Mandyphos

The parent ligand 1 was first reported by Schwink and Knochel and was later described as one of a class of FERRIPHOS ligands. Later publications rebranded the following structures differing only in the nature of the phosphorus substituents as MandyPhos ligands. The following lists reactions, organised by metal (Pd, RhRu, Ir, Cu, Ni) for which the application of these ligands has resulted in >80% ee. ACE = Asymmetric Catalytic Efficiency. Literature covered until end 2017 (16 entries).

MandyPhos-Ligands

Palladium

Pd-Cross-coupling CEJ98-4-950

PP-MandyPhos_CEJ98-4-950

 

Pd – Conjugative cross-coupling Science16-351-70

Mandyphos_Science16-351-70

The presence of lithium halide salts (even at 1-2 mol%) markedly erodes conjugative coupling efficiency. Later found that this inhibition may be overcome by the addition of NaOTf or KOTf such that vinyllithium may be generated from the addition of t-BuLi (2 eq.) to vinyl bromide and conjugative cross-coupling carried out with 2.2 eq. of KOTf. See JACS17-39-3153.

JACS17-139-3153

Mandyphos_JACS17-139-3153

JACS17-139-5027

Mandyphos_JACS17-139-5027

Allyl boron reagents containing 1- or 2-(Z)-substituents resulted in ee values <80%. Halide free vinyllithium employed generated from tetravinylstannane by Li-Sn exchange. Vinyl magnesium chloride and vinyllithium generated from vinyl bromide (+ 2 eq. t-BuLi) also used successfully provided 2 eq. of NaOTf or KOTf added, respectively (and at 2 mol% catalyst loading).

 

Rhodium

Rh-Hydrogenation TA98-10-375

PP-Mandyphos_TA99-10-375

TA04-15-2299

PP-MandyPhos_TA04-15-2299

Enamide MAC (methyl α-acetamidocinnamate) also hydrogenated (H2 – 1 bar) to give product in 99% ee with Mandyphos-1 and [Rh(NBD)2]BF4 in biphasic 1 : 1 [omin]BF4/H2O – see ASC04-346-1481.

ASC09-351-1423

PP-MandyPhos_ASC09-351-1423

Absolute configuration assigned by comparison to data in CEJ09-15-10983. Josiphos-3 has also been applied to this reaction.

CC12-48-9852

PP-MandyPhos_CC12-48-9852

 

Rh – Asymmetric ring opening JACS06-128-6837

Mandyphos_JACS06-128-6837

The ligand used is described as Ferriphos and is closely related to Mandyphos-1. It is reasonable to suggest that the latter woud give similar results (e.g. – see next entry).  Ferriphos not commercially avaialble. For synthesis see TA99-10-375 and earlier work by Hayashi in CC89-495.

Angew14-53-5951

PP-MandyPhos_Angew14-53-5951

 

Ruthenium

Ru – Hydrogenation TA04-15-2299

PP-MandyPhos_Ru_TA04-15-2299

Synthesis17-49-353

Mandyphos_Synthesis17-49-353

Diastereoselective hydrogenation in a biphasic system with the product isolated after separation of the aqueous phase from ionic liquid [EMIN][NTf2] followed by addition of HCl(aq). Catalyst phase reused for an additional 6 cycles with little loss of selectivity and conversion (so ACE = approximately 700).

 

Iridium

Ir – Transfer hydrogenation CEJ08-14-10388

PP-MandyPhos_CEJ08-14-10388

Absolute configuration assigned by comparison to the result obtained for the reduction under the 1% Ir/ligand conditions of acetophenone [72% ee (S)].

 

Copper

Cu – Beta borylation Angew08-47-145

PP-MandyPhos_Angew08-47-145_1

Similar ee values obtained with Josiphos-1.

CEJ09-15-1939

PP-MandyPhos_CEJ09-15-1939

Josiphos-1 also applied successfully to this reaction (more examples).

 

Nickel

Ni – Lactam C-acylation JACS16-138-8997

PP-MandyPhos_JACS16-138-8997_1