Passerini-type reaction

In a related study Denmark and Fan [22] investigated chiral Lewis base-catalyzed enantioselective a-additions of isocyanides to aldehydes in a Passerini-type reaction (Scheme 9.14). The development of the reaction was based on the concept of Lewis base activation of a weak Lewis acid such as SiCl4 forming a trichlorosilyl-Lewis base adduct which is capable of activating aldehydes towards nucleophilic attack. 

Scheme 9.14. Lewis base-catalyzed enantioselective Passerini-type reactions.

Denmark, S. E., Fan, Y. The First Catalytic, Asymmetric a-Additions of Isocyanides. Lewis-Base-Catalyzed, Enantioselective Passerini-Type Reactions. J. Am. Chem. Soc. 2003, 125, 7825-7827. 

In a Passerini type reaction treatment of arylglyoxals with cyanoacetic acid and isocyanide yields 3> aryl-2-cyanoacetoxy>3-oxopropionamides. Cyclization of these compounds under basic conditions gives 2>hydroxyfurans (2-fiiranones), albeit in low yield <93S783>. 

Mechanism of Lewis Acid-Promoted Passerini-type Reactions... 

A survey of the many examples of Lewis acid-promoted Passerini-type reactions, finds that most are characterized by one of four distinct processes a) nucleophilic attack of an additional equivalent(s) of isonitrile to form oligomeric products " (17) b) nitrogen dealkylation to give cyanohydrin-type products (18) c) intramolecular capture of tethered-nucleophiles to form cyclic products (19) and d) intermolecular capture of other weakly-basic nucleophiles such as dissociable counterions of the Lewis acid (20) such as the chloride ion for TiCk. 

Alternatively, cyclic enol ethers can serve as the electrophile in Passerini-type reactions as they undergo protonation by strong Bronsted acids to produce oxocarbeniums as the reactive partner. More recently, acyl cyanides have been demonstrated to participate as the carbonyl component in Passerini reactions, giving a-acyloxy-a-cyano amides in good yields. ... 

Aqueous mineral acids have been shown to be capable of promoting Passerini-type reactions, producing a-hydroxyamides in good yields. Both aldehydes and unencumbered ketones function well as appropriate substrates. 

Other acids that have been used in Passerini-type reactions include hydrazoic acid"" and its Lewis acid congenitors, such as A1(N3)3 and TMSN3. In these presence of azide salts the intermediate nitrilium is instead intercepted by azide in a stepwise [3 + 2]-cycloaddition to give the 1,5-... 

There are many examples of Passerini-tj e reactions mediated by Lewis acids with TiCU having the most widespread use. Passerini-type reactions using TiCU are compatible with a variety of functional groups as can be seen in the nearly quantitative reaction of a-isocyano phosphonate ester 25 with benzaldehyde. An examination of TiCU-mediated diastereoselective Passerini reaction failed to show any clear stereoselection with chiral isocyanide 26 among many other cases. Weaker Lewis acids such as SiCL can also mediate Passerini-twe reactions, but effectively do so only in the presence of a Lewis base. Demnark demonstrated that a-hydroxyamides, such as 27, could be formed in good yields, by using Lewis bases such as pyridine-7V-oxide to activate the SiCU-... 

Denmark has described several chiral bis-phosphoramides as Lewis base activators of weak Lewis acid SiCL and demonstrated their ability to mediate an enantioselective Passerini-type reaction. Catalytic bis-phosphoramide 36 and stoichiometric SiCU, in the presence of a proton scavenger (Htinig s base), promoted the formation of a-hydroxyamides with remarkably good enantioselectivity and yield. A variety of aromatic and unsaturated aldehydes and aryl, alkyl, and functionalized alkyl isocyanides proved to be useful and effective starting materials. High yields of Passerini products were attributed to the production of imidoyl chloride 37, which reduced the prevalence of the nitrilium intermediate and prevented the addition of a second equivalent of isonitrile. 

Almost simultaneously, the same research group disclosed a [(salen)Al "Me] 43-catalyzed enantioselective Passerini-type reaction of aldehydes, isocyanides, and hydrazoic acid 42, affording a great scope of tetrazole derivatives 44 with good to excellent enantioselectivities (51-95%) (Scheme 8.16) [39]. 

T. Yue, M.-X. Wang, D.-X. Wang, J. Zhu, Angew. Chem. Int. Ed. 2008, 47, 9454—9457. Asymmetric synthesis of 5-(l-hydroxyalkyl)tetrazoles hy catalytic enantioselective Passerini-type reactions. 

In 2008, Wang and Zhu s group reported the catalytic asymmetric Passerini-type reaction of aldehydes, isocyanides and hydrazoic acid with... 

Scheme 19.61 Asymmetric Passerini-type reactions catalysed by Al(salen).

Keywords Isocyanides, sy -chlorooximes, carboxylic acids, TEA, dichloromethane. Alcohols, room temperature, sy -a-oximinoamides, stereospecific synthesis, Passerini-type reaction, Mumm-type rearrangement... 

Scheme 7.1 Passerini-type reaction catalysed by chiral phosphoric acid catalysis and aluminium catalysis.

Denmark SE, Ean Y (2005) Catalytic, enantioselective a-additions of isocyanides Lewis base catalyzed Passerini-type reactions. J Org Chem 70 9667-9676... 

Denmark SE, Fan Y (2003) The first catalytic, asymmetric alpha-additions of isocyanides. Lewis-base-catalyzed, enantioselective Passerini-type reactions. J Am Chem Soc 125 7825-7827... 

Yue T, Wang M-X, Wang D-X, Zhu J (2008) Asymmetric synthesis of 5-(l-hydroxyaIkyl) tetrazoles by catalytic enantioselective Passerini-type reactions. Angew Chem hit Ed 47 9454-9457... 

Lewis acid catalysis serves for the Passerini-type reaction of aldehydes with isocyanides forming a-hydroxyamides. The catalytic system consisting of SiCU and (107) provides high yield and good to excellent enantioselectivity for the addition of t-butyl isocyanide to a wide range of aldehydes [167]. The amide product is formed from the imidoyl chloride intermediate (110) by hydrolysis (Scheme 9.78). Treatment of the intermediate product with methanol followed by hydrolysis gives a-hydroxyesters with the retention of enantioselectivity. 

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