Nitrile Oxides, Nitrones, and Nitronates in Organic Synthesis : Novel ...

614 NITRONATES
SiO
N
O
H R1 327
+
R 2
O
R1 = Et, n-C5H11 R2 = Ph, p-X-C6H4 (X = NO2, CN, MeO),
n-C5H11, PhH=CH
Cat
10% mol
HO
R 2
R- But , Ph;
n = 1, X – ClO4, PF6 n = 2, X – OTf, SbF6 Et
NO2
O
Scheme 3.193
Cat:
N N
R
CuXn R
MeO CF 3
Ph COCl
pyridine
CH 2Cl 2l
O
MeO
Ph
O
R 2
CF3
O
Et
NO 2
330
Yield 330 - 34%–81%
10:1 > dranti > 3:1
for anti: 65% > ee > 40%
This process involves C,C-coupling and silylation of the resulting product with
Me3SiX which is eliminated. The yields of target products (329) are 52 to 99%.
The excess of the erythro isomer de = 80 to 97%. The reactions with the use of a
catalyst containing a chiral ligand give the erythro isomer with an enantiomeric
excess of 83 to 98%. To prevent racemization of the target product, the process
shown in Scheme 3.192 was optimized with respect to the catalysts at −100 ◦ C.
The resulting products (329) can be considered as convenient precursors of chiral
unnatural amino acids and other biologically active compounds.
The application of this approach to the enantioselective “classical” Henry
reaction with SENAs (327) is exempliÞed in Scheme 3.193 (455).
As can be seen from the above data, the enantiomeric excess for target products
(330) is low. This process requires improvements.
3.5.1.1.2. Silyl Nitronates in the Mannich Reaction The Mannich reaction with
SENAs (Scheme 3.194) was also modiÞed (459). This reaction in nonpolar solvents
produced previously unavailable β-nitroamines (331), which are unstable
in water and other protic solvents.
In Scheme 3.194, this process is represented as proceeding through the sixmembered
cyclic transition state, although C,C-coupling of two ions generated
from the starting substrates cannot be ruled out. However, the structure of the
nitronate can be varied over a wide range; attempts to modify the siloxymethylene
component failed.
It should be noted that the demarcation between metal complex catalysis of
the Henry (454–458) and Mannich reactions is arbitrary, and that the catalyzed
process is sometimes called the Mannich reaction (see, e.g., Ref. 456).
3.5.1.1.3. Silyl Nitronates in the Michael Reaction The Michael reactions with
SENAs were unknown until recently. Competitive [3 + 2]-cycloaddition reactions
have been used instead of this process (for more details, see Section 3.4.3.).