The Allylic Trihaloacetimidate Rearrangement

Abstract

Sigmatropic rearrangements of allylic systems have found wide application in organic synthesis, with carbon‐carbon bond forming rearrangements such as the Cope and Claisen rearrangements being particularly well known. The sigmatropic rearrangement of allylic imidates offers a valuable entry into the preparation of protected allylic amines. Conversion of an imidate to the amide is essentially irreversible, with the transformation of the imidate to the amide being exothermic by about 15 kcal/mol. Since the discovery of the thermal allylic imidate rearrangement in 1937, a number of systems have been investigated for the practical preparation of allylic amines by this route. However, it was the discovery and development of the rearrangement of allylic trichloroacetamidates that demonstrated the utility of this synthetic method. This chapter is limited to the discussion of allylic trichloro‐ and trifluoracetamidate rearrangements. The [3,3]‐sigmatropic rearrangement of trichloracetamidates (now called the Overman rearrangement) or trifluoroacetimidates can be carried out either thermally or with Hg(II) or Pd(II) catalysis, The scope of this rearrangement is such that primary, secondary, and tertiary allylic amides are readily accessible, thus providing a wide entry into nitrogen‐containing products such as amino sugars, nucleotides, peptides, etc. The Overman rearrangement has found extensive application in the total synthesis of natural products. The recent development of the use of chiral Pd(II) catalysts bodes well for amine synthesis.

Palladium(II)-Catalyzed Alkene Functionalization via Nucleopalladation: Stereochemical Pathways and Enantioselective Catalytic Applications

“…This work was recently the subject of two reviews; 105 therefore, only a brief discussion of milestone developments will be presented here. As discussed in section 2.2.5, the reaction is proposed to proceed via aminopalladation to form Pd-alkyl intermediate 99 , followed by rapid collapse to generate the allylic amide product and re-form the Pd II -catalyst (Scheme 32).…”

Formation of DPM ethers using O-diphenylmethyl trichloroacetimidate under thermal conditions

“…In our earlier studies 22a we noted that DPM imidate 1 would rearrange to the corresponding acetamide 4 when heated in refluxing toluene (Figure 1). Allylic trichloroacetimidates are known to rearrange though a concerted [3,3]-sigmatropic rearrangement (the Overman rearrangement 24 ), but this mechanism is not available to imidate 1 . There have been previous reports of benzylic imidates undergoing rearrangement in the presence of strong acid, 25 likely through a cationic pathway.…”

Palladium-Catalyzed Regio- and Stereoselective γ-Arylation of Tertiary Allylic Amines: Identification of Potent Adenylyl Cyclase Inhibitors

“…[4] Various strategies have been developed for the construction of γ-arylated N,N -dialkylallylamine derivatives. [5] One of the most desirable and straightforward ways would be a Heck arylation of N,N -dialkylallylamines at the terminal olefinic carbon (γ-position). In general, Heck arylations work well with activated and biased olefins such as acrylates and styrenes.…”