Handbook of Functionalized Organometallics Applications in S

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7 Polyfunctional Zinc Organometallics for Organic Synthesis
(Scheme 7.91) [137]. Alkylzinc halides react only sluggishly with aldehydes or
ketones. This reactivity can be improved by activating the carbonyl derivative with
a Lewis acid. Excellent results are obtained with titaniumalkoxides [209], Me 3SiCl
[210] or BF 3´OEt 2 [48c]; (Scheme 7.92). Depending on the nature of the catalyst
either the 1,2-addition product (345) or the 1,4-addition product (346) is obtained
by the addition of the zinc±copper reagent 347 to cinnamaldehyde [48c].
Pr
Ph N CH 2OH
Ph
OBn
ZnBr
SiMe 3
+
+
Ph
CO2Et THF
ZnBr
183
O
Pr SiMe 3
1) THF, rt, 12 h
2) Pd(PPh3) 4 (cat)
65 ºC, 16 h
PrCHO
Ph
N O
Ph
O
341 :83%
CH 2OH
ZnCl
H ZnCl
-74 ºC tort Pr
Pr
342 343 344 :90%
Ph
340 :80%
OH
SiMe 3
Scheme 7.91 Reaction of allenic, propargylic and allylic zinc reagents with carbonyl derivatives.
In a noncomplexing solvent like CH 2Cl 2, alkylzinc reagents, such as 348 and
ent-348 react with polyfunctional aldehydes leading to highly functionalized alcohols,
such as 349a,b with high diastereoselectivity in the ªmatchedº case; Scheme
7.92 [158, 210]. Polyoxygenated metabolites of unsaturated fatty acids have been
prepared by the addition of functionalized zinc±copper reagents to unsaturated
aldehydes in the presence of BF 3´OEt 2 providing allylic alcohols of type 350 [211].
Allylic zinc reagents readily add to aldehydes with good stereoselectivity in some
cases. Thus, the addition of dicrotylzinc [212a] to the amino-aldehyde 351 furnishes
the alcohol 352 as one diastereomer in 82% yield. Interestingly, the corresponding
Grignard reagent leads to a mixture of diastereoisomers (Scheme 7.93)
[212b]. The addition of copper±zinc organometallics to imines is difficult. Benzylic
zinc reagents display, however, an enhanced reactivity and react directly under
well-defined conditions with in situ generated imines. A diastereoselective one-pot
addition of functionalized zinc organometallics can be realized by performing the
reaction in 5M LiClO 4 (in ether) in the presence of TMSCl. By using Reformatsky
reagents and a chiral amine like (R)-phenylethylamine diastereoselectivities with
up to 95% have been obtained. With the benzylic zinc reagent 353, the secondary
amine 354 is obtained in 60% yield and 70% de [213].