PPFA

The original. First synthesised by Hayashi, Yamamoto and Kumada using the diastereoselective lithiation of N,N-dimethyl-1-ferrocenylethylamine reported previously by Ugi et al. PPFA has principally been employed as an intermediate in the synthesis of many other ligands, there being relatively few reports on the use of this as a ligand in asymmetric catalysis. Examples of PdCu and Ag catalysis that result in >80% ee are listed below.  ACE = Asymmetric Catalytic Efficiency. Literature covered until end 2017 (12 entries).

C26H28FeNP_1

Palladium

Pd – Asymmetric Suzuki cross-coupling CC00-1723 and Tet04-60-4377

PNL2_CC00-1723 and Tet04-60-4377-1

CEJ06-12-9346

PN-L2_Pd_CEJ06-12-9346

 

Pd – Asymmetric Negishi cross-coupling TA06-17-2593

PN-L2_Pd_TA06-17-2593

BCSJ83-56-363

PN-L2_Pd_BCSJ83-56-363

Pd – Asymmetric Grignard cross-coupling JOC86-51-3772

PN-L2_Pd_JOC86-51-3772

 

Pd – Asymmetric organoindium cross-coupling EJOC13-2555

PN-L2_Pd_EJOC13-2555

 

Copper

Cu – 3 + 2 cycloaddition ACSCat17-7-210

PNL2_ACSCat17-7-210

One example with (S,Sp)-PN-L2 from a scoping study in which a Ming-Phos ligand gave a similar result (94% ee, 91% conversion, 15 : 1 dr at -40 oC). Further reaction optimisation and exemplification was with a Ming-Phos ligand.

 

Cu – Imine alkylation TA05-16-2531

PN-L2_Cu_TA05-16-2531

 

Cu – Conjugate addition TA06-17-136

PN-L2_Cu_TA06-17-136

Absolute configuration of products assigned by use of data in TA12-23-130

 

Cu – Beta (1,4) borylation OL16-18-3926

PNL1_OL16-18-3926_1

Silver salt rather than base used to avoid α-carbonyl epimerisation. Use of Phosferrox PN-L1a and Josiphos-1 reported to result in no product formation.

 

Silver

Ag – 3 + 2 cycloaddition JACS07-129-750

PN-L2_Ag_JACS07-129-750

Not an example of >80% ee but included as the corresponding  ligand with NMereplaced by NHresults in a hydrogen-bonding reversal of enantioselectivity (83% ee).

Ag – 3 + 2 cycloaddition and 1,4-addition OL17-19-5236

PNL2_OL17-19-5236