Current Organic Chemistry (year of 2017)

Lewis Acid and Base, Chemistry of Group 13 Element
May 30, 2017, #8, Makoto Yamashita (room 1031)
makoto@oec.chembio.nagoya-u.ac.jp

Lewis Acid and Base
Lewis acid:
Lewis base:vacant orbital
LB+LA

Lewis base Lewis acidcoordination bond
LB LA
Lewis acid-base adduct

Gilbert Lewis“Octet rule”
Lewis, G. N., Valence and the Structure of Atoms and Molecules.
Chemical Catalogue Company, Inc.: New York, 1923.

Collecting Literatures
Classification of literatures and their citation format(1)(2)
ex. Tsukahara, N.; Asakawa, H.; Lee, K.-H.; Lin, Z.; Yamashita, M., J. Am. Chem. Soc. 2017, 139, 2593-2596.
name of authorsabbreviatedjounal nameyear volumepages

For full-name of journal, google with a word of “abbreviation” and abbreviated journal name
→ J. Am. Chem. Soc. = the Journal of the American Chemical Society (sometimes further abbreviated as JACS)(3)

place of publisher

ex. Pauling, L., The Nature of The Chemical Bond. 3 ed.; Cornell University Press: Ithaca, 1960.
name of author

title of the book (italicized)

name of authors

title of chapter

editionname of publisherpublished year

title of the book (italicized)

ex. Yamashita, M.; Nozaki, K., Boryl Anions. In Synthesis and Application of Organoboron Compounds,Fernández, E.; Whiting, A., Eds. Springer International Publishing: 2015; pp 1-37.
name of editorsname of publisher

published year page of chapter

How to find the paper(1) go to http://sfx.nul.nagoya-u.ac.jp/nagoya/az/?lang=eng on browser of your PC(2) type the journal name into the textbox of “title” and hit “Go”
(3) you will find the title of the journal on the bottom, then click it(4) type year, vol, and start page, then hit “go”
(5) click PDF in somewhere of the website

Examples of Lewis Acids & Bases
Lewis acids
metals possessing vacant orbitals
can also be drawn withO-Mg covalent bond(no formal charge)
group 13 element compounds

heavy main group element compounds
possessing a low-energy σ* orbital

Lewis bases
heteroatoms having lone pair(s)transition metals having a filled d-orbital
OEt
FeOC CO+ ClOEt

OEt
FeOCOCOrg. Synth. 1988, 66, 95.

OEt

Strength of Lewis Acids
Donation of π-electron weakens Lewis acidity
Lewis acidity of boron compounds(high) BPh3 > B(OMe)3 > B(NMe2)3 (low)OMeOMeB

MeO

Enhancement of Lewis acidity by electron-withdrawing groups
Lewis acidity of boron compounds
F

application of strong Lewis acidF

MeMeZr(high)

F
F

F

B>

F
F

F F
F

F

F
F

F

F>

F

B

F

F F
F

F

F

F
F
F

(low)

F

B

Zr

Me+ [MeB(C6F5)3]

F

F F
F

Me+ B(C6F5)3
Me

F

F

JACS 1998, 120, 1772.

Enhancement of Lewis acidity by formal positive charge
HH
B H+ CH2Cl2HHH

B NEt3 + CH2Cl2
Hcoordination bondHBHClCH2ClBH H+ NEt3Cl CH Cl
2BNEt3H

cationic boron binds
a lone pair of CH2Cl2

application of strong Lewis acid
FFP
C6F5σ*P-F

C6F5
C6F5+ F R

C6F5

C6F5+ RPF

C6F5Science 2013, 341, 1374.
fluorophosphonium could absorb fluoride
even from alkyl fluoride to form alkyl cation

homework (1):
Design your own Lewis acidhaving cationic charge and draw its structureLewis Acid Catalyst (1)Basic concept:
remind Friedel-Crafts alkylation

coordination of carbonyl to Lewis acidto enhance the reactivity
O+ BF3 +OSSH

BF3SHSHSH

S+ H2O + BF3

BF3 is regenerated
to be used as catalyst

homework (2):Draw the remaining mechanismwith curved arrows(remind the formation of acetal)

AlCl3 is regenerated
to be used as catalyst

Application(1) Mukaiyama aldol reaction

Organic Syntheses, 1993, Coll. Vol. 8, 578.
BF3 absorbes OEt anion to forman oxonium intermediate(2) CBS (Corey-Bakshi-Shibata) reduction

oxazaborolidine

JACS 1987, 109, 5551.
Double activation:(a) N to BH3, (b) carbonyl to B
Stoichiometric amount of borane (BH3)+ catalytic amount of oxazaborolidine

Lewis Acid Catalyst (2)Application
Chemoselective reduction

MAD: methylaluminiumbis(2,6-di-tert-butyl4-methylphenoxide)

Ring-opening alternating co-polymerization ofepoxide and CO2 to produce biodegradable polymer

polymer from CO2
recently industrialized
Makromol. Chem. 1969, 130, 210.

“bulky” Lewis acid
JACS 1988, 110, 2650.

Ring-opening polymerization of cyclic carbonate ester
generated from CO2 to produce biodegradable polymerOrganometallics 2011, 30, 3217.

Lewis Base Catalyst
Basic concept:
acceleration of nucleophilic acyl substitution by cationic charge
N+H 3CMe2N

NOCOCO

CH3 +Me2N

OC

H 3C

N+ R OH
CH3OC

H 3C

Me2N

N

R OH
O++Me2N

RO
HO
CO
C+OH+
CH3 H3C

ROCOOO
CCH3N,N-dimethylpyridine
is regenerated to be
used as catalyst

homework (3):Draw resonance hybrid of the first intermediatewith four resonance structures

Application
Stetter reaction by using nucleophilic carbene catalyst: umpolung reaction of aldehyde
RNC H
S

R
R

R
RbaseR
OH
NC C
SR’R
RNCS
R
carbeneR
RNCS
RylideO

R H
N O
C C
SR’R
R

R’O
CH

RO
N
C C H
S
R’R
R

aldehyde can be considered as=O

R
R

R
NR’
C +C
S
O

OH

ACIE 1976, 15, 639.

carbene (ylide) is regenerated
to be used as catalystrstchd–reby70
on-rusalher
eirreLP
thed ametheonattes
tamuews.

Frustrated Lewis Pair (FLP)
generated the following question: Can one effect consecutive
Basic
concept:
delivery of proton and hydride to an organic substrate? If so, thisIf Lewis
andhydrogenationbase can system
not form
adductdue to steric hindrance,
would
yield aacid
metal-freethat would
regeneratetheshow
FLP to uniquefurther activate
H2, yielding
a catalytic
process.
theyreactivity
towardorganic
molecules
Indeed, this hypothesis was ﬁrst demonstrated to be true fornitrogen-based
unsaturated
molecules.
The mechanism of such
heterolytic
cleavageof hydrogen
metal-free imine reductions has been shown to proceed viaFFof the imine, followed by hydrideFF
initial protonationtransferHH
2 carbon (Scheme 1).11,12
from the hydridoborate to the iminium
MestheB(C6FandB(C6F5)3
ThisMes
net2Ptransfer of proton
2P phosphonium5)3 hydride fromΔH
borate to the imine regenerates the Lewis acid–base pair, whichFFFF
are then available for subsequent activation of H2 regenerating
the phosphonium-borate. This mechanism is consistent with theScience
2006, 314,
1124.
observed reactivity trends in which
the electron-richimine,tBuNvCPh(H) is reduced signiﬁcantly faster than the electronpoor imine, PhSO2NvCPh(H). In addition, the phosphoniumborate (Cy3P)(C6F4)BH(C6F5)2 13 was shown not to react withimine. These results are consistent with initiation of the imine
Application
reduction via protonation.

View Article Online

ACIE 2010, 49, 46.
Catalytic hydrogenation of imine, nitrile, aziridine, aromatic hydrocarbons, alkenes, and ketones

Scheme 7 FLP hydrogenation of a diimine.

Prof. Doug Stephan@U of Toronto, Canada

redH2

Commun.of 2012,48, heterocycles.
11963.
SchemeChem.
9 FLP hydrogenations
nitrogen-basedACIE
2007,46,8050.
Scheme 1 Mechanism for FLP hydrogenation of imine.

Organic Molecules Containing Group 13 Element
Electronic effect of boryl substituent

In all cases, a vacant p-orbital of B atom accept an electron pair
to form a negatively charged “borate” having four bonds“Inorganic benzene”: Borazine

Due to B=N double bond character,borazine is similar to benzene

BN-Containing aromatic molecules

ACIE 2009, 48, 973.
JACS 2011, 133, 11508.

Polarity of B=N double bond gives unique photophysical properties

Prof. Warren Piers@U of Calgary, Canada
general review:Can. J. Chem. 2009, 87, 8.

3-Center-2-Electron Bond
Structure of Be(CH3)2Be or Mg
HWilliam Lipscomb
Nobel Prize 1976

Electron deficient group 1, 2, and 13 element compounds
easily aggregate by sharing bonding electrons into vacant orbital(s)3-center-2-electron bond

Structures of CH5+ and B2H6
H

H
C
H

H
H+H

H
C
H

H
H

3-center-2-electron bond
Important intermediatein acid-catalyzed
cracking process of oil

H
B
H

H

H

H
B
H

H
H
B
H

H
B
H
H

H
H

H
B

B
H

hydride (H–) reagent in organic synthesis
George OlahNobel Prize 1994

homework (4):Draw the structure of (AlMe3)2 with 3c-2e bondwith description of orbitals and electrons

HHDiborane(4): Strong Lewis Acid & Reductant
B–B bond in diborane(4)HH

H
B

BHdiborane(6)

HH

H

H

B

B

H

O

H

Odiborane(4)OB B
O

B2pin2 1

Cf. Nomenclature of Inorganic Chemistry
IUPAC Recommendations 2005

bond length (Å) BDE (kJ/mol)
B–B
1.75
293
B–C
1.65
372
B–O
1.36
536
J. Emsley, The Elements, 3rd ed.,Oxford University Press, New York, 1998.

Diborane(4) can reduce C≡N triple bondHC
Mes (1 equiv.) Mes COH
B B
B
50%
HMesOpinB NtButBut
CO 20%ButBu N C(1 atm)
NN
MesMes (excess)
Mes
MesCCC B+B C
C BpinB OCpinB N
Mes pinB N
MestButBu
OtBu NThe unsymmetrical diborane(4) compound reactedwith isocyanide to cleave C≡N triple bondoverlapping of two vacant orbitals
lead to higher Lewis acidity

Asakawa, H.; Lee, K.-H.; Lin, Z.; Yamashita, M., Nat. Commun. 2014, 5, 4245.
Asakawa, H.; Lee, K.-H.; Furukawa, K.; Lin, Z.; Yamashita, M., Chem. Eur. J. 2015, 21, 4267.

Diborane(4): Strong Lewis Acid & Reductant
Highly Lewis acidic diborane(4) reacted with alkyne

Direct diboration of alkyne with controlled selectivity
Kojima, C.; Lee, K.-H.; Lin, Z.; Yamashita, M., J. Am. Chem. Soc. 2016, 138, 6662.

Further higher Lewis acidity leads direct reaction with H2H2B

B

hexaneRT, 2 h52%

BH
H

pyridine
BHBN

96%

The first example of direct metathesis between B–B and H–H bonds
H–H bond was reduced by reductive B–B bondTsukahara, N.; Asakawa, H.; Lee, K.-H.; Lin, Z.; Yamashita, M., J. Am. Chem. Soc. 2017, 139, 2593.

Boron Clusters via Accumulation of 3c-2e Bonds
Wade rule: Nomenclature for cluster compounds
Accumulation ofCounting in Wade ruleKenneth Wade(1) counting all electrons from formula of the cluster
ex. B: 3, H: 1, charges change the # of electrons(2) SEP (skeletal electron pair) is defined as[(total electrons) – 2×(B-H unit)]/2(3) all borane clusters can be classified byn = SEP – (# of B atoms)n = 1: closo-, n = 2: nido-, n = 3: arachno(4) determining the # of vertices
closo-, SEP–1; nido-, SEP–2; arachno-, SEP–3(5) # of vertices can give the structure
ex. B5H9all electrons = 5 x 3 (B) + 9 x 1 (H) = 24
SEP = [24 – 2×5]2 = 7
n = SEP – 5 = 2, can be considered as nido-borane# of vertices = SEP–2 = 5

Boron Clusters (2)Carborane: carbon-incorporated boron cluster[B12H12]2−[CB11H12]−

ortho[C2B10H12]

meta[C2B10H12]

para[C2B10H12]

Applications of carborane
use [C2B10H12] as a surrogate ofbenzene ring in medicinal chemistry

application in pharma (1)application in pharma (2)BNCT = Boron Neutron Capture Therapy

anti-inflammatory

amyloid synthesis inhibitor

activefor BNCT

important to concentratein cancer cells

Boron Clusters (3)Application of carborane:[CB11H12]– can be used as non-coordinating anion to stabilize unstable cation species(1) X-ray crystallographic
analysis of tert-Bu cationdC 334.2(SO2)(2) model for Whelandintermediate (SEAr reaction)(3) carborane acid: the strongest acid

3.530 Å3.489 ÅJACS 2005, 127, 7664.
JACS 2006, 128, 3160.
(4) application of carborane acid:protonation of C60

C–CH3 = 1.429(4)–1.459(4) Å==ACIE 2004, 43, 2908.
Cl interacted with the vacantp-orbital of carbocation= similar to the transition
state of SN2 reaction

JACS 1972, 94, 2034.
JACS 2003, 125, 1796.
positions of delocalized
cationic charge wereidentical to the old reportfor NMR observation

Science 2000, 289, 101.

Chemistry of Boronic Acid
Boronic acid: carbon-substituted
boric acid [B(OH)3] derivatives

H-bonding dimer

Reaction with H2O to liberate H+ (acid)

Fast formation of cyclic ester with diol

Application of cyclic ester (1): molecular recognition of sugar

chelate effect makes
product stable

Nature 1995, 374, 345.
Formation of a complex with sugar leads fluorescence

Application of cyclic ester (2): porous polymer

JACS 2008, 130, 11872.

Spontaneous shift of equilibrium
through reversible reactions
Porous material consisting of covalent bonds

Boronic Acids
edited by Deniss G. Hall
Wiley-VCH, 2011

Hydrometallation with Group 13 Element
Hydroboration

Representative hydroboration reagents
HBO
O BH3

Me2S BH3

http://www.chem-station.com/odos/2009/06/brown-brown-hydroboration.html

4-centered TSB HO
catecholborane

Herbert Brown
Nobel Prize 1979

9-borabicyclo[3.3.1]nonane(9-BBN)

Oxidation of alkylborane

disiamylborane
HB

B H

H
BH

thexylborane

B H

diisopinocampheylborane(R,R)-2,5-dimethylborolane

Metal-catalyzed hydroborationcat = Rh(PPh3)3Cl
0.05 mol%, 20 min, 83%

ACIE 1985, 24, 878.

JACS, 1964, 86, 3565.
Hydroalumination of alkene

electron-donating groups= syn addition

Reaction of alkenylaluminumelectron-withdrawing groups= anti addition
Reactive C–Al bond can be usedas organometallic nucleophilehomework (5):Explain the reason why anti-additon productwas obtained with electron-withdrawing groups
together with the structures of key intermediate(hint: after syn-addition, isomerization takes place)

Can. J. Chem. 1973, 51, 2098.

“Lewis Basic” Boron Compounds
Boron derivative of alkyllithium, “boryllithium”

crystal structure

HOMO represents lone pair characterLi
Dip N B N Dip
Br
Dip = 2,6-iPr2C6H3
H2O

THF

Dip N B N Dip
LinBuClDip N B N Dip
Li1) PhCHO
2) H2O

Dip N B N Dip Dip N B N Dip Dip N B N DipnBu
HCPh H OH

Boryllithium can undergo transmetallation
as a “boryl anion”

Science 2006, 314, 113. ACIE 2007, 46, 6710. JACS 2007, 129, 9570. ACIE 2008, 47, 6606.
JACS 2008, 130, 16069. Chem. Lett. 2008, 37, 802. JACS 2009, 131, 14162. JACS 2010, 132, 11449.
Chem. Commun. 2011, 47, 5888. ACIE 2011, 50, 920. Eur. J. Org. Chem. 2011, 3951. ACIE 2014, 53, 6259.
JACS 2016, 138, 3548. ACIE 2016, 55, 11426. ACIE 2016, 55, 12827. ACIE 2017, 56, 1658.

“Lewis Basic” Boron Compounds
Highly basic boryl anion to deprotonate benzene

TS for deprotonation (DFT)

crystal structure
Dip N B N Dip
LiK
Dip N B N Dip

Dip
N
N B H

Dip N B N Dip
10 h, rtcf. C6H6
pKa = 371)

B Ph
85%

Dip

Dip N B N Dip
HDip

B H
(NMR yield)

15%

LiB

K

N N Dip

C6H6 coordinated to K+
to enhance acidity of C-H

Ohsato, T.; Okuno, Y.; Ishida, S.; Iwamoto, T.; Lee, K.-H.; Lin, Z.; Yamashita, M.; Nozaki, K., Angew. Chem. Int. Ed. 2016, 55, 11426-11430.

Related “boron nucleophiles”
O
Cy3P·BH2I

LDBB

Cy3P·BH2–Li+Cy3P

B
H2Mn

COCOOC COMn B Mn

LiDME

OCMeIMnCl
B Cu•KClPh

Mn

COCOPh22–•

ACIE 2010, 49, 9166.

then, H2OOACIE 2008, 47, 5650. ACIE 2009, 48, 9735.
O
Et
EtO
O
Dip N C N Dip LDBB/TMEDA Dip N C N Dip
Dip N C N Dip
THF
BH I
BH Li
BH
LDBB = Li+PhO

Li+(DME)32Ph

then, H2O

pinBOPhPh
96%

CuCl, LiCl, KOAc

MeB

DME OC
OC

CO+O
O(B2pin2)

SiMe3

J. Org. Chem. 1994, 59, 6753.
J. Organomet. Chem. 1993, 462, 107.

ClB
OC
OC

B B

–•

LDBB = Li+Mn

ClSiMe3

CuOTf (10 mol%)nBu P (11 mol%)
3O

O

O

O

Et

Tetrahedron Lett. 2000, 41, 6821.
Chem. Lett. 2000, 29, 982.
J. Organomet. Chem. 2001, 625, 47.
Ph
Ph
Ph
Ph

pinB
53%Ph
B

Cl
Mes N

KC8

Ph
Mes
Et2O
NPh
Mes N

B

KPh
N Mes

MeI
Et2O

PhB
MePh
Mes
N

Mes NACIE 2010, 49, 2041.

About Homework
Solve all the problems [homework (1)-(5)] in this lecture and write down it to an A4 paper(you can use PC instead of hand-writing)Do not forget writing your name and student ID number on the report paper
Make a PDF file of the report paper or take a picture of the report paper,then send it as an attachment file of email to makoto@oec.chembio.nagoya-u.ac.jp
Deadline of homework: June 9 (Fri) 2017, 17:00