Handbook of Functionalized Organometallics Applications in S

7.3 Reactions of Organozinc Reagents
acids is possible by using the reaction of the zinc reagent with prenyl chloride in
the presence of CuBr´Me 2S (0.1 equiv). Under these conditions, a mixture of
S N2 and S N2¢-products (55:45) is obtained. They can be readily separated by taking
advantage of the higher reactivity of trisubstituted alkenes compared with terminal
alkenes towards MCPBA (Scheme 7.75) [169].
Although zinc±copper reagents do not open epoxides, the more reactive a,b-unsaturated
epoxides react readily with various functionalized zinc±copper organometallics
[170] or functionalized zinc reagents in the presence of a catalytic
amount of MeCu(CN)Li [171]. Thus, the opening of d-epoxy-a,b-unsaturated
esters such as 254 with Me 2Zn´CuCN proceeds with high anti-stereoselectivity
leading to the allylic alcohol 255 in 96% yield. Also the opening of the unsaturated
epoxide (256) affords the allylic alcohol 257 in 98% yield (Scheme 7.76).
TIPSO
O
Me CO 2Et
254
Me 2Zn (2 equiv)
CuCN (2 equiv)
DMF, 0 ºC
TIPSO
OH
Me Me
255: 96%
CO 2Et
MeCu(CN)Li (5-10 mol %)
O
+ Cl(CH2) 4ZnI
THF
Cl OH
256 257 :98%
Scheme 7.76 Opening of a,b-unsaturated epoxides with copper±zinc reagents.
Interestingly, the high S N2¢-selectivity of organozinc±copper derivatives allows
the performance of multiple allylic substitutions with excellent results. Thus, the
reaction of the multicoupling reagent [172] 258 with an excess of copper±zinc
reagent provides the double S N2¢-reaction product 259 in 89% yield (Scheme 7.77)
[48b]. Propargylic halides or sulfonates react with zinc±copper reagents leading to
the S N2¢-substitution product like the allenic amino-acid derivative 260. Interestingly,
the regioselectivity is reversed by performing the reaction in the presence of
catalytic amounts of palladium(0). Thus, the insertion of zinc powder into the Zalkenyl
iodide 261 is complete in THF at 45 C within 21 h. The resulting Z-zinc
reagent 262 (Z:E > 99:1) reacts with the propargylic carbonate 263 in the presence
of Pd(PPh 3) 4 (5 mol%) leading formally to the S N2-substitution product 264 in
58% yield (Scheme 7.77) [173].
Propargylic mesylates such as fluorine-substituted derivative 265 react with
PhZnCl in the presence of Pd(PPh 3) 4 (5 mol%) in THF at 0 C within 2 h and provide
the anti-S N2¢-product in excellent yield and complete transfer of the stereochemistry
leading to the allene 266 (Scheme 7.78) [174]. Copper(I)-catalyzed allylic
substitutions with functionalized diorganozincs proceed with high S N2¢-selectivity.
Thus, the reaction of the chiral allylic phosphate 267 [175] with 3-carbethoxypropylzinc
iodide in the presence of CuCN´2LiCl (2 equiv) furnishes the anti-S N2¢-
295