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I
I
Pd(P
t
Bu
3
)
2
(5 mol%)
NEt
3
(1 equiv)
PhMe, 110 °C
1-nap
O
O
1-nap
7.66
99:1 er
7.67
70% yield
99:1 er; 98:2 dr
Scheme 7.33
Synthesis of an optically enriched isochroman derivative.
Adapted from Ref. 102. Copyright 2012 American Chemical Society.
I
R
2
R
3
R
2
Pd(QPhos)
2
(5 mol%)
PhMe, 100 °C
R
3
R
1
R
1
I
R
3
R
3
7.68
7.69
up to 96% yield
Scheme 7.34
Synthesis of indenes by Pd(0)-catalyzed carboiodination.
(Figure 7.3b) in the carbopalladation step for the isochromans and chro-
mans, respectively. Furthermore, chiral substrate 7.66 derived from an
enantioenriched allylic alcohol could be effectively cyclized to isochroman
7.67 without any loss of optical purity (Scheme 7.33).
7.8.3 Indenes via Pd(0)-Catalyzed Carboiodination
In 2012, Lautens and co-workers reported a conjunctive carboiodination of
o-isopropenylaryl iodides 7.68 and alkynes that gave access to indene
products 7.69 (Scheme 7.34).
108
These studies were undertaken because at-
tempts to achieve carboiodination of an alkyne were not successful. The
presence of the o-propenyl group allowed the vinylpalladated species, arising
from intermolecular alkyne carbopalladation, to undergo cyclization to form
an sp
3
-Pd-I intermediate that was known to reductively eliminate.
A possible mechanism was proposed to rationalize the product formation
(Scheme 7.35). Substrate binding first occurs
100
to generate Pd(0) complex 7.70,
whichthenundergoesanoxidativeaddition to generate Pd(II) intermediate
7.71. Intermolecular alkyne insertion occurs to product 7.72, which can
undergo cyclic alkene carbopalladation to form 7.73. The indene product 7.74
is formed once intermediate 7.73 has undergone C-I reductive elimination.
Thus far, only moderate regioselectivities and no enantioselective variant have
been discussed, although these would be interesting and powerful methods.
7.8.4 Simultaneous Carboiodination/Mizoroki-Heck Reaction
Aromatics containing multiple carbon-halogen bonds are synthetically useful,
as more than one bond functionalization can be executed in a predictable
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