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

634 NITRONATES
Two procedures were developed for C,C-coupling reactions of silyl esters
of primary AN. One approach involves two steps and the synthesis of intermediate
SENAs according to standard procedures. Another procedure is based
on the one-pot reaction of AN with the DBU/TBSOTf system in a ratio of
1:1.1 followed by the addition of silyl ketene acetal and a catalytic amount of
TBSOTf.
SENAs derived from primary AN can undergo C,C-coupling reactions with
other silyl-containing nucleophiles (Eq. 2), which was exempliÞed by the reaction
of SENA derived from nitroethane. It should be noted that high diastereoselectivity
can sometimes be achieved by introducing a substituent at the reaction center
of the nucleophile.
The C,C-coupling reactions of ambident nucleophile CH2=CHCH=(OMe)OSi
occur regioselectively at the terminal C=C bond, but the reactions are characterized
by low stereoselectivity.
SENAs derived from secondary AN are not involved in catalytic C,C-coupling
reactions with silyl ketene acetals. This is possibly due to a decrease in both the
effective concentration of the cationic intermediate (the steric effect) and its lower
level of electrophilicity (see the lower entry in Table 3.23).
However, C,C-coupling reactions of sterically less hindered alkyl nitronates
derived from secondary AN with silyl ketene acetal were successfully performed
(Eq. 3). These reactions produced the target “mixed” nitroso acetals in moderate
yields.
Catalytic C,C-coupling reactions with Þve-membered cyclic nitronates were
reported (485) (Scheme 3.209).
The process was studied in sufÞcient detail for 3,5-disubstituted nitronates
(354). 2,6-Lutidine is added to bind TfOH as a by-product. Because of this addition
the temperature of C,C-coupling can be raised to −78 ◦ C, thus simplifying
R′
O N
R
O
OTBS
OMe
TfOSi (10−20%)
2,6-lutidine, −78 ° C
O N
+
R′
R
CO2Me
OTBS
354 355
R R′ Yield % dr
Me
Et
PhCH 2
PhCH2
n-C 6H 13
Me
MeO 2C(CH2)2
Ph
Ph
Ph
OEt
Ph
CO 2Me
Ph
77
76
71
93
91
73
50
Scheme 3.209
3.5:1
3.6:1
2.3:1
One isomer
4:1
10:1
3:1