ca01 only detailed ToC 1..24

54 Science of Synthesis 1.1 Organometallic Complexes of Nickel
Scheme 37 Ynal Cyclizations in Pumiliotoxin Synthesis [80]
N
H
H
O
OBn
Et 3SiH
Ni(cod) 2 2
Bu3P N
H
OTES
OBn
N
H
OH
OH
58 allopumiliotoxin 267A
Hodgson has developed a variant on the Nozaki–Kishi coupling [81] in which a haloalkene,
an alkyne, and an aldehyde undergo coupling to produce allylic alcohols with a tetrasubstituted
alkene (Scheme 38). [82] Only the fully intramolecular procedure is reported.
Scheme 38 Aryl Iodide–Aldehyde–Alkyne Coupling [82]
I
O
H
CrCl 2, NiCl 2
DMF, 25 o C
2-Methyl-4-propyloct-4-en-3-one (54): [77]
In a 50-mL stainless steel autoclave were placed under N 2, THF (8.50 mL), a soln of
[Ni(cod) 2] (2; 14 mg, 0.050 mmol) in THF (1.20 mL), and trioctylphosphine (0.046 mL,
0.10 mmol). The mixture was stirred for several min, then oct-4-yne (0.147 mL,
1.00 mmol) and isobutyraldehyde (0.136 mL, 1.50 mmol) were added. The mixture was
magnetically stirred for 20 h at 808C. The soln was concentrated to give a residue which
was purified by preparative layer chromatography (hexane/Et 2O 15:1) to give a 7:1 mixture
of 54 and a 2:1 adduct; yield: 0.124 g (60%).
Alkylative Cyclization of Ynals; General Procedure: [79]
A 0.5–0.6 M soln of ZnCl 2 (2.5–3.0 equiv) in THF was stirred at 0 8C, and the organolithium
or Grignard reagent (3.7–4.5 equiv) was added by syringe followed by stirring for 10–
15 min at 08C. A 0.02–0.04 M soln of [Ni(cod) 2](2; 0.05–0.20 equiv) in THF was added and
the resulting mixture was immediately transferred by cannula to a 0.1–0.2 M soln of the
ynal (1.0 equiv). After consumption of starting material as measured by TLC analysis (typically
0.25–0.5 h at 08C), the mixture was subjected to an extractive workup with NH 4Cl/
NH 4OH buffer (pH 8) and Et 2O followed by flash chromatography (silica gel).
Reductive Cyclization of Ynals; General Procedure: [79]
A 0.04–0.05 M soln of Bu 3P {4 equiv relative to [Ni(cod) 2]} in THF was added to [Ni(cod) 2](2;
0.05–0.20 equiv) at 25 8C followed by stirring for 3–5 min. The nickel soln was transferred
to a 0.5–0.6 M soln of commercial Et 2Zn (2.5–3.5 equiv) in THF at 0 8C, and the resulting
mixture was immediately transferred by cannula to a 0.10 M soln of the ynal (1.0 equiv)
in THF at 08C. After consumption of starting material as measured by TLC analysis (typically
0.25–2.0 h at 0 8C), the mixture was subjected to an extractive workup with NH 4Cl/
NH 4OH buffer (pH 8) and Et 2O followed by flash chromatography (silica gel).
Three-Component Couplings; General Procedure: [79]
A 1.0 M soln of ZnCl 2 (2.5–3.0 equiv) in THF was stirred at 0 8C, and the organolithium or
Grignard reagent (4.5–5.4 equiv) was added by syringe followed by stirring for 10–15 min
HO