Petasis boronic acid-Mannich reaction

R = alkyl R = alkyl OH, O-alkyl, -SOfeu, NHCOO Bu R = H, alkyl, R = H, -COOH, aryl R = alkenyl, aryl, heteroaryl 

The mechanism of the Petasis boronic acid-Mannich reaction is not fully understood. In the first step of the reaction, upon mixing the carbonyl and the amine components, three possible products can form iminium salt A, diamine B, and a-hydroxy amine C. It was shown that preformed iminium salts do not react with boronic acids. This observation suggests that the reaction does not go through intermediate A. Both intermediate B and C can promote the formation of the product. Most likely, the reaction proceeds through intermediate C, where the hydroxyl group attacks the electrophilic boron leading to an ate -complex. Subsequent vinyl transfer provides the allylic amine along with the boronic acid sideproduct. 

In the laboratory of A. Golebiowski, the high throughput synthesis of diketopiperazines was accomplished. These compounds can serve as 3-turn mimetics. The key step in this approach was a Petasis boronic acld-Mannich reaction between the Merrifield resin-bound piperazine-2-carboxylic acid, glyoxylic acid, and a wide range of commercially available boronic acids to provide a 1 1 mixture of the products. A specific example is shown below. 

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. 

Batey and co-workers developed a modification of the Petasis-boronic acid-Mannich reaction that occurs via N-acyliminium ions derived from A/-protected-2,3-dihydroxypyrrolidine and 2,3-dihydroxypiperidine derivatives. This method was utilized in the total synthesis of (+)-deoxycastanospermine. The formation of the A/-acyliminium ion was achieved by treating A/-Cbz-2,3-pyrrolidine with BF3-OEt2. ° Subsequent vinyl transfer from the alkenylboronic ester provided the product with excellent yield and diastereoselectivity. 

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Allylic amine from the three-component reaction of a vinyl boronic acid, a carbonyl and an amine. Also known as boronic acid-Mannich or Petasis boronic acid-Mannich reaction. Cf. Mannich reaction. 

Cytoxazone is a novel cytokine modulator. The total synthesis of this natural product and its enantiomer was accomplished by S. Sugiyama. The 3-amino-1,2-propanediol moiety was synthesized by a Petasis boronic acid-Mannich reaction between DL-glyceraldehyde, (R)-1-(1-naphthyl)ethylamine and 4-methoxyphenylboronic acid to provide a 1 1 mixture of the diastereomeric products. The diastereomers could be separated at a later stage in the synthesis and transformed into (-)- and (+)-cytoxazone. 

Portlock, D. E., Naskar, D., West, L., Li, M. Petasis boronic acid-Mannich reactions of substituted hydrazines synthesis of a-hydrazino... 

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