ca01 only detailed ToC 1..24

76 Science of Synthesis 1.1 Organometallic Complexes of Nickel
1.1.4.9 Method 9:
Alkene Carbozincation
The nickel-catalyzed carbozincation has been developed into a broadly useful method for
the cyclization of alkenes tethered to alkyl iodides (Scheme 78). [176–178] The functionalized
organozincs (e.g., 99) prepared by the nickel-catalyzed cyclizations may be further utilized
in a wide variety of copper-mediated alkylations of reactive electrophiles. The reaction
mechanism may not involve the formation of nickel–alkene complexes; however,
this reaction class is included owing to its synthetic relationship to many processes that
do include nickel–alkene complexes. A free-radical cyclization appears to be most consistent
with the data provided.
Scheme 78 Nickel-Catalyzed Carbozincation [176–178]
I
O
OR 1 R 2
98
+ ZnEt2
Ni(acac)2 1
R 1 O
O
99
CH2ZnI
A nickel-catalyzed carbozincation in which an allylzinc adds across the double bond of an
unsaturated acetal has also been reported (Scheme 79). [179] This procedure effectively provides
a reverse-polarity approach to the functionalization of unsaturated carbonyl derivatives.
Non-allylic Grignard reagents, however, add to cyclic unsaturated acetals with the
opposite regiochemistry. This latter procedure provides the basis for an enantioselective
conjugate addition to cyclic enones (in 53% ee for the cyclopentenyl substrate and 85% ee
for the cyclohexenyl homologue). [180]
Scheme 79 Addition of Organozincs to Unsaturated Acetals [179,180]
O
O
R 1 O OR 1
R 2 = alkyl or aryl
+
+
R 2 MgBr
ZnBr
Ph2
P
NiCl2
P
Ph2
NiBr2(PBu3)2
[(5-Butoxytetrahydrofuran-3-yl)methyl](iodo)zinc(II) (99, R 1 = Bu; R 2 =H);
Typical Procedure: [176]
A 50-mL three-necked flask equipped with an argon inlet, a magnetic stirring bar, an internal
thermometer, and a septum cap was charged with [Ni(acac) 2](1; 15 mg, 0.06 mmol,
2 mol%), and a soln of the iodoalkane 98 (R 1 = Bu, R 2 = H; 0.85 g, 3.0 mmol, 1 equiv) in THF
(5 mL) was added. The resulting green suspension was cooled to –788C, and ZnEt 2 (0.6 mL,
6.0 mmol, 2 equiv) was added dropwise. The mixture was allowed to warm to 0 8C and
stirred at this temperature for 2 h. The excess of Et 2Zn and the solvent were removed in
vacuo (rt, 2 h) to leave the crude product; no yield was reported.
OR 1
R 2
R 2
ZnBr
O
O