We report a synthesis method for the construction of quaternary aryl phoshonium salts at ambient temperature. The regiospecific reaction invovles the coupling of phosphines with aryl radicals derived from diaryliodonium salts under photoredox conditions

A. F. Fearnley

Bayne

Bentrude

Cano-yelo

Caputo

Cassity

Dunn

Enders

Fañanás-Mastral

Fumagalli

Gerritsma

Heng

Hoffman

Horner

Hounjet

Hwang

J. An

Kalyani

Kampmeier

M. Jackson

Malmgren

Manabe

Marcoux

McNulty

Merritt

Merzougui

Muneer

Neufeldt

P. Lindovska

Perez

Prier

Ptitsyna

Pérez

R. M. Denton

Redmund

Reichl

Rideout

Shirakawa

Smith

Sundalam

Tappe

Tobisu

Tucker

vom Stein

Wang

Werner

Xiong

Yusubov

Zhdankin

Fearnley, A.F.

An, J.

Jackson, M.

Lindovska, P.

Denton, R.M.

Nottingham ePrints

Fearnley, A.F. and An, J. and Jackson, M. and Lindovska, P. and Denton, R.M. (2016) Synthesis of quaternary aryl phosphonium salts: photoredox-mediated phosphine arylation. Chemical Communications . ISSN 1364-548X Access from the University of Nottingham repository: http://eprints.nottingham.ac.uk/32151/1/Phosphonium%20paper%20for%20deposition.pdfCopyright and reuse: The Nottingham ePrints service makes this work by researchers of the University of Nottingham available open access under the following conditions.This article is made available under the University of Nottingham End User licence and may be reused according to the conditions of the licence.  For more details see: http://eprints.nottingham.ac.uk/end_user_agreement.pdfA note on versions: The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher’s version. Please see the repository url above for details on accessing the published version and note that access may require a subscription.For more information, please contact eprints@nottingham.ac.ukSynthesis	of	Quaternary	Aryl	Phosphonium	Salts:	Photoredox-Mediated	Phosphine	Arylation	A.	F.	Fearnley,	J.	An,		M.	Jackson,	P.	Lindovska	and	R.M.	Dentona*	We	report	a	synthesis	method	for	the	construction	of	quaternary	aryl	phoshonium	salts	at	ambient	temperature.	 The	 regiospecific	 reaction	 invovles	 the	 coupling	 of	 phosphines	 with	 aryl	 radicals	derived	from	diaryliodonium	salts	under	photoredox	conditions.	Quaternary	phosphonium	salts	are	a	 fundamentally	 important	class	of	organophosphorus	compounds,	which	 have	 been	 applied	 as	 synthesis	 reagentsi	phase-transfer	catalysts, ii 	ionic	 liquids, iii 	anti-cancer	agentsiv	as	well	 as	 in	drug	delivery.v		More	 recently,	 phosphonium	 salts	 have	begun	 to	be	explored	 as	Lewis	acidsvi	as	a	result	of	their	low	lying	σ*	orbitals,	opening	up	an	exciting	new	class	of	organocatalysts.			 Despite	 this	 diverse	 range	 of	 applications	 methods	 for	 the	 construction	 of	 aryl-substituted	phosphonium	 salts	 are	 limited.	 Transition	metal-mediated	 couplings	 of	 phosphinesvii	and	 aryl	 halides,	such	 as	 the	 palladium-catalysed	 reactions	 reported	 by	 Charette	 and	 co-workers	 (Scheme	 1A),viib,c	 are	known	 but	 typically	 take	 place	 at	 high	 temperatures.	 An	 important	 alternative	 method	 was	 recently	reported	by	Juge	and	co-workers	(Scheme	1B)	and	involves	the	interception	of	in	situ-generated	arynes	with	 phosphines	 at	 room	 temperature.viii 	This	 method	 is	 limited	 somewhat	 by	 the	 availability	 of	 2-(trimethylsilyl)aryl	triflates	and	poor	the	regioselectivities	obtained	during	the	coupling	of	unsymmetrical	arynes	with	phosphines.		 With	 these	 limitations	 in	 mind	 we	 sought	 a	 method	 that	 could	 be	 conducted	 at	 ambitent	temperature	 and	was	 regiospecific	with	 respect	 to	 carbon-phosphorus	 bond	 formation.	We	 reasoned	that	 the	 arylation	 of	 tervalent	 organophosphorus	 compounds	 with	 iodonium	 salts,ix	first	 reported	 by	Reutov	 and	 co-workers	 in	 1965x	and	 subsequently	 revisited	 by	 Kampmeier,xi	could	 meet	 the	 above	criteria.	 The	 latter	 non-preparativexii 	mechanistic	 study	 corroborated	 a	 redox	 radical	 chain	 process	involving	 aryl	 and	 phosphoranyl	 radicalsxiii 	and,	 despite	 being	 overlooked	 since,xiv 	suggested	 that	 a	synthetically	useful	phosphine	arylation	 reaction	could	be	developed.	Herein	we	 report	a	photoredox-initiated	 arylation	 reaction	 between	 aryliodonium	 salts	 and	 phosphines	 under	 ambient	 reaction	conditions	(Scheme	1C).	Scheme	1.	We	 began	 by	 establishing	 a	 new	 method	 for	 the	 initiation	 of	 the	 putative	 radical	 chain	 at	 ambient	temperature	under	photoredox	conditions.xv	To	this	end	the	combination	of	visible	light	with	Ru(bpy)3Cl2	was	 explored	 (Table	 1).	 Gratifyingly,	 the	 photo-redox	 initiated	 arylation	 of	 triphenylphosphine	 with	diphenyliodonium	triflate	(entry	1)	gave	the	corresponding	phosphonium	salt	in	good	conversion.	Next,	the	analogous	reaction	without	the	10W	lamp	was	investigated	(entry	2)	and	gave	a	much-reduced	23%	conversion.	The	arylation	reaction	did	proceed	in	the	presence	of	visible	light	without	Ru(bpy)3Cl2,	albeit	more	slowly	(12%	conversion	after	20	mins,	entry	3).	XPR2R1 R3ArX(C) THIS WORK: radical arylation(B) Arylation via aryne intermediates(A) Transition metal-catalysed couplingPR2R1 R3XArPR2R1 R3ArXPd2(dba)3 1 mol%PR2R1 R3TMSOTfMeCN, room temp.xylenes, 125 oCR4MeCN, room temp.PR2R1 R3ArOTfPR2R1 R3Ru(bipy)3Cl2  6H2Ovisible lightAr1 Ar2ITable	1.	Survey	of	initiation	methods.		Entry	 Initiator		 Time		 Conversiona		 (mol%)	 (min)	 PPh3	 PPh3O	 PPh4		1	 10	W	lamp	Ru(bpy)3Cl2		2	mol%	20	 19	 10	 73	2	 Ru(bpy)3Cl2	2	mol%		20	 71	 6	 23	3	 10	W	lamp			20	 84	 6	 12	4	 None				120	 100	 0	 0	5	 AIBN	(80	°C)	10	mol%	240	 0	 50	 50		aDetermined	via	31P	NMR	analysis	of	the	crude	the	reaction	mixture.		Finally,	 in	the	absence	of	both	ruthenium	and	visible	light	(entry	4)	no	conversion	to	phosphonium	salt	was	obtained	after	120	minutes.	These	experiments	demonstrate	 that	Ru(bpy)3Cl2	in	combination	with	visible	 light	 from	 a	 10	 W	 lamp	 serve	 as	 an	 effective	 radical	 initiator	 in	 this	 system	 at	 ambient	temperature.xvi	For	 comparison	 initiation	 using	 AIBN	 proved	 to	 be	 less	 efficient	 (entry	 5)	 giving	 23%	conversion	at	80	oC	after	two	hours.	Having	established	that	the	combination	of	Ru(bpy)3Cl2	and	visible	light	was	effective	for	initiating	a	radical-based	coupling	reaction	we	proceeded	to	examine	the	scope	of	this	room	temperature	arylation	protocol.			 We	began	by	arylating	a	range	of	triarylphosphines	with	diphenyliodonium	triflate	(Table	2,	entries	1,3,4,5	and	6)	to	afford	the	corresponding	phosphonium	salts	2	 in	moderate	to	excellent	 isolated	yield	following	 flash	chromatography	and	 recrystallization.	The	arylation	of	methyldiphenylphosphine	 (entry	2)	was	also	efficient.		 Next	we	sought	to	prepare	further	phosphonium	salts	bearing	functional	groups	that	would	facilitate	further	 transformations	 after	 arylation.	 To	 this	 end	 we	 prepared	 two	 chlorophenyl(mesityl)iodonium	triflates	and	carried	out	arylation	reactions	with	a	range	of	phosphines	(entries	7-11).	The	phosphonium	salt	products	were	obtained	in	good	to	moderate	yields	and	are	suitable	for	further	functionalization	via	cross	coupling.viib	 In	each	case	selective	transfer	of	the	chlorophenyl	group	over	the	mesityl	group	was	observed.xvii 			 In	 summary	 the	 arylation	 protocol	 provides	 access	 to	 a	 range	 of	 functionalised	 aryl	 phosphonium	salts	under	ambient	conditions.									PPhPhPhMeCN, room temp.OTfPhPhIinitiatorPPhPhPhPhOTfTable	2.	Scope	of	the	arylation	reaction.																													Entry	 		 Product	Isolated	yield	(%)	1	 2a		85	2	 2b		74	3	 2c		82	4	 2d		57	5	 2e		69	6	 2f		51	7	 2g		63	8	 2h		65	9	 2i		Ar=4-fluorophenyl	71	10	 2j		Ar=4-methoxyphenyl	57	11	 2k		46	aTypical	 procedure:	 iodonium	 salt	 (1.0	 equiv,	 0.7-0.8	 mmol),	 phosphine	 (1.5	equiv)	 and	 Ru(bpy)3Cl2•6H2O	 (10	 mol%).	 Yields	 are	 for	 isolated	 phosphonium	salts	following	normal	phase	flash	chromatography	and	recrystalisation.		IArAr1PR2R1 R3ArOTfPR2R1 R3Ru(bipy)3Cl2  6H2O10 W lamp, MeCN, room temp.2 mol%1 2OTfPPhPh PhPhOTfPPhMe PhPhOTfPPhPhPh OTfNPPh OTfMeOOMeOMePPh OTfFFFPPh OTfClClClP PhPhOTfNClPPhPhPhOTfClPArArArOTfClPArArArOTfClPPhPhPhOTfCl	Scheme	1	(top)	Scheme	2	(right)	In	terms	of	the	mechanism	our	experimental	observations,	as	well	as	those	of	othersxviiiare	consistent	 with	 the	 pathways	 depicted	 in	Scheme	1.	 Visible	 light-induced	excitation	of	Ru(bpy)3Cl2	 results	 in	 population	 of	 the	excited	 state,	which	 is	 reductively	quenched	by	 the	 phosphine	 resulting	 in	 the	corresponding	 phosphoniumyl	 radical	cation.xix 	The	 derived	 ruthenium	 (I)	 species	now	 reduces	 the	 iodonium	 salt,	 resulting	 in	fragmentation	 to	 afford	 an	 aryl	 radical	 and	iodobenzene	 as	 a	 by-product.	 Formation	 of	the	product	phosphonium	salt	can	now	occur	through	 two	 pathways.	 Either,	 the	phosphoniumyl	radical	cation	combines	with	the	 phenyl	 radical	 (Scheme	 1B),	 or	 a	 radical	chain	 process	 intervenes	 (Scheme	 1C).	 The	radical	 chain	 reaction	 involves	 addition	 of	 a	phenyl	 radical	 to	 triphenylphosphine	 to	afford	an	intermediate	phosphoranyl	radical.xiii	Subsequent	oxidation	of	this	radical	by	the	iodonium	salt	affords	 the	 phosphonium	 salt	 product	 and	 propagates	 the	 radical	 chain.	 	 Support	 for	 above	 proposal	comes	the	following	experiments	depicted	in	Scheme	2.	An	arylation	reaction	conducted	in	the	presence	of	 1,1-diphenylethylene	 resulted	 in	 significantly	 reduced	 conversion	 to	 the	 product	 phosphonium	 salt	(16%	 compared	 to	 73%	 under	 standard	 conditions,	 entry	 1	 Table	 1).	 This	 is	 consistent	 with	 covalent	trapping	 of	 phenyl	 radicals,	 as	 is	 the	 production	 of	 increased	 amounts	 of	 triphpenylphosphine	 oxide	from	 the	 reaction	 of	 the	 intermediate	 phosphoniumyl	 radical	 cation	 with	 water. xx 	Secondly,	diphenyliodonium	 triflate	 is	 stable	 with	 respect	 to	 reductive	 fragmentation	 in	 the	 presence	 of	Ru(bpy)3Cl2	 and	 visible	 light	 (Scheme	2B).	 This	 rules	 out	 an	 alternative	 photoredox	 initiation	 involving	oxidative	quenching	of	 excited	 ruthenium(II)	 by	 the	 iodonium	 salt.	 In	 a	 third	 experiment	 (Scheme	2C)	diphenyliodonium	triflate	was	converted	into	 iodobenzene	and	benzene	in	the	presence	of	Ru(bpy)3Cl2	and	 triethylamine.	 These	 two	 observations	 are	 congruent	 with	 the	 Ru(I)-mediated	 reduction	 of	 the	iodonium	salt	depicted	in	Scheme	1A.	Finally,	an	arylation	reaction	in	which	irradiation	was	stopped	after	3	minutes	resulted	in	26%	conversion.	This	suggests	that	the	arylation	process	is	weighted	more	towards	Scheme	1B	than	the	radical	chain	process	(Scheme	1C)	.xxi			 The	reaction	also	proceeds	in	the	presence	of	visible	light	but	absence	of	Ru(bipy)3	(Table	1,	entry	3).	We	speculate	that	this	arylation	proceeds	through	a	charge	transfer	complexixf	(Scheme	1D)	from	which	[Ru(bipy)3] 2+[Ru(bipy)3] 2+*[Ru(bipy)3] 1+visiblelightIPhPhOTfIPh PhPR2R1 R3PR2R1 R3PR2R1 R3Ph PR2R1 R3PhPR2R1 R3Ph PR2R1 R3PhIPhPhOTf(A) (B)(C)Ph PhI(D)Ru(bipy)3 initiated pathwayBackground arylation reactionPR2R1 R3 IPhPhOTfPR2R1 R3 IPhPhOTfC.T. complexvisible lightPR2R1 R3IPhPhOTfRu(bipy)3Cl2  6H2O10 W lamp, MeCN, 30 minroom temp.2 mol%IPhPhOTfRu(bipy)3Cl2  6H2O10 W lamp, MeCN, 60 minroom temp.2 mol%IPhX PhHIPhPhOTf IPh PhHNEt3 1 equiv.>95% conversion(B)(C)OTfPPhPh PhRu(bipy)3Cl2  6H2O10 W lamp, MeCN, 30 minroom temp.2 mol%IPhPhOTfPPhPh PhPh(A)Ph Ph16% conversion 1 equiv.Ru(bipy)3Cl2  6H2O10 W lamp 3 minMeCN, 20 minroom temp.2 mol%IPhPhOTf(D)OTfPPhPh PhPh26% conversionPPhPh Phelectron	transfer	from	phosphine	to	iodonium	salt	may	occur	in	the	presence	of	visible	light	to	provide	the	phosphoniumyl	radical	cation	and	phenyl	radical.		 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Res.	1982,	15,	117.	xiv	For	recent	related	coupling	reactions	involving	arylation	of	P-H	and	P-OH	bonds	using	iodonium	salts,	see	(a)	J.	Xu,	P.	Zhang,	Y.	Gao,	Y.	Chen,	G.	Tang,	and	Y.	Zhao,	J.	Org.	Chem.,	2013,	78,	8176;	(b)	B.	Xiong,	X.	Feng,	L.	Zhu,	T.	Chen,	Y.	Zhou,	C.T.	Au	and	S-F.	Yin,	ACS	Catal.,	2015,	5,	537;	(c)	M.	Fañanás-Mastral	and	B.L.	Feringa,	J.	Am.	Chem.	Soc.	2014,136,	9894;	(d)	Y.	He,	H.	Wu	and	F.D.	Toste,	Chem.	Sci.,	2015,	6,	1194.	xv	For	selected	reviews,	see	(a)	K.P.	Prier,	D.A	Rankic	and	D.W.C.	MacMillan,	Chem.	Rev.,	2013,	113,	5322;	(b)	Y.	Xi,	H.	Yi	and	A.	Lei,	Org.	Biomol.	Chem.,	2013,	11,	2387	and	(c)	J.W.	Tucker	and	C.R.J.	Stephenson,	J.	Org.	Chem.	2012,	77,	1617.																																									 																																								 																																								 																																								 														xvi	Given	the	proximity	of	the	lamp	to	the	reaction	vessel	the	internal	temperature	was	monitored	and	found	to	be	32	°C.	A	further	1	h	control	experiment	between	Ph3P	and	Ph2IOTf	at	32	°C	resulted	in	the	formation	of	Ph3PO	(6	%)	and	Ph4POTf	(3%)	with	92%	of	Ph3P	remaining.	xvii	The	selective	transfer	of	electron	deficient	aryl	groups	over	the	relatively	electron	rich	mesityl	group	has	been	observed	previously	non-catalysed	nucleophilic	arylation	reactions,	see	(a)	J.	Malmgren,	S,	Santoro,	N,	Jalalian,	F.	Himo	and	B.	Olofsson,		Chem.	Eur.	J.	2013,	19,	10334;	(b)	S.	K.	Sundalam	and	David	R.	Stuart	,	J.	Org.	Chem.	2015,	80,	6456.	We	observed	no	arylation	between	triphenylphosphine	and	4-methoxyphenyl(mesityl)iodonium	triflate	under	the	reaction	conditions	depicted	in	Table	2.	xviii	R.	Muneer	and	T.W.	Nalli,	Macromolecules,	1998,	31,	7976	xix	For	 recent	work	 involving	phoshonium	 radical	 cations,	 see	K.D.	Reichl,	D.H.	Ess,	 and	A.T.	Radosevich,	 J.	Am.	Chem.	Soc.	2013,	135,	9354.	xx	For	electrochemical	generation	of	the	trimesityl	phosphoniumyl	radical	and	subsequent	reaction	with	water	to	afford	 the	 corresponding	 phosphine	 oxide,	 see:	 B.	 Merzougui,	 Y.	 Berchadsky	 and	 P.	 Tordo,	 G.	 Gronchi,	Electrochimica	Acta	1997,	42,	2445.	xxi	We	are	grateful	to	a	reviewer	for	suggesting	this	experiment.	xxii	There	are	several	other	methods	for	the	generation	of	aryl	radicals	under	photoredox	conditions,	for	example	from	diazonium	salts,	see	(a)	H.	Cano-yelo	and	A.	Deronzier,	J.	Chem.	Soc.,	Perkin	Trans.	2,	1984,	16,	1093;	(b)	H.	Cano-yelo	and	A.	Deronzier,	Tetrahedron	Lett.	1984,	25,	5517;	(c)	D.	Kalyani,	K.B.	McMurtrey,	S.R.	Neufeldt	and	M.S.	 Sanford,	 J.	 Am.	 Chem.	 Soc.,	 2011,	 133,	 18566.	 It	 is	 likely	 that	 further	 arylation	 reactions	 of	 tervalent	phosphorus	compounds	will	be	developed	along	these	lines.	

Synthesis of quaternary aryl phosphonium salts: photoredox-mediated phosphine arylation

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Synthesis	of	Quaternary	Aryl	Phosphonium	Salts:	Photoredox-Mediated	Phosphine	Arylation	A.	F.	Fearnley,	J.	An,		M.	Jackson,	P.	Lindovska	and	R.M.	Dentona*	We	report	a	synthesis	method	for	the	construction	of	quaternary	aryl	phoshonium	salts	at	ambient	temperature.	 The	 regiospecific	 reaction	 invovles	 the	 coupling	 of	 phosphines	 with	 aryl	 radicals	derived	from	diaryliodonium	salts	under	photoredox	conditions.	Quaternary	phosphonium	salts	are	a	 fundamentally	 important	class	of	organophosphorus	compounds,	which	 have	 been	 applied	 as	 synthesis	 reagentsi	phase-transfer	catalysts, ii 	ionic	 liquids, iii 	anti-cancer	agentsiv	as	well	 as	 in	drug	delivery.v		More	 recently,	 phosphonium	 salts	 have	begun	 to	be	explored	 as	Lewis	acidsvi	as	a	result	of	their	low	lying	σ*	orbitals,	opening	up	an	exciting	new	class	of	organocatalysts.			 Despite	 this	 diverse	 range	 of	 applications	 methods	 for	 the	 construction	 of	 aryl-substituted	phosphonium	 salts	 are	 limited.	 Transition	metal-mediated	 couplings	 of	 phosphinesvii	and	 aryl	 halides,	such	 as	 the	 palladium-catalysed	 reactions	 reported	 by	 Charette	 and	 co-workers	 (Scheme	 1A),viib,c	 are	known	 but	 typically	 take	 place	 at	 high	 temperatures.	 An	 important	 alternative	 method	 was	 recently	reported	by	Juge	and	co-workers	(Scheme	1B)	and	involves	the	interception	of	in	situ-generated	arynes	with	 phosphines	 at	 room	 temperature.viii 	This	 method	 is	 limited	 somewhat	 by	 the	 availability	 of	 2-(trimethylsilyl)aryl	triflates	and	poor	the	regioselectivities	obtained	during	the	coupling	of	unsymmetrical	arynes	with	phosphines.		 With	 these	 limitations	 in	 mind	 we	 sought	 a	 method	 that	 could	 be	 conducted	 at	 ambitent	temperature	 and	was	 regiospecific	with	 respect	 to	 carbon-phosphorus	 bond	 formation.	We	 reasoned	that	 the	 arylation	 of	 tervalent	 organophosphorus	 compounds	 with	 iodonium	 salts,ix	first	 reported	 by	Reutov	 and	 co-workers	 in	 1965x	and	 subsequently	 revisited	 by	 Kampmeier,xi	could	 meet	 the	 above	criteria.	 The	 latter	 non-preparativexii 	mechanistic	 study	 corroborated	 a	 redox	 radical	 chain	 process	involving	 aryl	 and	 phosphoranyl	 radicalsxiii 	and,	 despite	 being	 overlooked	 since,xiv 	suggested	 that	 a	synthetically	useful	phosphine	arylation	 reaction	could	be	developed.	Herein	we	 report	a	photoredox-initiated	 arylation	 reaction	 between	 aryliodonium	 salts	 and	 phosphines	 under	 ambient	 reaction	conditions	(Scheme	1C).	Scheme	1.	We	 began	 by	 establishing	 a	 new	 method	 for	 the	 initiation	 of	 the	 putative	 radical	 chain	 at	 ambient	temperature	under	photoredox	conditions.xv	To	this	end	the	combination	of	visible	light	with	Ru(bpy)3Cl2	was	 explored	 (Table	 1).	 Gratifyingly,	 the	 photo-redox	 initiated	 arylation	 of	 triphenylphosphine	 with	diphenyliodonium	triflate	(entry	1)	gave	the	corresponding	phosphonium	salt	in	good	conversion.	Next,	the	analogous	reaction	without	the	10W	lamp	was	investigated	(entry	2)	and	gave	a	much-reduced	23%	conversion.	The	arylation	reaction	did	proceed	in	the	presence	of	visible	light	without	Ru(bpy)3Cl2,	albeit	more	slowly	(12%	conversion	after	20	mins,	entry	3).	XPR2R1 R3ArX(C) THIS WORK: radical arylation(B) Arylation via aryne intermediates(A) Transition metal-catalysed couplingPR2R1 R3XArPR2R1 R3ArXPd2(dba)3 1 mol%PR2R1 R3TMSOTfMeCN, room temp.xylenes, 125 oCR4MeCN, room temp.PR2R1 R3ArOTfPR2R1 R3Ru(bipy)3Cl2  6H2Ovisible lightAr1 Ar2ITable	1.	Survey	of	initiation	methods.		Entry	 Initiator		 Time		 Conversiona		 (mol%)	 (min)	 PPh3	 PPh3O	 PPh4		1	 10	W	lamp	Ru(bpy)3Cl2		2	mol%	20	 19	 10	 73	2	 Ru(bpy)3Cl2	2	mol%		20	 71	 6	 23	3	 10	W	lamp			20	 84	 6	 12	4	 None				120	 100	 0	 0	5	 AIBN	(80	°C)	10	mol%	240	 0	 50	 50		aDetermined	via	31P	NMR	analysis	of	the	crude	the	reaction	mixture.		Finally,	 in	the	absence	of	both	ruthenium	and	visible	light	(entry	4)	no	conversion	to	phosphonium	salt	was	obtained	after	120	minutes.	These	experiments	demonstrate	 that	Ru(bpy)3Cl2	in	combination	with	visible	 light	 from	 a	 10	 W	 lamp	 serve	 as	 an	 effective	 radical	 initiator	 in	 this	 system	 at	 ambient	temperature.xvi	For	 comparison	 initiation	 using	 AIBN	 proved	 to	 be	 less	 efficient	 (entry	 5)	 giving	 23%	conversion	at	80	oC	after	two	hours.	Having	established	that	the	combination	of	Ru(bpy)3Cl2	and	visible	light	was	effective	for	initiating	a	radical-based	coupling	reaction	we	proceeded	to	examine	the	scope	of	this	room	temperature	arylation	protocol.			 We	began	by	arylating	a	range	of	triarylphosphines	with	diphenyliodonium	triflate	(Table	2,	entries	1,3,4,5	and	6)	to	afford	the	corresponding	phosphonium	salts	2	 in	moderate	to	excellent	 isolated	yield	following	 flash	chromatography	and	 recrystallization.	The	arylation	of	methyldiphenylphosphine	 (entry	2)	was	also	efficient.		 Next	we	sought	to	prepare	further	phosphonium	salts	bearing	functional	groups	that	would	facilitate	further	 transformations	 after	 arylation.	 To	 this	 end	 we	 prepared	 two	 chlorophenyl(mesityl)iodonium	triflates	and	carried	out	arylation	reactions	with	a	range	of	phosphines	(entries	7-11).	The	phosphonium	salt	products	were	obtained	in	good	to	moderate	yields	and	are	suitable	for	further	functionalization	via	cross	coupling.viib	 In	each	case	selective	transfer	of	the	chlorophenyl	group	over	the	mesityl	group	was	observed.xvii 			 In	 summary	 the	 arylation	 protocol	 provides	 access	 to	 a	 range	 of	 functionalised	 aryl	 phosphonium	salts	under	ambient	conditions.									PPhPhPhMeCN, room temp.OTfPhPhIinitiatorPPhPhPhPhOTfTable	2.	Scope	of	the	arylation	reaction.																													Entry	 		 Product	Isolated	yield	(%)	1	 2a		85	2	 2b		74	3	 2c		82	4	 2d		57	5	 2e		69	6	 2f		51	7	 2g		63	8	 2h		65	9	 2i		Ar=4-fluorophenyl	71	10	 2j		Ar=4-methoxyphenyl	57	11	 2k		46	aTypical	 procedure:	 iodonium	 salt	 (1.0	 equiv,	 0.7-0.8	 mmol),	 phosphine	 (1.5	equiv)	 and	 Ru(bpy)3Cl2•6H2O	 (10	 mol%).	 Yields	 are	 for	 isolated	 phosphonium	salts	following	normal	phase	flash	chromatography	and	recrystalisation.		IArAr1PR2R1 R3ArOTfPR2R1 R3Ru(bipy)3Cl2  6H2O10 W lamp, MeCN, room temp.2 mol%1 2OTfPPhPh PhPhOTfPPhMe PhPhOTfPPhPhPh OTfNPPh OTfMeOOMeOMePPh OTfFFFPPh OTfClClClP PhPhOTfNClPPhPhPhOTfClPArArArOTfClPArArArOTfClPPhPhPhOTfCl	Scheme	1	(top)	Scheme	2	(right)	In	terms	of	the	mechanism	our	experimental	observations,	as	well	as	those	of	othersxviiiare	consistent	 with	 the	 pathways	 depicted	 in	Scheme	1.	 Visible	 light-induced	excitation	of	Ru(bpy)3Cl2	 results	 in	 population	 of	 the	excited	 state,	which	 is	 reductively	quenched	by	 the	 phosphine	 resulting	 in	 the	corresponding	 phosphoniumyl	 radical	cation.xix 	The	 derived	 ruthenium	 (I)	 species	now	 reduces	 the	 iodonium	 salt,	 resulting	 in	fragmentation	 to	 afford	 an	 aryl	 radical	 and	iodobenzene	 as	 a	 by-product.	 Formation	 of	the	product	phosphonium	salt	can	now	occur	through	 two	 pathways.	 Either,	 the	phosphoniumyl	radical	cation	combines	with	the	 phenyl	 radical	 (Scheme	 1B),	 or	 a	 radical	chain	 process	 intervenes	 (Scheme	 1C).	 The	radical	 chain	 reaction	 involves	 addition	 of	 a	phenyl	 radical	 to	 triphenylphosphine	 to	afford	an	intermediate	phosphoranyl	radical.xiii	Subsequent	oxidation	of	this	radical	by	the	iodonium	salt	affords	 the	 phosphonium	 salt	 product	 and	 propagates	 the	 radical	 chain.	 	 Support	 for	 above	 proposal	comes	the	following	experiments	depicted	in	Scheme	2.	An	arylation	reaction	conducted	in	the	presence	of	 1,1-diphenylethylene	 resulted	 in	 significantly	 reduced	 conversion	 to	 the	 product	 phosphonium	 salt	(16%	 compared	 to	 73%	 under	 standard	 conditions,	 entry	 1	 Table	 1).	 This	 is	 consistent	 with	 covalent	trapping	 of	 phenyl	 radicals,	 as	 is	 the	 production	 of	 increased	 amounts	 of	 triphpenylphosphine	 oxide	from	 the	 reaction	 of	 the	 intermediate	 phosphoniumyl	 radical	 cation	 with	 water. xx 	Secondly,	diphenyliodonium	 triflate	 is	 stable	 with	 respect	 to	 reductive	 fragmentation	 in	 the	 presence	 of	Ru(bpy)3Cl2	 and	 visible	 light	 (Scheme	2B).	 This	 rules	 out	 an	 alternative	 photoredox	 initiation	 involving	oxidative	quenching	of	 excited	 ruthenium(II)	 by	 the	 iodonium	 salt.	 In	 a	 third	 experiment	 (Scheme	2C)	diphenyliodonium	triflate	was	converted	into	 iodobenzene	and	benzene	in	the	presence	of	Ru(bpy)3Cl2	and	 triethylamine.	 These	 two	 observations	 are	 congruent	 with	 the	 Ru(I)-mediated	 reduction	 of	 the	iodonium	salt	depicted	in	Scheme	1A.	Finally,	an	arylation	reaction	in	which	irradiation	was	stopped	after	3	minutes	resulted	in	26%	conversion.	This	suggests	that	the	arylation	process	is	weighted	more	towards	Scheme	1B	than	the	radical	chain	process	(Scheme	1C)	.xxi			 The	reaction	also	proceeds	in	the	presence	of	visible	light	but	absence	of	Ru(bipy)3	(Table	1,	entry	3).	We	speculate	that	this	arylation	proceeds	through	a	charge	transfer	complexixf	(Scheme	1D)	from	which	[Ru(bipy)3] 2+[Ru(bipy)3] 2+*[Ru(bipy)3] 1+visiblelightIPhPhOTfIPh PhPR2R1 R3PR2R1 R3PR2R1 R3Ph PR2R1 R3PhPR2R1 R3Ph PR2R1 R3PhIPhPhOTf(A) (B)(C)Ph PhI(D)Ru(bipy)3 initiated pathwayBackground arylation reactionPR2R1 R3 IPhPhOTfPR2R1 R3 IPhPhOTfC.T. complexvisible lightPR2R1 R3IPhPhOTfRu(bipy)3Cl2  6H2O10 W lamp, MeCN, 30 minroom temp.2 mol%IPhPhOTfRu(bipy)3Cl2  6H2O10 W lamp, MeCN, 60 minroom temp.2 mol%IPhX PhHIPhPhOTf IPh PhHNEt3 1 equiv.>95% conversion(B)(C)OTfPPhPh PhRu(bipy)3Cl2  6H2O10 W lamp, MeCN, 30 minroom temp.2 mol%IPhPhOTfPPhPh PhPh(A)Ph Ph16% conversion 1 equiv.Ru(bipy)3Cl2  6H2O10 W lamp 3 minMeCN, 20 minroom temp.2 mol%IPhPhOTf(D)OTfPPhPh PhPh26% conversionPPhPh Phelectron	transfer	from	phosphine	to	iodonium	salt	may	occur	in	the	presence	of	visible	light	to	provide	the	phosphoniumyl	radical	cation	and	phenyl	radical.		 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We report a synthesis method for the construction of quaternary aryl phoshonium salts at ambient temperature.</p

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Chemical Communications

http://eprints.nottingham.ac.uk/32151/1/Phosphonium%20paper%20for%20deposition.pdf

Synthesis of quaternary aryl phosphonium salts: photoredox-mediated phosphine arylation

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