Organometallics 1994,13, 190-199
190
Structure-Reactivity Correlations for the Formation of Zirconocene q2-ImineComplexes from Amines Nicholas Coles,’ Michael C. J. Harris,? Richard J. Whitby,**? and Julian Blaggt Department of Chemistry, Southampton Uniuersity, Southampton, Hunts SO9 5NH, England, and Pfizer Central Research, Sandwich, Kent CT13 9NJ, England Received October 5, 1999
The formation of q2-imine-zirconocene complexes (zirconaziridines) (CpzZr(NR1CR2R3)by elimination of R‘H from CpzZr(R4)(NR1CHR2R3) has been investigated with regard to the variation in R1, R2, R3, and R4, in particular by making use of Hammett type structure/rate correlations (R1, RZ, R4 = p - X C a 4 , X = MezN, MeO, H, C1, COZMe; R1, p = 3.2; R2, p = 0.5; R4, p = -1.6). The elimination is first order in the zirconocene complex, has a deuterium isotope effect for the hydrogen eliminated of 8.2 a t 20 “C, and kinetic studies on CpzZr(Me)(NPhCHMez) give the activation parameters AH*= 100kJ mol-’ and AS* = -19 J K-1 mol-’ for the elimination of methane. A cyclometalation involving deprotonation a to nitrogen by (R4)-best fits the data. The relationship between the rate of the reaction and the structure of the amine shows a marked dependency on both electronic and steric effects ranging between no reaction after 48 h at 110 “C for piperidine to below room temperature for silylamines and benzylanilines. For the first time +imine complexes have been formed even from simple amines such as dibutylamine and trapped with an alkyne to form secondary allylic amines on workup. In the absence of a trap t+(PhN==CMez)ZrCpz rearranges via a rapidly reversible hydride shift to afford a $-azaallylzirconocene hydride. Introduction The formation of zirconocene $-imine complexes 2 uia a C-H activation from methylzirconocene amides 1 and their trapping with alkenes, alkynes, allenes, and ketones
1
2
X
-
CR, CRR’. 0,N
to give azazirconacycles which afford elaborate amines on protic workup have recently been reported.lV2 This is a powerful synthetic transformation for organic chemistry since it accomplishes both a C-H activation and a carbometalation-reactions which are difficult using conventional reagents. Zirconocene +imine complexes have also been formed by rearrangement of iminoacyl complexes3and by ligand exchange between zirconocene butene and an imine? Bis(pentamethylcyclopentadieny1)zirconium v2-imine complexes have been formed by reaction between Cp*zZrHz (Cp* = MesCs) and A~NEC.~Bis(ary1oxy)titanium q2imine complexeshave been formed both by rearrangement ____
University of Southampton. t Pfier Central Research. Abstract published in Advance ACS Abstracts, November 15,1993. (1) (a) Coles, N.; Whitby, R. J.; Blagg, J. Synlett 1990, 271-272. (b) Idem. Ibid. 1992,143-145. (2) Buchwald, 5.L.; Wannamaker, M. W.; Wataon, B. T. J. Am. Chem. SOC.1989,111,776-777. Buchwald, S . L.; Wataon, B. T.; Wannamaker, M. W.; Dewan, J. C. Ibid. 1989,4486.4494. Grossman, R. B.; Davis, W. M.; Buchwald, S. L. Ibid. 1991,113, 2321-2322. (3) Davis, J. M.; Whitby, R. J.; Jaxa-Chamiec, A. Tetrahedron Lett. t
1992,33,5655-5658. (4) Jensen, M.; Livinghouse, T. J. Am. Chem. SOC.1989,111,44954496. Ito, H.; Taguchi, T.; Hanzawa, Y. Tetrahedron Lett. 1992, 33, 4469-4472. (6)Wolczanski, P. T.;Bercaw,J. E. J. Am. Chem. SOC.1979,101,64506452.
of iminoacvl comDlexes6 and bv loss of ethene from 1.1bis(arylox~)-l-ti~a-2-azacycl~pentanes7 (effectively a ligand exchange since these are formed from the imine and diaryloxytitanium-ethene). One limitation of the C-H activation method is that to date, the reaction 1 to 2 works well with just two classes of amines-N-arylamines and N-trimethylsilylamines, though dibenzylamine forms the corresponding trimethylphosphine stabilized +imine complex under vigorous conditions.2 The success of these two classes of amines has been explained by the reduced availability of the nitrogen lone pair for donation to the metal center due to conjugation &h the aromatic ?r-system,or overlap with the silicon d orbitals (or Si-C u* orbitals).l$ The mechanism of formation of 2 from 1 may be considered as either a &hydride transfer followed by a reductive elimination (path A or B depending on whether the imine remains bound to the metal) or as a concerted cyclometalation via a four-member transition state (path C) in which the hydrogen moves with either protic or hydridic character (Scheme 1). The individual steps of A and B have some precedent in the formation of CpzZrHCl by &hydride transfer from CpzZr(C1)(CRR’CHR’’R’’’)8 and reductive elimination of RH from CpzZr(R)(HI9 (though CpzZr(H)(Me)is sufficiently stable to be isolated at room temperaturelo). Crossover experiments have ruled out a dissociative mechanism analogous to B for the (6) Durfee, L. D.; Hill,J. E.; Fanwick, P. E.; Rothwell, I. P. Organometallics 1990,9, 75-80. (7) Hill, J. E.; Fanwick, P. E.; Rothwell, 1. P. Organometallics 1992,
11, 1775-1777. (8) Negishi, E. I.; Miller, J. A.; Yoshida, T. Tetrahedron Lett. 1984, 1979,101, 25,3407-3410. Carr, D. B.; Schwartz, J. J. Am. Chem. SOC. 3621-35.?1 - - - - - - - -. (9) Gell, K. I. Posin, B.; Schwartz, J.; Williams, G. M. J. Am. Chem. SOC.1982,104, 1846-1855. (10) Gell, K. I.; Schwartz, J. J. Am. Chem. SOC.1981,103,2687-2695
(but it has been suggested that elimination may be induced by donor ligands).
0276-733319412313-0190$04.50/0 0 1994 American Chemical Society
Formation of Zirconocene g-lmine Complexes
Scheme 1. Possible Mechanisms for the @-E Activation Route to Zirconocene +-Imine Complexes
formation of zirconocene alkene complexes from dialkylzirconocenes.1l The closely related formation of zirconocene thioaldehyde complexes has been studiedI2and a mechanism analogous to path C with a small polarization in favor of the hydrogen moving with positive charge proposed. C-H activation by early transition metals has been reviewed,13as has the mechanism of intramolecular C-H activation.14 The mechanism of the transformation 1to 2, and the nature of the transition state is important both in the context of a general understanding of the many pathways available for C-H activation, and to assist extension of its application to organic synthesis. We now report studies which define the electronic and steric effects which influence the success of the formation of zirconocene +-imine complexes 2 from zirconocene methyl amides 1, kinetic data which define the nature of the transition state, an improved method of carrying out the reaction on less reactive substrates, and the formation of a $-azaallyl zirconocene hydride by rearrangement of a zirconocene +imine complex. Results and Discussion In order to delineate the factors which govern the ease with which zirconocene q2-iminecomplexes can be formed by a C-H activation process from zirconocene methyl amides we undertook an NMR study of the rate of this reaction with a wide variety of substrates. An important additional aim was to extend the range of amines which undergo this &hydrogen activation/alkyne insertion procedure beyond the N-aryl and N-trimethylsilyl cases previouslyreported.'I2 The results are collected in Scheme 2 as are the yields of adducts obtained in preparative experiments trapping with 4-octyne. Zirconocene methyl amides derived from benzylaniline, and N-trimethylsilylamines eliminate methane to form the corresponding zirconocene q2-imine complexes too rapidly for convenient measurement-the reaction occurs below room temperatures2 The cyclic amine piperidine readily formed the zirconocene methyl amide complex Cp2Zr(Me)(N(CH2)3but this did not undergo elimination of methane to form an +-imine complex, being unchanged on heating at 110 OC for 48 h in the presence of 4-octyne. Thermolysis at 150 OC in a resealable Carius tube's was monitored by NMR and showed that the piperidine complex slowly decomposed (-75% after 30 h) to a (11) Negiahi, E.; Swaneon, D. R.; Takahashi, T. J. Chem. SOC.,Chem.
Common. 1990,1254-1255.
(12) Buchwald, S. L.; Nielsen, R. B. J . Am. Cb.em. SOC.1988, 110, 3171-3175. (13) RothweU, I. P. Polyhedron 1986,4,177-200. (14) Raybov, A. D. Chem. Rev. 1990,90,403-424. (15) Forrester, A. R.; Soutar, G. Chem. Ind. 1984,772-773.
Organometallics, Vol. 13, No. 1, 1994 191
plethora of products, none of which indicated the intermediacy of the q2-iminecomplex. On thermolysis at 110 OC in toluene in the presence of 4-octyne the zirconocene methyl amide formed from 1,2,3,4-tetrahydroisoquinoline gives only the zirconacyclopentadiene 9le from dimerization of 4-octyne together with 3,4-dihydroisoquinoline.It is reasonable that the expected g2-iminecomplex is formed initially, for which the rate can be estimated as -9.6 X 106 s-l at 110 OC (extrapolated to -9.4 X s-1 at 60 "C, relative rate 0.0025 on the scale of Scheme 2). Four conclusions can be drawn from the data presented in Scheme 2: (i) Delocalization of the lone pair on nitrogen by conjugation with a phenyl ring dramatically increases the rate of reaction. Comparing Scheme 2 cases 1and 9 suggests a 1000-fold increase in rate. (ii) Activating the hydrogen which is to be eliminated by making it benzylic increases the rate by a factor of around 100 (cf. cases 1and 4, and 9 and benzylaniline2). (iii) The marked stereoelectronic requirement for the cyclometalation is shown in the comparison of piperidine and tetrahydroquinoline (case 7) with their acyclic analogues (cases 1and 9). The effect can be quantified for aromatic amines by comparing cases 6 and 7 with 8 and 9, giving a rate drop factor of around 13 on constraining the system to a six-member ring. The effect is larger when the amine is not aromatic (piperidine cf. with dibutylamine and tetrahydroisoquinoline cf. with butylbenzylamine). (iv) There is a marked decrease in rate as the proton which is eliminated becomes more hindered (&fold decrease in rate from methylene to methine proton, entries 6 vs 7 and 8 vs 91, though the rate decreases again for methyl protons (entry 9 vs lo), presumably reflecting the slightly higher C-H bond strength. These relative rates are quite different from those recently reported17for the formation of zirconocene q2-alkenecomplexes by elimination of methane from Cp2Zr(Me)(CH&Hs), CpzZr(Me)(CH2CH2Me), and CpzZr(Me)(CHzCHMez): k X 104 at 20 "C = 8.72, 1.25, and 0.28 s-l, respectively. For application to organic synthesis the most important discovery is that benzylamines undergo the C-H activationhapping procedure in good yield and even simple acyclic aliphatic amines such as dibutylamine (case 1; see below) and N-methyloctylamine (case 3) give moderate yields of adducts with 4-octyne. The latter reaction is notable in being highly regioselective, only the product shown due to methyl proton activation being isolated. This is somewhat surprising in light of the small rate difference measured for activation of the CH3 and CH2 protons in N-methyl and N-ethylaniline, respectively (Scheme 2, cases 9 and 10). In a similar observation N-isopropylbutylamine gives only the product of C-H activation on the 'CHi side (case 2), the low yield being due to retroaddition and formation of the 4-octyne dimer 9, as below. Reversibility of the Insertion of 4-Octyne into $(BuN=CHPr)ZrCp2and the RslativeRates of Ligand (Imine/Alkyne) Exchange and Cocyclization. The reaction temperature and duration for the formation and trapping of the zirconocene q2-iminecomplex derived from (16) 9: 1H NMR (270 MHz C a s ) 6 0.19 (8, 10 H),2.57 (m,4 H), 2.43 (m,4 HI, 1.60 (wxtet, J = 7.3) Hz, 8 H), 1.21 (t, J = 7.3 Hz, 12 H); NMR (68 MHz, C a s ) 6 190.81 (E), 133.41 (a), 110.52 (d),40.99 (th31.83 (t),25.77 (t),24.04(t),16.03(q),15.49(q). Theidentityof9wascodmd by isolation of 5,&dipropyl-(E,JD-deca-4,6-diene on protic workup. (17) Negishi, E.; Nguyen, T.; Maye, J. P.; Choueiri, D.; Suzuki, N.; Takahashi, T. Chem. Lett. 1992, 2367-2370.
192 Organometallics, Vol. 13, No. 1, 1994
Coles et al.
Scheme 2. Rates of Formation of CpzZrNR1CRZRS by Methane Loss from CpzZr(Me)(NR1CHR2Ra)
Case
- rate' x 10~s-lrelative
Amine
Product
ratesb 1
R' Bu 'Pr n-CSHl7 Bu PhCH2
R2
2
R1.NkHH
3
H
4 5
R2
Pr Pr H Ph Ph
0.63 0 100"Ce 0.003
-
36% "\
2.22 0 70°C 2.O4@7O0C
0.21 0.19
0.92 0 70°C 2.50 0 70°C
0.087
NH
R2
16% 46%
Pr
55% 53%
Pr
R
67 8 9
10
a
H H
Ph.Nh: H Ph.NfiH H
R Me R H
75%
0.24
3.760 6OoC 1 12.9 0 60°C 3.4
Ph.N%pr
9.45 0 60°C 3.74 0 50°C
Ph* N
H
2.5
H
92%
Pr
90%
Pr
80%
Pr
a. 1st order rate constant for the disappearance of Cp2Zr(Me)(NR1CHR2R3)in the presence of 4-octyne. measured by n m r . in the heated probe of Broker 360MHz spectrometer. b. The rates were extrapolated to those expected at 60°C using the Arrhenius parameters calculated for 3 c. Product of 4octyne trapping of the q2-imine intermediate and protic work-up. d. Isolated yield from preparative experiments. e. An n m r . sample was heated at 1 0 0 C (steam) for various periods and monitored by n.m.r. at room temperature.
dibutylamine (Scheme 2, case 1)required careful control for maximum yield. On prolonged heating the azazirconacyclopentene 6 undergoes a "retroaddition" (C-C activation'*) to form the imine 719together with 4-octynezirconocene 8 which adds another molecule of the alkyne to give the zirconacyclopentadiene 9 (Scheme 3). Monitoring the reaction by NMR showed that initially 9 is formed concurrently with 6 at about half the rate, independent of the concentration of 4-octyne, but on continued heating the ratio of 9 to 6 increases (Figure la). A plot of this data assuming first order kinetics (Figure lb) allows the rate of "retroaddition" of 6 to be estimated as 9 X lo4 s-l (at 373 K)as well as providing a value for the rate of methane loss from 3 (6.3 X 106 s-1 at 373 K). The concurrent formation of 6 and 9 demonstrates that the rate of ring closure from the q2-imine-q2-alkynezirconocene complex 5 to give 6 is only twice the rate of extrusion of the imine 7. An alternative explanation is that "free zirconocene", CpzZr, is formed either by decomplexation of the imine from 4 or directly in the 8-hydrogen activation process (Scheme 1,path B). This would be expectedz0to selectively complex to the alkyne, forming 8. The high energy required to liberate Cp2Zr (18)Takahashi, T.; Fujimori, T.; Seki, T.; Saburi, M.; Uchida, Y.; R o W t , C. J.;Negishi,E.J. Chem. SOC.,Chem. Commun. 1990,182-183. Takahashi, T.; Kageyama, M.; Denisov, V.; Hara, R.;Negishi, E. Tetrahedron Lett. 1993,34,687-690.
-
(19) Theidenti@ofBuN=CHPrwasconfirmed bysynthesis: W N M R
(360MHz, C,D3 7.62 (t, J = 4.5 Hz, 1 H), 3.40 (t,J = 6.8 Hz), 2.18 (m, 2 H), 1.4-1.7 (m, 6 H), 1.04 (t, J 7 Hz,3 H), 0.98 (t, J = 7 Hz, 3 H); 'gc NMR (90MHz, C,D8)162.72 (d), 61.66(t),38.03 (t), 33.66 (t), 2 0.85 (0, 19.60 (0, 14.10 (q), 13.94 (t). (20)Negishi, E.;Holmes, S. J.; Tow, J. M.; Miller, J. A,; Cederbaum, F. E.; Swanson, D. R.; Takahashi, T. J.Am. Chem. SOC.1989,111,33363346.
Scheme 3. Thermolysis of CpZZr(Me)(NBuz) with 4-Octyne ( k =~ 2Kz) Bu
k = 6~10~s.' 3 Bu
Pr
7
Pr
and the mechanistic studies presented below render this explanation unlikely. With the zirconocene methyl amide derived from 1,2,3,4-tetrahydroisoquinoline, 9 is the only organometallic product though whether this results from unfavorable partition at a stage analogous to 5 or facile reversibility of the formation of the azazirconacycle analogous to 6 has not been determined. Mechanistic Investigation on the C-H Activation Process. For amore detailed study of the C-H activation process which forms the zirconocene +'-imine complexes lo21 we chose to study the obtained from N-isopropylaniline. In the presence of
Formation of Zirconocene +-Zmine Complexes 120
I
Fig. la
100 9
Organometallics, Vol. 13, No.1, 1994 193 IJ
k x lo's.'
I31
0
X
0
2000
4000
Time I s
323K 32SK 333K 338K 343K
- 1.29 -2.52 -4.80
-6.72 -11.29
6000
Figure 2. First order rate data for the thermolyis of 10.
Time I sec I
-7.0
n v
x
-c
0
100000
-8.0
200000
Time I sec
Figure 1. Course of the thermolysis of Cp2Zr(Me)(NBuz) with 4-octyne. 4-octyne as a trap for the supposed q2-imine complex a clean conversion of 10 into 1222is observed (eq 2)with no
10
11
Ph.
3/
N\ y Z Q 2
12
13 L=PMe2Ph 14 L=PMe3
buildup of intermediates, demonstrating that it is the formation of 11 which is rate limiting. Other observations were in agreement with this hypothesis, for example the phenyldimethylphosphine stabilized q2-iminecomplex 13 reacted with 4-octyne in 1-2 min23at room temperature to form 12. The trimethylphosphine complex 1424took 15 min23 to form the same adduct, suggesting that in this (21) 1 0 1H NMR (270 MHz, CDCb) 6 7.20 (t, J = 7.4 Hz,2 H),7.03 (tt, J = 7.4,l.l Hz, 1 H), 6.7-6.76 (m, 2 H),5.82 (8, 10 H),3.90 (heptet, J = 6.6 Hz, 1 H), 0.86 (d, J 6.6 Hz, 6 H); '8c NMR (68 MHz, CDCls) 6 163.63 (e), 129.72 (d), 127.46 (d), 116.04 (d), 109.89 (d), 62.77 (d), 22.08
,_.
(a). 20.48 ~- ~- (a). .ll,
(22) 12: 'H NMR (270 MHz, C a s ) 6 7.02 (t, J 7.1 Hz,2 H),6.71 (t, J = 7.2 Hz,1 H), 6.34 (d, J = 7.1 Hz, 2 H),6.86 (e, 10 H), 2.16-2.23 (m, 2 H), 1.92-2.10 (m, 2 H),1.4-1.7 (m, 4 H), 1.38 (e, 6 H), 1.02 (t, J = 6.8 Hz, 3 H),1.00 (t, J 6.8 Hz. 3 HI: 18c NMR (67.6 MHz, C a d 6 184.68 (e), 161.42 (e), 147.21 (e), 129.23.(d), 128.12 (d), 120.68.(dj, i12.67 (d), 70.43 (e), 40.48 (t), 33.38 (th26.66 (q), 24.96 (t), 24.60 (t), 16.47 (q), 16.28 (9).
(23) Addition of 4-octyne to an NMR sample of 13 gave a clear color change (very dark red/purple to liiht red/orange) in 1-2 min. The clean formation of 12 wan confiimed by NMR atter 7 min. The formation of 12 from 14 + Coctyne wae followed by NMR. (24) 14: 'H NMR (270 MHz, C& 6 7.73 (dd, J * 7.9, 7.2 Hz, 2 H), 7.29 (d, J 7.3 Hz, 2 H),7.10 (t, J 7.2 Hz,1 H), 5.61 (d, JPH= 1.6 Hz, 10 H), 1.90 (d, Jpw = 1.6 Hz,6 H), 1.06 (d, JPH 6 Hz,9 H); 1% NMR (68 MHz, C& 6 167.22 (8, Jcp 2.0 Hz),129.91 (d), 115 .71 (d), 114.66 (d), 106.34 (d), 41.37 (8, Jpc * 18.6 Hz), 30.79 (9, Jpc 2.0 Hz),17.77 (q, Jpc 16.6 Hz).
0.0029
0.0030
0.0031
1I T
Figure 3. Arrhenius plot for the reaction of 10. case it is the dissociation of the phosphine ligand which is rate limiting. The rate of disappearance of 10 was independent of the concentration of 4-octyne and was identical in the absence of the trap. The plot of In [lo]against time was linear over 4 halflives (Figure 2),showing that the reaction is first order in the zirconocene complex. Carrying out the thermolysis at five different temperatures (Figure 2)allowed an Arrhenius plot to be constructed (Figure 3),from which the activation energy (E, = 100 f 5 kJ mol-') and A factor (ln(A) = 28.3 f 1) can be calculated. Transition state theory2&allows the enthalpy and entropy of activation of the reaction to be calculated (AH*= 97 f 5 kJ mol-' (23f 1 kcal mol-'); AS* = -19 f 8 J K-I mol-l (-4.5 f 2 eu) at 333 K). The former is somewhat higher and the latter substantially smaller than that observed for the related formation of a zirconoceneq2-thioaldehydecomplex (AH* = 78.1 kJ mol-' (18.6kcal mol-'), AS*= -87.4 J K-' mol-' (-18.6eu) a t 80.4 OC).12 Both differences can be accounted for by the shorter N-Zr and N-C bond lengths (cf. S-Zr and S-C), giving a more strained transition state but one involving less loss of entropy from the initial state. The small negative entropy of activation rules out the second step of paths A and B (Scheme 1) (dissociative) as rate limiting, since these would be expected to have large positive entropies of activation, and supports the highly ordered cyclic transition state in path C. Kinetic Isotope Effects. A primary kinetic isotope effect for the cyclometalation was measured using the monodeuterated benzylaniline PhNH(CHDPh) obtained by LiAlD4 reduction of PhN-CHPh. Reaction of the derived methylzirconocene amide 15with4-octyne at room temperature (293 K) followed by protic workup gave a product 16 (eq 3) in which the integral for the proton (Y (26) Milton, J. M.; Wameer, C. C. Fundamentals of Organic Reaction Mechanisms; Wiley: Chicheeter, U . K . , 1976; pp 106-109.
Coles et al.
194 Organometallics, Vol. 13, No. 1, 1994 Ph ph
i. PrCdPr, r.t.,8 hn. t
H IS
ii.MeOH
rh
Pr
HN&Pr
(3)
IUD Ph 16
to nitrogen was only 10 f 1%I of that of the vinyl proton. This translates to a kinetic isotope effect kH/kD of 9 for the elimination of the hydrogen. Analysis by mass spectrometry gave the more accurate figure of k d k = ~ 8.6. A similar competitive experiment for the formation of a zirconocene thioaldehyde complex (from CpzZr(Me)(SCHDPh)) gave a primary kinetic isotope effect of 5.2at 80 O C (extrapolates to -7 at 20 OC).12 Both these experiments suffer from the presence of a secondary deuterium isotope effect when the C-H bond is broken, absent in the corresponding C-D breakage, which could distort the value given for the primary kinetic isotope effect by a factor of up to 1.5. To overcome this ambiguity, the rate of reaction of the deuterated complex CpzZr(Me)N(CDMe2)Ph was measured directly as -7.48 X lV 8-l at 333 K compared with the undeuterated complex 10 which gave a value of -4.80 X lo-' s-l under the same conditions. This yields a primary kinetic isotope effect k d k D of 6.4 at 333 K which extrapolates to 8.2 at 293 K by assuming normal Arrhenius behavior, suggesting that the secondary kinetic isotope effect in the reaction of 15 is small and confirms the remarkably high value of k d k D for this reaction. A similarly high kinetic isotope effect (9.7at 25 "C) has been observed by Bercaw for the analogous formation of a tantalum q2-iminecomplex.26 Recently, it was concluded that these high values are characteristic of multicenter transition states14though the theoretical basis for this has not yet been established. A small inverse deuterium isotope effect ( k d k =~ 0.88(k0.05)with three deuteriums) was observed for the elimination of CDsH from CpzZr(CDs)(NPhiPr)compared with CHI from 10 at 338 K. This is consistent with the methyl carbon bonding to both the zirconium and migrating H in the transition state (rehybridizationdecreases the strength of the C-D/H bonds). Overall the best model for the formation of zirconocene q2-iminecomplexes from zirconocene methyl amides is as a cyclometalation occurring via a four-membertransition state as in pathC (Scheme 1)above. The electronic nature of this transition state is investigated below. Hammett Type Structure/Activity Relationships. As shown by the rate constants in Scheme 2, a phenyl or trimethylsilyl substituent on the nitrogen increases the rate of @-hydrogenactivation by at least a factor of 1OOO. It is supposed that this is because the nitrogen lone pair is rendered less available for donation into the empty orbital on the zirconocene center by conjugation with the phenyl ring or by interaction with Si d orbitals (or C-Si u* orbitals). This idea was examined in a more quantitative fashion by measuring the rate of formation of q2-imine complexes from methylzirconocene amides 17derived from para-substituted isopropylanilines (Scheme 4). We found a strong correlation between the rate of formation of the +-imine complex and the electron withdrawing/donating ability of the substituent on the aromatic ring. In particular the rate was greatly increased by electton withdrawing substituents (COZMe, C1) and slowed by electron donating ones (OMe). The rates varied over such a wide range that the experiments could not all be done
at the same temperature-the relative rates quoted in Scheme 4 were obtained by extrapolating the observed rates to those expected at 55 OC using the activation parameters calculated for the parent complex 10 above. A rather poor correlation between these rates and the Hammett" substituent constants u is found giving a reaction constant p of 3.2(Figure 4,ArN)-the correlation with p+ was worse. This is a high value and may indicate a substantial negative charge buildup on the nitrogen in the transition state. A more likely explanation is that in the transition state of the cyclometalation much of the electron density in the breaking C-H bond is accepted by the empty a1 orbital on the metal (Figure 5 ) (agostic bonding). Competitive donation of the nitrogen lone pair into this orbital will destabilize the transition state,slowing the reaction, an effect which is reduced by electron withdrawingsubstituents. There is no systematic change in the chemical shift of the Cp rings in the complexes of the table in Scheme 4, which argues against a strong interaction between the nitrogen lone pair and the metal center in the ground state, and there is no NMR evidence for ground-state agostic bonding. For use in synthetic organic chemistry an important observation from this work is that the aromatic ester group did not interfere with the reaction, indicating a useful functional group compatibility. The yields of allylic amines obtained in preparative experiments are also given in Scheme 4. In order to further investigate the nature of the transition state, particularly whether the hydrogen is transferred as H+ or H-, we next probed the point from which this leaves by looking at a series of complexes Cp2Zr(Me)N(Bu)(CHr Ar) 19 (Scheme5 ) with substituted aromatic rings at this position. Butylbenzylamines gave convenient rates to measwe. As with the aryl substituent on nitrogen we found a significant increase in rate with electron withdrawing substituents, the p value of 0.5 (Figure 4) being similar to that of 0.3 observed by Buchwald in the analogous formation of zirconocene v2-thioaldehyde complexes.12 Together with the results from the substituted anilines above this shows that there is a movement of electrons toward the imine functionality in the transition state, implying that the hydrogen is moving as H+ not the "hydride" implied by the term "@-hydrideelimination". If paths A or B (Scheme 1)were followed,the first step would
(28) Mayer, J. M.;Curtb, C.J.; Bercaw, J. E. J. Am. Chem. SOC.1988, 106,2861-2860.
(27) J o L o n , C. D. The Hammet Equation; Cambridge Univereity Preee: Cambridge, U.K.,1973.
17
X Code CI
H OMe
k x 10'1s 6.43at 30°C 5.45 at 55°C 2.52at55OC 5.31 at 80°C
k,? 49.5 2.16 1 0.165
Yield of 18
&I (Cp) in 17
66% 69% 92% 78%
5.62 5.58 5.64 5.63
Extrapolated to 55% using Arrhenius parameters for 10
Organometallics, Vol. 13, NO.1, 1994 195
Formation of Zirconocene +-Imine Complexes
Scheme 6. Rates of Reaction of CPzZrbXCsH4)"r) (Ph)
2.5 r
H
CI
Ar
H
22 Ar = pX-C6H4
21
Ph
-.-
-1.0
-0.5
Q
0.0
0.5
X M%N
kx104/s 24.2 at50'C
kko
19.2atWC 6.06at85"C 2.76 at 65°C
H
Figure 4. Hammett correlations for @-Hactivation.
CI
k?, 10.2 2.86 0.902 0.41 1
5.715 5.683 5.627
x'
a rate relative to Cp&(Me)NPh(iPr)
Figure 5. Scheme 5. Rates of Reaction of pXCeH&HaN( Bu)(CpzZr(Me)) at 70 "C
x Me0 H CI
- k x 1 o 4 / ~ Yiekidm 51% 1.67 2.22 55% 3.04
56%
Pr
NHBu
20 Pr
have to be viewed as a deprotonation CY to nitrogen using the electrons in the Zr-N bond. The final part of the transition state which we were able to probe was at the eliminated group. We have previously shownlb that the +imine complexes may be generated by elimination of benzene from (pheny1)zirconoceneamides as well as methane from (methy1)zirconocene amides, so we could directly investigate the effect of electron donor/ acceptor with Cp2Zr@-XCsHd(NPhiPr)22. The transition state 23 for the concerted cyclometalation with these precursors should resemble the "Wheland intermediate" in electrophilic aromatic substitution, so a pronounced accelerating effect of electron donors would be expected. The required precursors 22 were prepared from the crystalline zirconocene chloroamide 21and the aryllithium, and the rate of reaction with 4-octyne was measured as before (Scheme6). Much to our delight we found that the para substituent did have a dramatic effect on the rate of reaction and rather more surprisingly a very good correlation with the Hammett substituent constant u, giving a reaction constant p of -1.56 (Figure 4). Synthetically important is that the use of p(dimethy1amino)phenyl as the eliminated group gives an 18-fold increase in rate compared to the elimination of methane. This result was extended to the less reactive amine benzyl butylamine in that the derived zirconocene amide CpzZr(p-MezNC&)(BuNCHzPh) eliminated p-(dimethylamino)benzene (k = -1.42 X s-l at 343 K)6.4 times faster than methane (Scheme2, case 4). In the hope of increasing the rather poor yield of the 4-octyne adduct obtained from 3 we also examined CpzZr@-Me2NCsH,)(NBu2). This was prepared in situ from the corresponding chloride CpzZr(NBu2)(Cl), in turn obtained from the remarkably clean
.
Cp99% monodeuterated. 23.77 (t),23.16 (t),15.16 (q), 14.18(9);IR 3419,1598,1496,1456, Bis(cyclopentadienyl)chloro( N4sopropylanilido)zirco1382,1316,1294,1255,1177,1093,817cm-l; MS m/z 279 (M+, nium, 21. N-isopropylaniline (2.19g, 15 mmol) was dissolved 49%)*, 264 (ll)*,236 (37)*,168 (45)*,153 (65),127 (97)*,111 in THF (20 mL) and cooled to -30 "C, nBuLi (6 mL of 2.5 M (45),97 (100)(* = C1 isotope pattern, only %C1signals reported); solution in hexanes, 15mmol) was added and the mixture warmed HRMS calc for C l 7 H d W l m/z 279.1738,found 279.1747. N-( (E)-l,l-Dimethyl-2-propyl-2-hexenyl)-4-methoxyani-to room temperature and stirred 10 min. This was added to a solution of zirconocene dichloride (3.2g, 11 mmol) in THF (20 line. The reaction mixture was heated at reflux in THF for 16 mL) at -50 OC, and the mixture was warmed to room temperature h. The crude amine was purified by column chromatography and stirred for 1 h. Solvents were removed in uacuo, and the (30% ether in petroleum ether) to afford the title compound as residue was dissolved in toluene and pawed through a no. 3sinter. a pale yellow oil (78% 1: lH NMR (270MHz, CDCl3) b 6.72 (d, Toluene was removed in uacuo and the residue washed with J = 9.1 Hz, 2 H), 6.63 (d, J = 9.1Hz, 2 H), 5.49 (t, J = 7.1 Hz, hexane (2 X 10 mL). The yellow solid was dissolved in the 1 H), 3.75 (e, 3 H), 3.4 (bra, 1 H), 2.05-2.20 (m, 4 H), 1.38 (8, 6 minimum volume of toluene and hexane layered onto the solution. H), 1.40-1.50 (m, 4 H), 0.96 (t, J = 7.3 Hz, 3 H), 0.95 (t,J = 7.3 Coolingto 0 OC induced formation of bright yellow needlee (title) Hz,3 H); 1% NMR (68 MHz, CDCla) 8 152.06 (s), 144.80 (SI, which were washed with hexane (2 X 10 mL) (3.78g, 88%); 'H 141.26 (a), 125.72 (d), 117.37 (d), 114.25 (d), 57.53 (a), 55.73 (q), NMR (270MHz, CDCls) b 7.27 (t,J = 7.3 Hz, 2 H), 7.1 (tt,J = 30.65 (t),30.52 (t),28.82 (q), 23.87 (0,23.18 (t),15.19 (q), 14.19 7.3,1.2 Hz,1 H), 6.8 (dd, J = 7.0, 1.3 Hz, 2 H), 6.10 (8, 10 H), (9);IR 3402,1616,1510,1464,1380,1237,1180,1041,821 cm-'; 4.32(heptet,J=6.4Hz,1H),0.94(d,J=6.4Hz,6H);'TNMR MS m/z 275 (M+, 33%), 260 (7),232 (231,164 (18),123 (100); (67.5MHz, CDCl3) 8 154.07 (s), 123.93(d), 112.92(d), 55.21 (d), HRMS calc for C l a a N O (M+) m/z 275.2249,found 275.2254. N-((E)-l-(4-Chlorophenyl)-2-~ro~~l-2-hexenyl)butyl-21.00 (9). amine. The reaction mixture was heated at reflux in THF for 12h. The crude product was pursed by column chromatography Acknowledgment. We thank Pfizer Central Research, (31 petroleum ether:ether) and by Kugelrohr distillation (110 Sandwich, England, and the Science and Engineering OC, 0.9mmHg)) to afford the title amine as a colorless oil (56%): for generous support of this work. Research Council (U.K.) 1H NMR (360MHz, CDC13) 7.29 (m, 4 HI, 5.59 (t, J = 7.2 Hz, We also thank Mrs. Joan Street for help in the NMR 1 H), 4.08 (a, 1 H), 2.55 (dt, J = 12.1,7.2 Hz, 1 H),2.42 (dt, J = studies. 11.5,7.1Hz,1 H), 2.05 (q, J = 7.3 Hz,2 H), 1.95 (ddd, J = 13.5, OM930687E 10.4,6.1Hz,1 H), 1.72 ( d d d , J = 13.5,10.1,5.6Hz, 1 HI, 1.3 (m,
m/z 231.1987,found 231.1987. Anal. Calc for CleHsN: C, 83.1; H, 10.8;N, 6.1 Found: C, 82.9;H, 10.6;N, 6.3. N-((R)-2-Propyl-2-hexenyl)aniline. The reaction mixture
+
