II. Isonitriles
- Page ID
- 24549
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
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
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.
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.
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
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