COMMUNICATION
Light-fluorous safety-catch arylgermanes – exceptionally robust,
photochemically activated precursors for biaryl synthesis by Pd(0)
catalysed cross-coupling{
Alan C. Spivey,*a Chih-Chung Tseng,a Joseph P. Hannah,a Christopher J. G. Gripton,b Paul de Fraine,c
Nigel J. Parrd and Jan J. Scicinskid
Received (in Cambridge, UK) 18th May 2007, Accepted 12th June 2007
First published as an Advance Article on the web 21st June 2007
DOI: 10.1039/b707517k
in the periodic table, the electronegativity of Ge is the closest to
that of C among group 14 elements (C, 2.50; Si, 1.74; Ge, 2.02; Sn,
1.72).9 This scandide contraction effect10 renders C–Ge bonds less
polar than C–Si and C–Sn bonds. Consequently, arylgermanes
possess significantly greater stability than their Si and Sn congeners
towards bases and nucleophiles,11 exhibit lower toxicity,12 and
require activation of the C–Ge bond for Pd(0)-catalysed cross-
coupling.13 They display slightly higher reactivity towards acids
and electrophiles than their Si congeners.14
A new class of arylgermane derivative that participate efficiently
in Pd(0)-catalysed cross-coupling reactions with aryl bromides
following photochemical activation is described.
Biaryls are ‘privileged’ constituents of natural products, pharma-
ceuticals, agrochemicals, dyes, organic semiconductors, liquid
crystals and ligands/auxiliaries for asymmetric synthesis.1 They
are generally prepared by transition metal catalysed cross-coupling
reactions between e.g. aryl–magnesium, –zinc, –tin, –silicon or
–boron compounds and aryl halides.2 All these aryl metals are,
however, also reactive towards major classes of reagents
commonly used in organic synthesis (e.g. bases and nucleophiles).
Consequently, they are rarely carried through synthetic sequences
prior to their deployment for cross-coupling. This limitation
applies particularly when contemplating the use of an aryl metal
bond as the key component of a linker for phase-tagged parallel
synthesis which could undergo cleavage from the phase tag
concomitant with cross-coupling to afford biaryl-containing
libraries.3
Here, we describe the scope of a new biaryl cross-coupling
method that employs light fluorous15 aryl bis(2-naphthylmethyl)-
germanes as robust safety-catch coupling precursors. These
derivatives display exceptional levels of stability towards bases
and nucleophiles and allow for purification using fluorous SPE15
prior to cross-coupling making them particularly attractive for
parallel synthesis of high value biaryls.
In previous studies we have shown that two heteroatom
substituents (e.g. Cl or F) on Ge are required to allow efficient
Pd(0) catalysed cross-coupling between arylgermanes and aryl
bromides and that 2-naphthylmethyl groups on Ge can be cleaved
by photooxidation with Cu(BF4)216 to generate germyl fluorides.17
Here we describe the union of these findings into a powerful
method for biaryl synthesis that allows introduction of a robust,
perfluorooctyl-tagged trialkylarylgermane early in a synthesis for
subsequent photolytic activation then cross-coupling with cleavage
from the phase-tag. The scope of the method has been explored for
a range of arylgermanes and aryl bromides (Table 1).
The reactivity of an aryl metal species, to a first approximation,
inversely correlates with the electronegativity of the metal (i.e.
Mg . Zn . Sn . Si . B). Hence, aryltrifluoroborate salts (which
show notable stability towards oxidants)4 and aryl triallylsilanes5
have emerged as the most robust biaryl cross-coupling precursors
to date. Other ‘safety-catch’ silyl groups6 such as the benzyldi-
methylsilyl (BDS) group,7 which can withstand some conditions
for silyl ether deprotection but which can be activated to give
silanol reactive intermediates by treatment with TBAF, have also
proved useful for cross-coupling of alkenyl systems. The salt
properties of the trifluoroborates and the inherent polarity of C–Si
bonds, however, limit the stability of all these groups, in particular
towards bases and nucleophiles.8
Arylgermanes 1a–f are readily prepared by reaction of the aryl
lithium or Grignard reagents with bis(2-naphthylmethyl)germyl
bromide, which in turn is easily prepared from commercially
available 1H2,2H2-perfluorooctyl iodide and germanium(II) chlor-
ide dioxane complex in four steps (y50% yield overall, see ESI{).
The photolytic activation process entails irradiation of a solution
of the arylgermane in a Pyrex Schlenk tube using a high pressure
Hg lamp (125 W) for y2 h. The progress of the photooxidation
reaction is not appreciably dependent on the nature of the aryl
group and can be monitored conveniently by 19F NMR.{
Following evaporation of the solvent, dissolution of the residue
in CH2Cl2 and washing with water to remove Cu salts, the crude
difluorogermane is subject directly to the TBAF-promoted cross-
coupling. The 2-naphthylmethyl ether photooxidation by-product
can be removed by sublimation at the difluorogermane stage but
does not interfere with the cross-coupling reaction.
We envisaged that more robust safety-catch cross-coupling
partners for biaryl synthesis could be developed by employing
arylgermane derivatives. Although Ge is located between Si and Sn
aDepartment of Chemistry, South Kensington Campus, Imperial College,
London, UK SW7 2AZ. E-mail: a.c.spivey@imperial.ac.uk;
Tel: +44 (0)20 75945841
bDepartment of Chemistry, University of Sheffield, Brook Hill,
Sheffield, UK S3 7HF
cDiscovery Chemistry, Syngenta, Jealott’s Hill, Bracknell, Berkshire,
UK RG42 6EY
dMedicinal Chemistry, GlaxoSmithKline, Gunnelswood Road,
Stevenage, Hertfordshire, UK SG1 2NY
Electron poor and electron rich arylgermanes and aryl bromides
can be coupled using this method and optimal yields are achieved
{ Electronic supplementary information (ESI) available: Experimental
1
procedures and all H/13C/19F NMR data. See DOI: 10.1039/b707517k
2926 | Chem. Commun., 2007, 2926–2928
This journal is ß The Royal Society of Chemistry 2007
Spivey, Alan C.
