Synthesis of novel cyclic α-amino acid derivatives via a one-pot sequential Petasis reaction/palladium catalysed process

A novel one pot Petasis reaction/palladium catalysed process is described involving 2-iodo/bromo benzylamine, ethyl glyoxalate and aryl/heteroaryl boronic acids. The in situ generated carbinolamine/imine undergoes the Petasis reaction to afford 2 which reacts with carbon monoxide or allene (1 atm) in the presence of Pd(0) to generate acyl palladium or π-allyl palladium species which are intercepted intramolecularly by the proximal secondary amine to afford isoindolone/4-methylene-3,4-dihydroisoquinoline α-amino acid derivatives in good yield.     

A convenient one-pot synthesis of polysubstituted pyrroles from N-protected succinimides

The dienamine products formed by the reaction between polysubstituted succinimides and the Petasis reagent were subjected to isomerization under mild acidic conditions to give polysubstituted pyrroles in excellent yields (85–95%). The scope and limitations of this methodology are explored.     

A one-pot procedure for methylenating carbonyl compounds using the Nysted reagent and titanocene dichloride

The combination of the Nysted reagent and titanocene dichloride methylenates aldehydes and ketones to give alkenes, and in a microwave-assisted process, esters and lactones give enol ethers. The methylenating agent in this one-pot procedure is presumed to be titanocene methylidene, which is the same reactive intermediate as that generated from Tebbe, Petasis and Grubbs reagents, each of which have to be prepared before use.     

Substituted hydrazides of hydroxycarboxylic acids XXVIII. Morpholinoacetyl derivatives of phenylhydrazides of diaryl and dialkyl glycolic acids

The action of morpholine on chloroacetyl derivatives of phenylhydrazides of diaryl- and dialkylglycolic acids gives hitherto undescribed morpholinoacetyl derivatives of the phenylhydrazides. Methiodides of a number of these compounds are prepared. The hitherto undescribed chloroacetyl derivatives of the phenylhydrazides of di(m-tolyl)-, di(o-anisyl)-, diamyl-, diheptyl-, and dioctylglycolic acids, and also the phenylhydrazide of diheptylglycolic acid are described.For Part XXVII see [1].     

Substituted hydrazides of hydroxycarboxylic acids XXVIII. Morpholinoacetyl derivatives of phenylhydrazides of diaryl and dialkyl glycolic acids

The action of morpholine on chloroacetyl derivatives of phenylhydrazides of diaryl- and dialkylglycolic acids gives hitherto undescribed morpholinoacetyl derivatives of the phenylhydrazides. Methiodides of a number of these compounds are prepared. The hitherto undescribed chloroacetyl derivatives of the phenylhydrazides of di(m-tolyl)-, di(o-anisyl)-, diamyl-, diheptyl-, and dioctylglycolic acids, and also the phenylhydrazide of diheptylglycolic acid are described.     

酰基苯肼的感染显影及反差促进剂的作用

研究了六种结构不同的酰基苯肼化合物(通式:R—PhNH—NH—COR′)对卤化银乳剂感光性能的影响。结果表明,感染显影作用程度与酰基苯肼的结构有密切的关系。另外本文还就反差促进剂(醇类化合物和胺类衍生物)的作用及其机理进行了较深入的研究。事实说明,显影液中加入反差促进剂,不但能消除单独使用酰基苯肼时出现的“自阻”效应,而且还大大促进了感染显影的进行,提高了乳剂的反差和感光度。同时,本实验在应用高压液相色谱、色-质联仪、顺磁共振等方法对酰基苯胼的还原反应产物及反应中间物进行分析的基础上,更加明确地解释了感染显影和反差促进的作用机理。     

Zirconocene‐Mediated Carbonylative Coupling of Grignard Reagents

Organozirconocenes are versatile synthetic intermediates that can undergo carbonylation to yield acyl anion equivalents. Zirconocene hydrochloride ([Cp₂ZrHCl]) is often the reagent of choice for accessing these intermediates but generates organozirconocenes only from alkenes and alkynes. This requirement eliminates a broad range of substrates. For example, organozirconocenes in which the zirconium center is bonded to an aromatic ring, a benzylic group, or an alkyl group that possesses a tertiary or quaternary carbon atom α to the carbon–zirconium bond can not be formed in this way. To provide more generalized access to acyl zirconium reagents, we explored the transmetalation of Grignard reagents with zirconocene dichloride under a CO atmosphere. This protocol generates acyl zirconium(IV) complexes that are inaccessible with the Schwartz reagent, including those derived from secondary and tertiary alkyl and aryl Grignard reagents.     

2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate as an efficient coupling reagent for the amidation and phenylhydrazation of carboxylic acids at room temperature

The synthesis of amides and phenylhydrazides from the reaction of corresponding carboxylic acids with primary aliphatic, aromatic amines or phenylhydrazine in the presence of triethylamine or diisopropylethyl amine as a base using 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) proceeds smoothly under mild conditions to afford the corresponding amides or phenylhydrazides in good to high yields in ethyl acetate at room temperature.     

Reformatsky Reaction of Methyl α-Bromoisobutyrate with 2-Arylmethylidenemalonic Acid Derivatives

Reformatsky reagent obtained by treatment of methyl α-bromoisobutyrate with zinc reacts with dimethyl 2-arylmethylidenemalonates to give trimethyl 2-aryl-3-methylbutane-1,1,3-tricarboxylates. The reaction of the same compound with ethyl 3-aryl-2-(4-methylphenylcarbamoyl)acrylates yields cyclic products, ethyl 4-aryl-5,5-dimethyl-1-(4-methylphenyl)-2,6-dioxopiperidine-3-carboxylates. Treatment of the latter with morpholine and phenylhydrazine leads to the corresponding 4-aryl-5,5-dimethyl-1-(4-methylphenyl)-2,6-dioxopiperidine-3-carboxylic acid morpholides and phenylhydrazides. The products are formed as a single diastereoisomer.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 7, 2005, pp. 1034–1038.Original Russian Text Copyright © 2005 by Shchepin, Fotin.     

Enantioselective organocatalytic three-component Petasis reaction among salicylaldehydes, amines, and organoboronic acids

The catalytic enantioselective three-component Petasis reaction among salicylaldehydes, amines, and organoboronic acids with a newly designed thiourea-binol catalyst is presented. A broad range of alkylaminophenols can be obtained in good yield (up to 92%) and good to high enantioselectivity (up to 95% ee). A possible reaction pathway for this catalytic enantioselective Petasis reaction is tentatively proposed.     

Studies in chlorin chemistry. II. A versatile synthesis of dihydrodipyrrins

[reaction: see text] Dihydrodipyrrins are key building blocks for the synthesis of hydroporphyrins, many of which have important biological activity. The title compounds were prepared in stereo- and regioselective fashion by a three-step sequence consisting of (1) Pd(0)-catalyzed coupling-cyclization of 2-iodopyrroles with gamma-alkynoic acids to afford enelactones of the desired substitution pattern, (2) methylenation at the lactone carbonyl group employing the Petasis reagent, and (3) in situ enol-ether hydrolysis and amination of the resultant 1,4-diketone to close the pyrroline ring (nine examples). Yields for each step were generally high, although in substrates not blocked by geminal substitution aromatization to a dipyrromethane is a competing side reaction.     

锆氢化反应研究（Ⅳ）：—芳腈的锆氢化反应及其在合成中的应用

芳腈在温和条件下进行锆氢化反应,所得产物经水解得到芳醛;若经酰基化则得到N-酰基不饱和胺。后者不稳定,在室温下与甲醇发生加成反应得N-(α-甲氧基苄基)苯甲酰胺。过量的锆氢化试剂与芳腈反应,继之进行酰基化,得到二元酰基化产物,两个酰基分别加到腈基的碳与氮原子上。     

A convenient synthesis of immunosuppressive agent FTY720 using the petasis reaction

A convenient synthesis of immunosuppressive agent FTY720 (1) using the Petasis reaction was developed. 4-Octylbenzaldehyde (9) was converted into 1-ethenyl-4-octylbenzene (11) by two-step synthesis. Hydroboration of 11 using catecholborane and hydrolysis gave (E)-2-(4-octylphenyl)vinylboronic acid (4). The Petasis reaction of 4, dihydroxyacetone (3), and benzylamine following catalytic hydrogenation afforded FTY720 (1).     

Catalytic diastereoselective petasis reactions

Multicomponent Petasis reactions: The first diastereoselective Petasis reaction catalyzed by chiral biphenols that enables the synthesis of syn and anti?β-amino alcohols in pure form has been developed. The reaction exploits a multicomponent approach that involves boronates, α-hydroxy aldehydes, and amines.     

Bis(2-methoxyethyl)amino]sulfur trifluoride, the Deoxo-Fluor reagent: application toward one-flask transformations of carboxylic acids to amides

The use of the Deoxo-Fluor reagent is a versatile method for acyl fluoride generation and subsequent one-flask amide coupling. It provides mild conditions and facile purification of the desired products in good to excellent yields. We have explored the utility of this reagent for the one-flask conversion of acids to amides and Weinreb amides and as a peptide-coupling reagent.     

Preparation of Polystyrene-supported N-phenyl-N-acyl Sulfonamide Resin and its Application in Solution-phase Synthesis of Amides

Polystyrene-supported N-phenyl-N-acyl sulfonamide resin was prepared by reacting polystyrene sulfonyl chloride resin with aniline and acylating in pyridine with either acid chlorides or anhydrides. Then, this resin was utilized as a new type of acyl transfer reagent to synthesize the amide library. It was approved to be a more effective acyl transfer reagent with higher amide yields than the polystyrene-supported N-methyl-N-acyl sulfonamide resin and N-benzyl-N-acyl sulfonamide resin. When the phenyl group bonded to the N atom on N-phenyl-N-acyl sulfonamide resin was substituted by the electron withdrawing group or electron donating group, a decreasing amide yield was obtained. N-phenyl-N-acyl sulfonamide resin could be regenerated many times.     

A Convenient Synthesis of Diacyl Selenides by Selenium Transfer Reaction of Primary Selenoamides

Aryl selenoamides are rather interesting compounds because they are versatile intermediates in organic chemistry1. It was reported that selenobenzamides have been used as selenium transfer reagents in the synthesis of alkyl diselenides from reactive halides2. We began to investigate the reactivity of arylselenoamides toward acyl chlorides and guess that this reaction would produce acyl diselenides. In surprise we could not find the diacyl diselenides (Scheme 1). Instead diacyl selenides a…     

Activation of carboxylic acids by Burgess reagent: an efficient route to acyl ureas and amides

Carboxylic acids upon treatment with Burgess reagent are converted to novel mixed sulfocarboxy anhydrides. Subsequent treatment of such mixed anhydrides with amines at elevated temperatures yields acyl ureas and amides. The ratio of the two products appears to be temperature controlled. The method provides a simple and convenient route to diverse acyl ureas starting from carboxylic acids and amines.     

Bromination of Enamines from Tertiary Amides Using the Petasis Reagent: A Convenient One-Pot Regioselective Route to Bromomethyl Ketones

An original one-pot synthesis of bromomethyl ketones is achived using the Petasis reagent (dimethyltitanocene) as a key for enamine generation. Several amides were used to test the limits of the procedure by changing either the alkyl chain R or the amino portion of the starting materials. The enamines generated in situ were allowed to react with bromine at low temperature followed by hydrolysis to yield bromomethyl ketones in excellent yields (85 to 95%). Mechanistic details and optimum conditions for the reaction are briefly discussed. The present approach offers several advantages such as regioselectivity in enamine formation, good yields, mild reaction conditions, and ease of experimentation.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource: Full experimental and spectral details.]     

Synthesis of polymer containing lipoic acid as a polymeric reagent for acyl transfer

Lipoic acid was immobilized on crosslinked polystyrene beads to generate a polymeric reagent. The acyl transfer reaction of the p-nitrobenzoyl group from the polymer-bound lipoic acid to cyclohexylamine was investigated spectrophotometrically and was compared with a monomeric model compound. The acceleration effect of silver ion on the acyl transfer reaction also was studied.