ASYMMETRIC CARBON – CARBON BOND- FORMING REACTIONS - Catalytic Asymmetric Synthesis - page 622

OPO(OEt) 2

Zn

1)

2
CuCN (10 mol %)/ L76a ,
THF, 78°C, 48 h

2) KOH, EtOH, 80°C

− 82% ee (82%)

TsO TsO

Sporochnol

Scheme 8B.99. Synthesis of sporochnol.

n-Hept OPO(OEt) 2 Ph OPO(OEt) 2

CO 2 t Bu

O

92% ee (73%) 92% ee (74%)

N

N NHBu

Pent

Pent

O

OH

OPO(OEt) 2 OPO(OEt) 2

L77b

96% ee (76%) 91% ee (77%)

Figure 8B.40. Substrates used in Et 2 Zn additions in the presence of ligand L77b .

O O

O

O O

Cl S

S

N H

H H

OH

PPh 2

L78 L79

Cl

Figure 8B.41. Sulfonamide ligands used in Cu-catalyzed allylic alkylations.

Unfortunately, with this ligand, the γ , α-selectivity dropped, in some cases to a 1:1
mixture. But in most cases, the selectivities were satisfying (Fig. 8B.40).
As the result of their excessive ligand screening, Hoveyda et al. were able to propose
a mechanistic rational explaining the stereochemical outcome of the reaction (Scheme
8B.100 ). Complex A with a pseudotetrahedral Cu(I) represents the resting state of the
chiral complex. Addition of the allylic substrates probably generates complex B where
the allylic double bond is coordinated to the copper ion. The larger substituent R l at the
double bond is orientated away from the peptide backbone and the terminal amide
functionality directs the allylphosphate via a zinc complex to one face of the ligand Cu
complex. Finally, the catalytic alkylation probably proceeds through the formation of a
Cu III -alkyl intermediate, followed by reductive elimination toward the desired product.
In 2002, Piarulli, Gennari, and others described the use of structurally related sulfon-
amide ligands L78 (Fig. 8B.41) in the Et 2 Zn addition toward cinnamyl phosphates [365],
giving 40% ee as the best selectivity (Table 8B.62, entry 10).