six-membered heterocyclic subunit of homophthalimides can be obtained by a direct, hitherto unprecedented, radical cyclisation onto an aromatic ring starting from a xanthate precursor.     

Expedient synthesis of cyclopropane alpha-amino acids by the catalytic asymmetric cyclopropanation of alkenes using iodonium ylides derived from methyl nitroacetate

A highly enantioselective (up to 97.5% ee) and diastereoselective (95:5 dr trans/cis) Cu(I)-catalyzed cyclopropanation of alkenes using phenyliodonium ylide generated in situ from iodosobenzene and methyl nitroacetate is reported. The cyclopropanation took place with high enantioselectivity for a wide range of alkenes, and the reaction was performed at room temperature. 1-Nitrocyclopropyl esters are versatile building blocks to access the corresponding cyclopropane amino esters and aminocyclopropanes in two and three steps, respectively, from commercially available products.     

An expedient route for the practical synthesis of pachastrissamine (jaspine B) starting from 3,4,6-tri-O-benzyl-d-galactal

A practically efficient stereoselective synthesis of pachastrissamine (jaspine B) is described starting from 3,4,6-tri-O-benzyl-d-galactal in eight steps and 11% overall yield.     

An expedient method for the synthesis of 6-substituted uracils under microwave irradiation in a solvent-free medium

Condensation of malonic acid 1 and ureas 2a-f proceeds smoothly in the presence of acetic anhydride 3 under microwave irradiation in solvent-free conditions to give 6-hydroxy-uracils 4 in excellent yields. Under identical conditions, the condensation of cyanoacetic acid 5 and ureas 2a,b,g and h in the presence of acetic anhydride 3, followed by cyclization in the presence of sodium hydroxide affords 6-amino-uracils 6 in high yields. The work-up procedures are simple and products need no purification.     

Enantioselective synthesis of non-natural aromatic alpha-amino acids

We present two complementary methods for the stereoselective synthesis of non-natural alpha-amino acids with aromatic or heteroaromatic side chains. One approach is based on the chemical transformation of methionine, whereas the other applies the stereoselective Myers alkylation of glycine. The resulting product types differ in the linker length between glycine and the aromatic substituent. Since methionine and pseudoephedrine are available in both absolute configurations, R- or S-configured enantiopure amino acids with either C(2) or C(3) linkers can be obtained on gram scales. In each case the key step of the synthesis is hydroboration of the unsaturated building blocks 9 and 17, followed by palladium-catalyzed Suzuki cross-coupling with aryl halides. Attention must in certain cases be paid to the stereochemical integrity when basic Suzuki conditions are applied. Our initial difficulties are reported as well as the final "racemization-proof" procedures. The protecting groups chosen for the alpha-amino acids should be compatible with solid-phase peptide synthesis. This was confirmed by the successful synthesis of a series of tripeptides.     

An expedient synthesis of mellitic triimides

Heating of the solid ammonium salts obtained from treatment of mellitic acid with 3 equiv of a primary amine yields trisubstituted mellitic triimides via dehydration and imide ring closure. This surprisingly simple synthetic approach is amenable to incorporation of alkyl, aryl, and amino acid ester substituents, thereby opening broad access to a family of C(3)-symmetric organic electron acceptors.     

An expedient route for the practical preparation of optically active (−)-gossypol

A simple and practical procedure has been developed for the resolution of racemic gossypol. The commercially available l-amino acid esters have been employed as the resolving agents with the l-tryptophan methyl ester (l-Trp-OMe) as the best reagent of choice. The individual diastereoisomeric gossypol adducts derived from l-Trp-OMe are readily separated by a simple filtration step to give the (−)-diastereoisomeric adduct, and its (+)-diastereoisomeric adduct can be easily obtained by simple evaporation of the mother liquor. Acid hydrolysis of the separated adduct gave (−)-gossypol and (+)-gossypol, respectively, in high chemical yields (quantitatively) and in high enantiomeric excesses (>95%).     

An expedient asymmetric synthesis of platencin

A short and efficient synthesis of enone 3, a key intermediate in the total synthesis of platencin (2), based on an intramolecular Diels-Alder reaction is described.     

An expedient synthesis of substituted indoles

Condensation of carboxylic acid esters with organodilithium reagents derived from N-trimethylsilyl-o-toluidine or N-trimethylsilyl-o-ethyl aniline affords substituted indoles.     

1,5-Dimethyl-4-phenylimidazolidin-2-one-derived iminic glycinimides: useful new reagents for practical asymmetric synthesis of alpha-amino acids

New 1,5-dimethyl-4-phenylimidazolidin-2-one-derived acyclic chiral iminic glycine reagents have been prepared and diastereoselectively alkylated with activated alkyl halides and electrophilic olefins in the presence of lithium chloride under (a) strong bases (LHMDS, KOBu(t)) and low temperature (-78 degrees C) conditions, (b) solid-liquid phase-transfer catalysis reaction (LiOH, TBAB, -20 degrees C) conditions, and (c) in the presence of organic bases (DBU, BEMP, TMG, -20 degrees C). In the case of dielectrophiles C- and N-alkylation takes place to afford heterocyclic derivatives. Hydrolysis of alkylated products has been carried out (a) in two-step procedures with LiOOH or LiOH followed by acidic hydrolysis or Dowex purification, (b) in one single-step under refluxing water to give the corresponding alpha-amino acid, (c) in the presence of DBU in methanol to provide N-protected alpha-amino acids methyl esters, or (d) by a protection-hydrolysis procedure to afford N-Boc-protected alpha-amino acids. The chiral imidazolidinone has generally been recovered in good yield. This methodology has been shown to be useful for the synthesis of acyclic and heterocyclic (S)- and (R)-alpha-amino acids.