Isocyanides, acid catalyzed reaction

The acid-catalyzed reaction of oxetanes with t- butyl isocyanide gives 2-iminotetra-hydrofurans, boron trifluoride etherate being used as catalyst (equation 26). The authors proposed that the isocyanide reacts with the protonated oxetanes by an N2 mechanism (70S475). 

The chemistry described by Saegusa, Kobayashi, and others (Sehemes 1 to 4 and Table 1) is reminiscent of the earlier work by Zeeh (Scheme 5) [16-18]. These Lewis acid-catalyzed reactions of isocyanides with ketones are shown in equation 3. The A/-/crt-butyl group in 37 is removable by boron trifluoride etherate. A suggested pathway is illusttated in equation 3 and is initiated by BE3 activation of the aryl ketone (38). Some indoles prepared by Zeeh are 39-41 [17]. The elegant free-radical cyclization of aryl isocyanides developed by Fukuyama is presented in Chapter 49. 

Synthesis of a-hydroxycarbo mides by acid catalyzed reaction of an isocyanide with an aldehyde or ketone (see 1st edition)... 

The above Lewis acid-catalyzed reaction between NSBVs 6-1 and isocyanides represents a formal [5 h- 1] cycloaddition pattern. This cycloaddition reaction has several features. (1) Site-selective. The cyclization occurred exclusively at the 4,8-positions, other than the 4,6-positions. (2) Highly reactive. The strained ring tension remarkably weakens the C-N bond in 6-1. In comparison, insertion of isocyanides with simple aziridines is very rare [30, 31]. (3) The active involvement of the whole ring skeleton of the NSBV compound makes it unusual. (4) Synthetically useful. Poly-V-heterocyclic skeletons are constructed efficiently in one-pot. 

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. 

Almost accidentally, Bienayme and Bouzid discovered that heterocyclic amidines 9-76 as 2-amino-pyridines and 2-amino-pyrimidines can participate in an acid-catalyzed three-component reaction with aldehydes and isocyanides, providing 3-amino-imidazo[l,2-a]pyridines as well as the corresponding pyrimidines and related compounds 9-78 (Scheme 9.15) [55]. In this reaction, electron-rich or -poor (hetero)aromatic and even sterically hindered aliphatic aldehydes can be used with good results. A reasonable rationale for the formation of 9-78 involves a non-con-certed [4+1] cycloaddition between the isocyanide and the intermediate iminium ion 9-77, followed by a [1,3] hydride shift. 

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. 

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). 

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. 

Lewis Acid-Catalyzed Site-Selective Cycloadditions of 2,6-Diazasemibullva-lenes with Isocyanides, Azides and Diazo Compounds Novel Reaction Patterns Leading to Diaza- and Triaza-Brexadiene Derivatives. 

Herein, the author reports Lewis acid-catalyzed diverse cycloaddition reactions of NSBVs 6-1 with a wide variety of isocyanides, azides, and diazo compounds. These reactions afforded 5,8-diaza- and 2,5,9-triaza-brexadiene derivatives as highly fused A -containing polycyclic frameworks, which are structurally and chemically interesting cage-shaped compounds, but not readily accessible by other means. Unique and unprecedented rearrangement-cycloaddition patterns are revealed. These reaction patterns are not only different from our previously reported reaction with DMAD or RNCO, but most notably, very different from the reactions... 

Zhang S, Zhang WX, Xi Z (2013) Lewis acid-catalyzed site-selective cycloadditions of 2,6-diazasemibullvalenes with isocyanides, azides and diazo compounds novel reaction patterns leading to diaza- and triaza-brexadiene derivatives. Angew Chem Int Ed 52 3485-3489... 

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>. 

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