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.     

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).     

Diastereoselective Petasis Mannich reactions accelerated by hexafluoroisopropanol: a pyrrolidine-derived arylglycine synthesis

A diastereoselective synthesis of pyrrolidine-derived arylglycines has been developed using the Petasis boronic acid Mannich reaction. High diastereoselectivities in the reactions of chiral amines, aryl boronic acids, and glyoxylic acid monohydrate have been demonstrated for the first time. Key to the implementation of this method is the discovery that hexafluoroisopropanol accelerates the Petasis process, reducing reaction times from multiple days to less than 24 h.     

Synthesis of indoles via alkylidenation of acyl hydrazides

Indoles have been synthesised via alkylidenation of acyl phenylhydrazides using phosphoranes and the Petasis reagent, followed by in situ thermal rearrangement of the product enehydrazines. The Petasis reagent provides an essentially neutral equivalent of the [acid-catalysed] Fischer indole synthesis, but with acyl phenylhydrazides as starting substrates. Alkylidene triphenylphosphoranes convert aroyl phenylhydrazides to indoles, but acyl phenylhydrazides derived from aliphatic carboxylic acids undergo a Brunner reaction to form indolin-2-ones.     

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.     

Microwave assisted Petasis boronic-Mannich reactions

We have used a design of experiments (DOE) approach to optimise rapidly a set of microwave assisted conditions for the Petasis reaction. The optimal conditions involved the microwave heating of the reaction components in dichloromethane (1 M concentration) at 120 °C for 10 min in a focussed microwave (CEM Explorer). These conditions were successfully applied to a range of Petasis reactions employing either glyoxylic acid or salicylaldehyde as the carbonyl component along with a number of aryl/heteroaryl boronic acids and amine components.     

Lewis acid-catalyzed Mannich type reactions with potassium organotrifluoroborates

Three-component Lewis acid-catalyzed Mannich type reactions using potassium organotrifluoroborates (aryl, vinyl, and allyl reagents) has been developed as an extension of the standard Petasis reaction.     

Remarkable stereoselectivity in intramolecular Borono-Mannich reactions: synthesis of conduramines

An unprecedented intramolecular Petasis condensation provides a novel approach to biologically important conduramines. The compounds are produced with an exclusive anti stereoselectivity for the newly created β-amino alcohol motif. The stereochemical outcome of the reaction is opposite to the one usually observed in the intermolecular reaction.     

Asymmetric Traceless Petasis Borono‐Mannich Reactions of Enals: Reductive Transposition of Allylic Diazenes

The traceless Petasis borono‐Mannich reaction of enals, sulfonylhydrazines, and allylboronates, catalyzed by chiral biphenols, results in an asymmetric reductive transposition of the in situ generated allylic diazene. Acyclic 1,4‐diene products bearing either alkyl‐ or aryl‐substituted benzylic stereocenters are afforded in excellent yields and enantiomeric ratios of up to 99:1. The use of crotylboronates in the reaction results in concomitant formation of two stereocenters in either a 1,4‐syn or anti relationship from the corresponding E ‐ or Z ‐crotylboronate used in the reaction. The use of β‐monosubstituted enals in the asymmetric traceless Petasis borono‐Mannich reaction of crotylboronates installs tertiary methyl‐bearing stereocenters in good yields and high enantioselectivities.     

Solvent-free Synthesis of Alkylaminophenols via Petasis Boronic Mannich Reaction in One Pot without Catalysts

By using solvent‐free and heat conditions, the Petasis boronic Mannich reaction of salicylaldehydes with various boronic acids and secondary amines without catalyst is described. The alkylaminophenols were obtained in moderate to good yields in a shorter reaction time than the traditional methods.     

Use of Anilines in the Petasis Reaction: DFT Mechanistic Study

Russian Journal of Organic Chemistry - Five 2-[(4-R-anilino)(phenyl)methyl]phenols with potential anticancer activity were synthesized by the Petasis reaction. Three of these compounds were...     

Copper-catalyzed Petasis-type reaction: a general route to α-substituted amides from imines, acid chlorides, and organoboron reagents

A copper-catalyzed Petasis-type reaction of imines, acid chlorides, and organoboranes to form α-substituted amides is described. This reaction does not require the use of activated imines or the transfer of special units from the organoboranes and represent a useful generalization of the Petasis reaction.     

Diversity-oriented synthesis of novel polycyclic scaffolds using polymer-bound reagents

A concise sequence utilizing a Petasis three component reaction followed by a tandem aza-Cope-Mannich cyclization afforded novel polycyclic heterocycles in good yield; alternative iminium cyclization based on a Pictet-Spengler reaction or aminal formation led to divergent pathways affording skeletal diversity.     

Determination of glyoxylic acid in urine by liquid chromatography with fluorescence detection, using a novel derivatization procedure based on the Petasis reaction

The Petasis reaction is the multi-component reaction of a carbonyl compound, amine, and arylboronic acid to form an α-amino acid or a β-aminoalcohol. In this work, as the first analytical application of the Petasis reaction, a high-performance liquid chromatographic (HPLC) method with fluorescence detection was developed for determination of glyoxylic acid. The glyoxylic acid was derivatized with 1-pyreneboronic acid, as fluorescent arylboronic acid, in the presence of N-methylbutylamine, as amine, to give a fluorescent α-amino acid. HPLC separation of the fluorescent derivative was performed within 30 min on an octyl column eluted with a gradient prepared from acetonitrile and 50 mmol L(-1) acetate buffer (pH 4.0). The detection limit (S/N=3) for glyoxylic acid was 5.0 nmol L(-1) (20 fmol/injection). The method can be used to determine the concentration of glyoxylic acid in human urine without interference from biological components.     

Unusual behaviour of pyridinylboronic acids in the Petasis boronic Mannich reaction

The implementation of the Petasis boronic Mannich reaction in pyridine series allowed us to obtain original compounds whose structure was investigated and determined a stable complex (1:1) of dioxaborolanone and amine.     

A new and efficient one-pot synthesis of 2-hydroxy-1,4-dihydrobenzoxazines via a three-component Petasis reaction

The secondary amines synthesized by the reaction between 2-aminophenols and aromatic aldehydes, via the reduction of the corresponding imines, were employed in the synthesis of new 2-hydroxy-2H-1,4-benzoxazine derivatives through a one-pot Petasis multicomponent reaction in good to excellent yields.     

Novel Petasis boronic acid reactions with indoles: synthesis of indol-3-yl-aryl-acetic acids

Indoles can serve as substrates for the Petasis boronic acid-Mannich reaction, providing a practical synthetic route for C-C bond formation in α-(N-substituted indole)carboxylic acids. The scope and limitations of this method have been examined.     

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.     

Novel Petasis boronic acid reactions with 1,3,5-tri-oxygenated benzenes

1,3,5-tri-Oxygenated benzenes can serve as substrates for the Petasis boronic acid reaction, providing a practical synthetic route for the two CC bond formation of α-(1,3,5-tri-oxygenated phenyl)carboxylic acids. The scope and limitations of this method have been examined.     

Petasis three-component coupling reactions of hydrazides for the synthesis of oxadiazolones and oxazolidinones

An application of readily available hydrazides in the Petasis 3-component coupling reaction is presented. An investigation of the substrate scope was performed to establish a general, synthetically useful protocol for the formation of hydrazido alcohols, which were selectively converted to oxazolidinone and oxadiazolone ring systems through triphosgene-mediated cyclization reactions.