Petasis reactions synthesis

Scheme 8.2 Two variants of a three-component Petasis reaction synthesis of, (a) p,y-unsattn ated amines, (b) P,Y-unsaturated a-amino acids...

Three-component Mannich Reaction of Functionalized Alkenyl Boronic Adds (Petasis Reaction) Synthesis of, y-Unsaturated a-Amino Acids... 

A straightforward enantioselective synthesis of aZ/o-difluorothreonine is based on a three component Petasis reaction (enantiopure difluorolactic aldehyde. 

Naskar, D., Roy, A., Seibel, W. L., Portlock, D. E. Hydroxylamines and sulfinamide as amine components in the Petasis boronic acid-Mannich reaction synthesis of N-hydroxy or alkoxy-a-aminocarboxylic acids and N-(tert-butyl sulfinyl)-a-amino carboxylic acids. 

Sugiyama, S., Aral, S., Ishii, K. Short synthesis of both enantiomers of cytoxazone using the Petasis reaction. Tetrahedron Asymmetry 2004, 15, 3149-3153. 

Golebiowski, A., Klopfenstein, S. R., Chen, J. J., Shao, X. Solid supported high-throughput organic synthesis of peptide 3-turn mimetics via tandem Petasis reaction/diketopiperazine formation. Tetrahedron Lett. 2000,41,4841-4844. 

An interesting example of the Petasis reaction was employed as a highly stereoselective synthesis of indolyl jV-substituted glycines by the reaction of indolyl-3-boronic acids <01TL2545>. Thus, reaction of 7V-tosyl-3-indolylboronic acids 176 with (R)-a-methyl-benzylamine (177) and glyoxylic acid (178) provides the indolyl iV-substituted glycines 179 in optically pure form. 

An enantioselective variant of Petasis reaction catalyzed by the chiral biphenol 10 was applied to the synthesis of optically active amines 11 (eq 7) (32). Enantioselective addition ofalkyne catalyzed by the chiral copper-phosphine ligand in MCR offers a practical pathway to obtain homochiral propargylamines like 12 (eq 8) (33). The last decade has also wimessed the emergence of organocatalysts, derived from natural products like amino acids (with more emphasis... 

In this pivotal example, the authors have demonstrated the ability of bifunctional thiourea organocatalyst 28 to provide the sufficient activation of organoboronic acids in the Petasis reaction using quinolones 26, as a powerful method for the enantio- and regioselective synthesis of 1,2-adducts 29 against the possibility of generation of 1,4-adducts (Table 4.1) [28],... 

S. Sugiyama, S. Aral, M. Kiriyama, K. Ishii, Chem. Pharm. Bull. 2005, 53,100-102. A convenient synthesis of immunosuppressive agent FTY720 using the Petasis reaction. 

See, for instances (a) S. Santra, R R. Andreana, Org. Lett. 2007, 9, 5035-5038. A one-pot, microwave-influenced synthesis of diverse small molecules by multicomponent reaction cascades, (b) M. Presset, Y. Coquerel, J. Rodriguez, Org. Lett. 2009, 11, 5706-5709. Microwave-assisted domino and multi-component reactions with cyclic acyUcetenes expeditious syntheses of oxazinones and oxazindiones. (c) W.-J. Hao, B. Jiang, S.-J. Tu, X.-D. Cao, S.-S. Wu, S. Yan, X.-H. Zhang, Z.-G. Han, F. Shi, Org. Biomol. Chem. 2009, 7,1410-1414. A new mild base-catalyzed Mannich reaction of hetero-arylamines in water highly efficient stereoselective synthesis of 3-aminoketones under microwave heating, (d) P. Nun, J. Martinez, F. Lamaty, Synthesis 2010, 2063-2068. Microwave-assisted neat procedure for the Petasis reaction. 

In this chapter that highlights the synthesis of arylamines, we will discuss the most recent and relevant developments in the catalytic arylations of imine substrates, which incidentally are mostly enantioselective. The application of organomet2Jlic cat2dysts bearing Pd, Rh, Ru, and other metal catalysts will be considered, as well as the recent multicomponent Petasis reaction. 

The Petasis reaction is a multicomponent condensation occurring between boronic acids, amines and aldehydes. The asymmetric version of this reaction is very attractive for the synthesis of chiral a-amino acids.In this context, Schaus and Lou reported the use of chiral biphenols as organocatalysts for the asymmetric Petasis reaction of ( )-diethyl styrylboronate with secondary amines and ethyl glyoxylate. The corresponding a-amino esters were obtained in high yields and enantioselectivities of up to 97% ee by using a vaulted biaryl phenol such as (5)-VAPOL as the organocatalyst in the presence of 3-A molecular sieves (Scheme 2.59). 

Synthetic highlights The synthesis of 1,2-DQs exemplifies asymmetric organo-catalysis in which enantioselective synthetic reactions are catalyzed by small organic molecules. To generate 1,2-DQs, achiral thiourea and axially chiral biphenols are used as catalysts for the enantioselective Petasis reaction. This is an illustration of a multicomponent reaction (MCR), for which the general concept and examples are also described. 

The Petasis reaction represents a boronic acid variant of the Mannich reaction, and therefore is also referred to as a borono-Mannich reaction. It was first explored with formaldehyde as the carbonyl component and alkenyl, or ot,p-unsaturated organoboronic acid (III) as a nucleophile (route a in Scheme 8.2) [13]. It was later developed in a practical synthesis of a-amino acids (VI) from ot-keto acids (IV) and alkenyl boronic acids (III) [14] (route b in Scheme 8.2). 

A favourable feature of the Petasis reaction, in relation to NDE synthesis, is its triple convergence to form products with multiple sites for introduction of chemical diversity. Moreover, ready availability of alkenyl boronic acids in stereochemically (E or Z) pure forms and their easy handling, prompted development of this new method for broad application in organic synthesis. Particularly important is the extension of the Petasis reaction to a-keto-carboxylic acids (V) in a practical synthesis of p,y-unsaturated a-amino acids (Scheme 8.2, route b). 

Scheme 8.3 The Petasis reaction in diastereoselective synthesis of a,P-aminoalcohols XI...

This type of diastereoselective Petasis reaction was elaborated by Nanda et al in pyrrolidine-derived arylglycine synthesis (Scheme 8.4) [16]. 

The enantioselective, organocatalytic variant of the Petasis reaction, developed by Takemoto and coworkers from the University of Kyoto, represents a breakthrough in the synthesis of enantiopure 1,2-dihydroquinolines. As mentioned before, this structural unit is present in many natural products and biologically active compounds, and therefore an effective and short synthetic route via the Petasis-type reaction to enantiopure compounds in this class is a major leap forwards. Screening of the new thiourea catalysts in the Takamoto group resulted in a highly effective catalyst 13, specifically designed for the Petasis reaction. 

Synthesis of novel cyclic a-amino acid derivatives via a one-pot sequential Petasis reaction/palladium catalysed process. Tetrahedron Letters, 44,... 

SCHEME 40 Quinoxaline synthesis via MW-assisted Petasis reaction. 

Moreover, recently the boronic acid Mannich reaction, mostly referred to as Petasis reaction [163,164], has evolved as a powerful entry to polyhydroxylated pyrrolizidine, indol-izidine, and tropane alkaloids, among others [165, 166]. For example, Pyne and coworkers disclosed a short total synthesis of calystegine (270) starting from (-)-o-lyxose in 4.7% overall yield (Scheme 11.55), which involved, besides a ring-closing metathesis, the Petasis reaction as key step [167]. In a similar fashion, castanospermine (86) was prepared in 14 steps from (-)-L-xylose in 1.5% overall yield (Scheme 11.55) [168]. 

Using chiral biphenol catalyst 107, Lou and Schaus developed a three-component domino Petasis reaction between alkenyl boronates 149, a wide range of secondary amines 148, and ethyl glyoxylate (147) for the synthesis of chiral a-amino acids 150 (Scheme 42.33) [81]. 

Scheme 3.53 Synthesis of amino-acids using the Petasis reaction.

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