Petasis reactions, salicylaldehydes

Wang, Q., Finn, M. G. 2H-Chromenes from Salicylaldehydes by a Catalytic Petasis Reaction. Org. Lett. 2000, 2,4063-4065. 

Scheme 6.47 The enantioselective organocatalytic Petasis reaction among salicylaldehydes, amines, and organoboronic acids described by Yuan and coworkers [66].

Three-component Petasis reactions among salicylaldehydes, amines, and organo-boronic acids have been catalysed with a chiral thiourea BINOL catalyst to prepare alkylaminophenols with yields and ee values of up to 92% and 95%, respectively. Formation of amino esters Et02CCH(Ar)NR2 by Petasis combination of Et02CH0, R2NH, and ArB(OH)2, catalysed by Cu(I), is believed to involve transmetallation from boron to copper from which Ar is delivered intramolecularly to the iminium group of the coordinated intermediate. ... 

M.G. Finn and co-workers developed a procedure for the preparation of 2/-/-chromene derivatives that includes a Petasis three-component reaction between salicylaldehyde, vinylic- and aromatic boronic acids, and dibenzylamine. The hydroxyl group of the salicylic aldehyde is essential for the activation of the boronic acid. The initially formed allylic amine undergoes a cyclization upon ejecting the dibenzylamine, thus rendering the process catalytic in the amine. 

So far, all of the reported Petasis-Akritopoulou reactions were carried out in organic solvents such as methanol, ethanol, dichlorometane, toluene, dioxane, and acetonitrile. Even HFIP was applied with success in some cases [ 58,59]. However, these procedures required either a long reaction time or MW activation. Gois and coworkers [60] reported an interesting study where water was successfully used as solvent for this reaction, using different aldehydes such as salicylaldehyde, glyoxalic acid, and gly-coaldehyde. Density functional theory (DFT) studies were performed to understand the mechanistic... 

Microwave acceleration of reactions is a valuable tool for organic synthesis [39], and various specialized instruments are now commercially available. Tye and co-workers have reported the microwave-assisted Petasis borono-Mannich reaction of arylboron-ic acids and primary or secondary amines with either glyoxylic acid or salicylaldehyde [40]. Optimized reaction conditions employed didiloromethane as solvent, and microwave assisted heating at 120 °C for 10 min. Products were obtained in generally modest yields (10-83%), in part due to incomplete reaction conversion imder the reported conditions. 

Finn and Petasis have independently shown that salicylaldehyde is a suitable aldehyde for the Petasis borono-Mannich reaction, with alkenyl, aryl and heteroaryl-boronic acids (Equation 6) [30, 31]. The reaction works best for aliphatic secondary amines, as in the formation of 41 primary amines give modest yields of adducts 41. Benzaldehydes lacking ortho hydroxyl functionality do not react, with even ortho methoxy functionality being unsuitable, which is consistent with a tethering mechanism via putative intermediate 9 (Figure 7.3). Petasis and Boral reported that reactions occurred at room temperature over 24-36 h, using EtOH, MeOH or acetonitrile. 

Microwave-assisted Petasis borono-Mannich reactions of arylboronic acids, secondary amines and salicylaldehyde have been carried out in CH2CI2 at 120 °C for 10 min [40], The main problem encountered here was incomplete conversions, resulting in modest adduct yields (23-76%). The reaction of a primary amine (p-ani-sidine) under the same conditions failed to produce the desired adducts, giving instead only the imines (cf. reactions with glyoxylic acid). 

Finn also showed the formation of 2H-chromenes under the same reaction conditions, using alkenylboronic acids and morpholine in dioxane at 90 °C. A more convenient route to the 2H-chromenes was then developed using a catalytic amount of dibenzylamine in the presence of alkenylboronic adds and salicylaldehyde (42, Scheme 7.11) [30]. Chromenes 43 were reported to arise from the initial Petasis borono-Mannich adducts 44 via an add promoted intramolecular S 2 attack of the ortho-hydroxyl group onto the protonated allylic amine of intermediate 45. A more likely mechanism involves elimination from 45 to intermediate 46, followed by 6n-electrocychzation to the product The reaction is tolerant of various functional groups and substitution patterns on the salicylaldehyde, and could also be promoted using a polymer-supported base, such as Merrifield resin-supported dibenzylamine (40-50 mol%) [30]. 

Functionalized 2,5-dihydrofurans (21) have been prepared by a Petasis borono-Mannich reaction, using a 4-substituted l,2-oxaborol-2(5//)-ol and salicylaldehyde. ° The amine-catalysed process combines a boronic-acid-based Mannich reaction with an intramolecular Sj 2 cyclization. 

For reaction of arylboronic adds with salicylaldehyde/amine N. A. Petasis,... 

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