Regioselectivity of the Reactions of Heteroatom-Stabilized Allyl ...

712
Scheme 171 Scheme 172
where the heteroatom and nonallylic substituent do
not play a significant role. The latter is stabilized by
the phenylthio group and has cis geometry. An NMR
study on 1-(dimethylamino)allyllithium is currently
being carried out in the group of Ahlbrecht (private
communication).
The three adducts 866 (Scheme 169), formed from
diethyl (1-cyclohexenyl)methylphosphonate and the
corresponding aldehydes, possess erythro configurations
as demonstrated by NMR. Attractive intramolecular
hydrogen bonding between the hydroxy and
phosphoryl groups, as well as less steric repulsion if
the large substituents are gauche to the vicinal
hydrogen, is considered to be responsible for this
configuration. 199
Gais et al. 124 described R,R-dilithioallyl phenyl
sulfone 869 to be more thermodynamically stable
than the isomeric R,O-dilithioallyl phenyl sulfone 870
(Scheme 170). One equivalent of n BuLi lithiates
phenyl 2-propenyl sulfone in THF to give the R-monolithiated
compound. Under kinetic control, the second
equivalent metalates the ortho position of the ring
relative to the sulfonyl group. Upon heating to 50 °C,
the more stable R,R-dilithiated product 868 is formed.
Both steps have been monitored by 1 H NMR spectroscopy.
NOESY experiments on �-substituted γ-keto sulfoximines
845 (Scheme 163) show characteristic
cross-peaks. Hence, the N-tosyl group is near the
protons R to the keto group. A “hairpin structure” is
preferred, which allows the anti configuration of the
sterically demanding S-phenyl group and the rest of
the side chain. 150
The anions of the allylphosphonic diamides 871-
873 (Scheme 171, R ) Me, i Pr) 421 were found to exist
in both E- and Z-forms in solution except for one
species 872 (R ) i Pr). In toluene a greater portion of
the Z-isomer than in THF was identified. Toluene
coordinates to a lesser extent to lithium than THF
does; therefore, different anion conformations are
observed in solution in agreement with theoretical
calculations (see section VIII).
VIII. Summary of MO Calculations
A. r- and γ-Substituted Allylmetals: Substituent
Effects on Reactivity and Structure
Tonachini et al. investigated halogen-substituted
allyllithiums on various levels of ab initio
theory. 5,282,422-424 With 3-21+G geometry optimizations
and MP2/6-31+G single point energy calculations
they estimated the structures 874 (monofluoroallyllithium)
and 875 (difluoroallyllithium) to be
most stable 5 (Scheme 172).
Slightly different structures were found as energy
minima for the corresponding chloro- and dichloroallyllithium
compounds. The most stable [CH2dCH-
CCl2]Li structure, the Li + prefers a C(R)/C(γ) bridging
position. 282 In both cases the regioselectivity predictions
agree with the experimental findings, although
the interpretation is more or less based on the HSAB
principle and on the effect of the polarization of
HOMO of the allylic unit: These interpretations
show that monofluoroallyllithium should have a less
pronounced tendency to R-attack. For both 1-fluoropropenide
and 1,1-difluoropropenide the HOMO is
polarized toward the R-carbon. Furthermore, double
fluorine substitution causes a substantial flow of
charge toward the halogen groups. Hence, a hard
electrophile sensitive to charge distribution and a soft
electrophile which is mainly sensitive to the HOMO
polarization would both favor an attack at the
R-carbon. For a similar discussion compare a paper
by Venturello et al. 278 in which the importance of
lithium complexation with 12-crown-4 in the reaction
of (1,1-dichloroallyl)lithium with carbonyl compounds
is discussed along the same lines.
Unfortunately, transition structures for the alternative
R-orγ-attack of carbonyl or other electrophiles
are not included in these investigations. The same
authors also investigated the monomer-dimer equilibrium
in lithium gem-difluoroallyl and methyl
systems. 422,423 Their ab initio methods show the
equilibrium shifted in favor of the dimeric species,
even after taking into account the oxygen-cation
interactions of the solvent (water molecules were
used to simulate ether), the equilibrium still seems
to be on the side of the dimeric species.
The calculation of transition structures is included
in a recent paper 424 in which the addition reaction of
formaldehyde with (1,1-difluoroallyl)lithium and (1,1dichloroallyl)lithium
was investigated at the HF and
the MP2 level, together with selected CAS-MCSF
calculations. In general, MP2/3-21G(*) geometries
were used for recomputing the energy barriers at the
MP2/6-31G* level. Tonachini and Canepa found that
for difluoroallyllithium, dichloroallylpotassium, and
for both the free anions, R-attack is significantly
preferred. Dichloroallyllithium can show a dichotomy
of behavior as the energy difference between the two
transition structures turns out to be much smaller
and to favor the γ-pathway. Scheme 173 shows the
Scheme 173