ca01 only detailed ToC 1..24

58 Science of Synthesis 1.1 Organometallic Complexes of Nickel
Reductive Cyclization of Alkynyl Enones; General Procedure: [91]
A 0.03–0.06 M soln of Ph 3P (0.2–0.3 equiv) in THF was added to [Ni(cod) 2] (2; 0.04–
0.06 equiv) at 258C and stirred for 3–5 min. This soln was then transferred to a 0.5–0.6 M
soln of Et 2Zn in THF at 08C, and the resulting mixture was immediately transferred by
cannula to a 0.10–0.50 M soln of the unsaturated substrate (1.0 equiv) in THF at 0 8C. After
consumption of starting material as judged by TLC analysis (typically 0.25–2.0 h at 0 8C),
the mixture was subjected to an extractive workup of NaHCO 3/EtOAc or NH 4Cl/NH 4OH
(pH 8) buffer and Et 2O followed by flash chromatography (silica gel).
1.1.3.7 Method 7:
[2+2+2] Cycloadditions
Dating from the original discovery from Reppe [65] on the cyclooligomerization of acetylene,
nickel-catalyzed multicomponent cycloadditions have attracted considerable attention
(see also Houben–Weyl, Vol. E 18, pp 987, 993). [96] Metallacycles have been proposed as
important intermediates in most classes of cyclotrimerizations. The mechanism is likely
to involve initial oxidative cyclization to a five-membered metallacycle, followed by insertion
of a third unsaturated component, and finally reductive elimination to afford sixmembered
ring products (Scheme 46).
Scheme 46 General Mechanism of Nickel-Catalyzed [2+2+2] Cycloadditions [96]
R 1
R 1
L n
Ni
R 1
R 1
R 1
R 1
Ni
R 1
1 R R1
R 1
R 1
R 1
L n
Ni
R 1 R 1
A common limitation of most classes of cyclotrimerizations is the difficulty associated
with controlling the chemoselectivity of the process. In most instances involving intermolecular
couplings, multiple incorporation of the same alkyne unit is unavoidable.
However, with systems in which two alkynes, or one alkene and one alkyne are tethered,
synthetically useful processes become possible. The first example of a selective addition
of two equivalents of an alkyne and one alkene was reported by Chalk. [97] Tsuda has applied
this process to applications in polymer chemistry, [98] and Ikeda has developed a similar
method employing cyclic enones (Scheme 47). [99]
Scheme 47 Fully Intermolecular [2 + 2+2] Cycloadditions [99]
O
+
H
R 1
Me3Al, Ni(acac) 2 1
Ph3P, PhOH
O
R 1
R 1
major isomer
(after oxidation)
Bhatarah and Smith have reported that nickel(0)-promoted cyclizations of diynes and simple
alkynes afford good yields of substituted benzenes. [100] Mori has developed the corresponding
cyclotrimerization to 63 in an asymmetric fashion by using bis(ç 4 -cycloocta-1,5diene)nickel(0)
(2) and a chiral phosphine (Scheme 48). [101] Ikeda has developed a cyclotrimerization
to 64 that introduces two sp 3 -hybridized centers by cycloaddition of a diyne
with an enone (Scheme 48). [102] Montgomery reported that four contiguous stereocenters
may be introduced to give 65 by the 1:1 cycloaddition of alkynyl enones and simple
R 1
R 1
R 1
R 1
R 1
R 1
R 1
R 1