The Heck Reaction: Mechanistic Insight into a ... - The Stoltz Group

Regioselectivity in Migratory Insertion
Intramolecular Heck Reaction
• regioselectivity of intramolecular Heck reactions is almost always determined by sterics
exo-trig
endo-trig
Pd
L X
PdL n X
Pd
L X PdL n X
for small rings (5, 6, or 7 carbons)
exo-trig dominates
for large rings / macrocycles (more than 9 carbons)
endo-trig is generally preferred
• disfavored regioselectivity in intermolecular Heck reactions can be
realized by using a cleavable tether to furnish a desirable exo-trig product (TL 1999, 40, 4901)
X
I
+
OMe
X
I
OMe
X
MeO
X
MeO
Y
OBn
RO 2 C
Y
O
O
Y
Heck
O
O
Y
OBn
CO 2 R
Termination Step
• after migratory insertion and before reductive elimination there are several options for transforming the
organopalladium complex
(1) Pd-H elimination / !-hydride elimination (this is the most common)
(2) Pd-M elimination (eg. Pd-SiX 3 )
(3) palladotropic shift: Ar Pd X
O
OMe
XPd
O
OMe
XPd
O
OMe
Ar
if Pd-H elimination is not possible because of stereochemical reasons or is very slow,
Ar
(4) nucleophillic attack at Pd (nucleophillic substitution or reductive elimination),
which results in a net syn Ar-Nu addition across an olefin
(5) cascade reactions: allylic substitution
cross coupling
carbonylation
another Heck
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