Isocyanides, acid catalyzed addition reactions

Various a-addition reactions are observed to be metal- or acid-catalyzed, or to be uncatalyzed. In this review only the metal-catalyzed reactions will be discussed, since it is generally assumed that metal isocyanide complexes are involved in these systems. A number of metal-catalyzed a-addition reactions have been mentioned recently. Copper(I) oxide seems to be the most commonly used catalyst, although other metal complexes sometimes are satisfactory. Table III presents a partial survey of this work. 

Additionally, for catalyzed reactions, an example for synthesis of tetrazoles by reacting isonitriles and azides was reported. Yamamoto et aL reported that the acid-catalyzed [3-1-2] cycloaddition between isocyanides 322 and trimethylsUyl azide (146) in the presence of methanol gives the desired 1-substituted tetrazoles 323 in good yields (Scheme 68) [ 177-179). 

Disubstituted isocoumarins arise from the copper(II)-catalyzed addition of o-halobenzoic acids to active internal alkynes (13JOC1660), rhodium(III)-mediated oxidative coupling ofbenzoic acids with disubsti-tuted alkynes (13T4454), palladium(II)-catalyzed tandem annulation reaction of o-alkynylbenzoates with methyl vinyl ketone (13T8626), and nickel(II)-promoted t-butyl isocyanide insertion in 2-(o-bromophenyl)-1-ethanones followed by hydrolysis (Scheme 69) (13SC3262). 

Acid-catalyzed iminium ion 57 fonnation is followed by isocyanide 54 addition and capture of the remaining nitrilium ion 58 by the carboxylate of 56 to generate compound 59. A rapid O N acyl transfer takes then place in order to obtain dipeptide 60 as a mixture of epimers at C4. Although the control of the stereochanistry of the newly formed stereocenter still remains a problan of the Ugi reaction, it nicely demonstrates the force of the Ugi MCR, as all of the carbon atoms needed are successively assanbled in a single step [22], Mannich-type 4CR are often used for the synthesis of natural products. One example is the synthesis of the alkaloid ( )-roelactamine 65 (Scheme 6.6). The reaction of piperonal 61 with methylamine, Grignard reagent 62, and acid chloride 63 results in the formation of amide 64, which... 

T. Yue, M.-X. Wang, D.-X. Wang, G. Masson, J. Zhu, Angew. Chem. Int. Ed. 2009,48, 6717-6721. Brpnsted acid catalyzed enantioselective three-component reaction involving the a-addition of isocyanides to imines. 

A few additional Pd-catalyzed schemes have been employed for Ilac type cyclization chemistry. Palladium-phenanthroline complexes were used by the Ragaini group to prepare indoles via the intermolecular cyclization of nitroarenes and alkynes in the presence of carbon monoxide <06JOC3748>. Jia and Zhu employed Pd-catalysis for the annulation of o-haloanilines with aldehydes <06JOC7826>. A one-pot Ugi/Heck reaction was employed in the preparation of polysubstituted indoles from a four-component reaction system of acrylic aldehydes, bromoanilines, acids, and isocyanides <06TL4683>. 

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. 

The [3 + 2] addition of type IIbd is a significant method for synthesis of both simple and complex pyrrole derivatives. One manifestation of this pattern is seen in the base-catalyzed condensation of tosylmethyl isocyanide with alkenes having strong electron-accepting substituents. The aromatization by elimination of the arenesulfinic acid occurs under the reaction conditions (equation 117) (72TL5337). This reaction can be applied to the synthesis of 2,3,4-trisubstituted pyrroles by using C-alkylated tosylmethyl isocyanides or AT-tosyl-methyl-51-methylthioimidates (77H(7)77, 8IJHCII27). 

Denmark and Fan developed a chiral Lewis base (138)-catalyzed asymmetric a-addition of isocyanides to aldehydes with good to excellent enantioselectivity (Scheme 5.41) [84]. The protocol is applicable to non-chelating aldehydes, but it is a bimolecular transformation since the carboxylic acid is excluded from the reaction. 

Aqueous inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid and, preferentially, sulfuric acid, as well as some Lewis acids, e.g. boron trifluoride etherate and titanium tetrachloride, catalyze the a-addition of the isocyanides, yielding the a-hydroxycarboxamides (24) in 12-88% The catalysis of this reaction by acids is due to an enhancement of the electrophilic reactivity of the carbonyl compound (4). 

The mechanism is presumed to involve a pathway related to those proposed for other base-catalyzed reactions of isocyanoacetates with Michael acceptors. Thus, base-induced formation of enolate is followed by Michael addition to the nitroalkene and cyclization of nitronate to furnish the nitro-isocyanide after protonation. Loss of nitrous acid (HNO2) and aromatization then affords the pyrrole ester. 

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