Chemistry Reference
In-Depth Information
5.2.1 Use of P1 Base
5.2.1.1 Alkylation of C-Nucleophile
The catalytic enantioselective alkylation of the benzophenone imine of glycine tert-butyl
ester was realized by an efficient homogeneous reactionwith alkyl halides, the phosphazene
base (BEMP or BTTP) and chiral quaternary ammonium salts derived from the cinchona
alkaloids. Wang-resin bound derivatives of the glycine Schiff base ester were alkylated in
the presence of quaternary ammonium salts derived from cinchonidine or cinchonine using
phosphazene bases to give either enantiomer of the product
-amino acid derivatives in 51-
89% ee. The enantioselective conjugate addition of Schiff base ester derivatives to Michael
acceptors either in solution (56-89% ee) or in the solid phase (34-82% ee) gave optically
active unnatural
a
-amino acid derivatives. The reaction was conducted in the presence of
chiral quaternary salts derived from the cinchona alkaloids using phosphazene bases.
Reacting imine derivatives of resin-bound amino acids with
a
a
,
o
-dihaloalkanes provides
highly versatile intermediates to racemic
-disubstituted amino acids withwide variety of
side-chain functionality. They allow the creation of amino acids with diverse functionalities
placed at varying chain length from the
a
,
a
-center of the amino acid [17] (Scheme 5.3).
Iminic derivatives of (4R,5S)-1,5-dimethyl-4-phenylimidazolidin-2-one have been dia-
stereoselectively alkylated with activated alkyl halides or electrophilic olefins either under
phase transfer catalysis (PTC) conditions or in the presence of the phosphazene base BEMP
at
a
20
C in the presence of lithium chloride (LiCl). Hydrolysis of the alkylated imino
imides gave (S)-
-amino acids with recovery of the imidazolidinone chiral auxiliary [18].
The phenylsulfinyl fluoroacetate can be alkylated with a wide range of alkyl halides and
Michael acceptors. Subsequent thermal elimination of phenyl sulfinic acid leads to
a
a
-unsaturated ethyl carboxylates, an important class of intermediates for
fluorine containing biologically active compounds [19] (Scheme 5.4).
Using a phosphazene base allows unreactive nitroaromatic compounds to condense with
ethyl isocyanoacetate to give C-annelated pyrroles. Stable 2H-isoindoles with electron-
withdrawing groups have been prepared using the reaction of dinitrobenzene derivatives
with isocyanoacetate in the presence of a phosphazene base (BTPP). The structure of an
isoindole was confirmed by X-ray crystallographic analysis, and this substance existed in
the solid phase only as the 2H-isomer. The reaction of 6-nitroquinoline gave a pyridine
fused isoindole [20] (Scheme 5.5).
-fluoro-
a
,
b
RBr or RI
Ph
Ph
Ph
Ph
COO
t
Bu
t
Bu
N
N
BEMP, CH
2
Cl
2
Cinchonidine
(
S
)
R
Scheme 5.3
Alkylation of glycinate in the presence of BEMP
O
1. BEMP, DMF
COOEt
S
+
R-CH
2
I
R
Ph
CHFCOOEt
2. toluene, 110
o
C
F
Scheme 5.4
Alkylation of sulfoxide
