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Transition States for Hydride and Methyl 1,2-Migrations in Carbene Rearrangements to Alkenes: an AM1 SCF-MO Study

Transition States for Hydride and Methyl 1,2-Migrations in Carbene Rearrangements to Alkenes: an AM1 SCF-MO Study

Indian Journal of Vol. 44B, October 2005, pp. 2138-2148

Transition states for and methyl 1,2-migrations in carbene rearrangements to : An AM1 SCF-MO study

Peter G S Dkhar & R H Duncan Lyngdoh* Department of Chemistry, North-Eastern Hill University, Shillong 793 022, India Received 17 October 2003; accepted (revised) 24 May 2004

The AM1 SCF-MO theoretical method to investigate transition states for hydride and methyl 1,2-migrations in the rearrangement of 27 different singlet carbenes to alkenes or their analogues has been used. This study focuses only on qualitative trends regarding structural effects upon reaction facility, which include the effects of (a) bystander group(s) at the migration origin, (b) various groups at the migration terminus, (c) varying ring size in cyclic carbenes, and (d) methyl migration instead of hydrogen. Calculated AM1 activation energies for the 1,2-shift are much larger than those calculated by more sophisticated regimes. However, the qualitative trends follow those obtained from highly accurate theoretical methods, and also follow the expectations of chemical intuition. Hydride migration is predicted to be kinetically favoured by branching at the migration origin, but thermodynamically preferred from electronegative atoms than from atoms. Methyl migration is predicted to be kinetically less favourable than hydride migration. The transition state geometries are described in detail, all centering around a three-membered cyclic moiety in line with a concerted one-step mechanism for the . These are described as “early” or “late”, these descriptions being linked to the various structural features present.

Keywords: Carbene- rearrangements; hydride and methyl 1,2-migrations; AM1 SCF-MO method; transition state stability; “early” and “late” transition states IPC: Int.Cl.7 C 07 C

Carbene rearrangements to alkenes by intramolecular may bear a substituent Y, whose structure also 1,2-migration have been much studied experi- influences reaction facility. Figure 1b considers an α- mentally1-17 and theoretically18-39. The migrating group undergoing 1,2-migration, when X may be hydride, methyl, , or other groups. becomes C1MeB1B2. We here investigate hydride and methyl 1,2-shifts for Some experimental findings on carbene reacti- 27 different singlet carbenes using the semi-empirical vity. The reactions of carbenes9 in gas phase4 and in AM1 SCF-MO method40. The aim is to locate and solution5 include insertions into C-H single bonds14, characterise the transition states involved, as well as into C=C double bonds15, bond cleavages16 and to predict trends connecting structural and substituent various rearrangements including 1,2-migrations. factors to reaction facility. The 1,2-shift is assumed to Carbene 1,2-migrations have been reviewed1 with be a concerted, one-step process involving a three- regard to migratory aptitudes and bystander membered cyclic transition state for both hydride and assistance. Hydride migration has been regarded as methyl migrations, which can occur only in singlet more facile than methyl migration17. carbenes1. Some theoretical findings. Much theoretical work Figure 1a depicts the general case of hydride 1,2- has been done on various carbene systems18-38 from migration in a carbene1. The migration origin is the structural, stability and reactivity considerations. The 11,15,17,18,34 α-carbon C1, while the migration terminus is the landmark work of Schaefer’s group eluci- carbene centre C2. Bystander groups on the α-carbon dated the structure and stability of in the are represented as B1 and B2 (both being hydrogen for face of experimental results. The singlet–triplet the unsubstituted methylcarbene), which may assist or splitting has been calculated by many workers27-34 for hinder the reaction, depending upon their structure. various systems. Theoretical work on carbene They may also migrate, competing with hydride. The reactivity includes insertion into saturated hydro- 35 36 whole group C1HB1B2 from which the hydrogen , (addition to alkenes) , 37 38 migrates is termed here as X. The carbene centre C2 cycloadditions and rearrangements including 1,2-

DKHAR et al.: CARBENE REARRANGEMENTS TO ALKENES BY INTRAMOLECULAR 1,2-MIGRATION 2139

Figure 1 ⎯ Reaction course of (a) 1,2-hydride migration, and (b) 1,2-methyl migration during rearrangement of singlet alkylcarbenes to alkenes migrations. We concern ourselves here with intra- groups at the α-carbon, or replacement of the carbon molecular 1,2-migrations, much studied already by atom migration source by electronegative atom theoreticians18-26. sources (N, O, S and P); Scope of this study. We incorporate an over- b) incorporation of various Y on the lapping total of 27 different singlet carbenes, 26 cases migration terminus C2 with varying electron-donating, being studied with regard to hydride migration, and 8 electron-withdrawing and steric effects; cases with regard to methyl migration. Acyclic c) effects of ring size and strain in cyclic carbenes; carbenes are described here as X-C-Y, where X and Y d) comparison of methyl migration with hydride are the two groups attached to the divalent carbene migration. centre. Cyclic carbenes are referred by their molecular Besides the effect of these factors upon kinetic and formulae. These all comprise 10 sets, Sets I to VIII thermodynamic favourability of the reaction, their being studied with regard to hydride migration, and effects on transition state geometries are also studied Sets IX and X with regard to methyl migration. here. This study aims only for qualitative comparisons concerning structural effects upon kinetic and Theoretical Methodology thermodynamic facility for hydride and methyl 1,2- We employed the semi-empirical AM1 SCF-MO migrations. Reproduction of accurate values on par method40 of the MOPAC 6.0 package to compute with higher level calculations or experiment is not energy-minimised structures and wave-functions for possible with semi-empirical methods. Instead, we 27 different singlet carbenes, their 34 products consider a large number of cases together to attempt (alkenes or their analogues) along with the 34 achieving meaningful qualitative trends. Such trends transition states for hydride and methyl migrations. may still be desirable, appealing to chemical intuition Various conformations were considered for the and the basic structural theory of . carbene reactant, the transition state and the alkene The hydride 1,2-migration of methylcarbene product in some representative cases to enable rearranging to is the prototype case here. selection of only the lowest energy conformers. Various structural features may alter the picture here, Transition states were located using the SADDLE which include: keyword (interpolating between the carbene reactant a) structural changes in the group serving as the and the olefin product), and identified as such by migration origin, like the presence of bystander diagonalisation of the force constant matrix to 2140 INDIAN J. CHEM., SEC B, OCTOBER 2005

confirm only one negative eigenvalue. We tabulated For such 1,2 shifts having small activation barriers, the activation enthalpy Ea and reaction enthalpy ΔHr the Hammond postulate predicts that the transition in kcal mol-1 and the single negative Hessian state would resemble the carbene reactant in energy -1 eigenvalue νi in mdyne cm . Note was taken of the and geometry (an “early” transition state). For large dihedral angle τ in the carbene reactant encompassing activation barriers, the concepts of “early” and “late” the carbene substituent atom Y, the carbene atom C2, transition states can still apply, being deduced from the α-carbon atom C1 and the migrating atom (α- the transition state geometries instead. We propose hydrogen H or α-methyl carbon Cme), as shown in that the ratio of the length of the old bond being Figures 1a and 1b for hydride and methyl migrations broken to that of the new bond being formed in the respectively. transition state gives an indication of the relative Geometrical parameters associated with the position of the transition state along the reaction triangular moiety of the transition state are portrayed coordinate. For hydride migrations, this ratio is given in Figures 2a and 2b for hydride and methyl by R1h/R2h, while for methyl migrations, the ratio is migrations respectively. Figure 2a portrays the R1c/R2c. Smaller values of this ratio indicate “earlier” general case of a substituted methylcarbene X-C-Y transition states, and vice versa. Note that these definitions of “early” and “late” are all only relative, whose α-hydrogen migrates from the C1 atom of and the values of the ratios used to define position on group X (C1HB1B2) to the carbene centre C2 having a substituent Y. Geometrical parameters include the the reaction coordinate are likewise not absolute. Rather than describing any particular transition state bond distances shown (R12, R1h and R2h) and the as being “early” or “late”, we can only say that one dihedral angles ϕ1, φ2 and φ3 encompassing the atoms case is “earlier” or “later” than another. Y-C2-C1-H, atoms Y-C2-C1-B1 and atoms Y-C2-C1-B2 in turn respectively. Figure 2b portrays the Abbreviations. Groups X and Y in an acyclic corresponding methyl migration in α-substituted carbene X-C-Y include the following groups carbenes, with the α-methyl group migrating from the (abbreviations in brackets) : methyl (Me), ethyl (Et), C (CH )B B group. Similar geometry markers apply 1 3 1 2 isopropyl (Pri), (CHO), phenyl (Ph), here, given as the bond distances R , R and R , and 12 1c 2c trichloromethyl (CCl ), tert-butyl (But), amino (NH ), the dihedrals φ , φ and φ encompassing atoms Y-C - 3 2 1 2 3 2 phosphino (PH ), sulphhydryl (SH), hydroxy (OH), C -C , Y-C -C -B and Y-C -C -B respectively, C 2 1 me 2 1 1 2 1 2 me methoxy (OMe), fluoro (F), and chloro (Cl). being the α-methyl carbon. The Hammond postulate applies when activation Results and Discussions barriers are not too large, and relates the position of a transition state on the reaction coordinate to the These AM1 calculations are discussed with respect thermodynamics of the reaction. Since the carbene to (I) kinetic and thermodynamic criteria for reaction reactants are so unstable compared to their alkene facility, and (II) geometries of the transition states, as products, the 1,2 migration is invariably exothermic. given below :

2a

2b

Figure 2 ⎯ Geometrical parameters in transition states for (a) 1,2-hydride migration, and (b) 1,2-methyl migration during rearrangement of alkylcarbenes to alkenes DKHAR et al.: CARBENE REARRANGEMENTS TO ALKENES BY INTRAMOLECULAR 1,2-MIGRATION 2141

I. Kinetic and thermodynamic criteria for migra- Table I ⎯ AM1 data* for hydride 1,2-migration in carbenes of tion facility Sets I and II

The kinetic criterion for reaction facility is given No X Y Source of Ea νi ΔHr τ here by the activation energy Ea, while the reaction migrating enthalpy ΔHr gives the thermodynamic criterion, as hydride discussed below for the hydride and methyl shifts. Set I Their effects upon reaction outcome are also 1 Me H Me 14.92 -1.554 -71.22 122.8 discussed for cases with more than one possible 2a Et H Et 11.83 -1.460 -74.86122.9 reaction course. i i 3a Pr H Pr 10.56 -1.386 -76.86 112.8 4 CHO H CHO 3.33 -0.655 -70.50 90.2 (i) Salient features of hydride migrations Set II The AM1 values for the 1,2-hydrogen shift 5 Me Me Me 19.24 -1.768 -61.83 119.6 activation enthalpy Ea, the single negative Hessian 6a Et Me Et 17.07 -1.610 -64.69 123.6 eigenvalue νi, the reaction enthalpy ΔHr and the 7a Pri Me Pri 15.57 -1.552 -67.69 109.7 dihedral τ defined above are presented in Tables I, II, 8a CHO Me CHO 8.76 -2.007 -57.94 95.5

III, IV and V for Sets I and II, Set III, Sets IV, V and -1 -1 VI, Set VII and Set VIII, respectively (to be defined *Ea and ΔHr in kcal mol ; νi in millidyne Å ; τ in degrees in due course later). Each carbene is numbered in order of appearance in these tables. Carbenes studied directly to the carbene centre. The hydride group may migrate either from the α-carbon of the alkyl groups from two or three points of view are assigned the i identifying letters a, b or c for each case successively. Me, Et and Pr (for 1, 2a, 3a, 5, 6a and 7a) or from the CHO carbon (for 4 and 8a). Migration from an alkyl Tables I to V indicate mostly large activation group forms alkenes, while that from the CHO group -1 enthalpies Ea, ranging from 3.33 kcal mol (for 4) to yields . The Ea values range from 3.33 kcal -1 47.37 kcal mol (for 12b). These unrealistic values mol-1 (4) to 19.24 kcal mol-1 (5). A good correlation is are compared with higher level theoretical results for observed between values of Ea and νi for Sets I and II some systems (see Table VII later). The semi- (coefficient of rank correlation = 1.00), taking on a empirical MO strategy apparently overestimates curvilinear plot (not shown). activation barriers through inaccurate treatment of The dihedral angle τ in the reactant affects reaction electron correlation. We therefore look for general facility. Previous studies30,31 predicted greater facility qualitative trends rather than absolute magnitudes, for τ = 0o (the syn conformer) than for τ = 180o (the where the semi-empirical methodology may yet yield anti conformer). We chose values of τ with the useful correlations with experiment and chemical migrating hydrogen gauche to the lone pair on the intuition, and even with higher level calculations. The carbene center, as occurs in the freely optimised 1,2 rearrangement is predicted to be very facile geometry of the carbene reactant (τ = 109.7 to 123.6° thermodynamically (reaction enthalpy ΔHr ranging for most cases). Such τ values actually allow the -1 from -17.81 to -77.61 kcal mol , indicating exotherm- reactant to transform most easily into the product icity). Though probably inaccurate, these during 1,2-hydride shift. Values of τ around 180° unanimously negative values of ΔHr indicate correctly would not be feasible, since this orients the migrating that the carbene species are much less stable than their hydride group towards the carbene lone pair causing alkene isomers. repulsive interactions. Neither would τ values approaching 0° be suitable, since the substituent Y (ii) Hydride shifts in mono- and dialkylcarbenes would afford steric hindrance to the incoming Table I presents the AM1 data for Sets I and II. hydride. The values of τ adopted here fall between Set I incorporates the monoalkyl-carbenes: CHX, these extremes, indicating optimum migratory facility where X is Me (1), Et (2a), Pri (3a) and CHO (4). Set within the freely optimised reactant itself. Cases 4 and II consists of the corresponding substituted 8a have τ values closer to 90°, with the carbonyl methylcarbenes: CMeX, where X is Me (5), Et (6a), group perpendicular to the rest of the . Pri (7a) and CHO (8a). We also include the aldehyde Effects of group X (migration origin). Group X is i group CHO here, since it involves a carbon bonding successively Me, Et, and Pr for 1, 2a and 3a (Set I) 2142 INDIAN J. CHEM., SEC B, OCTOBER 2005

and also for 5, 6a and 7a (Set II), indicating Table II ⎯ AM1 data* for hydride 1,2-migration in carbenes progressive branching at the sp3 hybridised α-carbon of Set III with zero, one or two bystander methyl groups. For X 2 No E = CHO, an sp carbon serves as the migration origin X Y a νi ΔHr τ with oxygen as the bystander group (cases 4 and 8a). Set III Absolute magnitudes of Ea and νi both follow the 1 Me H 14.92 -1.554 -71.22 122.8 i order Me > Et > Pr > CHO, implying the reverse 5 Me Me 19.24 -1.768 -61.83 119.6 order for kinetic facility (true for both Sets I and II). 6b Me Et 20.24 -1.604 -60.48 122.3 Absolute values of reaction enthalpy ΔHr follow the 7b Me Pri 18.86 -1.649 -62.80 121.9 i order Pr > Et > Me > CHO in both Sets I and II, 9a Me But 19.05 -1.446 -62.84 121.6 which is the order for thermodynamic facility. The 8b Me CHO 14.83 -1.441 -58.73 122.5 hydride shift is thus predicted to be both kinetically 10 Me Ph 20.12 -1.478 -62.95 122.1 and thermodynamically favoured by the degree of α- 11 Me CCl 16.42 -1.505 -62.93 123.2 carbon branching in X, the trend being the same 3 -1 -1 whether the substituent Y is H or Me. We attribute *Ea and ΔHr in kcal mol ; νi in millidyne Å ; τ in degrees this to the electron-donating and steric effects of the Et), we predict hydride migration as kinetically more bystander α-methyl group(s), making the α-hydrogen facile from the (in 6a) than from the depart more readily as hydride. Migration is predicted methyl group (in 6b), inferring cis-2- rather to be most facile kinetically (but least facile than 1-butene as the major kinetic product from thermodynamically) when X = CHO (cases 4 and 8a), methylethylcarbene 6. Likewise, comparison between where the electronegative oxygen atom repels the 7a (X = Pri, Y = Me) and 7b (X = Me, Y = Pri) migrating hydride group. Change in C atom 1 predicts that the hydride shift would be more facile hybridisation, however, would not assist here, since from the isopropyl group (in 7a) than from the methyl sp2 hybridisation would impart greater acidic group (in 7b), predicting 2-methyl-2-butene rather character to the migrating hydrogen, diminishing its than 3-methyl-1-butene as the major kinetic product character as a nucleophilic migrating group. from methylisopropylcarbene 7. Here too, α-carbon Structural effects of group Y at migration branching at the migration source is predicted to terminus. Table II presents the data for 8 facilitate hydride migration kinetically. This applies to methylcarbenes 1, 5, 6b, 7b, 9a, 8b, 10 and 11, where thermodynamic facility as well, where the more stable X = Me for all, and Y = H, Me, Et, Pri, But, CHO, Ph, isomeric products from 1,2 hydride migration of and CCl respectively. For cases 1, 5, 6b, 7b and 9a 3 carbenes 6 and 7 are respectively cis-2-butene and 2- (Y = H, Me, Et, Pri and But respectively), the order of methyl-2-butene again. magnitude followed by E with respect to Y is Et > a Comparison of E values between 8a and 8b Me > But > Pri > H, not clearly correlating reaction a predicts hydride migration as more facile from the facility with progressive bulk and branching in Y. For aldehyde group (for 8a) than the methyl group (for 8b, 10 and 11, the order is Ph > CCl > CHO, pointing 3 8b), implying methylketene rather than to steric and electronic effects of the group Y. crotonaldehyde as the major kinetic product from We now compare cases where Y = H with the carbene 8. This would then tautomerise to the more corresponding cases where Y = Me. Comparing Set I stable crotonaldehyde. For carbene 4 (X = CHO, Y = and Set II, we note that for each pair of carbenes H), E is remarkably small (3.33 kcal mol-1), the 1,2- having the same X group, the activation enthalpy E is a a shift being further assisted by the small size of the Y invariably larger when Y = Me than when Y = H. group (here a hydrogen). This is no doubt related to the greater bulk and electron-donating capacity of the Me group as (iii) Hydride shifts in carbenes with bonded compared to the H group when placed in the Y electronegative atoms position. Alternative migration routes in dialkylcarbenes. Table III gives the AM1 data for Sets IV, V and For carbenes 6, 7 and 8, hydride migration may occur VI. Set IV comprises 4 methyl-carbenes 12a, 13a, 14 from either of the two groups present since both have and 15 (given as Me-C-Y, where Y = NH2, OH, OMe α-hydrogens. Comparing Ea values for 6a in Table I and F) so that the Y groups all involve bonding of (X = Et, Y = Me) and 6b in Table II (X = Me, Y= first-row electronegative atoms to the carbene atom. DKHAR et al.: CARBENE REARRANGEMENTS TO ALKENES BY INTRAMOLECULAR 1,2-MIGRATION 2143

Table III ⎯ AM1 data* for hydride 1,2-migration in carbenes of Sets IV, V and VI

No X Y Source of Ea νi ΔHr τ migrating hydride Set IV

12a Me NH2 Me 41.44 -1.931 -17.81 122.0 13a Me OH Me 34.93 -1.863 -32.16 122.6 14 Me OMe Me 35.39 -1.814 -33.83 121.8 15 Me F Me 31.36 -1.861 -39.56 122.1 Set V

16a Me PH2 Me 12.43 -1.449 -69.86 122.2 17a Me SH Me 26.90 -1.793 -50.36 122.7 18 Me Cl Me 24.71 -1.755 -52.59 121.4 Set VI

12b NH2 Me NH2 47.37 -2.291 -26.76 179.9 13b OH Me OH 46.05 -4.102 -43.26 180.0

16b PH2 Me PH2 31.46 -1.203 -77.61 48.7 17b SH Me SH 26.34 -1.964 -51.18 179.8

-1 -1 *Ea and ΔHr in kcal mol ; νi in millidyne Å ; τ in degrees

Set V has 3 methylcarbenes 16a, 17a and 18, (given predicts that for carbenes 12, 13 and 16, migration is as Me-C-Y, where Y = PH2, SH and Cl) so that the kinetically favoured from the methyl group than from carbene atom is bonded here to a second-row the electronegative group, leading to aminoethylene, electronegative atom. Sets IV and V are treated vinyl and vinylphosphine as products. These considering the methyl group carbon atom as the are, however, less stable thermodynamically than the hydride migration source. Set VI (comprising the products of migration from the methyl group. The methylcarbenes 12b, 13b, 16b and 17b) is treated by predicted course of reaction for carbenes 12, 13 and considering hydride migration from the electro- 16 would thus take place firstly by hydride migration negative atom (N, O, P and S respectively) instead. from the methyl group in each case, followed by Effect of group Y at migration terminus. tautomerism to yield the more stable methylimine, Table III gives the order of magnitude of Ea for Set acetaldehyde and phosphimine products. IV as NH2 > OH ≈ OMe > F, suggesting electro- Effects of X and Y in alkylhalocarbenes. Table negativity of Y as an assisting factor. This inference IV gives data for two groups of alkyl-halocarbenes X- may also be drawn from comparing values of reaction C-Y comprising Set VII (X = Me, Et and Pri), where enthalpy ΔHr. The Ea values of Set V give the 15, 19 and 20a are alkylfluorocarbenes (Y = F) and ordering SH > Cl > PH2, not simply explainable by 18, 21 and 22a are the corresponding alkylchloro- . Considering both Sets IV and V, the carbenes (Y = Cl). The branching effect of the i order of magnitude for Ea becomes NH2 > OMe ≈ OH bystander methyl group(s) in X gives the order Pr > > F > SH > Cl > PH2, suggesting at least that second Et > Me for reaction facility, predicted by both Ea and row elements in the Y position gives overall smaller ΔHr. Secondly, comparing Y = F with Y = Cl for any i Ea values than first row elements. one alkyl group (whether Me, Et or Pr ) predicts Alternative migration origins. The rearranged greater reaction facility for the chlorosubstituted case products for Sets IV and V are all substituted than the fluorosubstituted one, suggesting an containing a C=C double bond, formed by electronegativity effect of Y, where F is more hydride migration from a methyl group. In contrast, electronegative than Cl. Set VI incorporates the cases 12b, 13b, 16b and 17b where hydrogen shift occurs from the electronegative (iv) Hydride shifts in cyclic carbenes group instead (NH2, OH, PH2 and SH), giving Table V presents data for hydride migration in four products with carbon-heteroatom double bonds. carbocyclic carbenes (Set VIII), including cyclo- Comparison of Ea values between Sets IV, V and VI propylidene 23, cyclobutylidene 24, cyclopentylidene 2144 INDIAN J. CHEM., SEC B, OCTOBER 2005

Table IV ⎯ AM1 data* for hydride 1,2-migration in carbenes of Set VII

No X Y Source of Ea νi ΔHr τ migrating hydride Set VII 15 Me F Me 31.36 -1.861 -39.56 122.1 19 Et F Et 28.13 -1.668 -42.28 124.8 20a Pri F Pri 25.65 -1.661 -45.34 121.9 18 Me Cl Me 24.71 -1.755 -52.59 121.4 21 Et Cl Et 21.55 -1.542 -55.61 123.9 22a Pri Cl Pri 18.57 -1.756 -56.84 119.9

-1 -1 *Ea and ΔHr in kcal mol ; νi in millidyne Å ; τ in degrees

25 and cyclohexylidene 26, which rearrange to Table V ⎯ AM1 data* for hydride 1,2-migration in cyclic , , and cyclo- carbenes (Set VIII) respectively. Activation energies range from No Carbene E 18.58 to 37.24 kcal mol-1, and reaction enthalpies a νi ΔHr τ from -63.70 to -46.24 kcal mol-1. Although most Set VIII likely exaggerated, these values indicate a definite 23 :C3H4 37.24 -1.757 -46.24 108.8 trend. The order of magnitude for Ea, given as 23 > 24 24 :C4H6 28.77 -1.537 -53.93 116.6

> 25 > 26, indicates that smaller ring size would 25 :C5H8 19.61 -1.564 -60.34 122.2 progressively retard the reaction kinetically. The order 26 :C6H10 18.58 -1.180 -63.70 119.9 for thermodynamic facility predicted from ΔHr is 23 < *E and ΔH in kcal mol-1; ν in millidyne Å-1; τ in degrees. 24 < 25 < 26, indicating a similar effect of ring size. a r i

Angle strain operates obviously, although, for each C -Y, where the alkyl group X (or MeB B C ) is the case, the carbene reactant, transition state and olefin 2 1 2 1 methyl migration origin (B and B being bystander product are all similarly strained systems, having the 1 2 groups) and Y is the other carbene substituent. Set IX same number of carbons in the ring. incorporates X = Et, Pri and But for 3 We rationalise the above trend by proposing monoalkylcarbenes 2b, 3b and 27 (Y = H) and 3 different degrees of strain destabilisation for the alkylmethylcarbenes 6c, 7c and 9b (Y = Me). Set X carbene reactant and for the alkene product. Although comprises 4 substituted isopropylcarbenes (X = Pri for each cycloalkene is more strained than the all, with Y = H, Me, F and Cl respectively). corresponding cyclic carbene, this difference in strain Effects of X on migration facility. The data for between carbene and alkene is greatest for the three- Set IX predicts that, for both monoalkyl- and alkyl- membered case 23 and least for the six-membered methylcarbenes, the E values give the order of case 26. This may be estimated from departures in the a magnitude with respect to group X as Et > Pri > But, values of the relevant bond angles as found in the so that kinetic facility of methyl migration increases cyclic carbenes and alkenes from the unstrained with branching in the alkyl group. The steric effect of values in acyclic systems like dimethylcarbene and the bystander methyl group(s) is obvious here. Their cis-butene. As the cyclic carbenes rearrange to cyclic electron-donating effects also impart partial negative alkenes, the net contribution of these destabilising charge to the α-carbon, facilitating nucleophilic strain differences is most pronounced for the 3- migration of the methyl group. membered system and least for the 6-membered Effect of change in group Y. We now compare system in the order 23 > 24 > 25 > 26, resulting in the the monoalkylcarbenes 2b, 3b and 27 with their above predicted trend. corresponding alkylmethylcarbenes 6c, 7c and 9b to assess the effect of replacing Y = H by Y = Me in Set (v) Methyl migrations in various substituted IX. In each case, this replacement decreases both carbenes kinetic facility and thermodynamic facility as Table VI presents data for methyl 1,2-migration in indicated by higher values of Ea and ΔHr respectively. various substituted carbenes of the form MeB1B2C1- This reiterates our earlier predictions concerning DKHAR et al.: CARBENE REARRANGEMENTS TO ALKENES BY INTRAMOLECULAR 1,2-MIGRATION 2145

Table VI - AM1 data* for methyl 1,2-migration in carbenes of Table VII ⎯ Calculated AM1 values* of activation energy Ea Sets IX and X for 1,2 hydride migration in some acyclic carbenes compared with corresponding accurate theoretically calculated values18 No X Y Source of E ν ΔH τ 39a,39b o a i r and values of the Hammett-Taft substituent constant σ R migrating hydride o No Carbene AM1 MP4/6-311G**/ σ R Set IX MP+ZPE 2b Et H Et 30.97 -1.965 -77.05 122.6 1 CH3-C-H 14.92 0.6 0.00 3b Pri H Pri 29.20 -1.943 -80.86 120.1

27 But H But 26.61 -1.491 -84.09121.1 15 CH3-C-F 31.36 19.0 0.34 6c Et Me Et 38.99 -2.090 -63.88 123.0 18 CH3-C-Cl 24.71 11.5 0.23 7c Pri Me Pri 32.84 -1.899 -69.14120.4 13a CH3-C-OH 34.93 24.5 0.43 9b But Me But 30.32 -0.806 -72.10 118.1 14 CH3-C-OMe 35.39 27.2 0.43 Set X 5 CH3-C-CH3 19.24 - 0.10 3b Pri H Pri 29.20 -1.943 -80.86120.1 12a CH3-C-NH2 41.44 - 0.48 7c Pri Me Pri 32.84 -1.899 -69.14120.4 6b CH3-C-C2H5 20.24 - 0.09 20b Pri F Pri 46.84 -1.708 -43.60124.3 10 CH3-C-C6H5 20.12 - 0.10 22b Pri Cl Pri 39.44 -1.808 -58.66125.2 *All values of activation energies in kcal mol-1 -1 -1 *Ea and ΔHr in kcal mol ; νi in millidyne Å ; τ in degrees.

o constant σ R is an empirically derived measure of the replacement of Y = H by other alkyl groups, being electron-releasing capacity of the substituent Y. For similarly rationalised. For the substituted carbenes 1, 15, 18, 13a, 14 we note a very good isopropylcarbenes of Set X, the order predicted for correlation between our AM1 values and the accurate both kinetic and thermodynamic facility is F < Cl < values of Evanseck and Houk18, although absolute Me < H, again implying higher electronegativity of values may differ greatly. Likewise, there is a fairly the group Y as a hindering factor. good correlation between these AM1 activation Comparing methyl and hydride migrations. For energies and the Hammett-Taft substituent constant o each case of Table VI, methyl migration may be σ R. These correlations establish that the AM1 method compared with the corresponding hydride migration is reliable for furnishing the same qualitative trends as by referring to other tables. The AM1 activation more accurate levels of theory, besides concurring energy Ea is always larger for methyl migration than with empirical estimates for electron-donating effects. for the corresponding hydride migration, inferring hydride migration as kinetically more facile than II. Transition State Geometries methyl migration. However, the reaction enthalpy ΔHr Figures 2a and 2b depict the geometrical predicts the methyl migration product as always more parameters associated with the transition states for stable than the corresponding hydride migration hydride and methyl 1,2-migrations respectively. product. When activation barriers are appreciably Table VIII presents value ranges for the bond high both ways, as here, the kinetic factor controls the distances R12, R1h and R2h and the ratio R1h/R2h for Sets outcome, predicting that the major rearranged product I to VIII corresponding to hydride migration. For in each case would result from hydride migration methyl migration, similar data for the bond distances rather than methyl migration. R12, R1c and R2c and the ratio R1c/R2c are given in Table VIII for Sets IX and X. Table IX gives value (vi) AM1 activation energies correlated to other ranges for the dihedral angles φ1, φ2 and φ3 for Sets I values to X. The general value ranges for these parameters Table VII presents AM1 activation energies values are quoted for each set, giving exceptions where for 9 different acyclic carbenes 1, 15, 18, 13a, 14, 5, required. Some quotes incorporate only two cases. 12a, 6b, 10 along with the theoretically calculated MP4/6-311G**/ MP+ZPE values18 for many of them, (i) Bond distances for hydride shifts besides the Hammett-Taft substituent constant39a,39b The triangular moiety within the transition state for for the Y group on those carbenes. The Hammett-Taft hydride migrations (Sets I to VIII) takes on a roughly 2146 INDIAN J. CHEM., SEC B, OCTOBER 2005

Table VIII ⎯ Range of values* for bond distances (R12, R1h, R2h) associated with transition states for hydride and methyl 1,2-migrations in carbene rearrangement to alkenes

Set Nos X Y R12 R1h R2h R1h/R2h I 1-3a R H 1.377-1.394 1.333-1.350 1.411-1.421 0.943-0.957 4 CHO H 1.320 1.227 1.657 0.740 II 5-7a R Me 1.377-1.395 1.357-1.366 1.387-1.400 0.969-0.984 8a CHO Me 1.310 1.321 1.509 0.875 III 6b–11 Me R 1.375-1.389 1.332-1.369 1.386-1.415 0.941-0.983 8b Me CHO 1.360 1.369 1.382 0.991 IV 12a-15 Me EN 1.392-1.405 1.408-1.445 1.316-1.360 1.035-1.098

V 16a Me PH2 1.397 1.273 1.493 0.853 17a,18 Me SH,Cl 1.378,1.390 1.378,1.378 1.375,1.384 1.076,0.996

VI 12b,13b NH2,OH Me 1.286,1.294 1.246,1.287 1.377,1.318 0.905,0.976

16b,17b PH2,SH Me 1.647,1.606 1.481,1.491 1.546,1.500 0.958,0.994 VII 15-20b R F 1.405-1.422 1.405-1.433 1.338-1.365 1.029-1.088 18-22b R Cl 1.390-1.399 1.371-1.438 1.322-1.399 0.980-1.071 VIII 23-26 cyclic 1.394-1.436 1.321-1.441 1.312-1.428 0.925-1.098 IX 2b–27 R H 1.378-1.395 1.809-1.853 1.808-1.875 0.988-1.018 6c,7c,9b R Me 1.378-1.407 1.827-1.845 1.836-1.978 0.925-1.005 X 3b,7c Pri H, Me 1.383,1.395 1.840,1.827 1.808,1.946 1.018,0.939 20b,22b Pri F, Cl 1.412,1.393 1.982,1.941 1.883,1.868 1.053,1.039

*Distances in angstrom; for sets IX and X replace R1h and R2h by R1c and R2c respectively equilateral triangular shape for most cases, with R12, hybridised CHO carbon diminishes C1-C2 bond R1h and R2h all generally ranging from 1.322 to orders. Cases 4 and 8a also show relatively shorter R1h 1.438 Ǻ. The range of 1.375 to 1.422 Ǻ for the C-C distances and longer R2h distances, resulting in bond length R12 corresponds to a bond order between relatively “earlier” transition states (R1h/R2h ratios of one and two. This is as expected in the transition state 0.740 and 0.875). However, putting the CHO group in for this C-C bond while rearrangement occurs from the Y position (8b of Set III) does not result in such carbene (single-bonded) to alkene (double-bonded). departures. The values for the C-H bond distances R1h and R2h Putting electronegative groups or atoms in the Y (generally from 1.322 to 1.438 Ǻ) indicate C-H bond position (Sets IV and V) usually increases R12 and R1h orders less than unity, as expected for the C-H bonds lengths while decreasing R2h lengths as compared being formed and broken here. The general range for with the typical cases of Sets I and II. This increases the ratio R1h/R2h is usually close to unity, being 0.941 the R1h/R2h ratio (1.035 to 1.098), indicating some to 1.088 for most cases. delay in the transition state along the reaction The above range for R12 covers the general cases of pathway. However, when Y = PH2 (16a), the small Set I (1-3a), Set II (5-7a), Set III (6b-11), Set IV R1h/R2h ratio of only 0.853 indicates a markedly (12a-15), Set V (16a-18) and Set VII (15-22b). The “early” transition state. Incorporation of electro- above range for R1h and R2h includes the general cases negative groups in the X position (Set VI) has varied of Set I (1-3a), Set II (5-7a), Set III (6b-11) and Set effects. VII (15-22b). The above range of values for the ratio Putting X = NH2 or OH (12b and 13b) decreases R1h/R2h covers the general cases of Set I (1-3a), Set II R12 and R1h values, while putting X = PH2 or SH (16b (5-7a), Set III (6b-8b), Set VI (12b-17b), Set VII and 17b) noticeably increases their values, along with (15-22b) and Set VIII (23-26). Exceptions outside those of R2h, all attributable to atom sizes relative to these general ranges may be noted as follows: carbon. The transition states of Set VI are “early” in For 4 and 8a where X = CHO, the R12 values the order NH2 > PH2 > OH > SH. (1.320, 1.310 Ǻ) fall below the general value range In Set VII, putting Y = F and Cl, with X = Me, Et for Sets I and II (X = Me, Et and Pri), since the sp2 and Pri, results in fairly usual values for the geometry DKHAR et al.: CARBENE REARRANGEMENTS TO ALKENES BY INTRAMOLECULAR 1,2-MIGRATION 2147

parameters. For any alkyl group at the X position, the R1c/R2c and R1h/R2h ratios. Each case examined transition state for Y = F is invariably “later” than that (individual data not cited) predicts the transition state for Y = Cl. for methyl migration is invariably “earlier” than the The cyclic carbenes (Set VIII) display steady corresponding transition state for hydride migration. variations in transition state geometry as ring size Within Set IX, we compare the monoalkylcarbenes increases for 24, 25 and 26. The R12 and R2h distances (2b, 3b and 27) with their methyl-alkylcarbene decrease in the order 24 > 25 > 26, with the reverse counterparts (6c, 7c and 9b) to assess the effects of order for R1h, so that the transition states become replacing H by Me at the Y position. Each case predicts successively “earlier” as ring size increases. The 3- an “earlier” transition state for Y = Me than for Y = H, membered case 23 is an exception here though. maybe because the methyl Y substituent tends to push back the incoming methyl group during migration (due (ii) Bond distances for methyl shifts to steric and electronic factors). Set X compares methyl The methyl 1,2-migrations of Sets IX and X migration in the isopropylcarbenes 3b and 7c (Y = H, present triangular moieties within the transition states Me) with 20b and 22b (Y = F, Cl). Halo-substitution which roughly resemble isosceles triangles. The R1c lengthens the R1h distance, causing “later” transition and R2c C-C bond distances fall within the range states, where the halo substituents tend to withdraw the 1.808 to 1.982 Å, while the R12 C-C bond is much bonding electrons by an inductive effect. shorter (1.378 to 1.412 Å). These long R1c and R2c distances point to bond orders less than unity as (iii) Dihedral angles in transition states expected for C-C bonds forming and breaking in the Table IX presents values of the dihedral angles φ1, transition state. The R1c/R2c ratio is more or less close φ2 and φ3 within the triangular moiety of the transition to unity, ranging from 0.925 to 1.053. states for hydride migration (Sets I to VIII) and for These methyl migrations are compared with their methyl migration (Sets IX and X), where EN signifies corresponding hydride migrations regarding the as electronegative group. We consider the central relative positions of their transition states along the triangle C1C2H of Figure 2a and the central triangle reaction pathway by comparing the corresponding C1C2Cme of Figure 2b as being in the plane of the

Table IX ⎯ Range of values for geometrical parameters φ1, φ2 and φ3 associated with transition states for hydride and methyl 1,2-migrations in carbene rearrangements to alkenes*

Set Nos X Y φ1 φ2 φ3 I 1-3a R H 103.5 to 106.0 -4.6 to -9.4 -162.6 to -166.8 4 CHO H 121.2 -77.9 - II 5-7a R Me 112.2 to 113.0 -2.7 to 4.6 -152.4 to -160.3 8a CHO Me 104.9 -106.7 - III 6b–11 Me R 111.8 to 114.7 -1.9 to -4.6 -156.9 to -159.2 8b Me CHO 117.4 -5.4 -155.2 IV 12a-15 Me EN 111.7 to 118.0 -4.7 to -6.8 -159.6 to -164.1

V 16a Me PH2 105.6 -8.6 -156.9 17a,18 Me SH, Cl 110.2, 111.8 -6.2, -4.0 -163.1, -161.2

VI 12b,13b NH2, OH Me -179.6, -180.0 0.1, - --

16b,17b PH2, SH Me 109.8, -179.3 -162.0,- - VII 15-20b R F 109.4 to 111.7 -5.7 to 0.2 -159.4 to -163.2 18-22b R Cl 110.4 to 113.2 -4.0 to 7.4 -154.4 to -161.2 VIII 23-26 cyclic 111.3 to 117.4 -1.4 to -5.2 -148.5 to -161.0 IX 2b-27 R H 100.6 to 107.1 -0.4 to -5.8 -159.4 to -164.3 6c,7c,9b R Me 105.5 to 117.3 -4.6 to2.0 -152.7 to -156.6 X 3b,7c Pri H,Me 106.2 to 114.5 -0.4 to -0.7 -152.7 to -159.4 20b,22b Pri F,Cl 107.8 , 111.6 -4.0 , 1.3 -166.4 , -161.5

*All angles in degrees

2148 INDIAN J. CHEM., SEC B, OCTOBER 2005

paper. The value range for φ1 is generally 100.6 to 4 Jones Jr M, Acc Chem Res, 7, 1974, 415. 118.0°, indicating an out-of-plane alignment for group 5 Jones W M, Acc Chem Res, 10, 1977, 353. Y (above the plane of the paper). The general value 6 Liu M T H & Bonneau R, J Am Chem Soc, 114, 1992, 3604. 7 Stevens I D R, Liu M T H, Soundararajan N & Paike N, range for φ2 (from -0.4 to -9.4°) signifies group B1 is Tetrahedron Lett, 30, 1989, 481. also out-of-plane, being on the same side as group Y. 8 Nickon A, Stern A G & Ilao M C, Tetrahedron Lett, 34, 1993, The range of -148.5 to -166.4° for φ3 indicates group 1391. 9 Moss R A, Acc Chem Res, 22, 1989, 15. B2 is approximately transverse to group Y, on the other side of the triangular plane. 10 Altmann, Csizmadia I G & Yates K, J Am Chem Soc, 96, 1974, 4196. However, when X = CHO (for 4 and 8a), φ2 equals 11 Sulzbach H M, Platz M S, Schaefer III H F & Hadad C M, J 2 -77.9º and -106.7º respectively, owing to the sp Am Chem Soc, 119, 1997, 5682. hybridised state of the carbon. Set VI also represents 12 Shustov G V, Liu M T H & Rauk A, J Phys Chem A, 101, 1997, 2509. significant departures from the usual values for φ2, where the α-carbon is replaced by heteroatom groups. 13 Bodor N & Dewar M J S, J Am Chem Soc, 94, 1972, 9103. 14 Shevlin P B & McKee M L, J Am Chem Soc, 111, 1989, 519. Here, the cases 12b, 13b and 17b (X = NH2, OH and 15 Scuseria G E, Duran M, Maclagan R G A R & Schaefer III H SH) give φ1 values close to 180°, indicating the group F, J Am Chem Soc, 108, 1986, 3248. Y (here methyl) is coplanar with the triangular moiety 16 Irikura K K, Goddard III W A & Beauchamp J L, J Am Chem XC2H. This may be taken as signifying appreciable Soc, 118, 1992, 48. involvement of the heteroatom lone pairs in the 17 Ma B & Schaefer III H F, J Am Chem Soc, 116, 1994, 3539. 18 Gallo M M & Schaefer III H F, J Phys Chem, 96, 1992, 1515. reaction. However, case 16b (X = PH2) gives a usual 19 Khodabandeh S & Carter E M, J Phys Chem, 97, 1993, 4360. φ1 value (109.8°), implying that the phosphorus lone 20 Baird N C & Taylor K F, J Am Chem Soc, 100, 1978, 1333. pairs play no major role here. 21 Tomioka H, Sugiura T, Masumoto Y, Izawa Y, Inagaki S & Iwase K, J Chem Soc, Chem Commun, 9, 1986, 693. Conclusions 22 Dix E J, Herman M S & Goodman J L, J Am Chem Soc, 115, This semi-empirical molecular orbital study leads 1993, 10424. 23 Storer W J & Houk K N, J Am Chem Soc, 115, 1993, 10426. to the following predictions : 24 Celebi S, Leyva S, Modarelli D A & Platz M S, J Am Chem (i) Our AM1 activation energies for carbenes 1,2- Soc, 115, 1993, 8613. hydride shift correlate quite well with those calculated 25 Tomioka H, Ueda H, Kondo S & Izawa Y, J Am Chem Soc, by much more sophisticated regimes, as well as with 102, 1980, 7818. Hammett-Taft substituent constant for the group Y. 26 Tomioka H, Ozaki Y & Izawa Y, Chem Lett, 1982, 843. 27 Moss R A, Acc Chem Res, 13, 1980, 58. (ii) Branching on the migration origin facilitates both 28 Xu G, Chang T, Zhou J, McKee M L & Philip P B, J Am hydride and methyl 1,2-migrations kinetically as well Chem Soc, 121, 1999, 7150. as thermodynamically. 29 Modarelli A D & Platz M S, J Am Chem Soc, 113, 1991, (iii) For methyl carbenes with an electronegative 8985. group attached to the centre, hydride migration is 30 Evanseck J D & Houk K N, J Phys Chem, 94, 1990, 5518. preferred from the methyl group than from the 31 Altmann J A, Csizmadia I G & Yates K, J Am Chem Soc, 96, 1974, 4196. electronegative group, which is followed by 32 Evanseck J D & Houk K N, J Am Chem Soc, 112, 1990, 9148. tautomerism to yield the stable product. 33 Keating A E, Garcia-Garibay M A & Houk K N, J Am Chem (iv) Hydride shifts are more facile than the Soc, 119, 1997, 10805. corresponding methyl group shifts. 34 Bauschlicher Jr C W, Schaefer III H F & Bagus P S, J Am Chem Soc, 99, 1977, 7106. (v) Methyl migration gives “earlier” transition states 35 Bach R D, Su M, Aldabbagh E, Andres J L & Schlegel H B, than the corresponding hydride migration cases. J.Am Chem Soc, 115, 1993, 10237. 36 Fujimoto H, Ohwaki S, Endo J & Fukui K, Gazz Chim Ital, Acknowledgement 120, 1990, 229. One of the authors (PGSD) is grateful to the 37 Evanseck J D, Mareda J & Houk K N, J Am Chem Soc, 112, Directorate of Higher Technical Education, Government 1990, 73. 38 Schoeller W W & Brinker H, J Am Chem Soc, 100, 1978, of Meghalaya, for a post-graduate research scholarship. 6012. 39 (a) Taft R W, Price E, Fox I R, Lewis I C, Andersen K K & References Davis G T, J Am Chem Soc, 85, 1963, 3146.

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