3.1.3 The Origins of Chemoselectivity of the 82:9 Ratio for
PR11/PR12
As shown in Scheme 2 entry 1, when the R substituent in alkyne2a is the n-propyl (R1 ) group, the ratio ofPR11 (alkenyl chloride) toPR12 (trisubstituted olefin) is 82: 9. In this
section, we explore the paths that finally end intoPR11 and PR12 and
subsequently disclose the origins of the chemoselectivity. With the
alkenyl PdII intermediate 7 as the starting
point (Figure 3a), there are two potential regiodivergent pathways,
leading to PR11 andPR12 , respectively. Figure 3a shows the free
energy profiles. The right pathways leads toPR11 , and the left pathway generatesPR12 . Optimized geometries of key intermediates
and transition states involved are exhibited in Figure 3b. Along the
right pathway of Figure 3a, a ligand exchange (7 →8 ) is
required, in which aromatic ring moiety is replaced by Cl atom to give
the less unstable intermediate 8 ready for subsequent
1,4-chlorine migration. In 8 , the distance of Pd and Cl atoms
is 2.09Å(see Figure 3b). Then, oxidative addition with C(aryl)-Cl bond
cleavage of 8 occurs via TS8-9 with an energy demand
of 16.0 kcal/mol, giving a five-membered palladacycle 9 . This
step is calculated to surpass an overall barrier of 21.3 kcal/mol (the
difference between TS8-9 and 13 ), with a slight
exergonicity of -4.6 kcal/mol. From Pd(IV) species 9 , the
C(alkenyl)-Cl bond reductive elimination takes place to give the
four-coordination intermediate 10 , which is almost isoenergetic
with 9 (-41.5 & -42.3 kcal/mol). The barrier calculated in
this transformation is 16.2 kcal/mol. In fact, the two successively
oxidative addition with cleavage of the C(aryl)-Cl bond of 8and reduction elimination by the construction of the Cl-C(alkenyl) bond
realizes a formal 1,4-chlorine migration. Next, 10 undergoes
ligand substitution to give intermediate 11 with the
endoergonicity of 2.3 kcal/mol. Subsequently, protonation occurs with
HOAc molecule to obtain product-coordinated adduct 12 . The
barrier involved for this step is 15.6 kcal/mol
(TS11-12 →11 ). Finally, the removal of active catalyst(K) from 12 generates alkenyl chloride product
(PR11 ).
On the other hand, along with the left pathway of Figure 3a ending inPR12 , the aromatic ring moiety in alkenyl
PdII intermediate 7 is substituted with
carbonyl oxygen of HOAc to form a 16e intermediate 13 .
subsequently, 13 evolves into product-coordinated adduct14 by undergoing protonation process via TS13-14 with
a barrier of 23.1 kcal/mol (TS13-14→13 ). In the final step, the
release of the active catalyst (K) from 14 gives
trisubstituted olefin product (PR12 ). Notably,
in 14 , Pd actually coordinates with the C-H σelectrons of the
double bond (Pd-H: 2.04 Å; Pd-C: 2.58 Å) instead of the double bond,
which can be attributed to steric repulsion.