Chemistry in Overcrowded Systems—Concept and Application—

Organic Seminar 11/06/06Tatsuo Kojima (D2)PI: Prof. Nakamura

Steric Effect in Organic Chemistry1

Crowded

Ph o-Tol Mes Tip Mes* (Supermesityl)

R

R

A-value

Si

Me Et i-Pr Cy Me3Si t-Bu

1.74 ~1.75 ~2.15 2.15 ~2.5 4.9

Use of Steric Effect2

Development of XPhos

Isolation of Unstable Compounds

t-Bu OTs HN+

2% Pd(OAc)25% Ligand

toluene/t-BuOH(5/1)

110 ˚C, Cs2CO3

t-Bu

N

PR2

i-Pr i-Pr

PR2

Me Me

i-Pr

1: R = Cy2: R = t-Bu3: R = Et

4: R = Cy5: R = t-Bu

Yield (GC):

1 2 3 4 5

84% 38% 0% 8% 12%

Buchwald, S. L. et al. JACS, 2003, 125, 6653.

t-Bu

t-Bu

t-Bu

t-Bu

N NP P

Mes*

Mes*

Si Si

Mes

Mes Mes

Mes

West (1981) Yoshifuji (1981) Arduengo (1991)Maier (1978)

Kinetic stabilization

Kinetic Stabilization vs Thermodynamic Stabilization3

MM

M

kinetic thermodynamic

cyclobutadiene

NEt2

Et2N

EtO2C

CO2Et

t-Bu

t-Bu

t-Bu

t-Bu

Overcrowded Ligands for Kinetic Stabilization4

SiMe3

SiMe3

SiMe3

Me3Si

SiMe3

Me3Si

Tbt =i-Pri-Pr

Ar' =

i-Pr i-Pr

M

TbtTbt

MAr

Ch

M = Si, Ge, SnCh = S, Se, Te

Si

Si

Si

Si

Si

Bbi =

JACS, 2011, 133, 6890.

Co

!5-C60Ar5

ChCh

Ch

(Ch = S, Se)

Cr Cr

Ar'

Ar'

Si SiBbi

Bbi

Acc. Chem. Res, 2000, 33, 625.Acc. Chem. Res, 2004, 37, 86. Science, 2005, 310, 844.

Science, 2004, 305, 1755.

Thermodynamic Effect in Overcrowded Systems5

Biali et al. JACS, 1990, 112, 9300.

The thermodynamic stability can be reversedin overcrowded systems.

Conformation of all-trans-polyisopropylcyclohexane

all-eq all-ax

Crowded

all-eq all-ax

reverse order

i-Pr

i-Pri-Pr i-Pr

i-Pr

i-Pr ••••••i-Pr

i-Pri-Pr

i-Pr

i-Pr

i-Pr

Todayʼs Topic6

Crowded

The hidden nature of the molecule can be extractedin overcrowded systems.

Frustrated Lewis Pair Thermochromism of overcrowded alkenes Unidirectional molecular motor based on overcrowded alkenes

Frustrated Lewis Pair (FLP)7

Metal-free activation of H2

Classical Lewis pair Frustrated Lewis pair

P B+ P B P B+

Mes2P B(C6F5)2

F F

F F

H2

heatMes2P B(C6F5)2

F F

F FH

H

Stephan, D. W. et al. Science, 2006, 314, 1124.

R3P + B(C6F5)3

H2R3P + B(C6F5)3H H

Stephan, D. W. et al. JACS, 2007, 129, 1880.(R = t-Bu or Mes)

Theoretical Study of FLP8

The frustrated complex can be accessed only in an overcrowded pair.

P B

P B

Frustrated complex

Pápai et al. ACIE, 2008, 47, 2435; JACS, 2009,131, 2029.Grimme, S.; Erker, G. ACIE, 2010, 49, 1402.

Mechanism of the Activation9

P B

Frustrated complex(flexible)

P B

H2

Electronic fieldby donor and acceptor

HH

P BH

H!+

!–

P BH H

H–H is easily cleaved in the preorganized space.

Boundary of Two Complexes10

Does the boundary between theclassical adduct and thefrustrated complex exist ?

Two types of the complexes are not mutually exclusive.

N B(C6F5)3 N B(C6F5)3+ N B(C6F5)3+H HH2

Stephan, D. W. et al. JACS, 2009,131, 3476.

Application of FLP11

Metal-free catalytic hydrogenation

Activation of alkenes and CO2

Ph R

Nt-Bu

R = Me or H

Ph R

HNt-Bu

toluene, 25 ˚C

H2 (1.5 bar)

Mes2PB(C6F5)2

Mes2PB(C6F5)2

H

H

(5-20 mol%)

ca.80%

Stephan, D. W. Erker, G.et al. ACIE, 2008, 47, 7543.

Stephan, D. W. et al. ACIE, 2007, 47, 4968.Stephan, D. W. Erker, G.et al. ACIE, 2009, 49, 6643.

(t-Bu)3P + B(C6F5)3B(C6F5)3

(t-Bu)3P OO

(t-Bu)3P B(C6F5)3+CO2, rt

–CO2, 70 ˚C

Overcrowded Alkenes12

M

M

HH HHCrowded Steric hindranceAround fjord region

planar planar

ΔE

twist anti syn

We can use various conformations of the alkenein overcrowded alkenes.

Themochromism of Overcrowded Alkenes13

O

O

The availability and the order of the stabilityof the conformations are important.

A

heat

Byellow green / blue

Thermochromic

O

O

Thermochromic Not thermochromic

twist anti syn

Colored Coloreless or pale yellow

(Meyer, 1909)

Agranat, I. et al. Chem. Commun. 2001, 954.

twist

anti twist

ΔE < 30 kJ/mol

Molecular Motors Based on Overcrowded Alkenes14

The nonplanar conformation leads to helical chiralityand two diastreomers.

1st generation motorFeringa, B. L. et al. Nature, 1999, 401, 152.

2nd generation motorFeringa, B. L. et al. JACS, 2000, 122, 12005.

+

S

S

rotor

axle

stator

Unidirectional Rotation of Molecular Motors15

Meax Meeq

MeaxMeeq

hv

thermalhelix inversion

thermalhelix inversion

hv

Acceleration of Molecular Motors16

Review: Adv. Funct. Mater. 2007, 17, 819.Recent acceleration: CEJ, 2009, 15, 2768.

S

R

OMe

t1/2 = 0.67 h

makelower partflexible

109 fold

acceleration

decrease

ring size

3x104 fold

acceleration

increase

substituent size

t1/2 = >1300 year

107 fold

acceleration

t1/2 = 190 s t1/2 = 5.74 ms

decreasehelicenesize

13 foldacceleration

t1/2 = 15 s t1/2 = 0.16 ms(R = PhCC-)

1x106 fold

acceleration

decrease

helicene size

44 rotation/s(cf. F1-ATPase130 rotation/s)

S

S

OMe OMe

S

S

O O

(CH2)8 (CH2)8

HS HS

Brust-Schiffrinmethod

S

S

O O

(CH2)8 (CH2)8

S S

Toward a Realistic Application17

Rotating speed fast enough against “Brownian storm” Unidirectionally controlled axles

Molecular motors on the gold surface

Feringa, B. L. et al. Nature, 2005, 437, 1337.

Au251(motor)26t1/2 = 1.2x103 s

Aut1/2 = 5.6x102 s

Nano Car with a Molecular Motor18

S S

Proposed propulsion scheme on a heated substrate

Tour, J. M. et al. OL, 2006, 8, 1713..

Asymmetric Synthesis with the Molecular Motor19

Feringa, B. L. et al. Science, 2011, 331, 1429.

R

R

NH

HN

N

NMe2 HN

S

CF3

CF3

(2R,2R')-(P,P)-trans-1

A B

Asymmetric Synthesis with the Molecular Motor20

Feringa, B. L. et al. Science, 2011, 331, 1429.

(P,P)-trans-1

(M,M)-cis-1

(P,P)-cis-1

Summary21

Crowded

The hidden nature of the molecule can be extractedin overcrowded systems.

P B

Frustrated complex

twist

anti

Colored

Colorless

Two conformations forthemochromism Unidirectional motor