Handbook of Functionalized Organometallics Applications in S

256
7 Polyfunctional Zinc Organometallics for Organic Synthesis
ity of -NHR [27]. Interestingly, a free phenolic function is tolerated in cross-coupling
reactions.
Me
Boc(H)N
I
Zn dust
Me3SiCl cat.
DMF, 0ºC
Me
HN
t-BuO
ZnI
O
CH2Cl CuBr·Me2S (5 mol %)
Me
Boc(H)N
23 22 24 :60%
Scheme 7.9 Generation of a b-amino alkylzinc reagent in DMF.
Organozinc reagents bearing a free NH-function in b-position such as 22 can
be readily prepared by the direct insertion of zinc dust previously activated with
TMSCl in DMF in to the corresponding b-iodoamino derivative 23. Interestingly,
the best reactivity of this chelate-stabilized zinc species can be obtained by using
catalytic amounts of CuBr´Me 2S (5 mol%). In the case of the reaction with propargyl
chloride the corresponding allene 24 is obtained in 60% yield via an S N2¢mechanism
(Scheme 7.9) [28].
During the preparation of allylic zinc reagents, the formation of Wurtz-coupling
products may be observed, especially if the intermediate allylic radical is
well stabilized. However, the direct insertion of zinc foil to allyl bromide in THF
at 5 C is one of the best methods for preparing an allylic anion equivalent. Allylic
zinc reagents are more convenient to prepare and to handle than their magnesium-
and lithium counterparts [15]. Similarly, electron-rich benzylic bromides
such as 25a often lead to homo-coupling products. The use of the corresponding
phosphate 25b and catalytic amounts of LiI in dimethyltetrahydropyrimidinone
(DMPU) provides the corresponding zinc reagent in quantitative yield (Scheme
7.10) [29]. The presence of LiI generates small concentrations of the benzylic
iodide, which is converted to the zinc reagent. Little homo-coupling is observed
under these conditions.
O
O
X
25a :X=Br
25b :X=OP(O)(OEt) 2
Zn, LiI (cat.)
DMPU, 50 ºC, 12 h
X = OP(O)(OEt) 2
Zn, THF, 0 ºC, 2 h
X=Br
O
O
O
O
ZnX
Scheme 7.10 Importance of the precursor for the preparation of benzylic zinc reagents.
The addition of lithium iodide and bromide mixtures allows also the performance
of the zinc insertion with primary alkyl chlorides, tosylates or mesylates as
starting material (Scheme 7.11) [29]. Thus, the alkyl tosylate 26 is converted in
Zn
2