The Isocyanide–Cyanide Rearrangement; Mechanism and Preparative Applications

Abstract

The cover picture (center) shows a CPK model of the structure of a hemicarcerand-a global minimum calculated with the MM2 force field (with the phenylethyl groups omitted). Quite astounding transformations have been carried out in its cavity. Reactions that occur within the host are gold-colored and the one that occurs outside is blue. The golden orb in the middle shows the locations of the guests within the hemicarcerand and highlights the small portal through which the guests enter and exit the interior of the host. "Incarcerated" cyclobutadiene is stable at room temperature and above in the absence of oxygen, but reacts with oxygen that enters the "container" to give incarcerated maleinaldehyde. This new type of chemistry promises to open a whole new field involving the study of electronically and sterically unperturbed reactive species. Review Art icl esOptically active cyanides (l), which are synthetically useful building blocks, may be obtained from naturally occurring a-amino acids (2) in overall yields of up to 60% and with ee values of > 98%. The key feature of the approach discussed here is the isocyanide rearrangement of 3, induced by flash photolysis. Thus this rearrangement, which has long been investigated primarily in terms of mechanism, now constitutes one step in a preparatively useful procedure.

Magnesium Cyanide or Isocyanide?

“…S ince HCN is aw eak acid, the cyanide anion is ar elatively strong base that can deprotonate water, epecially when this is acidified by coordination to as trong Lewis acid like Mg 2+ .U sing liquid ammonia as areaction medium circumvents this problem and led to first preparations of pure Mg(CN) 2 . [11] Thec rystal structure of B(CN) 3 ·pyridine shows CN/NC disorder with am ain contribution of the cyanide form (B À CN/B À NC = 95:5). [9] This essential isotropic coordinative behavior of the spinning cyanide anion is typical for ionic metal cyanides and explains its description as ap seudohalide.…”

Asmic Isocyanide‐Nitrile Isomerization‐Alkylations

“…In the absence of TMEDA, the lithiated isocyanide 18 evolves to a lithiated azirine similar to the thermal isocyanide‐nitrile mechanism . Distortion of 18 through a bending at the central nitrogen leads to transition structure 19 in which lithium maintains an interaction with the formally anionic carbon (2.10 Å) and the isocyanide carbon (2.76 Å).…”

“…Addition of BuLi to a –78 °C, THF solution of the acyclic and cyclic isocyanides 2a – 2c followed by BnBr triggered a remarkably facile synthesis of the corresponding benzylated nitriles 4a – 4c (Scheme 1). The rapid rearrangement at –78 °C in less than 5 minutes is extremely unusual because isomerization of isocyanides to their thermodynamically more stable nitrile counterparts typically requires temperatures in excess of 200 °C …”

Integrating Microwave‐Assisted Synthesis and Solid‐Supported Reagents

“…Interestingly, the same reagent was also used in the conversion of isothiocyanates to isocyanides under conventional thermal conditions. Whilst isocyanides were successfully produced, the products were discovered to be highly susceptible to a competing rearrangement process, generating the equivalent nitriles after prolonged heating 147 .…”