Palladium-Catalyzed Allylic Transposition of (Allyloxy) Iminodiazaphospholidines:  A Formal [3,3]-Aza-phospha-oxa-Cope Sigmatropic Rearrangement for the Stereoselective Synthesis of Allylic Amines

Abstract

The synthesis of N-protected allylic amines has been achieved utilizing a palladium(II)-catalyzed, [3,3]-rearrangement of (allyloxy) iminodiazaphospholidines. This [3,3]-aza-phospha-oxa-Cope sigmatropic rearrangement reaction is thermodynamically driven by a P=N to P=O interconversion and is an alternative to the Overman rearrangement. The overall process involves the nucleophilic displacement of an allylic alcohol onto a P(III) precursor, followed by a Staudinger reaction to generate the (allyloxy) iminodiazaphospholidine precursors. Pd(II)-catalyzed [3,3]-aza-phospha-oxa-Cope rearrangement then gives a phosphoramide, which is readily hydrolyzed under acidic conditions to yield allylic amine derivatives. Pd(II) catalysis is believed to occur in a fashion analogous to that of the rearrangement of allylic imidates. The scope of racemic, diastereoselective, and enantioselective variants of this rearrangement is described. The use of chiral diamine auxiliaries in diastereoselective rearrangements is reported. Rearrangement of chiral N,N'-dimethyl cyclohexanediamine derived diazaphospholidines gives rise to phosphoramides with moderate diastereoselectivities (up to 3.5:1 dr). The same major diastereomeric product in these rearrangements was prepared irrespective of the starting allylic alcohol geometry. An enantioselective variant of the reaction was demonstrated for the rearrangement of cis-(allyloxy) iminodiazaphospholidines with cobalt oxazoline palladacycle (COP-X) catalysts (5 mol %) in high yield and enantioselectivity (up to 96% ee).

Total Synthesis of (±)-Phomactin A. Lessons Learned from Respecting a Challenging Structural Topology

“…Exposure of tertiary alcohol 43 to acylation as well as formylation conditions 38 may have provided the desired acetate or addition product, but the high impurity resulting from the reaction forced us to abandon this approach. At this point we became very interested in obtaining carbonate 53 in the hope of transposing the allylic alcohol stepwise through revisiting palladium π-allyl chemistry via complex 54 , 39–41 or thermally via a seemingly well positioned [3,3]-sigmatropic rearrangement [see Model of 53 in Scheme 14]. 42 However, an attempted removal of the PMB group using DDQ in CH 2 Cl 2 /H 2 O met with failure 43 while exposure of MOM-ether 44 to bromocatechol borane resulted in extensive decomposition.…”

Transition metals in organic synthesis: Highlights for the year 2005

“…Palladium catalyzed a Cope rearrangement [1463] and an [3,3]-aza-phospha-Cope rearrangement (Eq. (352)) [1464]. Tungsten catalyzed a Cope rearrangement of allenyl silyl enol ethers (Eq.…”

Chemistry of the highly stable hindered cobalt sandwich compound (η5-Cp)Co(η4-C4Ph4) and its derivatives

“…The ferrocenyl oxazoline and cobalt oxazoline palladacycles [203,205,207] Overman-Claisen rearrangement of trichloroacetimidates to trichloroacetamides has been a standard reaction carried out to compare the efficiency of many catalysts especially in terms of Overman, Richards and coworkers fine tuned some of these catalysts for better yield and enantioselectivity and a range of catalysts, basically varying in the additional ligands bound to palladium were reported [204,[208][209][210] [204,[208][209][210] Sutherland reported a tandem aza-Claisen rearrangement and ring closing metathesis for the synthesis of cyclic trichloroacetamides using the COP catalysts [216]. Batey and coworkers reported [3,3] sigmatropic rearrangements of 2-allyloxy pyridines and allyloxy iminodiazaphospholidines using the COP catalysts [217,218]. The COP-Cl catalyst was also utilized in the asymmetric synthesis of unsaturated moncyclic and bicyclic nitrogen heterocycles [219].…”