Handbook of Functionalized Organometallics Applications in S

R
R
12
2 Polyfunctional Lithium Organometallics for Organic Synthesis
1,2-hydride shift to give an enolate or (c) a-ring opening followed by attack of an
alkyllithium and subsequent elimination of lithium oxide affording an olefin.
Only stabilized anions carrying electron-withdrawing or coordinating substituents,
or heteroatomic, aromatic or unsaturated groups are stable enough to react
with electrophiles. Lithiooxirane 35 was prepared by deprotonation with s-BuLi in
the presence of TMEDA in THF at ±98 C and reacted with electrophiles [30] with
retention of the configuration. The same reaction conditions were used in the
preparation of oxazolinyloxiranyllithiums 36 [31], which reacted with nitrones to
give, after hydrolysis and catalytic hydrogenation, a-epoxy-b-aminoacids [32]. Oxyranyllithium
37 was prepared by lithiation a to the silicon with n-BuLi in ether at
±116 C with retention of the configuration of the oxirane [33]. Ethynyl oxirane
anionic species 38 was prepared by deprotonation with n-BuLi at the propargylic
position and trapped with electrophiles to give trisubstituted oxiranes [34].
O
N
TMS
Ph O
R
O
O
TBDMS
O
Li Me
Li R
Li
Li
35 36 37 38
OTMS
Nonstabilized oxiranyl anions were generated by lithiation of terminal epoxides
in the presence of a diamine ligand [35], this methodology being applied to the
asymmetric deprotonation of meso-epoxide 39 in the presence of (±)-sparteine.
The resulting organolithium compound 40 reacted with different electrophiles to
give compounds 41 in up to 86% ee (Scheme 2.6) [36].
O
s-BuLi, (-)-sparteine
Et2O, -90ºC
39 40
R
R
Li
O
1. E
2. H2O [E = CD 3OD,PhCHO,PhCONMe 2, EtCHO, Et 2CO, EtCONMe 2,EtOCOCl,n-Bu 3SnCl, Me 3SiCl, MeI]
Scheme 2.6
R
R
X
O
41 (48-84%, 73-86% ee)
A a-oxygenated organolithium compound acts as a reaction intermediate in a
spiroannulation reaction from 2-cyanotetrahydropyrans. The key feature of this
method is the use of a nitrile to facilitate alkylation (to generate the corresponding
precursor) and as a precursor of an alkyllithium reagent. Thus, reductive decyanation
of compound 42 led to the intermediate 43 [37], which underwent intramolecular
carbolithiation and, after carboxylation and reaction with CH 2N 2, gave spirocyclic
ester 44 as a single diastereomer (Scheme 2.7) [38].