P-chiral 1-phosphanorbornenes: from asymmetric phospha-Diels–Alder reactions towards ligand design and functionalisation

Abstract

The principle of stereotopic face differentiation was successfully applied to 2H-phospholes which undergo a very efficient and highly stereoselective Diels-Alder reaction giving phosphorus-chiral 1-phosphanorbornenes with up to 87% yield. The observed reaction pathway has been supported by theoretical calculations showing that the cycloaddition reaction between 2H-phosphole 3a and the dienophile (5R)-(-)-menthyloxy-2(5H)-furanone (8) is of normal electron demand. Optically pure phosphanes were obtained by separation of the single diastereomers and subsequent desulfurisation of the sulfur-protected phosphorus atom. Finally, divergent ligand synthesis is feasible by reduction of the chiral auxiliary, subsequent stereospecific intramolecular Michael addition, and various functionalisations of the obtained key compound 13a. Furthermore, the unique structural properties of phospanorbornenes are presented and compared to those of phosphanorbornanes.

Review on asymmetric cycloaddition reactions at phosphorus (III) atom

“…22 The observed reaction pathway has been supported by theoretical calculations showing that the cycloaddition reaction between 2H-phosphole 10 and MOxF is of normal electron demand. 23 The [4+2] cycloaddition products were converted to their air stable sulfur derivatives, which were isolated and the endo-and exo-isomers were separated by column chromatography. The phosphorus atom in the obtained cycloadducts 11 and 12 was easily desulfurized to give the corresponding P(III)-species, which were further functionalized and yielded different bidentate phosphines.…”

Efficient Oxidative Resolution of 1-Phenylphosphol-2-Ene and Diels–Alder Synthesis of Enantiopure Bicyclic and Tricyclic P-Stereogenic C-P Heterocycles

“…Ready synthesis of enantiomers of 1 opens up the possibility of synthesizing also other optically active P-stereogenic heterocyclic compounds by employment of the conjugated double bond functionality present in its structure [24,28,30,33,[45][46][47][48][49][50]. To illustrate this potential, we decided to use (SP)-1 as a dienophile in the Diels-Alder reactions with acyclic and cyclic dienes to synthesize optically active bicyclic and tricyclic C,P-heterocycles [56][57][58][59][60][61]. The additions of rac-1 to acyclic dienes have been already described to occur at 260 °C and to afford the endo cycloadduct [46].…”

Facile Synthesis of Enantiomerically Pure P‐Chiral 1‐Alkoxy‐2,3‐dihydrophospholes via Nucleophilic P‐N Bond Cleavage of a 1‐Phospha‐2‐azanorbornene

“…[11] For several decades 2Hphospholes have played a key role in the production of Pheterocyclic compounds [12] including the preparation of P-chiral phosphorus heterocycles via HDA reaction. [13] The use of activated imines as dienophiles in an aza-Diels-Alder reaction proved to be a powerful method to produce heterocyclic compounds with feasible control over stereoselectivity as well as regioselectivity. [14] Based on this approach, we reported the first chemo-and regioselective phospha-aza-Diels-Alder reaction between 2H-phospholes and an N-sulfonyl α-imino ester to afford diastereomers of 1-phospha-2-azanorbornenes (PANs) as racemates (Supporting Information, Section 1.1).…”