Chemistry Reference
In-Depth Information
Cat. M
[O]
C
1
C
2
C
1
C
2
H
H
Scheme 5.1 Cross-dehydrogenative coupling (CDC) reaction.
Copper-catalyzed CDC reactions reported by Li and others use
t
BuOOH,
1
O
2
,
2
NBS,
3
and diethyl azodicarboxylate (DEAD)
4
as ecient oxidants.
Other transition metal catalyzed oxidation systems such as rhodium-T-
HYDRO (70% in water),
5
iron-(
t
BuO)
2
/
t
BuOOH,
6
vanadium-
t
BuOOH,
7
and
ruthenium-O
2
8
systems also showed high activities in CDC reactions. In
addition, the reaction could proceed in the absence of oxidant by using
platinum as catalyst.
9
Although good results could be achieved in all the
above cases, these reactions still possess some limitations: (1) The use of
unrecoverable metal catalysts. Only one example of adopting recyclable silica
supported iron terpyridine complex for CDC reactions of tertiary amines
with various carbon nucleophiles was reported, recently by Liu.
10
However, a
relatively long reaction time and high temperature were required. (2) The use
of explosive oxidants or volatile organic solvents along with long reaction
time or high reaction temperature. (3) Although several solvent-free CDC
reactions have been reported, relative excess of oxidants or reaction sub-
strates were taken as the role of solvent.
The concept of green chemistry has inspired chemists to investigate the
possibility for greener CDC reaction, which is characterized by solvent-free
and mild conditions. The ball mill protocol, which is normally carried out
without, or with minimal use of, solvents, could potentially offer a greener
alternative to their solution-based counterparts, where a high concentration
of materials in the reaction vials is presented.
11
Different C-C coupling reactions under ball milling and their
application to the preparation of various useful molecules have been illus-
trated in Chapter 2. The main goal of the present chapter is to introduce
the combination of ball milling technique with CDC reactions, which
lead to a more ecient and environment-friendly method for C-C bond
formation.
5.2 Cross Dehydrogenative Coupling Reactions
under Ball Milling Conditions Applied to the
Synthesis of Functionalized
Tetrahydroisoquinolines
The synthesis of nitrogen-containing compounds, especially tetra-
hydroisoquinoline derivatives which are widely present in nature, has attracted
much attention in industrial and academic research because of their biological
and pharmaceutical properties.
12
A series of reactions of tetrahydroisoquinolines and pronucleophiles
under high-energy vibrational ball milling was first reported by our group,
13
Search WWH ::
Custom Search