Page 719 - Advanced Organic Chemistry Part B - Reactions & Synthesis

O 695
O
Zn 0 SECTION 8.1
(CH ) CBr (CH ) CZnBr
3 3
3 3
10 mol% CuI, Organocopper
)
C(CH 3 3 Intermediates
1.5 equiv BF ,
3
2.0 equiv TMS Cl 96%
Ref. 73
Several examples of mixed organocopper-zinc reagents in synthesis are given in
Scheme 8.5. Entries 1 and 2 show the use of functionalized reagents prepared from
the corresponding iodides by reaction with zinc, followed by CuCN-LiCl. Entry 3
uses a similar reagent to prepare a prostaglandin precursor. Note the slightly different
pattern from Entry 3 in Scheme 8.4; in the present case the addition is to an exocyclic
methylene group rather than to an endocyclic cyclopentenone. Entry 4 involves gener-
ation of a mixed reagent directly from an iodide, followed by conjugate addition to
methyl acrylate. Entries 5 and 6 are substitutions on allylic systems. The arylzinc
reagent used in Entry 5 was prepared from 2-nitrophenyllithium, which was prepared
by halogen-metal exchange, as discussed on p. 632. Entry 7 is a stereospecific
S 2 displacement on an allylic methanesulfonate. Entry 8 is a substitution on a -

N
sulfonyloxy enone. The zinc reagent is mixed dialkyl zinc. This reaction may proceed
by conjugate addition to give the enolate, followed by elimination of the triflate
group. Entry 9 shows the use of a tertiary mixed zinc reagent in the preparation of
a ketone.

8.1.2.6. Carbometallation with Mixed Organocopper Compounds. Mixed copper-
magnesium reagents analogous to the lithium cuprates can be prepared. 74 The precise
structural nature of these compounds, often called Normant reagents, has not been
determined. Individual species with differing Mg:Cu ratios may be in equilibrium. 75
These reagents undergo addition to terminal acetylenes to generate alkenylcopper
reagents. The addition is stereospecifically syn.

C H MgBr + CuBr C H CuMgBr 2
2 5
2 5
C H CuMgBr 2 C H H
2 5
2 5
H O
2
C H CuMgBr + CH C CH C C C C
2 5
2
3
CH 3 H CH 3 H
The alkenylcopper adducts can be worked up by protonolysis, or they can be subjected
to further elaboration by alkylation or electrophilic substitution.
Mixed copper-zinc reagents also react with alkynes to give alkenylcopper species
that can undergo subsequent electrophilic substitution.

73
R. D. Rieke, M. V. Hanson, J. D. Brown, and Q. J. Niu, J. Org. Chem., 61, 2726 (1996).
74 J. F. Normant and M. Bourgain, Tetrahedron Lett., 2583 (1971); J. F. Normant, G. Cahiez, M. Bourgain,
C. Chuit, and J. Villieras, Bull. Soc. Chim. Fr., 1656 (1974); H. Westmijze, J. Meier, H. J. T. Bos, and
P. Vermeer, Recl. Trav. Chim. Pays Bas, 95, 299, 304 (1976).
75
E. C. Ashby, R. S. Smith, and A. B. Goel, J. Org. Chem., 46, 5133 (1981); E. C. Ashby and A. B. Goel,
J. Org. Chem., 48, 2125 (1983).