On the Preparation of Enantiomerically Pure Isonitriles from Amino Acid Esters and Peptides

An improved method for the synthesis of enantiomerically pure isonitriles from amino acid esters and dipeptides is described.     

Preparation of Racemic and Enantiomerically Pure Cyclic Ketene Acetals

Cyclic ketene acetals have been prepared from a-haloaldehyde dimethylacetals by transacetalization and subsequent elimination in PTC without solvent conditions. No racemization has been observed when an enantiomerically pure diol has been used. Stability and storage conditions have been studied.     

Preparation of Enantiomerically Pure 1,3-Butanediol from Threonine

Enantiomerically pure R or S 1,3-butanediols were prepared in four steps from L or D threonine by nitrous deamination in the presence of bromide ion followed by esterification and reduction.     

Mechanistic Implications of the Tetrameric Cubic Structure of Lithium Enolates

The tetrameric cubic structure established for lithium enolates in the solid state is used as a model to discuss several facets of enolate chemistry: solubility, effects of cosolvents, addition to aldehyde and acid chloride, influence of mixed aggregates on diastereo- and enantioselectivities.     

Synthesis and Structure of an Enantiomerically Pure C2 Symmetric Ferrocenyl Carbene

The straightforward, high‐yield synthesis and X‐ray structural analysis of the air‐stable planar‐chiral bis(ferrocenyl)carbene 1,3‐bis‐{(1R)‐1‐[(1R)‐1‐(trimethylsilyl)ferrocen‐2‐yl]ethyl}imidazol‐2‐ylidene ( 5 ) is reported. Compound 5 is obtained in four steps from the amine [(1R)‐1‐(dimethylamino)ethyl]ferrocene ( 1 ) upon diastereoselective silylation, methylation, nucleophilic substitution by imidazole, and deprotonation. The X‐ray crystal structure of the free carbene shows the typical conformational features of the 1,2‐disubstituted ferrocenyl units, as found in other ferrocenyl ligands derived from 1 .     

Preparation and Olfactory Characterization of the Enantiomerically Pure Isomers of the Perfumery Synthetic Galaxolide®

The commercially important isochromane musk odorant Galaxolide^® (=1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta[g]-2-benzopyran; HHCB; 3 ) was separated into its diastereoisomers via the tricarbonyl(η⁶-cyclopenta[g]-2-benzopyran)chromium complexes 10 . Since GC/olfactometry indicated that only one enantiomer of each diastereoisomer (4RS,7RS)- 3 and (4RS,7SR)- 3 determines the odor characteristics of the commercial product, all four stereoisomers (4S,7R)-, (4S,7S)-, (4R,7S)-, and (4R,7R)- 3 were synthesized by Friedel-Crafts alkylation of 1,1,2,3,3-pentamethylindane ( 11 ) with (S)- and (R)-methyloxirane ((S)- and (R)- 12 , resp.), acid-catalyzed reaction of the resulting products with paraformaldehyde, and separation of the formed diastereoisomer pairs via the tricarbonyl(η⁶-cyclopenta[g]-2-benzopyran)chromium complexes 10 . The powerful musk odor of Galaxolide ^® ( 3 ) was thus attributed to its (−)-(4S)-isomers (4S,7R)- and (4S,7S)- 3 , while the (+)-(4R)-isomers (4R,7S)- and (4R,7R)- 3 were weak to almost odorless.     

Peptide Enolates. C-Alkylation of Glycine Residues in linear tri-, tetra-, and pentapeptides via dilithium azadienediolates

The Boc-protected tripeptides Boc-Val-Gly-Leu-OH ( 1 ), Boc-Leu-Sar-Leu-OH ( 2 ), Boc-Leu-Gly-MeLeu-OH ( 3 ), and Boc-Val-BzlGly-Leu-OMe ( 64 ), tetrapeptide Boc-Leu-Gly-Pro-Leu-OH ( 9 ), and pentapeptides Boc-Val-Leu-Gly-Abu-Ile-OH ( 4 ), Boc-Val-Leu-Sar-MeAbu-Ile-OH ( 5 ), Boc-Val-Leu-Gly-MeAbu-Ile-OH ( 6 ), Boc-Val-Leu-BzlGly-BzlAbu-Ile-OH ( 7 ), and Boc-Val-Leu-Gly-BzlAbu-Ile-OH ( 8 ) are prepared by conventional methods (Schemes 4–7) or by direct benzylation of the corresponding precursors (Scheme 8). Polylithiations in THF give up to Li₆ derivatives containing glycine, sarcosine or N-benzylglycine Li enolate moieties ( A–H ). The polylithiated systems with a dilithium azadienediolate unit ( C, F–H ) are best generated by treatment with t-BuLi. The yields of alkylation of the glycine or sarcosine residues are up to 90%, with diastereoselectivities from nil to 9:1. Normally, the newly formed stereogenic center has (R)-configuration (i.e. a D -amino-acid residue is incorporated in the peptide chain). Electrophiles which can be employed with the highly reactive azadienediolate moiety are: MeI, EtI, i-PrI, allyl and benzyl bromide, ethyl bromoacetate, CO₂, and Me₂S₂ (Schemes 11–13). No epimerizations of the starting materials (racemization of the amino-acid residues) are observed under the strongly basic conditions. Selected conformations of the peptide precursors, generated by shock-freezing or by very slow cooling from room temperature to ?75° before lithiation, give rise to different stereoselectivities (Scheme 11). The latter and the yields can also be influenced by tempering the lithiated species before (Scheme 9) or after addition of the electrophiles (Scheme 12). Besides the desired products, starting peptides are recovered in the chromatographic purification and isolation procedures (material balance 80–95%). The results described are yet another demonstration that peptides may be backbone-modified through Li enolates, and that whole series of analogous peptide derivatives with various side chains may thus be produced from a given precursor.     

Synthesis of Enantiomerically Pure 2-Isoxacephems

Summary. (R,6R,7R)-7-(1-Acetoxyethyl)-3-methyl-2-isoxacephem-4-carboxylic acid and its enantiomer have been prepared. The ring systems were formed from the corresponding enantiomerically pure N-unsubstituted -lactams. The reduction of methyl [(R,2S,3R)-3-(1-acetoxyethyl)-1-(4-methoxyphenyl)-4-oxoazetidine-2-carboxylate] has been solved via a hemi-acetal. The structure and the configuration of a new stereogenic center in this intermediate was predicted by using 2D NMR technique and unambiguously proven by x-ray.     

Synthesis of Enantiomerically Pure 2-Isoxacephems

(R,6R,7R)-7-(1-Acetoxyethyl)-3-methyl-2-isoxacephem-4-carboxylic acid and its enantiomer have been prepared. The ring systems were formed from the corresponding enantiomerically pure N-unsubstituted -lactams. The reduction of methyl [(R,2S,3R)-3-(1-acetoxyethyl)-1-(4-methoxyphenyl)-4-oxoazetidine-2-carboxylate] has been solved via a hemi-acetal. The structure and the configuration of a new stereogenic center in this intermediate was predicted by using 2D NMR technique and unambiguously proven by x-ray.     

真空热还原-蒸馏法制备高纯金属锂

金属锂具有质量轻,负电位高,比能量大等优点,成为新的电池能源材料^[1]。2000年全世界生产锂电池3．76亿只,消耗金属锂约400吨。目前,国内外研制的核聚变反应堆有200多座,一旦受控核聚变反应堆工业化,世界每年需要用于反应堆的金属锂在5000－10000吨,金属锂的另一重要用途是生产制造航空器中的铝－锂,镁－锂合金等。该合金具有重量轻,强度高、高拉伸强度和低密度等优点。     

C-Alkylation of Sarcosine Residues in Cyclic Tetrapeptides via Lithium Enlates

The cyclic tetrapeptides cyclo(-Leu-Sar-Gly-), cyclo(-Val-Sar-Sar-Gly-), and cylco(-Meleu-Gly-D -Alasar-) have been synthesized from the component amino acids (BOP-Cl coupling), using the pentafluorophenyl esters for the cyclization step (42, 13, and 30% yield, respectively). Multiple deprotonation (LDA in THF/LiBr/DMPU) and addition of highly reactive electrophiles (CF₃CO₂D, MeI, CH₂O, CH₂CHCH₂Br, PhCH₂Br) produce cyclic tetrapeptides with additional substituents introduced diastereoselectively (70 to > 98% ds) in yields ranging from 20 to 90%. The C-alkylatd products are all derived from a sarcosine-enolate moiety adjacent to another N-methylamino acid. The structures of the resulting products are determined by NMR spectroscopy (DNOE and ROESY techniques) and by hydrolysis to the parent amino acids, suitable derivatization, and analysis by chromatography on a chiral GC column. It was shown in two cases that the overall yield of cyclization/alkylation to give a disubstitued cyclic tetrapeptide is higher than that of a synthesis of the same product from the corresponding amino-acid building blocks. Surprising temperature and salt effects on the yields and selectivities of the reactions of the cyclic tetrapeptide enolates are presented, and possible mechanistic interpretations are discussed.     

对映体纯1-甲基-7-氧杂双环[2.2.1]庚烷-2-酮的制备

1-甲基 - 7-氧杂双环 [2 .2 .1 ]庚烷 - 2 -酮 ( 1 )是萜类天然产物全合成中的重要中间体 ,能被广泛地应用于多种桉烷 ( Eudesmane)、沉香呋喃 ( Agarofuran)和降胡萝卜素 ( Norcarotenoids)等倍半萜天然产物的全合成[1,2 ] .我们以对映体纯化合物 1为原料 ,实现这类天然产物的不对称全合成 [3～ 6 ] .消旋的化合物 (± ) - 1可以 2 -甲基呋喃和 2 -氯丙烯腈为原料 ,经 3步反应得到 [2 ] .但对映体纯化合物 1的制备尚未见报道 .本文用化学拆分方法 ,成功地制备了对映体纯的 ( + ) - 1和 ( - ) - 1 ,并确定了其绝对构型 .1　结果与讨论为减…     

Aggregation and Cooperative Effects in the Aldol Reactions of Lithium Enolates

Density functional theory and Car–Parrinello molecular dynamics simulations have been carried out for model aldol reactions involving aggregates of lithium enolates derived from acetaldehyde and acetone. Formaldehyde and acetone have been used as electrophiles. It is found that the geometries of the enolate aggregates are in general determined by the most favorable arrangements of the point charges within the respective Li_nO_n clusters. The reactivity of the enolates follows the sequence monomer?dimer>tetramer. In lithium aggregates, the initially formed aldol adducts must rearrange to form more stable structures in which the enolate and alkoxide oxygen atoms are within the respective Li_nO_n clusters. Positive cooperative effects, similar to allosteric effects found in several proteins, are found for the successive aldol reactions in aggregates. The corresponding transition structures show in general sofa geometries.     

Synthesis of All Enantiomerically Pure Diastereomers of Aprepitant

Syntheses of all eight enantiomerically pure diastereomers of aprepitant and assignment of absolute configuration at newly generated stereocenters by NMR and x-ray crystallographic analysis were achieved.     

Synthesis of Enantiomerically Pure Carbohydrate-Derived Annulated Cyclopentadienes and Ferrocenes

The cyclopentadienes 3a/b/c, 8b/c, 12a/b/d , and 16a/b/d were prepared as mixtures of regioisomers from the D -mannitol-derivatives 1,6,10 , and 14 and transformed into the ferrocenes 17, 18 , and 19 (73%; 38:17:45), 23, 24 , and 25 (70%; 6:42 :52), 26 (31%), and 27 (27%), respectively. Deprotection of 17–19 with HCl/MeOH gave the H₂O-soluble ferrocenes 20–22 ; chloromercuration and iodination of 17 via 29 led to the C₂-symmetric diiodo-ferrocene 30 . The mono(chloromercurio) derivative 28 , obtained as a by-product, was also transformed into 29 . The structure of the ferrocenes 18 and 19 , and of the bis(chloromercurio)ferrocene 29 has been established by X-ray analysis. The starting cyclopentadienes 3 were obtained in 50% yield from 1 by dialkylation of CpNa, followed by thermolysis of the spiro-annulated 2 . Similarly, dimesylate 6 (from 4 ) gave the spiro-annulated diene 7 and the annulated dienes 8 in about equal amounts; thermolysis transformed 7 into 8 (62%). The dienes 12 were prepared in 15% yield from the ditriflate 10 via 11 , the dimesylate 9 proving insufficiently reactive, and the dienes 16 (49%) from 14 via 15 .