Table Of ContentFOREWORD
The whole field of ligand coupling has only emerged in the last decade as a basis
for new synthetic transformations. As Professor Finet shows in this
comprehensive survey, the recent clarification of reaction mechanisms of ligand
coupling process around heteroatom centres, now provides an understanding of
these reactions which are certain to permit their application in organic synthesis,
thereby achieving transformations which are quite difficult to achieve by other
methods. This book will be of interest to all chemists engaged in organic
synthesis both in academia and industry.
J E Baldwin, FRS
xi
Preface.
The concept of eht elor of dnagil gnilpuoc ni Organic sisehtnyS is due ni(
lacitebahpla )redro ot Oac and ot .tsorT These srohtua made lanimes snoitubirtnoc ot eht
.dleif The ylrae work on iodonium compounds, osla of lanimes ,ecnatropmi by rcgnireB
was confused by eht ,feileb shared by many, taht such snoitcaer must be lacidar ni
.retcarahc The ylrae work of McEwen on antimony compounds osla does ton hsiugnitsid
between lacidar gnilpuoc and dnagil .gnilpuoc
More tnecer work on ,htumsib lead and iodonium compounds sah deifiralc eht
ecnatropmi of dnagil gnilpuoc over lacidar .gnilpuoc
The dleif sah now deniatta a ytirutam and ytilasrevinu where a evisneherpmoc
noitatneserp of dnagil coupling ni Organic sisehtnyS ni a elgnis monograph si yltnegru
.dedeen
This book by .rD erreiP-naeJ Finet, ruetceriD de Recherche au C.N.R.S. ta
,elliesraM sedivorp ni a thorough and ylralohcs way, a balanced egarevoc of eht whole
.dleif tI should eviecer a warm noitpecer from citehtnys and citsinahcem .stsimehc
D.H.R. Barton
Dow dehsiugnitsiD rosseforP of Chemical noitnevnI
Xlll eoe
This book owes much to Professor Sir Derek Barton, first and foremost, for his many
seminal contributions to the chemistry of ligand coupling reactions with various
heteroatomic elements, and second for giving me the opportunity to work in this field
and to bring my own contribution to a better understanding of the importance of this
mechanistic concept in heteroatomic chemistry. It is with a very great sadness for me
that Professor Barton passed away just a few weeks before this book, that he had
initiated, was published. I would like to dedicate it to his memory as a tribute to the
perenniality of his enlightening spirit.
This book would not have been possible without the support of the "Centre National de
la Recherche Scientifique" which gave me the bread and butter together with the
necessary freedom for bringing this enterprise to completion.
I am also very thankful to all my colleagues for their help, fruitful discussions and
various contributions. I would particularly mention Professors Dervilla M.X. DonneUy,
Kin-ya Akiba, Victor A. Dodonov, Shigeru Oae, John T. Pinhey and Paul Tordo, as
well as Doctors Christiane Bernard-Henriet, Alexei Fedorov, Patrick J. Guiry, Alexei V.
Gushchin, Pascal Suisse de Sainte Claire and Mr Sdbastien Combes. I would also like to
thank all the collaborators with whom I have been associated over the years of my
involvement in this field. Their contributions helped me to shape up my understanding
of this concept.
This book constitutes an attempt to cover as comprehensively as possible the various
facets of the reactions of organic chemistry occurring by the ligand coupling
mechanism. Considering the number of heteroelements which are covered in this
monograph, I am highly conscious of the difficulties to reach this goal of complete
coverage. Therefore, I am aware that the work of some contributors to the field will
unfortunately have been overlooked or not been given its due. I do apologise in advance
and comments are welcome.
This book will hopefully make organic chemists more familiar with the chemistry of the
different elements reacting by this still unsufficiently recognized mechanism and will
foster new developments in this promising field.
March 1998
xiv
Abbreviations
An 4-Methoxyphenyl
Bipy Bipyridine
BPR Berry pseudorotation
BTMG N-te rt-buty l-N'~',N ",N "-tetrameth y l guani dine
Bz Benzoyl
Bzl Benzyl
DMAP 4-Dimethylaminopyridine
DME enahteyxohtemiD-2,1
DMF N,N-dimethylformamide
DMSO Dimethylsulfoxide
DPE enelyhtelynehpiD-1,1
HMPA Hexamethylphosphorotriamide
BITH Hydroxytosyloxyiodobenzene
L.C. Ligand coupling
LDA Lithium diisopropylamide
L.E. Ligand exchange
Ms Methanesulfonyl
Ox Oxidation
noitatoroduesP
Phen Phenanthroline
yP Pyridyl
RT room temperature
.T.E.S single electron transfer
SP square pyramid
TBP trigonal bipyramid
TBDMS tert-Butyldimethylsilyl
Tf Trifluoromethanesulfonyl
THF Tetrahydrofuran
THP Tetrahydropyranyl
TMG N,N,N',N'tetramethylguanidine
TMS Trimethylsilyl
Tol Methylphenyl
TR Turnstile rotation
Ts 4-Toluenesulfonyl
V'X
Chapter 1
Introduction
1.1 DEFINITIONS
The word "ligand" was first introduced by Stock in 1917 in a discussion on the similarities between
carbon and silicon chemistry. 1 This term has been mostly used by chemists to describe atoms or
groups attached to a central atom in coordination compounds or organometallic compounds. 2 It has
been used only infrequently by organic chemists, although Fieser employed it to describe the
substituents of a phosphorus compound. 3 In the past decade, it has gained wider acceptance in organic
chemistry, in agreement with its original definition as given by Stock: 1
"Zur Verhtitung von Mil$verstandnissen sind die Bedeutung einiger hier gebrauchter
Worte erklart. Affinit~it ist der Ausdruck rOf die Festigkeit, mit welcher ein Element andere
Elemente oder Radieale (allgemein: ,,Liganden~ [ligare, binden]; die Einfiihrung eines - bisher
fehlenden - Wortes for diesen, wohl ohne weiteres verstandlichen Begriff vereinfacht die
Ausdruckweise) bindet. - Valenz bedeutet die Krafteinheit, die einen einwertigen Liganden
binden kann; positive Valenzen binden negative, negative Valenzen positive Liganden. -
Wertigkeit ist die Zahl der Valenzen, die ein Atom betatigt; Htchstwertigkeit die Htchstzahl der
bei einem Element beobachteten Valenzen."
and translated by Brock 2 as:
"To prevent misunderstandings the meaning of several words used here must be
explained. Affinity is the expression for the firmness with which one element binds other
elements or radicals (generally: "Ligands" (ligare [Latin], to bind); the introduction of a word
hitherto lacking simplifies the manner of expression for this immediately clear eoncept).-
Valence (Valenz) means the unit of force which can bind a univalent ligand; positive valencies
bind negative ligands, negative valencies bind positive ligands.- Atomicity (Wertigkeit) is the
number of valencies which an atom manifests; the highest atomicity is the highest number of
valencies observed for an element."
The term "reductive elimination" is widely used in organometallic chemistry, particularly in
organotransition metal chemistry, where it is generally associated with the reverse "oxidative
addition". 4 However, in organic chemistry, reductive elimination is a term generally associated with
various reactions dealing with the regio- and stereo-controlled synthesis of alkenes from 1,2-disubs-
tituted alkanes, as well as the union of two fragments or the creation of a ring. 5 This is, for example,
the case of the reductive elimination of 1,2 or 1,4-dihalides or halohydrins, of oxiranes and thiiranes,
Ligand Coupling Reactions with cimotaoreteH sdnuopmoC
the Julia alkenylation or the reductive elimination of 13-substituted nitroalkanes. 5 Ramberg-B~icklund
reaction is another variety of reductive elimination of an episulfone. 6 This reaction has proven very
efficient for the synthesis of large rings, such as the core structure of neocarzinostatin. 7
The term "extrusion reaction" defines reactions in which an atom or group of atoms bonded to two
other atoms is lost. Among the most frequently lost atoms or group of atoms are: azo, carbonyl,
sulfonyl, thio, carbon dioxide. The two atoms formerly bonded to the lost group can become directly
bonded together: this is the restricted definition of March. 8
c\BZ
A----- C + B
If the fragmentation of the two atoms from the group, to which they were bonded, takes place in a
concerted process resulting in the formation of a conjugated system, this is a cheletropic extrusion.
Thus, the two possibilities can be found in the case of the loss of a SO2 group: SO2 extrusion from an
episulfone, as in the Ramberg-Biicldund reaction, is an extrusion reaction, but SO2 extrusion from a
cyclic sulfolene is a cheletropic reaction. 9
",A B',C = A C
\_/ \\ // + B
The term "cheletropic reaction" defines reactions in which two o bonds to a single atom are made
or broken concertedly. 01 A widely studied example, theoretically as well as experimentally, is the
cheletropic elimination of sulfur dioxide from a cyclic sulfolene to generate stereochemically pure
dienes or polyenes. 11
O ~ + SO2 and 2 - + SO 2
1.2 LIGAND COUPLING
The term "iigand coupling" in hypervalent compounds was used by Oac to describe an extrusion of
two ligands, with a pair of electrons, from a central atom which undergoes a return to its more stable
valency. 21
X X
NuO + LnM~ : ye + LnM~ :- NuX + LnM
Y Nu
According to Oae, to be a ligand coupling the process requires a cohesive interaction between an
axial and an equatorial ligand by overlap of orbitals of both axial and equatorial ligands. 21 If the
coupling reaction between the axial and the equatorial ligands proceeds concertedly, the configuration
of both ligands will be retained in the final product.
Chapter :1 Introduction
X L
Nu ~ M + NuX
L
~M denotes coupling of the two ligands on M atom
In chapter 2, we shall see that this stereochemical conception is too narrow to accommodate all the
systems which belong to the group of ligand coupling reactions. These can be defined as reactions
involving the intramolecular coupling of two groups bonded to a highervalent heteroatomic element
occurring in a concerted manner. As stated by Whitesides, "the most valuable single type of
information to have in characterizing the mechanism of a reaction that makes or breaks bonds at a
tetrahedral carbon atom is the stereochemistry of the transformation at that carbon". 31 In the case of
the ligand coupling mechanism, formation of C-C, C-H or C-X bonds must proceed with retention of
configuration at carbon. The same retention of configuration is observed in the case of ligand coupling
reactions with stereochemically defined vinyl systems.
This concept of ligand coupling can also be applied to a variety of organometallic reactions, as in
the following example: 51,41
e M (
C4Hlo + MeAuPPh 3
-uA
I 70oC
Et- PPh 3
reL 15
Et
C3H s + EtAuPPh 3
The ligand coupling mechanism has also been suggested to occur during a number of oxidation
reactions involving metal oxides, such as for example: 61
Ar~ I~C=O _~ O
S + !I
S~ -4 C=O
"eM O=Cr- O Ar" Me I /
O=Cr- O
II
O
In this book, the ligand coupling reactions which are surveyed are multistep sequences involving
the formation of an hypervalent intermediate generated by one of the two following types: either
substitution of a o-ligand by the nucleophile or addition of the nucleophilic substrate on a ~-ligand:
| | Nu
Nu + LnM(N+2)Xy ~ X + LnM(N+.~ ~ NuY + nL )N(M
Y
or
| Nu
Nu + xY)2+NfMRL -- -". LnM(N+2)"~ ~ e "~ Y -= NuY + L n~ M )N(e
Ligand Coupling Reactions with Heteroatomic Compounds
The compounds involved in these two types of reactions which will be surveyed in the following
chapters are the higher-valent derivatives of the main-group p-block elements which include:
-"hypervalent organo-nonmetallic" molecules of group V-VIII, as defined by Musher 91-71
- "main-group organometallic" compounds in their higher valences, which afford, after the
ligand coupling step, an inorganic by-product which is stable in the lower oxidation state
[e.g. organolead Pb(IV) to inorganic Pb(II) salts 02 or organothallium TI(III) to inorganic
TI(I) salts].
Although they are not ligand coupling reactions occurring on the main-group element derivative,
but due to their synthetic interest, I shall also describe some copper-catalysed reactions of main-group
higher-valent compounds. However, it will exclude the reductive elimination reactions which are
frequently observed in the case of organotransition metal derivatives. With these metals, the reductive
elimination step can take place either on the stoichiometric highervalent organometal derivative, or as
part of the oxidative addition-reductive elimination catalytic system. This is featured by cobalt, iron,
rhodium, palladium, platinum, nickel, copper among others.4, 12
A classification of hypervalent organo-nonmetallic derivatives, which have an electron-rich
multicenter bonding system, has been devised by Perkins et .la in 1980. 22 This system, (the N-X-L
system), describes the valence electron count and the coordination number. For an atom (X), the
overall bonding system is described first by the number of valence shell electrons (N) formally directly
associated with the atom (X), and by the number fO ligands (L) directly bonded to it. A number of
examples is shown below.
R Cl
,,~,.P~ R-- 2:,P l'' R Ph--
R / R ]'~R [~
R R IC
8-P-3 5-P-Ol 3-I-01
Br F F
..eomIIF ,,F ..... ;''l F
F ~" ~F
\ rS F F
3-S-01 10-S4 12-S-6
1.3 PSEUDOROTATION
Pentacoordinate model structures have been used in the interpretation of a wide variety of reactions
occurring on phosphorus derivatives. 32 These pentacoordinate compounds can exist as two basic
structures, trigonal bipyramid (TBP) and square pyramid (SP), which are generally non rigid and
undergo facile stereomutation. The ligand rearrangement involved in the stereomutation is generally
called pseudorotation, and two mechanisms have been proposed. In 1960, Berry suggested that the
stereomutation in group V compounds takes place via a TBP-SP-TBP pathway, which results in an
exchange between the apical and equatorial ligands through bond bending. 42 In the equilibrium TBP
(D3h) conformation, a molecule 5LM has three equatorial bonds (e) and two apical bonds (a). In the
first step of the Berry pseudorotation mechanism, the TBP structure evolves into a tetragonal pyramid
(C4v). During the deformation, one equatorial bond becomes the apical bond of the square pyramidal
Chapter :1 Introduction
structure and the other two equatorial and two apical bonds move concertedly to form the basal bonds
of the square pyramid. In the second part of the process, the two formerly equatorial and the two
formerly apical bonds exchange their positions in such a way that eventually the two former apical
bonds become equatorial in the new conformation. (Scheme 1.1)
L4,,~I 3L ~" ,r162 -- 3L ~ -!(t / 3L E L -.
- L4
h3D v4C h3D h3D
Scheme 1.1: The Berry pseudorotation
et .la
An alternative mechanism, the turnstile rotation mechanism (TR), was later proposed by Ugi
to explain these intramolecular rearrangements, particularly when the pentavalent structure
incorporates ring systems. 52 The turnstile mechanism consists of three consecutive steps. The first step
is a deformation of the (D3h) conformation, in which there is an angle compression between L4 and L5,
so that the angle )5L-M-4L(0 closes from 120 ~ down to 90 ~ The three groups L2, L4 and 5L form with
M a regular trigonal pyramid. Simultaneously, the other two groups 1L and L3 undergo an angle
.ac
deviation 10 = 9 ~ towards the 2,-1 group, the angle )3L-M-1L(0 remaining constant equal to 90 ~ In
the new conformation, the C3 symmetry axis of the trigonal pyramid corresponds to the C2 symmetry
axis of the isosceles triangle formed by L ,1 L3 and M. (Scheme 1.2.1)
1L
~I 1L 3L
..cnn . dll x /
5L ,SL M,N. I
120o~ ..... 3L - --
9o o ..--~,'-
L~'" [
4L 90o ~,/,~'.'- 2L
L2 2L ~,L
Scheme 1.2.1: The turnstile rotation mechanism: first step
The second step corresponds to a torsion of the two units by 60 ~ so that the new arrangement is
equivalent to the arrangement reached at the end of the first step. The second step is represented by a
topside view in Scheme 1.2.2.
L..r, I
",,,,..~ ))'Ll 1L
...,,,4L 5L _. L4,,,,.~. [email protected] L 5 ..~,,,~L ,,,,.. 5L
3L)~ ) ~- 3L
L2
30 ~ 60 ~
Scheme 1.2.2: The turnstile rotation mechanism: second step
Ligand Coupling Reactions with Heteroatomic Compounds
The third step is the reverse path of the first step, the two groups 3L and L1 undergoing an angle
deviation 0_ 1 = .ac 9 ~ At the same time, there is an angle decompression between L2 and ,5,-I so that
the angle 0(L2-M-L5) opens up from 90 ~ to 120 ~ The overall moves restore the stable new TBP
structure. (Scheme 1.2.3)
1L L3 : 3L 3L
M . . . . . 5L09 . ~ . 4~ ..... ~ 120o~~. =:~.~L1
,,"/\
L~ L 4 L 4
Scheme 1.2.3: The turnstile rotation mechanism: third step
Although the Berry pseudorotation mechanism (BPR) is the most frequently used to interpret the
experimental results, it has been shown that these two mechanisms can be topologically equivalent. 62
The Berry pseudorotation can be viewed as a 1( + 4) process, as the equatorial group L5 remains in
equatorial position in the new TBP structure. The turnstile mechanism can be viewed as a (2 + 3)
process, in which one equatorial and one apical groups interchange their positions, and in parallel, two
equatorial and the other apical group also interchange their positions. However, in the latter three
groups, one equatorial group eventually remains in the equatorial plane. This overall turnstile
mechanism results in the interchange between two apical and two equatorial groups, as in the Berry
pseudorotation. In the following scheme (Scheme 1.3), the interchanges between the two extreme
configurations occurring in the two mechanisms are summarized. For clarity sake, the equatorial
ligands are marked e ,1 e2 and e3, and the apical ligands are considered equivalent.
Berry Pseudorotation: a 1( +4) process
a I% e3
el' . . M ! ...... ti,. e 3 ,,,,1 a
_,NI M ...o1111I||| el M I\ ...It
a e2
(aa ee) (ee aa)
Turnstile Rotation: a (2+3) process
011 e 3 .0111 ..... .~l~a
M ...... e 2
e l - - - ..... ___
a e 1
(ae eea) -, ._ .... (ca eae)
Scheme 1.3: Topological equivalence of Berry pseudorotation and turnstile rotation mechanisms
