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 (78 ) 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 (TS11-1211 ). 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.