10.1021/om011049w.s001
Simon Doherty
Simon
Doherty
Edward G. Robins
Edward G.
Robins
Mark Nieuwenhuyzen
Mark
Nieuwenhuyzen
Julian G. Knight
Julian G.
Knight
Paul A. Champkin
Paul A.
Champkin
William Clegg
William
Clegg
Synthesis of a New Class of
1,4-Bis(diphenylphosphino)-1,3-butadiene Bridged
Diphosphine, NUPHOS, via Zirconium-Mediated
Reductive Coupling of Alkynes and Diynes: Applications
in Palladium-Catalyzed Cross-Coupling Reactions
American Chemical Society
2002
copper diene reagent
catalyst mixtures
NUPHOS derivatives 2
bi
intramolecular reductive cyclization
phenyl boronic acid
regioselective reductive cyclization
TOF
Ph
BINAP
2002-03-07 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Synthesis_of_a_New_Class_of_1_4-Bis_diphenylphosphino_-1_3-butadiene_Bridged_Diphosphine_NUPHOS_via_Zirconium-Mediated_Reductive_Coupling_of_Alkynes_and_Diynes_Applications_in_Palladium-Catalyzed_Cross-Coupling_Reactions/3769473
Zirconium-mediated inter- and intramolecular reductive cyclization of alkynes and diynes has
been used to prepare a new class of bidentate phosphine, based on a four-carbon sp<sup>2</sup>-hybridized
tether. Intermolecular coupling of diphenylacetylene and but-2-yne with Negishi's reagent followed
by transmetalation with copper chloride prior to quenching with chlorodiphenylphosphine affords
the corresponding acyclic diphosphines 1,4-bis(diphenylphosphino)-1,2,3,4-tetraphenyl-1,3-butadiene (<b>2a</b>; 1,2,3,4-Ph<sub>4</sub>-NUPHOS) and 1,4-bis(diphenylphosphino)-1,2,3,4-tetramethyl-1,3-butadiene
(<b>2b</b>; 1,2,3,4-Me<sub>4</sub>-NUPHOS), respectively. A single-crystal X-ray analysis of the former has been
obtained. Surprisingly, 1-phenylpropyne undergoes a highly regioselective reductive cyclization
to afford 1,4-bis(diphenylphosphino)-1,3-diphenyl-2,4-dimethyl-1,3-butadiene (<b>2c</b>; 1,3-Ph<sub>2</sub>-2,4-Me<sub>2</sub>-NUPHOS). Similarly, transmetalation of the zirconacyclopentadiene generated from 3,9-dodecadiyne and 1,8-diphenyloctadiyne followed by electrophilic liberation of the resulting copper
diene reagent with chlorodiphenylphosphine gave 1,2-bis(1-(diphenylphosphino)prop-1-ylidene)cyclohexane (<b>2d</b>; 1,4-Et<sub>2</sub>-2,3-cyclo-C<sub>6</sub>H<sub>8</sub>-NUPHOS) and 1,2-bis(1-(diphenylphosphino)benzylidene)cyclohexane (<b>2e</b>; 1,4-Ph<sub>2</sub>-2,3-cyclo-C<sub>6</sub>H<sub>8</sub>-NUPHOS), respectively. This methodology provides a
convenient and versatile one-pot synthesis of a wide range of 1,3-diene bridged diphosphines.
Single-crystal X-ray analyses of [(1,2,3,4-Ph<sub>4</sub>-NUPHOS)PdCl<sub>2</sub>], [(1,3-Ph<sub>2</sub>-2,4-Me<sub>2</sub>-NUPHOS)PdCl<sub>2</sub>],
and [(1,4-Ph<sub>2</sub>-2,3-cyclo-C<sub>6</sub>H<sub>8</sub>-NUPHOS)PtCl<sub>2</sub>] reveal that these new phosphines coordinate to
palladium and platinum in much the same manner as BINAP and dpbp, with a significant
torsional twist about the C(2)−C(3) bond of the backbone. The copper diphosphine intermediate
[Cu(1,4-Et<sub>2</sub>-2,3-cyclo-C<sub>6</sub>H<sub>8</sub>-NUPHOS)Cl]<sub>2</sub> (<b>1d</b>) has also been isolated and characterized by single-crystal X-ray analysis and exists as the chloro-bridged dimer in which the 1,2-bis(1-(diphenylphosphino)prop-1-ylidene)cyclohexane coordinates in a bidentate manner. Palladium complexes
of these new diphosphines are highly active for the cross-coupling of bromobenzene and <i>sec</i>-butylmagnesium bromide. Catalyst mixtures based on 1,2,3,4-Ph<sub>4</sub>-NUPHOS are far superior to
those based on BINAP, with activities of 6900 and 260 (mol of product) (mol of palladium)<sup>-1</sup> h<sup>-1</sup>,
respectively. In fact, catalysts based on 1,2,3,4-Ph<sub>4</sub>-NUPHOS are ∼30 times more active than
the most active catalyst reported to date for this coupling. In comparison, the selectivity of the
corresponding cross-coupling with 2-bromopropene depends markedly on the nature of the
NUPHOS derivative. In general, those based on NUPHOS derivatives with acyclic tethers, namely
<b>2a</b>−<b>c,</b> are highly selective for the formation of 2,3-dimethylpentene, while those formed from
<b>2d</b>,<b>e</b> gave a mixture of 2,3-dimethylpentene, 2-methylhexene, and 2,3-dimethylbutadiene. The
initial TOF, measured after 20 min, also shows a marked variation on the nature of the phosphine
and while all NUPHOS-based catalysts outperform those based on BINAP, catalyst mixtures
based on dppf showed both high selectivity (>99%) and impressive activity. Mixtures of Pd<sub>2</sub>(dba)<sub>3</sub> and the NUPHOS derivatives <b>2a</b>−<b>e</b> also catalyze the Suzuki cross-coupling of bromobenzene
and 4-bromoacetophenone with phenyl boronic acid, with conversions up to 100% at catalyst
loadings as low as 0.0001 mol % Pd (TON = 1 × 10<sup>6</sup>).