Organometallics 1983,2,467-469 methyl group (position t).% Protonation at a was found to lead to a slight increase in the activation energy ( ~ 0 . 0 5 eV), while protonation at c t o t showed no change. If the metal-carbonyl and carbon-oxygen bond lengths were decreased (0.05 A) and increased (0.1 A), respectively?8 the activation energies with protonation a t a and t decreased to -0.6 and -0.7, respectively. These results are disappointingly inconsistent with our presumption of the importance of the energy of a predominantly 7r* orbital on the acceptor CO. They are much more in accord with the suggestion33that the principal contributor to the activation barrier is the repulsive interactions between the Me- and the CO u lone pairs and that the extent of destabilization decreases as the energy of the latter decreases.33 These conclusions are easily extrapolated to the iron and molybdenum systems studied here, however, as oxidation of the metals would lower the metal CO u bond orbitals even more than would protonation of the oxygen. Thus the Lewis acid-induced kinetic effect observed by Shriver et aL30and the oxidation-induced effect observed here and in eq 2 and 3 may be similar in origin.
Acknowledgment. We thank the Natural Sciences and EngineeringResearch Council for a scholarship to A.C. and for operating grants to V.H.S. and M.C.B. Registry No. 1,13601-24-6;2,71518-89-3; $-C,H$e(CO),H, 35913-82-7;$-C5H5Mo(C0)3H,12176-06-6;ethyl formate, 10994-4; methyl formate, 107-31-3;propyl formate, 110-74-7. (36) Force constant calculationss7 suggest that the extent of backbonding, and hence the basicity,13J4is greater for the CO trans to methyl than for the others. (37) Kaesz, H. D.;Bau, R.; Hendrickson, D.; Smith, J. M. J. Am. Chem. SOC.1967,89,2844. (38) These are the directions anticipated from spectroscopic data.13J4 The 0.1 A is the increase in CO bond length on going from Cr(CO)Bto Cr(CO)6+.38 (39) Hubbard, J. L.;Lichtenberger, D. L. J. Am. Chem. SOC.1982,104, 2132.
Nucleophilic Addition to ($-Alkyibenzene)Cr( CO), Complexes. Dependence of Regloselectivity on the Size of the Alkyl Group and the Reactivity of the Nucieophlie M. F. Semmelhack,' J. L. Garcia, D. Codes, R. Farlna, R. Hong, and B. K. Carpentert Department of Chemisrw, Princeton University Princeton, New Jersey 08544 Department of Chemishy, Cornell university Ithaca, New York 14853 Received October 27, 1982
Summary: The regioselectivity of addition of carbanions to (~s-aIkylbenzene)Cr(CO)3complexes correlates well with a frontier orbital picture using the lowest energy arene-centered molecular orbital in the (arene)Cr(CO), complex. However, the selectivitii is sensitive to both the size of the alkyl substituent on the arene and the reactivity of the carbanion. Para substitution can become important with large alkyl groups and more stabilized
* To whom correspondence should be addressed at Princeton University. + Cornell University. 0276-7333/83/2302-0467$01.50/0
467
carbanions. Systematic variation of anion reactivity using 2aryC1,3dithiane derivathres shows the effect clearly. A rationale based on a balance of charge control and orbhl control is presented, employing extended Huckel theory calculations on the complexes.
Regioselectivity in the addition of carbon nucleophiles to substituted (&arene)Cr(CO), complexes has been studied ex~erimentally;l-~ correlations of substituent effects on selectivity have been put forward by using a frontier orbital picture based on LUMO for the free arene' and based on the conformation of the Cr(CO), A theoretical analysis of the influence of the Cr(CO), conformation on the pattern of charge densitiess is consistent with the powerful meta-directing effects of resoF)2and the enhanced nance donor substituents (OR, para selectivity in the reaction of (tert-buty1benzene)Cr(CO), with LiC(OR)(CH,)CN, where R = C(CH3)OC2H5 [35% meta/65% para compared to 95% meta in reaction of the same anion with (toluene)Cr(CO),].' This one-parameter analysis-where the substituents influence the regioselectivity solely through their effect on the conformational preferences of the Cr(CO), groups -requires that ortho and para positions have similar reactivity and differ from the meta position. Unfortunately, it fails to account for preferred addition both ortho and meta (and not para) with toluene and chlorobenzene ligandd2 and the special selectivity in additions to (o-dimeth0xybenzene)-,' (naphthalene)-,' and (indole)Cr(CO): complexes. It does not provide an explanation for the several reports of a change in regioselectivity with a change in the carbon n~cleophile.'-~For example, 2-lithio-1,3-dithiane adds primarily a t C-7 in the $-N-methyl indole ligand, while LiC(CH3)2CNadds primarily a t C-4.3 In this paper, we report a series of experiments in which the size of the alkyl substituent and the reactivity of the carbon nucleophile are systematically varied in nucleophilic additions to (~~-alkylbenzene)Cr(CO)~ complexes. The data require a new picture, and we offer a rationalization based on a balance of orbital control and charge control features. Complexes la-e were prepared by standard proceduresg and sublimed or recrystallized to high purity; anions A-E were prepared according to standard procedures. In a typical experiment, the solid complex la-e (1.0 mmol) was added at -78 "C to a solution of the carbanion in THF (5 mL) containing HMPA (1.0 mmol), and the solution was allowed to stir at 0 "C for 0.5 h. The solution was then cooled to -78 OC and quenched by addition to a solution
w,
(1) Semmelhack, M. F.; Clark, G. R.; Farina, R.; Saeman, M. J . Am. Chem. SOC.1979, 101, 217. (2) Semmelhack, M. F.; Clark, G. J. Am. Chem. SOC.1977,99, 1675. (3) The regiospecificity in addition to the indole ligand is particularly interesting: (a) Kozikowski, A. P.; Isobe,K. J. Chem. SOC., Chem. Commum. 1978, 1076. (b) Semmelhack, M. F.; Clark, G. R.; Garcia, J. L.; Harrison, J. J.; Thebtaranonth,Y.; Wulff, W.; Yama~hita,A. Tetrahedron 1981,37, 3957-3966. (c) Semmelhack, M. F.; Wulff, W.; Garcia, J. L. J. Organomet. Chem. 1982, in press. (4) Jackson, W. R.; Rae, I. D.; Wong, M. G.; Semmelhack, M. F.; Garcia, J. L. J. Chem. SOC.,Chem. Commun. 1982, in press. (5) Rose, E. J. Organomet. Chem. 1981,221, 147. (6) Solladie-Cavallo,A.; Wipff, G. Tetrahedron Lett. 1980,3047-3051. (7) Direct evidence for the proposed conformational preferences in solution is obtained for NMR correlations. For relevant data and leading references, see: Solladie-Cavallo, A.; Suffert, J. Org. Magn. Reson. 1980, 14, 426-430. (8) Albright, T. A.; Carpenter, B. K. Inorg. Chem. 1980, 19, 3092. (9) For la, see: Jackson, W. R.; Nicholls, B.; Whiting, M. C. J.Chem. SOC.1960, 469. For l b and IC, see: Jackson, W. R.; Jennings, W. B.; Rennison, S. C.; Spratt, R. J . Chem. SOC.B 1969, 1214. For Id, see: Nicholls, B.; Whiting, M. C. J. Chem. SOC.1959,551. For le, see: van Muers, F.; van der Toorn, J. M.; van Bekkum, H. J. Organomet. Chem. 1976, 113, 341-351.
1983 American Chemical Society
468 Organometallics, Vol. 2, No. 3, 1983
Communications
Table I. Variation in the Size of the Alkyl S u b s t i t u e n t
entry
product ratio anion o : m : p b
complex
1
a , X = Me
2 3 4
b, X
5
e , X = CH(t-Bu), a , X = Me d, X = t-Bu e , X = CH(t-Bu), a,X=Me a,X=Me c,X=i-Pr d , X = t-Bu a,X=Me d, X = t-BU
C C C C C
= Et c , X = i-Pr d , X = t-BU
6 7d
8 gd 10 11 12 13d 14
B B B D E
E E A A
0:96:4f 0:94:6 0:80:20 0:35:65
combined yield," % 75 89
88 86 (17)C*e 95 78
0:O:lOO 1:97:2 0:55:45
0:O:lOO
63
52:46:2 52:46:2 47:46:7 45:32:23 35:63:2 28:48:24
94 96
86 88 88 51
a Yields a r e based o n weight of isolated material a f t e r distillation a n d / o r c h r o m a t o g r a p h y . T h e ratios are f r o m GLPC. This reaction could n o t be driven to m o r e t h a n 40-50% conversion. F r o m ref 2. T h e yield is based o n p+oducts 2 , 3 , a n d 4 with R = COCH, as d e scribed in t h e t e x t . f This yield was d e t e r m i n e d b y q u a n titative GLPC.
Table 11. Variation in Reactivity of the Nucleophile
3
2 1
s u b s t i t u e n t series: a, X = Me; b, X = E t ; c, X = i-Pr; d, X = t-Bu; e, X = CH(t-Bu), a n i o n series: A, R = CH,CN; B, R = C(CH,),CN; c , R = C(OR,)(CH,)CN, R , = C(CH,)OC,H,; D, R = 1,3-dithian-2-yl; E, R = CH,SPh; F, R = x
4 ~~
entry c o m p l e x 1 2 3
4 5 6 7
8
Id
Id Id Id
Id Id Id Id
anion F
X = 0X = NMe, X = NMe, X = OMe X=Me X = H X = H X = C1
ratio m:p
~
combined yield,c % on f o r X
73:27" 63:37' 57:43b 54:46" 43~57" 28:72' 23:7Tb 21:79"
84 80 78 71 75 75
85 80
-0.83 -0.83 -0.27 -0.17
0 0 +0.23
The m e d i u m is THF. A mixture of THF/HMPA ( 4 : l ) was used. The yields are the average of at least two runs, based on distilled and/or c h r o m a t o g r a p h e d a
material.
of iodine (10 mmol) in 5 mL of THF. After 3 h a t 25 "C, the mixture was partitioned between ether and water, the excess iodine was removed with sodium bisulfite and from the ether was isolated a mixture of disubstituted arenes 2,3, and 4 that was analyzed by GLPC to generate the data in Table I. For anion C, substitution in the ortho position is never significant; the relative amounts of meta and para substitution are strongly dependent on the steric bulk of the alkyl group, with a range of 96% meta (la) to 100% para (le) (entries 1 and 5 , for example). The anion of 2-lithio-2-methylpropionitrile (B) gave a similar pattern
under identical conditions (entries 6-8). The sulfur-stabilized anions such as 2-lithio-173-dithiane(D, entry 9) and LiCH2SPh (E, entries 10-12) give powerful selectivity for ortho and meta substitution, with para becoming significant (23%)only with the tert-butylbenzene ligand and at the expense of meta. Similarly, LiCH2CN (A, entries 13 and 14) reacted with the toluene ligand primarily at the ortho and meta positions; again the tert-butyl substituent gave enhanced para selectivity and relatively less meta. While it is reasonable to assume that anions such as B and E differ in reactivity, they are likely also to differ in other properties that might influence regioselectivity. To get a less complicated picture of the relation between regioselectivity and anion reactivity, we carried out the set of experiments summarized in Table 11. A series of 2(para-substituted phenyl)-2-lithio-l7&dithianeswere preparedlo in THF and allowed to add to Id. Oxidation with excess iodine as before gave mixtures of 2,2-diaryl-1,3dithianes (3F, 4F) that were identified after hydrolysis to benzophenone derivatives.ll In all cases, the product (2F) from ortho attack was present in a yield of less than 3 %. It was assumed that the reactivity of the anions would parallel the up constants determined12for substituents X, increasing down the columns of Table 11. The selectivity ratio of meta:para also changed in a regular way, from 73:27 for the most reactive anion (entry 1)to 23:77 for the least reactive anion (entry 7). A plot of In (parax/paraH) vs. up gives a straight line of slope 0.97 with correlation coefficient 0.96. While systematic kinetic studies have not been completed, we have shown by competition experiments that the relative reactivities toward Id of anions F (X = H) and F (X = Me2N) are in the ratio l:lO, suggesting a direct relation between up constant and reactivity toward Id. We suggest these data demonstrate a strong dependence of selectivity on anion reactivity. Taken together, the results presented in Tables I and I1 allow several general conclusions. (1)Steric effects are important when comparing primary, secondary, and tertiary carbanions; ortho substitution is nearly completely inhibited with tertiary anions, no matter what the substituent on the arene ligand, but steric effects of substituents on the arene are less severe. (2) When steric effects are less dominant, ortho substitution can be comparable (10) The 2-aryl-l,3-dithianeswere prepared from the corresponding p-substituted benzaldehydes, 1,3-propanedithiol,and boron trifluoride etherate. The anions F were generated n-butyllithium under standard conditions: Seebach, D.; Corey, E. J. J. Org. Chem. 1975, 40, 231. (11)The product 2,2-diaryl-1,3-dithianes,3F and 4F,were treated with red mercuric oxide, aqueous THF, and boron trifluoride etherate according to a general procedure: Vedejs, E.; Fuchs, P. L. J. Og.Chem. 1971,36,366. The resulting benzophenones were analyzed and separated by GLPC and fully characterized by 'H NMR spectral data. The regioselectivity in the reaction is assumed to be directly reflected in the ratio of benzophenone isomers detected. We have shown that a typical mixture of the dithiane products can be hydrolyzed without selective loss of one of the isomers. There is still the question as to whether the oxidative quenching of the reaction perturbs the regioselectivity. We have no direct way of calibrating this process, but we have shown in related work thatother modes of quenching (such as addition of strong acid and protonation of the cyclohexadienyl ligand) instead of oxidation give the same mixture of regioisomers. (12) The substituent constants were obtained from the compilation appearing in: Gordon, A. J.; Ford, R. A. "The Chemist's Companion"; Wiley: New York, 1972; p 152. No comprehensive correlation of the reactivity of anions F in addition to Id and up has been reported. We are unaware of pK, data related to anions F that could reveal a correlation of up with anion stability. However, a para phenyl substituent (anion F,X = phenyl) lowers the pK, by 2 units (Streitweiser, A.; Ewing, S. P. J.Am. Chem. SOC.1975,97,190). The parent anion (F,X = H) has been shown to exist as a monomer in THF/TMEDA and as a contact ion pair in the solid state (see: Amstutz, R.; Dunitz, J. D.; Seebach, D. Angew. Chem., Int. E d . Engl. 1981, 20, 4051. Our analysis is based on the assumption that the para substituents will have a strong effect on the reactivity of anions F.
Communications
complex (conformatn)
Organometallics,Vol. 2, No. 3, 1983 469 Table 111. EHT Coefficients for the Lowest Unoccupied Arene-CenteredI6 Molecular Orbital in MoncrSubstituted (Arene)Cr(CO), Com.plexes LUMO coefficients 1 2 3 4 5 6
total energy, eV
0.00
-0.55
0.41
0.00
-0.41
0.55
-1311.885
0.00
-0.41
0.55
0.00
-0.55
-0.41
-1311.865
-0.03
-0.54
0.52
0.08
-0.49
0.46
-1311.899
0.00
-0.55
0.41
0.00
-0.41
0.56
-1628.845
0.00
--0.41
0.55
0.00
-0.55
0.41
-1628.347
0.01
-0.55
0.51
0.10
-0.50
0.45
-1628.198
+
to meta, reaching up to 1:l ratios of ortho:meta with reactive anions. (3) Para substitution becomes important only with large alkyl substituents on the arene ligand and primarily at the expense of meta substitution. (4) The extent of para substitution is very sensitive to the stability of the nucleophile, with higher para selectivity correlating with a more stabilized carbanion. Table I11 displays the results of EHT calculations on selected monosubstituted (arene)Cr(CO)3 ~omp1exes.l~ From these data, we conclude the pattern of coefficients in the relevant LUMO16 is relatively insensitive to the conformation of the Cr(C0)3unit,17 is closely parallel in distribution of coefficients with the pattern for LUMO of the uncomplexed arene,ls and is consistent with orbitalcontrolled substitution at the ortho and meta positions. We favor an explanation of the experimental results (13)All calculations were performed by wing the extended Htickel method." A modified Wolfsberg-Helmholz formula was used.Is The parameters used were described before: except that the elements Hi] were unweighted. (14)(a) Hoffmann, R. J. Phys. Chem. 1963,39,1397. (b) Hoffmann, R.;Lipscomb, W. N. Zbid. 1962,36,3179,3489.(c) Hoffmann, R.; L i p scomb, W. N. Zbid. 1962,37, 2872. (15)Ammeter, J. H.; Biug, H. B.; Thibeault, J. C.; Hoffmann, R. J. Am. Chem. SOC.1978,100,3686. (16)There are several unoccupied molecular orbitals calculated to be within 1.0eV of the calculated LUMO. Only one of these is substantially localized on the arene ligand (arene r*-like), typically located in the calculationat about 0.5-0.75 eV above LUMO. The f i t prediction from these data is that nucleophile addition would be most favorable at the carbonyl ligand or at the chromium atom, where the calculated LUMO is primarily localized. Since it is clear that the first detectable intermediate in nucleophile addition is from exo addition to the arene ligand, several possible explanations can be put forward. (1)The relative energy ordering of the lower unoccupied orbitals in the complexes from the EHT calculations is not proper, and the arene-centered orbital is, in fact, the LUMO. (2) The initial addition is at the CO or Cr atom, but it is reversible and the product-determining step is anti addition to the arene ligand (controlledby the arenecentered UMO). (3)While frontier orbital control would predict addition at the Cr or CO, other factors such aa steric effects may disfavor this mode of addition. In any case, the work described here is not intended to address the question of why addition o c c m at the arene ligand but seeks to develop a correlation through frontier MO theory that gives useful predictions of regioselectivity. Therefore, we focus on the lower UMO that is arene centered. The full results of the calculations will be presented in the article describing this work. (17)In ref 8,it was established that according to EHT calculations, charge densities on the arene ligand are sensitive to conformation; charge-controlled ortho/para selectivity was proposed. (18)(a) Heilbronner, E.;Straub, P. A. 'HMO"; Springer-Verlag: New York, 1966. (b) Bowers, K. W. In 'Radical Ions"; Kaiser, E.T., Keven, L., Eds.; Znterscience, New York, 1968,p 211. (c) Bowers, K. W. Adu. Magn. Reson. 1965,I , 317.
based on the perturbation theory analysis of Klopmannlg and Salem.m We assume the important orbital interaction is between the lowest energy arene-centered unoccupied MO (UM0)16 (Table 111) and HOMO for the carbanion, and that HOMO for the anion lies at lower energy than the relevant UMO for the complex. The picture is clearest with the substituted 2-aryl-1,3-dithianyl anions, F (Table 11). With the relatively high-energy HOMO for anion F (X = 0-),frontier orbital overlap dominates the expressionlg for interaction of the reactants; ortho/meta (only meta is observed) addition is favored relative to para. As the energy of the HOMO of F is lowered (descending Table 11) frontier orbital interaction is weakened and chargecontrol begins to dominate; the polarization of the arene ligand induced by conformational effects in the complex leads to ortho/para selectivity (only para is observed) consistent with the earlier analysis.*J7 We feel the orbital control vs. charge-control also applies to the unusual selectivity features in addition to (~f-indole)Cr(CO),~ and may have general application.21 Acknowledgment. We wish to acknowledge support from the National Science Foundation (Grant CHE 7905561) and useful discussions with Professors Albright (Houston) and Hoffmann (Cornell). (19)(a) Klopmann, G.J. Am. Chem. SOC.1968,90,223. (b) Klopmann, G. "Chemical Reactivity and Reaction Paths"; Wiley; New York, 1974. (20)Salem, L. J. Am. Chem. SOC.1968,90,543 and 553. (21)Other explanationsfor the dependenceof regioselectivity on anion reactivity can be presented. For example, the nature of the transition state leading to the intermediate i might be more reactant-like as the reactivity of the anion increases. Conformational barriers in the intermediates (i) are not known but are expected to be large,2l and therefore the particular geometry of the product shown in i would be strongly preferred. If Substituents (X in i) exert steric or electronic effects on the stability of i, then these factors might be important for reactions with a late, product-like transition state (addition of a more stabilized anion). This picture can account for the experimental facts available now but needs to be solidified with more information about the effect of substituents on the stability of i, the conformational barriers in i, and the nature of the transition state leading to i.
P X
dI
H
(22)Albright, T.A.; Hofmann, P.; Hoffmann, R. J.Am. Chem. SOC. 1977,99,7546.
