Coupling Reactions - Organic Synthesis Using Transition Metals - page 57

P( t -Bu) 2 Me

Ph Pd

P(2)

Br

P(1)

Me( t -Bu) 2 P

Pd(1)

Br(1)

2.310

Figure 2.1 An alkylpalladium(II) complex. Reprinted with permission from Kirchhoff, J. H.; Netherton, M. R.
et al. J. Am. Chem. Soc. 2002 , 124 , 13662. c 2002 American Chemical Society.

2.7 Silicon: The Hiyama Reaction

The coupling of silicon derivatives is known as Hiyama coupling. 110 The use of silicon derivatives has two
practical benefits: silanes are often cheap, and the silicon-containing by-products are almost completely non-
toxic. Nevertheless, the Hiyama reaction has seen much less use than some of the other coupling reactions. This
is likely to be due to the quite harsh conditions originally required. The same issue of low reactivity is observed
with silicon as with boron. As with Suzuki coupling, it is solved by addition of a Lewis base as an activating
reagent, commonly a fluoride source due to the high affinity of this anion for silicon (Scheme 2.100). 111 The
role of the Lewis base is to form a hypervalent silicon “ate” complex 2.313 , which is more reactive towards
transmetallation than the parent, neutral silane. Even so, simple silanes still tend to have low reactivity and
need quite forcing conditions for coupling. The scope of the reaction may be widened if some of the alkyl
“dummy” groups on silicon are changed to electronegative atoms, such as fluorine (Scheme 2.101) 112

and

oxygen (Scheme 2.102). 113 Preformed “ate” complexes 2.321 can also be used (Scheme 2.103). 114
The importance of the use of a Lewis-basic activating reagent is demonstrated in a synthesis of nitidine
2.328 (Scheme 2.104). 115 Without the activating reagent, the carbon-silicon bond of a vinyl silane 2.324
proved to be inert, and a Heck reaction with aryl iodide 2.326 occurred. A second aryl group could then be
introduced by Hiyama coupling with iodide 2.326 in the presence of an activator.
A particularly noteworthy variant of the Hiyama coupling is the Denmark modification. 116 Silacyclobutanes
2.329 were found to be excellent partners in the reaction with enhanced reactivity (Scheme 2.105). 117 This
effect was found not to be due to the strain of the four-membered ring directly, but due to the rapid ring
opening to give silanols 2.333 and disiloxanes 2.334 that were the active and competent coupling partners.

I

SiMe 3
[(allyl)PdCl] 2 ,
(Et 2 N) 3 S Me 2 SiF 3

Me

Me

Si
Me

F

2.311 2.312 2.313

Scheme 2.100

[(allyl)PdCl] 2 ,
(Et 2 N) 3 S Me 2 SiF 3

I

SiMe 2 F +

n -Bu

n -Bu

2.314 2.315 2.316

Scheme 2.101