Handbook of Functionalized Organometallics Applications in S

380
Li
Li
9 Polyfunctional Organocopper Reagents for Organic Synthesis
CuI·PBu3 PBu3 0 ºC, THF
Cu*
Br CO2t-Bu -78 ºC, 1 h
Et
OH
2: 87%
CO 2t-Bu
Scheme 9.1 Opening of an epoxide with a functionalized alkylcopper reagent.
Et
O
Cu CO 2t-Bu
1
, -10 ºC
Thus, the treatment of t-butyl 4-bromobutyrate with such activated copper(0) at
78 C leads to the corresponding copper derivate 1 that readily reacts with epoxides
furnishing the corresponding alcohol 2 in 87% yield. Remarkably, the reactive
copper(0) obtained by the reaction of CuCN´2LiCl [7] with lithium naphthalenide
at lowtemperature is ideally suited for the preparation of functionalized allylic
copper reagents such as 3 (Scheme 9.2).
O NMe2 CuCN·2LiCl
Cu*
Cl
-100 ºC -100 ºC, THF
Ph
OH
4: 96%
O
O NMe 2
Scheme 9.2 Generation of functionalized allylic copper reagents.
O
Cu
PhCHO
(1.2 equiv), -90 ºC
O
O NMe 2
Its reaction with benzaldehyde provides the desired homoallylic alcohol 4 in
96% yield [8]. An improved procedure allowing the generation of an exceptionally
active copper(0) reagent is obtained by the low-temperature reduction of lithium
2-thienylcyanocuprate 5 with lithium naphthalenide [9]. In this case, 1,4-additions
to enones in the presence of Me 3SiCl [10] proceed especially well.
Thus, ethyl 4-bromobutyrate is converted at ±100 C to ±78 C to the corresponding
copper reagent 6 that reacts with cyclohexenone and Me 3SiCl affording the
1,4-adduct 7 in 80% yield (Scheme 9.3) 9 . By reducing the complex salt system
3