光催化苯胺与DIPEA合成2,3-二胺反应方法学

邻二胺骨架广泛存在于各类天然产物以及药物分子中，同时也是过渡金属催

化反应中常见的配体。并且，在过去的几十年里，已经成功设计出多种构建邻二

胺分子的合成转化策略(Figure1)。然而，上述的方法常需使用化学计量的金属

试剂以及需要亚胺的预制备。受到近年来有机光化学反应方法学⑶以及三烷基胺

作为碳源参与相关反应方法学】的启发，这里，报道一种全新的可见光促进二异

丙基乙胺(DIPEA)与苯胺反应方法学，进而成功完成一系列2,3-二胺分子的构建。

diamination

a)

metalcatalyst

NH

0

4

OORZnorCu

b)N

Ar—«OR4

ArNHCHAr2

NHAr

TiCatalyst

Ar-NH“NHAr

c)R

RNHAr1

TiCatalystR

ANJ

d)PH

RRNHAr2

reductive

couplingH

e)RN.小

ArH

thiswork

RCHO,4CzlPNH

、N，Ar

Ar-NH2

MeCN,454nmH

首先，作者采用苯胺la与(i-Pr)2NEt2a作为模型底物，进行相关反应条件的

优化筛选(Tablel)o进而确定最佳的反应条件为：采用4CZIPN作为光催化剂,

苯甲醛作为氢原子转移试剂，20W蓝色LEDs(454nm)作为光源，在乙晴反应溶

剂中,反应温度为室温,最终获得82%收率的产物3a(2:1

Table1.Preliminarydevelopmentof'eductivecouplingconditions0.

8V==・crSV0.

IM>a*

EntryPhotocatalystSolventYIHdla(%rdr

1M-MPPV).01aoi531:1

2CH1cH6923

4QPN.4QTPN,4f-

304CH42.55.6t561:1

BuQIPN,4DPAIPNa

RudWhOj

Benzophenone,EosinY,

4

ODaRMdammB,CH1cMtraceocM./

Ribo<lavine,Xanthone.

1.4-Dvcyanobentene

54QIPNTHFM2:1

6giPNxetone581:1

74QIPNDMFS22:3

Toluene；

84C1IPNDMSO;EtOH：tr»c«/

MFIP

94QIPN501:1

104OIPNoa6S1:2

ir4QIPNCH,CNn.d./

12-giPNn.<t/

13*4Q1PNCHjCNtrace/

1，4OIPNCMjCN822:1

•Reactionconditions;la(0.3mmol).(Pr^NEt(0.6mmol),PhCHO

(0.3mmol)andphotoc«t>ly$t(2mo/%)insolvent(2ml)room

temperatureunderargonand20WblueLED(454nm)irradiation,

unlessotherwisestated;•Isolatedyieds,dr=diastereomericratio;c

ThereactionwascarriedoutIndark;1Thereactionwascarriedout

3t70℃rThereactionwascarriedcutunderairatmosphere;'10

mol%4CzlPN.

在上述的最佳反应条件下，作者分别对一系列苯胺底物(Table2)以及苯甲醛

底物(Table3)的应用范围进行深入研究。

T«bl«2.Phenylaminesubstratesscope

£T.V^©鹏分

tMg.»•

CrYQq/*qYQ

3ai

»1313H«)%«•115

qVQqrYQQV"

Mrrw.«r-«fM.<•%.♦-«1TW.72%,«r-1:1S

H.g・・”7A⑶5•141

“6Mbdr>I14M.8、9•11■“、dr.125

Ws^y8Tsia"“o"八Q»

«14M11M.••才1

SZ

•]Q®Y^||^'»r*^y*T^nx^er,

Reactionconditions：la-z(0.3mmol),(iPr)2NEt(0.6mmol),

PhCHO(U.3mmol)and4CZIPN(1Umol%)inCHjCN(2mL)at

roomtemperatureunderargonand20WblueLED(454nm)

irradiation,unlessotherwisestated.Isolatedyieldsof3a-zare

provided.

NotesofTable3

a.Whenthepara-positionofthebenzaldehydehaselectrondonatinggroupssuch

as-Me,-OMe,-Phand-OBn,moderatetogoodyieldscanbeobtained.

b.Halogen-substitutedbenzaldehydesubstratesarealsosuitablefor

photocatalyticsystemsandtargetproductscanbeobtainedinmoderatetogood

yields(5hr51).

c.Thesterichindranceeffecthasagreatinfluenceonthereaction,forexample,

theyieldsof2-OMe,3-OMeand4-OMesubstitutedbenzaldehydesincreasedwith

theincreaseinsterichindranceandwere63'V73and82respectively.The

reasonforthismaybethatasthesterichindranceincreases,thephenylethanol

radicalbecomesmorestable,whichfavoursitsformation.

d.Theheterocyclicthlophene-formaldehydeandfuran-formaldehydecanalso

yieldthetargetdiols.

e.Inaddition,adamantanecontainingbenzaldehydecanalsobereactedin56%

yield.

同时，该小组还对烷基醛试剂（Scheme1）的应用范围进行深入研究。

0r丫Q.0rHdQ

MeCN.BkjtlED♦M1产、

of。

Scheme1.Alkylaldehydereagentscope

NotesofScheme1

a.Acetaldehydeincreasestheyieldofthediamine3ato85%(Scheme1a).

b.Whenpropanalisused,notonlythesymmetricdiamine3aisformed,butalso

symmetric6andasymmetric7,resultingfromincorporationofC2andC3fragments

fromdiisopropylethylamineandpropanal,respectively(Scheme1b).

c.Invalidationofthisobservation,butanalbehavedsimilarlytoprovideaC4fragment

andamixtureof3a,symmetric8andasymmetric9(Scheme1c).

d.Whenthealdehydeisreplacedbybenzophenone,thereactionproceedssmoothlyto

giveonlyasingleproduct3a,indicatingthatbenzophenoneactsonlyasanoxidant,

acceptinghydrogeninthereaction(Scheme1d).

之后，该小组通过如下的•系列研究进一步表明，这•全新的合成策略具有

潜在的合成应用价值（Scheme2）。

Scheme2.Syntheticapplicationsofthereaction.

接下来，作者对上述反应过程的反应机理进行进一步研究(Scheme3)。

Scheme3.Controlexperiments.

NotesofTable

a.Foranilinesubstratesbearingsubstituentsatthepara-positionofthebenzenering,

bothelectrondonatingandwithdrawinggroupsaretoleratedtogivethe

correspondingproduct3inmoderatetoexcellentyields.

b.Para-substitutionwith-Me,-Et,-jPrandsterically-hinderedfBugave77,80,76and

66%yields,respectively.

c.Halogensubstitutedsubstrates1f-hgave60-72%yields.

d.Theanil