Raymond E. Dessy' and Frank Paulik Un~versitvof Cincinnati Cincinnati, Ohio
I(
Multicenter and Assisted Mechanistic Pathways in the Reactions of ~r~anometallic Compounds
If one examines the possible mechanistic pathway that substitution a t an attacked saturated center may take, two main divisions may be easily listed without consideration of fine detail: (1) nucleophilic, SN, and (2) electrophilic, SE,processes. These are illustrated below, with X-1- the substrate, and E-N the attacking reagent in molecular form. The notations employed are the basic Ingold classification scheme (1). In the same manner, simple addition processes may be divided into similar categories. (Table 1,2) The SNseries involving saturated carbon centers has
' Alfred P. Sloan Fellow;
Reaction
Texaeo, Inc., Predoctoral Fellow.
Tmnsition state
Classification
been the subject of a great deal of work, and though some minor disagreements still exist concerning intimate details, particularly solvent participation, our over-all picture of the area is relatively clear. S Nreactions ~ usually yield product with inverted configuration, SN1processes may proceed with racemization, predominant inversion, or predominant retention of confirmration. while S w i Drocesses give a ~ r i o retention r of configura&on. (The' work ofUsom&er has shown that at saturated silicon centers 3 ~ processes 2 may proceed with retention of configuration (Z), presumably because of d orbital participation allowing front-side attack by the nucleophile.) SE processes are less completely understood, fundamentally because the generation of an incipient or free carbanion in the rate determining process implies the use of organometallic compounds, most of which are labile to water and/or oxygen, necessitating vacuumline or inert atmosphere box techniques. Only one isolated case of an S E reaction ~ in an organometallic system (organomercurial) has been reported (S), and no detailed stereochemical or mechanistic investigation was undertaken. However, from the excellent work of Cram (4) on the system indicated below it is known
-
0-Mi
"\ b-C-C-d I
I
+ HB
-
a
\
solvent
b-C-H
,
e
retention, raeemisation, inversion
-rz leaving group .- . ..-.
Transition state
Reaction
X
=
Y
+E -N -
- 1
X-Y
lE
Volume 40, Number
:
Classification
Adr
4, April 1963
/
185
that the possible stereochemical consequences of S E ~ reactions are similar to those of S Nreactions ~ (Fig. 1). Factors contributing to the specific courses taken by any one reaction have been discussed by Cram (4), benzylie earbanion Streitwieser (5), Corey (6), and Goering (7), with Sulfone carbanions appear to he asymmetric because particular emphasis on those reactions involving H/D of stabilization by the adjacent SOz function, through exchange a t an optically active center via carbanion overlap of the carbanion (spa)= orbital and empty (ion-pair) intermediates. The temperature, solvent, sulfur d orbitals, while benzylic carbanions would appear availability of internal proton, and cation of the base are all apparently important. Three distinct types of optically active centers have been employed. Cram has investigated hydrogen exchanges a to a nitrile, amide, or ester function. Streitwieser, and Cram have investigated benzylic hydrogen exchanges, while Corey, Goering, and Cram sulfone carbanion have studied the exchange reactions of hydrogens a to be predominantly symmetrical because of delocalizato an activating sulfone grouping. The first case is of tion of the charge into the ring. Tet, both types of little interest here since exchange seems to involve an carbanions are capable of exhibiting exchange processes ambident anion capable of protonating on the most that are predominantly racemizing, or retentive in electronegative element to give an unstable tautomer nature (Table 3). It would seem essential to invoke which reverts to exchange product with a priori some type of solvent participation to explain the reracemization (Fig. 2). The latter two cases are insults obtained. The concepts of Cram regarding teresting in the sense that some light is shed on the the intimate salvation pictures which lead to retention relationships between the factors mentioned above, as and racemization (or inversion) are charted in Figure 3. well as the effect of the structure of the carbanion. At present there is no clear agreement concerning the exact nature of the solvent interactions leading to H-B retention: Cram feels that ". . .the active catalytic species are heavily solvated metal-alkoxide ion pairs and the carbanion-metal cation pair produced is heavily solvated on the front side with deuterium donors because of the solvent orienting powers of the intim+e aolvenkseparated dissociated metal cation. Thus deuterium capture from the front anlon ion p a r Ion paw side is the favored reaction path." Streitwieser, on the other hand, feels that front-side attack predominates because reaction a t the rear produces charge separation in a media of poor ionizing power. If he can "formulate this distinction in operational terms that may be subject to experimental test," our exact knowledge in this important area will be greatly improved. asymmetric /ntimak Lon p a r
symmetric solvated earbanion
asymmetric shielded carbanion
Table 3. Carbanion-Solvent-Base Systems Classified According lo Their Svmmetrv Pro~erties
Class retention of configuration
loss of configuration
inversion of configuration
Carbanion
Solvent shell
I
Symmetric
Symmetric
11
Symmetric
Asymmetric
111
Asymmetric
Symmetric
IV
Asymmetric
Asymmetric
Figure 1.
stable potentially asymmetric tautomers
symmetrical smhident anions
Figure 2.
186
/
Journal of Chemicol Education
unstable symmetric tautomers
Examples 2-Phenyl-2-hutyl anion in either dimethyl sulfoxide-potassium l-butoxide, or t-butyl alcoholquaternary ammonlurn hvdroxide 2-Phenyl-2-butyl anion in either 1-butyl alcoholpotassium t-hutoxide, or ethylene glycol-potassium ethylene glycoside 2-Phenylaulfonyl-2-octyl muon in dimethyl sul-
nium hydroxide 2-Phenylsulfonyl-2-octyl anion in 1-hutyl alcoholhnt~ssiurnt-butoxide
The detailed aspects of S Ereactions ~ have been most clearly discussed by Winstein (8,9) and more recently by Charman, et al. (10).
Winsteiu concluded that, a priori, it is difficult to predict whether front-side attack (retention) or back side attack (inversion) will be the normal mode of substitution by this mechanistic pathway. The dichotomy arises from the fact that in 8 ~ transition 2
states it is not necessary for carbon to "expand its octet" as in S N processes. ~ The electronic repulsions between incoming and departing groups, which in S N reactions ~ give rise to the drastic differences in activation energies for front-side versus back-side attack, are not important in S E processes. Winstein has pointed out that 3-center bonding may indeed favor front-side attack as compared to back-side attack in such reactions.
as mmetrically so&ated anion
.1
loss of configuration
At least one case involving a three-center transition state has been reported. Hawthorne (11) has, on the basis of deuterium isotope studies, claimed that the acid cleavage of a b-H bond is a three-center process.2
symmetrically solvated anion
Inversion Mechanism:
e
Qi
C-H
I
Qi I
ROD
O-R
AR-O-D.
..CB.. H 4 - R
asymmetricdly solvated anion
Sufficient data to settle the dichotomy is not yet available. Two series of reactions which might be ~ have been investigated. labeled S E processes symmetrically solvated anion
inversion of configuration
\
RzHg
lass of configuration Retention Mechanism:
R
Qi
C-D
D-C
I
iD
D-0
4: &H I
I
I
e
II ROD
.'
\!
'
'H aaymmetriczlly solvated intimate ion pair
symmetrically solvated anion
I
\i +-
..D\ C?
OR
I ..a : M'
H-6~ retention of configuration Figure 3.
+ RHgX
The relative sequence of reactivities found for various R groups in the above reactions, or related reactions, are listed in Table 4. Two reaction types seem indicated by a casual observation of this data. Charman, Hughes, and Ingold (HgX,/EtOH) have suggested that they were observing an SE2 reaction. Use of optically active R groups (seobutyl, 4-methyl'The symbolism m is used to represent a metal and one of its valencies-it is a useful notation that avoids having to portray the rest of the organometallic compound, which is often very complicated, and perhaps the structure of which is unknown. I t replaces the older symbolism ( l / n ) M , where n is the valence of the metal. For example in the Ziegler type olefin, aluminum alkyl reactions R / /(caH4)"R AI--R 3mC1H,--t AI-(C2H4),R (n p q/3 = m)
,
\
+
\
+ +
R \ ( c ~ , R are obviously more easily written and understood aa Ral mCsH, + R(C,H&al An excellent example of the use of this symbolism is found in the chapter by K. Ziegler in ZEISS,H., "Organometallic Chemistry," ACS Monograph No. 147. I t is of obvious advantage in dealing with the reactions of Grignard reagents, where the exact structure is unknown in ether; thus R-mg, not RMgX which is incorrect, or RnMg.MgX2which is awkward, or "RMgX" which is perhaps the only reasonable alternative. I t also focuses on a particular bond when a, series of related, but different compounds are omployed, i.e., RSnQ, R-SnRnC1, R-SnRClz, etc., may be represented 8.8 R-sn.
+
II
qC-D i
RH
I
D-OR
L
-
O...M~
R solvated intimate ion pair
loss of configuration
+ HX
asymmetrically solvated intimate ion pair
Volume 40, Number
4, April 1963
/
187
cyclohexyl, and isoheptyl) by three different groupsJensen (12) in California, Charrnan, et al. (13) in England, and Reutov (14) in Russia had shown that retention of configuration is observed under a variety of experimental conditions for similar reactions. Transition states of the following type seem ap propriate for the reactions reported by Charman, Kreevoy (HCIOr/HOAc), and possibly for some of Jensen's reactions, the conclusion being that SE2 processes involving the cleavage of a carbon-mercury bond proceed by front-side attack, and retention of conIiguration. I t is not possible to extrapolate
series, and those previously indicated for cleavage of carbon-mercury bonds. Two separate sequences of reactivity as a function of R exist in both systems, and aprotic and aprotic-polar environments lead to one (CH1 < R), while protic environmeuts lead to the other (CHs > C2H5 > C3H7 > i-CaH,). Presumably the latter is due to a mechanism of the type SE2, while the former is the result of a four-center process. In the mercury case it seems established then that the stereochemical consequences of SEZ processes are retention of configuration. Retention of configuration is, of course, an a priori result of four-center processes. Multicenter Processes
these findings in the process of electrophilic substitution a t a saturated carbon center, without restriction, to the cleavage of other carbon-metal bonds. (Brown (15) has shown, that in a constrained ring system the cleavage of carbon-boron bonds proceeds with retention, but the mechanism of the reaction is unclear, and may involve concepts similar to those which follow.) This still leaves unexplained the different sequence of reactivities found for cleavage of carbon-mercury bonds in dimethylsulfoxide/dioxane by HX, and in dioxane by HgXz compared to the sequence found in HC104/HOAc and HgX,/EtOH cleavages, and the fact that Jensen reports that non-polar solvents and halogen acids enhance the stereospecificity of the acid cleavages. Dessy (16) has interpreted the kinetic findings associated with the first reaction, under these conditions, as involving a four-center transition state, e.g., R-Hg..:R t
...a
1
The transition state for HgXn/dioxane clzavages appears to be four-center in character also, but there is uncertainty about its exact n a t ~ r e . ~ The conclusion would be that the change in solvents resulted in a change of mechanism. Although stereochemical and kinetic studies on the same system in a variety of solvents in the mercury system have not been undertaken, some work by Gielen (18) suggests that this interpretation is correct. Summarized in Table 5 is the relative sequence of reactivities for the cleavage of R-sn bondsZ by a variety of reagents, under a variety of conditions. Gielen has pointed out that there is an obvious correlation between these observations in the tin
A survey of the literature makes it appear that multicenter processes are being suggested with an increasing frequency to explain experimental results. An n-center reaction is one that involves a transition state in which bonding changes are occurring simultaneously at n different sites arranged in a ring system. The following are some examples of such multi-center reactions. Three-center processes have been postulated, notably in carbene insertions (19) and in acid cleavage of b-H bonds2as
mentioned earlier but little more is known of this potentially important pathway. a The problem involved may best he summed up by viewing the reaction
RHgR'
-
+ Hg"Xn
RHgX RHg*X RHg*X
+ I ++ R'Hg'S R'Hg*S I1 R'HgS 111
Winstein (39) (R = neophyl, R' = cis-2-n~ethoxyeyclohexyl) and Dessy (16) (R = phenyl, R' = ethyl) find case 11: Broderson (40)(R = phenyl, R' = butyl) reports case I,n-hile Routov (41) (R = phenyl, R' = ethyl) reports case 111. Until this trichotomy is rerrolved it is not known whether transition states a and/or b and/or care involved:
Extensive investigations under a variety of conditions will probably reveal a multiplicity of mechanism. Table 4. \E-N,
\ solvent
1
\ R
CH.
i-CsH, . .
+
Hgb"
\ I
Too slow to measure 1.63 1.86 1.60
/
N+ Table 5.
HC16 HClOt HgXld D M dioxme
HOAc
1
1
1
6.3 3.9 4.3
0.65 0.36
0.42
Ref. ( 1 6 ~ ) ;Ref. (16b); a Ref. (17);
188
4- k
Relative Reactivities for Rhg RE HgN
Journal o f Chemical Education
.
..
Ref. (46).
I\'
EtOH
R
R6n f E - N
sohent
, L "
HCI -C6H6 .
RsSnN
+ RE
MeOH
... ...
a
Ref. (18); *Ref. (19); 'Ref. (43); "Ref. (49).
Ld HOAc
Four-writer rrartions in normal carbon chemistry are rare. The dirnrrizxinn of tetrafluoroetl~vlrneor the reaction of ketene and cyclopentadiene appear to be four-center in nature (19)
Kinetic and mechanistic data adequately substantiating multicenter mechanisms are hard to obtain. Stereochemistry and the expected lack of solvent effects on these non-ionic mechanisms are the most persuasive tools. Despite these difficulties the four-center mnechanism appears with regularity in discussions of organometallic reaction mechanisms for reasons which will be discussed.' The Four-Center Mechanism
Five-center transition states have been brought to the fore-front recently by the excellent work of Huisgen (20) on 1,3dipolar additions.
Since a four-center transition state may be defined as a condition in which bonding changes are simultaneously occurring a t four different atoms in an activated transition state complex, it thcn follows that in a multicenter transition state the rate and course of reaction should be dependent upon the bonding properties of a11 attacked and attacking sites. Broadly speaking, such "properties" would be reflected in the electron donating and electron accepting properties of these sites. This being so, it should be possible to change the bonding characteristics of any one or all of these sites by varying the groups initially attached to them, and then to observe the effects of these changes on the reaction rate. This is illustrated by the reaction of silanols with silylamines (21).
where for example
and
Six-center reactions are, of course, quite familiar. For example one might cite the Cope, Claisen, DielsAlder and Chugaev reactions, and the pyrolysis of esters
\I
,C-C
0
\
(Did--4lder)
I/ \
H ZZ
C=S I CHB ( e f . ester pyrolysis)
-
\
,C=C,
/
0
\C-S I
CHaS (Chugaev)
/"
Varying the groups on the silanol would not only affect its ability to coordinate with the silylamine (sites 1 and 2), but would also affect its acidity and therefore the proton transfer to the nitrogen atom (sites 3 and 4). The kinetic data obtained indicates that when the same silylamine is used, thp reaction rate increases with the acidity of the silanol, (CsH& SiOH > EtrSiOH. I t appears then that the coordinating properties of the silanol are not as important as its acidity; however, it is important to note that such coordination by the silanol also reinforces its acidity. The change of the acidity or other physical and chemical properties of a ligand upon coordination has long been an area of interest in inorganic chemistry. When the groups around the nitrogen atom in the silylamine are varied, the basicity of the nitrogen atom and its ability to bond to the proton are also changed (sites 3 and 4). Thus +I groups will increase basicity and -I groups will decrease basicity. Examining the kinetic data, we find that the more basic silylamines, R" being constant, react more rapidly and N , N dialkyl > N-alkyl. Finally, varying the groups around silicon, site 2, would alter its ability to coordinate with the silanol, -I groups facilitating this interaction and +I groups retarding it. Thus, when the amine 'The authors have prepared an annotated bibliography of these four-center merhanisms. They either have been nmuosed by the original investigator, or sugcient data are av&l;le to suggest a four-center reaction. Organometallie compounds involving Li, Be, Mg (6 caaes), B (10 cases), Hg 16 rases), Zn, Cd, TI, Si and Sn ( 7 rases) are represented. The list is by no means complete since mechanisms are not abstracted. Copies of the bibliography me available from the authors upon request. The authors would appreciat,e correspondence wibh interested readers who may he able to call attention to reactions otherwise not noted. Volume 40, Number 4, April 1963
/
189
residue is held constant, the more electronegative silicon, which coordinates more strongly with the silanol, is more reactive and the order of reactivity was found to be (CH&Si > (EthSi > (n-Bn)& (Steric factors may be present here also.) Conceptually then, one can visualize the transition state for a concerted four-center process (Table 1, 2) as intermediate between the limits 8 ~ 2 8132, , or A ~ N , Ad*.
involved in using isolahility of an intermediate complex as a criterion for mechanistic assignment. The reasoning is as follows: the existent SEinomenclature (substitution, electrophilic, intramolecular) should be limited to those reactions in which the attacking electrophile is contained within a stable molecule and the rate determining process is unimolecular and assisted by the coordination step. A four-center transition state is involved. X-y
+ E-N
k,
SF
S E ~
A ~ E
E-N
Sx2
A ~ F
(2)
Y--v
A ~ N
Product
I
S Eor~SF.
(E-N)
This presupposes an isolable coordination complex, in equilibrium with the factors. If kz is large, and steady state conditions are approximated, this complex is not isolable and this substitution process can be described as an assistedfour-center reaction. X-Y
k, + E-N k-t=
d p = - . k2k' dl k-, k-.
+
X-Y E-N
a,
t -Product
SF?
(X-Y) (E-N)
If a completely concerted process is involved or the attack by E occurs so rapidly after the coordination of N to Y as to make consideration of a stepwise process meaningless then X-Y
.
t
$! = ?&) ( X - Y )
Although such totally concerted processes would be disfavored by entropy considerations, in most cases they would be favored by enthalpy considerations, since they do not require that as high a charge be placed on the atom(s) undergoing bonding changes as the potential barrier is crossed. In a further consideration of the four-center substitution mechanism, it is very meaningful to ask searching questions about the timing involved. If we label the various bond making/breaking processes as indicated below it seems reasonable to expect, as mentioned
I
ka
6 X-Y k-*
+E
-N
ki
Product
.
Substitution
before, that a totally concerted process (1,2,3,4) will he unfavorable, entropy-wise, and it is possible that lower energy routes are available. I n organometallic compounds, R-M (X = R, Y = M), where M possesses an incomplete octet, or can expand its octet, a pre-rate determining complexing of the type E - N + Y - X would seem reasonable, leading to a sequence
Assisted Mechanisms
One might consider then that the bond making process 3, an electrophilic attack from the point of view of E, (E,N or E-N will be considered to be the attacking reagent in the following discussion), is an assisted process, assisted by the coordination of N. Similar reasoning would apply to addition reactions." Focusing on the substitution reactions possibly involving pre-rate determining attack by nucleophile, it would be difficult in many cases to characterize a given reaction involving X-Y and E-N into any one mechanistic category, a priori, because of the uncertainty 6 Much is gained in considering addition reactions involving orgsnometdlic compounds by redefining attacking reagent and E and N. If R-M is considered the substrate X-Y, and the
multiply bonded elements
\
C4, - C e N ,
/
or
\
C=N-,
/
are considered E=N, then direct parallels may be drawn with the concepts developed by consideration of substitution processes.
190 / Journal o f Chemical Education
This involves substitution by a four-center bimolecular process. Similar reasoning would apply to electrophilic assistance and internal nucleophilic reactions (SF: SNi). These are the limiting cases to be considered. Obviously shading of one mechanism into another will occur, but the theory serves as a useful guide for further experimentation as indicated below. Having established that the bonding properties of all four sites are important in a multi center cyclic transition state, it seems reasonable that the concept could be extended to noncyclic transition states where the nucleophile and electrophile as well as their respective sites of attack on the substrate might he separated. (Symbolized by An-" B.) It is then conceivable to visualize a series of assisted reactions, S N ~SE" , and multicenter depending upon whether the rate determining process is nucleophilic, electrophilic, or leads to a multicenter (n-center) transition state, e.g.,
It is important at this point to distinguish between complexing, or coordination, and assistance. Complexing, and coordination, focus on the process of replacement of ligand by ligand; assistance, on the other hand, induces an increased reactivity in an adjacent part of a molecule by a coordination step, and it is this increased reactivity to which attention is drawn in this paper. The chemistry of suchcoordinated ligands is a fresh and new field in the area of inorganic chemistry and there is an increasing trend toward considering alkyl and aryl groups attached to a metal as ligands. Just as electrophilic assistance i s expected lo be evident i n systems containing available lone pairs of electrons near the reaction site, one wmld expect nucleophzlic assistance to occur where "electron deficiency" was present near the attacked site. The criterion of "electron deficiency" is met admirably by organometallic compounds, where the metal always possesses an incomplete octet or is capable of expanding its octet, and this would perhaps explain the sudden surge of interest in fourcenter reactions in such systems. The following paragraphs will suggest, however, that solvents play an important role in systems where assistance might be observable just as solvents play an essential part in determining the course of S Nor~S Ereactions ~ In the area of carbon chemistry, the concept of electrophilic assistance and/or catalysis is evident in the "push-pull" mechanisms of C. G. Swain ($2). It has been demonstrated that in displacement reactions of organic halides in benzene sulution there must always be both a nucleophilic (or pushing) agent to attack carbon, and an electrophilic (or pulling) agent to attack halogen in a rate determining concerted step regardless of whether the reaction is S Nor~8 ~ 2 .
Electrophilic assistance in reactions has been observed and may he due to a solvent or added solute such as mercury or silver mlts or other uncharged electrophiles. In order to illustrate this, consider the S N reaction ~ of triphenylmethylchloride with phenol and methanol, separately and in mixtures using benzene as the solvent. The kinetics indicate that the reaction with methanol is exactly third order, first order in halide and second order in methanol. When phenol is used, ether formation is 1/50 as rapid, but the reaction is still third order (second order in phenol). If the reactions were pure'S~1,one would have expected phenol to react faster than methanol since it is known to form stronger hydrogen bonds with halogens. The slower reaction of phenol is best explained by assuming that a solvation of the carbon is required in which phenol is less effective than methanol. When both methanol and phenol are present, only the methanol is consumed, but the reaction is many times faster than in the absence of phenol. The increase in rate is due to the greater electrophilic assistance of the phenol over methanol in the "push-pull" mechanism. I n protic solvents it is often difficult to observe the above effects, since few solutes are sufficiently more
reactive to make up for differences in concentration; and it is only in cases where the solvent is relatively ineffective in both roles of nucleophile and electrophile and/or the assistor is exceptionally active that such effects would be kinetically observable. Thus solvent serves as an unseen assistor in many cases. I n a consideration of other specific solvent effects on electrophilic assistance, increased cation activity is found with a decrease in cation solvation, as would be expected. Parker (23) has been able to make some generalizations concerning cation solvation in the sense that cations appear to be more strongly solvated in polar solvents where the charge on the negative end of the dipole becomes increasingly localized, as on the oxygen atom in dimetbylsulfoxide. However, if the negative portion of the dipole is dispersed (as in nitrobenzene), is a poor electron donor atom, or is subject to steric hindrance, the molecule becomes less effective as a cation solvator. (It should be noted that specific solvent-cation interactions tend to interfere with this generalization: e.g., silver salts are more soluble in acetonitrile than water because of rr bonding between the nitrile linkage and the silver ion (argentation).) That these cation solvation effects are important in organometallic reactions is indicated by the following
($4) ;
In ether, where the lithium ion is highly solvated, the highly independent butyl carbanion serves to extract a proton from substrate-while in benzene, a poor cation solvator, the substrate serves as solvent and reactant, to yield the addition product. Thus differences in solvation can lead to differences in observed rates or products. The relationship between the concepts involved here, and those proposed by Gielen concerning the cleavage of C-sn bondsZ is obvious, as the following development suggests. A consideration of some of the fundamental principles concerning solvation which have been developed in recent years also indicates where nueleophilic assistance is most likely to be observed (M). It is not surprising that kinetic evidence for nucleophilic assistance by anions has only recently been demonstrated, since Hudson and Saville (25) have correctly pointed out that anion solvation is usually greater than that of the cation, in the usual "kinetic" solvents which are protic in nature. This would lead to a masking or leveling of anion effects. Considering anionic assistors one could easily see that protic solvents strongly solvate anions through hydrogen bonding, thereby decreasing and leveling their activity (Cl- versus Br- versus I-) and potential importance as nucleophilic reagents. When a dipolar aprotic solvent is used, solvation of the Volume 40, Number 4, April 1963
/
191
anion is less appreciable (no hydrogen bonding) and activity is increased as well as over-all differentiation of anionic activity. This is exemplified by the strength of halogen acids in dipolar protic solvents as compared to aprotic dipolar solvents. Thus, since solvation of anions in protic solvents is greater the smaller the anion, and bond strengths are greater the smaller the anion, the acids strengths are leveled. I n dipolar aprotic solvents, the reverse is true, and anion solvation assists dissociation of the acids with the most polarizable anion, and weakest H-X bond, to differentiate acid strength. Similar arguments would hold for uncharged nucleophiles (L~wisbases). A consideration of these concepts would lead to the conclusion that nucleophilic assistance would be most successfully sought and observable in aprotic or aprotic-polar solvents, such as dimethylsulfoxide, dimethylformamide, acetonitrile, or hydrocarbons. I n the cleavage of carbon-mercury bonds in various types of organomercury systems nucleophilic attack on mercury (assistance), in addition t o the expected electrophilic attack on carbon, has been considered as a possible, and significant interaction ($6), but in some cases it has been looked upon only as an alternative due to the lack of actual proof. Once considered, the idea has often been discarded on the basis of incorrect interpretation and scanty experimental evidence ($7). Furthermore, a consideration of the fundamental principles concerning solvation discussed above makes it evident that such nucleophilic participation, if it did exist, was minimized by solvent interaction in . specific . many cases Thus, as Gielen's correlation for C-hgZ and C-snZ cleavages suggest, whenever solvent impedes participatiou by the nucleophile associated with the attacking reagent (by solvation for example) the mechanistic pathway will be SE2 in character, whereas if the solvent is a poor coordinator itself and does not solvate this nucleophile the pathway may he an assisted one (solvent itself may assist but this is difficult t o detect kinetically). I n a t least tv-o cases definite kinetic evidence for assistance has been found in organometallic systems. Both of the reactions were conducted in dimethylsnlfoxide (DMSO), a solvent which should enhance potential assistor activity. The first reaction involves the decomposition of carbomethoxy-mercury derivatives by weak acids. R0.k~
QHgCO1CH8-AQHgX XB.DMSO
+ CO + CHsOH + OAc-
Acetic acid does not decompose phenyl carbomethoxymercury (Q = CsH;) but the addition of chloride ion leads t o immediate reaction. An investigation of the consequence of changing the nature of the added assistor led t o the conclusion that the sequence of assistor activity lvas RSH > I- > Br- > CI- > (CeH&P + O > (CeH&P, and CeH50H. Note that neutral nucleophilic assistors are possible, suggesting that as in the electrophilic case solvents may also assist. I n a consideration of the electronic interactions responsible for assistance in this case, it is readily apparent that the ligand or mercury has three possible interactions with the metal: (a) r-honding via donat,ion from a ligand lone-pair t,o an empty sp2 192
/
lournal o f Chemical
Education
hybrid orbital of mercury previously occupied by solvent, (b) d, - d, back-bonding involving a 5d1° orbital of mercury and an empty d of the ligand, and (c) ?r anti-bonding involving a filled p (or sp" hybrid) orbital of the ligand and an empty p (or sp2 hybrid) orbital of mercury ($8). The fact that phosphorus does not serve as an assistor is indicative of the importance of anti-bonding, a (c) as compared to d, - d, hack bonding, ( b ) . One could conclude then that 2 lone-pairs are uecessary for assistance in this case. We can picture such assistance as follows:
If step 3 occurred in a pre-rate determining equilibrium, then the observed rate law (eq. 29) should not he obeyed since acetate ion is produced in the reaction. Since sulfide-, Halide-, and the amine-mercury complexes are known and isolable (29), it seems likely that step l a occurs before 2 , 3 .
Thus l a can be conceptually divided into several phases, the most important of which appears to be a anti-bonding which gives rise to lb. The latter could also be the result of induced polarization by the assistor. This results in increased freedom of the COzMe grouping and therefore increased electron density on the methoxyl oxygen. Attack by proton is thereby facilitated, or assisted by the ligand attached to mercury. The basic arguments involved are to be found in discussions of polarization theory and the so called transeffect. I n summary, whatever the source, the effect of covalency is t o delocalize (render more diffuse) the electronic distribution around the metal atom and to weaken the carbon-metal bond. A more detailed discussion of the mechanism may be found in the original article on this reaction (SO). G. Wright has investigated the so-called deoxymercuration reaction which is similar in nature in methanol and found no evidence for halide assistance, undoubtedly because of the solvent used (SIO). As explained above protic solvents hinder anionic nucleophilic assistance. Work in these laboratories indicates that assistance may be also found in the reaction of tin hydrides xith weak acids in dimethylsulfoxide (DMSO). (CaHe).SnH
+ HOAc
x-
d(C4Hp)&OAc
DMSO
+ Hn
Here rate measurements suggest that the assistor activity is truly catalytic. Surprisingly the sequence of assistor activity is decidedly different than in the > Br- > I- > (C6H5)9-+ 0. mercury case-C1It is interesting t o note that Kuivila (Sla) found no evidence for such assistance when methanol was used as a solvent.
The concept of assistance explains a number of facts conceruing organometal reactions. Thus, it appears that in many organometallic compounds the rate of cleavage of the metal-carbon or metal-hydrogen linkages is not a function of the acidity of the acid used alone but is also related to the ability of the atom to which the hydrogen is attached to coordinate with a metal atom. For example; Coates and Huck (38) have reported that the rates of cleavage of dimethylberyllium by active hydrogen compounds is in the order ROH > RINH > RSH. Also the cleavage of C-b2 bonds is accomplished more readily with carboxylic acids than with HCI (SS), since oxygen is a better donor than halogen? The rates of reaction of LiBH* with HA increases along the series H6C8,CIHIN, t-BuOH, CH30H,as HA is varied while the Ks.' of the acids increases along the series ChHsN, t-BuOH, CH30H, C6HB(48). Finally, Coates (43) has introduced a nearly identical concept to explain the different orientations of cleavages in the reactions C8F6HgR HCI -, and CaF5HgR Br+. In addition of organometallic compounds (RM) to unsaturated linkages (:C=O, X=N-, or -C=N) coordination of the nucleophilic hetero-atom with the metal is a possible source of assistance for the subsequent attack and bonding processes involving the establishment of the R-Ct linkage^.^ The practical applications of this concept of assistance seem very evident. It should he possible to increase the ability of an organometallic compound to donate a carbanion to a substrate or increase the ability of a metal hydride to donate a hydride ion to a substrate. Brownstein (44) has shown that the D M bonds in (C2HS)3A1 and (CzHs)aGaare weakened by solvation with ethers, and the h-H bonds in BH,- are weaker than those in BHa (45).
+
+
Conclusion
It is felt that this discussion points out the advantages to be gained by the application of the basic philosophies and nomenclature of the inorganic chemist to the field of reaction mechanisms involving organometallic compounds. An over-all view of the concepts described above indicates an encouraging similarity to some of the arguments put forth by Swain (%), Bender (36) and othen, in cases involving carbon as the focal point, or center of reaction. A survey of the literature indicates clearly that the concepts, and nomenclature, of electrophilic or nucleophilic assistance (often including catalysis), and multicenter processes (often
The exact sequence of donor ability among a set of ligands ( 0 , N, S, X, etr.) will of course depend on orbital availabilities and the size and charge of the reference metal and ligand. Pertinent discussions of this problem may be found in references (60) and (61) where a. division of various metals into a and b groupings, depending on ligand affinity, is made. ' The mechanisms involved in enolization, and ester or amide hydrolysis have been largely elucidated by deuterium isotope studies. There is increasing evidence which would suggest that a more oareful examination of the origin of the observed isotope effects should be made. An excellent introduction to this complicated area is given in the articles by Bender (56,38).
including bifunctional catalysis, or electrophilic-nucleophilic catalysis) have been considered by physicalorganic chemists. The systems are not always simple to interpret, as close observation7 of the following examples would suggest.
I
a
,
N-E
1
6
>) N+E
N-E
Mutarotation of glucose CHsCOIH He CHaCOze
-
(36)
= CHC02 + He
+ RCONHR e RCONHzmR(pre-equil.) CHICOOOCR + KH?R (slow) I
+ RCONHleR
-
CH,CO,H
+ RCO,H
Electrophiliedly catalyzed hydrolysis of amides (37)
+N
RC09CsH5
- slow
fast
complex
RC02H
+ HOCeHs
Hz0
Nucleophilically catalysed hydrolysis of phenyl esters (38)
The conclusion is however, inescapable that nucleophilic amistance and multicenter reaction mechanisms are general throughout the periodic table. In fact it appcars that such mechanistic features have not received the attention they deserve merely because most of our kinetic efforts to date have involved carbon centers, where these features are not likely to be distinct, given the electronic nature of a saturated carbon center. Indeed i t is obvious that it is only a t unsaturated carbon centers (cf. above examples) that even partial evidence can be gotten, and the protic solvents often used in kinetics have, as mentioned previously, done their part in masking the area. With the increased interest in the kinetic and mechanistic aspects of reactions at elements other than carbon in aprotic solvents, these ideas and concepts will be of increasing importance and usefulness. Literature Cited
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