Enantioselectivity Petasis reaction

In 2012, Yuan and coworkers [66] reported an enantioselective Petasis reaction among salicylalde-hydes, amines, and organoboronic acids catalyzed by a new thiourea-binol catalyst (Scheme 6.47). 

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 chiral thiourea organocatalyst for the catalytic enantioselective Petasis reaction... 

Scheme 6.82 Proposed reactive complex of the Petasis reaction utilizing a-hydroxy aldehydes, amines, and organic boronic acids (A) and bifunctional mode of action of chelating thiourea catalyst 65 in the enantioselective Petasis-type 2-vinylation of N-acetylated quinolinium ions (B).

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

Yamaoka, Y, Miyabe, H. and Takemoto, Y. (2007) Catalytic enantioselective Petasis-type reaction of quinolines catalyzed by a newly designed thiourea catalyst. Journal of the American Chemical Society, 129, 6686-6687. 

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... 

Later, Schaus group reported a new organocatalytic enantioselective example of Petasis reaction employing chiral biphenol-derived diol 30 as effective catalyst to promote... 

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. 

Figure 6.4 Products derived from the catalytic enantioselective Petasis-Akritopoulou reaction of quinolones catalyzed by a thiourea catalyst, as described by Takemoto s group [65].

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). 

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. 

Scheme 42.33 Enantioselective domino Petasis reaction of ethyl glyoxylates, secondary amines, and various vinyl boronates.

Scheme 42,34 Enantioselective domino Petasis reaction of salicaldehydes, cyclic secondary amines, and boronic acids using a hybrid biphenol-thiourea catalyst.

Similarly, the reaction of alkenyl boronic acids with azomethines can be found. Indeed, the corresponding 3-CR was used by Petasis [33] for the enantioselective synthesis of a-amino acids starting from amines, a-keto acids and alkenyl boronic acids. 

To create stereochemical diversity within MCRs there is need for stereoselective (or -specific) reactions. Since many MCRs involve flat intermediates, like imines and a,p-unsaturated ketones, they result in the formation of racemic products. Moreover, often mixtures of diastereomers are obtained if more than one stereo-genic centre is formed. However, there are several examples known of asymmetric induction, by the use of chiral building blocks (diastereoselective reactions). For example, it has been successfully applied to the Strecker, Mannich, Biginelli, Petasis, Passerini, Ugi, and many other MCRs, which has been excellently reviewed by Yus and coworkers [33]. Enantioselective MCRs, which generally proved to be much harder, have been performed with organometaUic chiral catalysts and orga-nocatalysts [33, 34]. 

The same catalyst has been used by this research group in synthesis of j -amino-aldehydes (146) by combining two catalytic reactions, i.e. a Ni(II) complex-catalyzed isomerization of a double bond and a chiral phosphoric acid (127)-catalyzed aza-Petasis-Ferrier rearrangement in a highly dia-stereo- and enantioselective manner (Scheme 39). ... 

Ionic liquids [61], were found to accelerate the Petasis boron Mannich reaction of 2-hydroxy aryl aldehydes, secondary amines, and arylboronic acids, under mild conditions, by the group of Yadav [62]. As far as we are aware, these authors were the first (and only ) to report the use of ionic liquids in this reaction. The remarkable features of this procedure were the improvement of yields in the synthesis of the desired products, as well as enhanced reaction rates and the possibility of recycling the ionic liquid for up to five times without apparent loss in enantioselectivity. 

Scheme 7.8 Enantioselective synthesis of a-amino acids using a diastereoselective Petasis borono-Mannich reaction.

The use of chiral boronic esters in the Petasis borono-Mannich reaction has been reported to result in low levels of enantioselectivity of the adducts at room temperature (6-15% ee) [48]. Auxiliaries used in this study by Scobie and co-workers included pinanediol and tartaric acid derived alkenylboronates. Morpholine was the only secondary amine used, with the primary amine ethyl glycinate failing to react. 

Subsequently, the same group demonstrated an asymmetric synthesis of 3-amino aldehydes via catalytic double-bond isomerization/enantioselective aza-Petasis-Ferrier rearrangement reaction (Scheme 2.93) [128]. Similarly, the hemiaminal allyl ether substrates 346 were first isomerized by Ni(II) complexes to stereoselectively form Z-configured vinyl ethers 347, which then underwent a phosphoric acid-catalyzed... 

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