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II. Isonitriles

  • Page ID
    24549
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    A. Reactions

    1. Group Replacement

    a. Isocyano Groups

    Reaction of tri-n-butyltin hydride with carbohydrates containing iso­cyano groups replaces each of these groups with a hydrogen atom. Such replace­ment is known to occur when isocyano groups are attached to ano­meric,1,2 secon­dary,3–9 and pri­mary7–9 carbon atoms. An example of replace­ment at an anomeric carbon atom is shown in eq 1,5 while both primary and secondary groups are replaced in the reaction described in Scheme 1.7,9

    II16(1).png

    II16s1.png

    Isocyano group replacement is remarkably temperature sensitive. Reac­tion of the secondary groups in 1 takes place at 70 oC, but the primary iso­cyano group is unreactive (Scheme 1).7,9 When the temperature of the reac­tion mixture is raised to 80 oC, both groups are replaced. This tem­per­ature dependence provides a basis for regioselective reaction.

    A mechanism for isocyano group replacement with a hydrogen atom is pictured in Scheme 2.10 In the first step of this process the tri-n-butyltin radi­cal adds to the carbon atom of the isocyano group to produce an imidoyl radi­cal (2). Fragmentation of this radical (2) then generates the carbon-centered radical R·, which abstracts a hydrogen atom from Bu3SnH to complete the reac­tion sequence. If R represents a phenyl or substituted-phenyl group, fragmentation to give an aryl radical does not occur; rather, an addition reaction takes place.11 When tris(tri­methyl­silyl)­silane replaces tri-n-butyl­tin hydride in reduction of isonitriles, compounds containing primary, secon­dary, or tertiary isocyano groups all are reactive.12

    II16s2.png

    b. Sulfhydryl Groups

    An isonitrile can participate in replacement of a sulfhydryl group by a hydro­gen atom.13 Such a reaction is pictured in Scheme 3, where replace­ment begins when the sulfur-centered radical 4 forms from the thiol 3 by hydrogen-atom abstraction. Addition of 4 to t-butyl isocyanide gives the adduct radical 5, which then fragments to produce the pyranos-1‑yl radical 6. Hydrogen-atom abstraction by 6 from another molecule of the starting thiol (3) completes the cycle and begins a new reaction sequence. Sulfhydryl group replacement repre­sents another pathway for generating carbon-centered, carbohydrate radi­cals.

    II16s3.png

    2. Elimination Reactions

    Reaction of tri-n-butyltin hydride with a carbohydrate that has adjacent ­isocyano and O-thio­carbonyl groups generates a product with a C–C double bond (Scheme 4).4 In this reaction radicals 7 and 8 are both possible inter­medi­ates. Study of the diiso­nitrile 9 provides infor­mation helpful in choosing between 7 and 8. Reaction of 9 with Bu3Sn· produces a carbon-centered radi­cal (10) with an isocyano group attached to the carbon atom adjacent to the radical center (Scheme 5).8 The intermediate 10 does not expel a cyano radi­cal to form a multiple bond but rather abstracts a hydrogen atom from tri-n-butyltin hydride. Extrapolating the behavior of 10 to the reaction shown in Scheme 4 leads to the conclusion that the radical 8 is an unlikely inter­mediate in this process.

    II16s4.png

    II16s5.png

    3. Addition Reactions

    As a part of the replacement process shown in Scheme 2, an isonitrile reacts with Bu3Sn· to produce an intermediate, carbon-centered radical R·. Normal completion of this reaction involves hydrogen-atom abstraction by R· from Bu3SnH; however, if R· is formed without a hydrogen-atom transfer present, it will add to a molecule of isonitrile (Scheme 6). A specific example of this type of reaction is found in eq 2, which describes the α addition of a pyranos-1-yl radical, formed from a carbohydrate telluride, to an aromatic isonitrile.14

    II16s6.png

    II16(2).png

    B. Synthesis

    It is possible to produce isonitriles from isothiocyanates by radical reac­tion (eq 3).2 A pro­posed mechanism for such a structural change is shown in Scheme 7. Isonitrile formation results when reaction is conducted at room temperature (eq 3), but if the reaction temperature is raised to 110 oC, the iso­nitrile is not isolated because it undergoes isocyano group replacement by a hydrogen atom (eq 4).2,15

    II16(3).png

    II16s7.png

    II16(4).png


    This page titled II. Isonitriles is shared under a All Rights Reserved (used with permission) license and was authored, remixed, and/or curated by Roger W. Binkley and Edith R. Binkley.

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