Handbook of Functionalized Organometallics Applications in S

7.3 Reactions of Organozinc Reagents
Cicaprost by reacting the chiral zinc reagent 298 with 1-bromopropyne leading
to the functionalized alkyne 299 (Scheme 7.85) [189]. This cross-coupling has also
been used to prepare a pheromone (300) [48d].
EtO2C Cu(CN)ZnI +
O
MeO ZnI
Me
298
AcO(CH 2) 6I
1) Zn, THF
2) CuCN· 2LiCl
3)
I Hex
-50ºC, 16 h
296
CuCN·2LiCl
Ph
O
Et Br MeO
Me Et
-60 ºC, 20 h
299
AcO(CH 2) 6
I
O
THF, -80 ºC to-55ºC, 1 h
Hex
i-Pr 3Si
H2 / Lindlar-Pd cat
PhCH3 /Py
0 ºC, 48 h
Scheme 7.85 Cross-coupling of zinc±copper organometallics with 1-haloalkynes.
Ph
O
56 %
OH
297
AcO(CH 2) 6
Substitution at C sp2-centers can also be accomplished as long as the haloalkene
is further conjugated with an electron-withdrawing group at b-position. Thus,
3-iodo-2-cyclohexenone reacts with the zinc reagent 301 bearing a terminal alkyne
affording the functionalized enone 302 [11]. Similarly the stepwise reaction of
3,4-dichlorocyclobutene-1,2-dione (303) with two different zinc±copper reagents
furnishes polyfunctional squaric acid derivatives, such as 304 [190]. By using
mixed diorganozinc reagents of the type FG-RZnMe [191], a catalytic additionelimination
can be performed with a wide range of b-keto-alkenyl triflates. Thus,
the penicillin derivative 305 reacts with the mixed copper reagent 306 providing
the desired product 307 in excellent yield (Scheme 7.86) [191].
Functionalized heterocycles such as 308 can be prepared in a one-pot synthesis
in which the key step is the addition-elimination of a functionalized copper±zinc
reagent 309 to the unprotected 3-iodoenone 310 producing the annelated heterocycle
308 in 41% (Scheme 7.87) [192].
Besides enones, several Michael acceptors having a leaving-group in b-position
react with zinc±copper reagents. Thus, diethyl malonate [(phenylsulfonyl)methylene]
(311) reacts with zinc±copper reagent 312 providing the addition substitution
product 313 in 90% yield [193]. Similarly, the zinc±copper reagent 314 reacts
with 2-phenylsulfonyl-1-nitroethylene (315) providing the intermediate triene 316
that cyclizes on silica gel at 25 C within 4 h affording the Diels±Alder product 317
in 85% (Scheme 7.87) [194]. The cross-coupling reaction with unactivated alkenyl
301
Me Et
Hex
300 :98%
E:Z= 99.4 : 0.6
CO 2Et