Carbocations terminology: historically, R 3 C was referred to as a carbonium ion but:

Transcription

1 arbocations terminology: historically, 3 was referred to as a carbonium ion but: vs carbonium carbenium (hypervalent) (hypovalent) 5 bonds to -rare 3 bonds to -commonplace moot point until the advent of super acids (George lah, obel 96) ex: 4 FS 3 - SbF 5 S 2 (l) "super acid" (also F - SbF 5 ) SbF 6 3 methanonium ion (see lah, JAS 1972, 94, 808; EMTE 1971, 1, 566) extremely non-nucleophilic, non-basic counterion structure: empty p orbital '' ' quite standard sp 2 hybridization sp 2 hybridized planar structure note: it lacks an octet unstable 3 - center, 2e - bond What about? empty sp 2 orbital (very unstable) -can t rehybridize to give empty p orbital 114

2 contrast this with benzenonium ion: and benzyl cation: stability: kcal general trend: 3 o > 2 o > 1 o > 3 (due to hyperconjugation of β - bonds) special case: 3 Si 2 very stable (hyperconjugation of - Si) extra stability: > > (resonance) ~ ( 3 ) 3 p orbital special case: ' overlap of empty p orbital with cyclopropyl Br Br tropylium ion - very stable (Doering, JAS 1954, 76, 3203) α - heteroatom: Y > > ( 3 ) 3 Y = l < < 2 < S 115

3 Why this order? consider resonance: Y Y so, order is dictated by a balance of electronegativity & π bond energy Why is Y so stable when Y is more electronegative than? Y is hypervalent, not hypovalent has a full octet unstable cations: bridgehead carbocations (can t planarize), -sp 2, sp carbocations (can t empty a p orbital) hypovalent heteroatoms (,, etc.) on - lassical arbocations used to describe carbocations stabilized by 3-center, 2e - interactions 1 2 ex: 3 question: what is the structure of the cation? 1 2 or 3? The answer to this question has been debated for 35 years players: Winstein (3) vs. Brown (1 2) We will discuss this question more later on

4 Methods of Generation of arbocations 1) Ionization by heterolytic bond cleavage Y LA + Y LA LA depends on Y Example: Y LA l, Br, I Ag +, FeX 3, AlX 3, SnX 4 (F with SbF 5 ) Y = l, Br, I,, S Til 4, TMS-Tf, TMS-I, BF 3, 2 All; +, +, Sc 3+, Yb 3+, Eu 2+ S g ++, u + 3 BF3 Et 2 2) Addition of an electrophile to a multiple bond alkenes: E E + = +, X +, Se +, S +, 3 +, Pt + E Y E E Y E Y Y E + Til 4, Sn(Tf) 2, BF 3, TMS-Tf, Et 2 All, + S gl 2, g(bf 4 ) 2 BF 3, Til 4, Yb(Tf) 3, Sc(Tf) 3 Example: BF 3 BF 3 Et 2 BF 3 117

5 3) ydride abstraction (very exotic) FS 3 - SbF SbF 6 S 2 (l) lah, JAS 1967, 89, 4739 eactions of arbocations 1) ucleophilic attack 3 + :uc 3 - uc :uc =, S, X -, alkene (produces new carbocation), Ar note: this is the opposite of ionization (#1 of previous section) 2) β - elimination Y Y also: uc: Si 3 uc: Sn 3 note: this is the opposite of generation method #2 118

6 3) earrangements 1,2 hydride shift - favors more stable cation (VEY fast reaction) 3 3 Wagner - Meerwein shift (less fast, but still fast) Wagner-Meerwein rearrangement is an equilibrium reaction; ex: B: 2 2 S 4-2 B: + + (note: this is not a good thing if you re trying to synthesize something!) arbanions M occurs as a complex with M, either ionic or covalent M =, a, K, Mg I X, u I, Zn II X, e III l 2, r II l, Al

7 structure: sp 3 orbital sp 3 hybridized carbanions, except when 1 = -rapid epimerization of stereogenic (Still, JAS 1978, 100, 1481 & JAS 1980, 102, 1201) sp 2 does not easily invert sp stability: 3 o < 2 o < 1 o < allylic, benzylic sp 3 < sp 2 < sp [note: these trends are exactly opposite those of carbocations] 3 Si < 2 < S << (enolate) < S generation of carbanions 1) reduction of σ bonds M o X M + M X M 120

8 ex: Br Mg o Et 2 MgBr Grignard eaction l Ba o Bal Yamamoto, JAS 1994, 117, 6130 other bonds (besides -X) can be reduced: "lithium naphthalide" - single electron reductant SPh Accts. hem. es. 1989, 22, 152 SPh TF, - 78 o axial to -20 o (stable at -78 o ) (>99:1) -inverse anomeric effect ychnovsky, JAS 1992, 57, ) Metallation (deprotonation) -very basic reagents can deprotonate - -like any acid / base chemistry, it s an equilibrium dictated by pk a so, we use n-bu, s-bu, t-bu, Ph Me tbu Me ex: TF, 0 o J 1979, 44, 2004 Why that product? sp 2 next to most acidic (pk a 30) K eq 10 (50-30)

9 also: KtBu Bu TF z isomer is favored "LIK" "Schlosser base" Schlosser, JAS 1978, 100, 3258 structure of LIK base: Venturello, Tetrahedron 1996, 52, 7053 note that many hydrocarbons can t be easily deprotonated due to kinetics another special case: Et 2 n-bu TMEDA TF, -78 o Et 2 ortho metallation (stabilized by - bond) also: s-bu TF J 1977, 42, 1823 Me s-bu Me J 1979, 44,

10 3) Transmetallation 1 M M 2 1 M M 1 equilibrium favors putting more electropositive M on more acidic ex: tbu ZnBr + tbuznbr + corrollary: MgBr 2 MgBr + Br (consider Br as 2 ) ZnBr 2 ZnBr + Br el 3 el 2 + l (very synthetically useful) ui 2 u + I (very synthetically useful) this follows electropositivity:, a, K > Mg II, a II > Zn II > u I > Pd II related exchange reactions: (ionic) hard Bu SnBu 3 + Bu 4 Sn soft (covalent) stable, chromatographable works if is more acidic than butane (pk a 46) also, metal - halogen exchange: 1 X X -110 o to -30 o X = Br, I -equilibrium governed by basicity of 1, 2 (favors less basic -) -very fast reaction! (competes with proton transfer) 123

11 mechanism: 1 X + 2 (+ e - ) 1 X X X (+ e - ) sequential single electron transfers evidence is the formation of 1-2 as a minor side-product (so-called Wurtz coupling) this can be made irreversible: I tbu (2eq) + I elimination + I + Seebach, TL 1976, 4839 haracteristic eactions 1) acid / base chemistry 2) transmetallation / metal-halogen exchange 3) nucleophilic addition M + ' Y Y ' M (works best when Y =,, 2, X; = 1 o, allylic, sp 2, sp) 124

12 4) nucleophilic substitution (uncommon) M + ' X ' + M X -note that this is the Wurtz oupling, a side reaction of / X exchange most common when M = u I,, but probably isn t S 1 or S 2 Ylides - a special class of carbanions base 2 Y n 2 Y 2 When a carbon α- to a positively charged heteroatom is deprotonated, it forms an ylide ( yl = ; ide = ) -very stable carbanions ex: 2 P 3, 2 S 2, 2 3 (less stable) (note that 2 S 2, 2 P 3, 2 2 can be viewed as ylides) Enolates - another special class of carbanions base Abstraction of acidic α-proton produces resonance-stabilized carbanion => very useful 125

13 Free adicals - Species containing unpaired electron(s) hybridization of carbon varies between sp 3 & sp 2 depending on the substituents ( 3 is planar ) => 7 valence electrons (electron deficient like carbocations) like carbanions, free radicals can be chiral, but invert too rapidly stability: look at - bond strengths (first handout) 1 o < 2 o < 3 o < benzylic, allyl, acyl (similar to cation) sp < sp 2 < sp 3 EWG 2 > 3 EWG =, 2, S 2,, Y Why do electron - withdrawing substituents stabilize α-radicals? through resonance, primarily: ' ' very stable radicals: Ph 3 stable & isolable 126

14 unstable radicals:, 2, (note that S is quite stable) Methods of generation: 1) homolytic bond cleavages! or h" (AIB)! or h" ( - 2 ) 2 X h! X + (X = I, Br, l) 127

15 2) photochemical excitation of π bonds ' h#! = 300nm (n " * ) ' diradical - behaves much like 2 isolated radicals haracteristic reactions: 1) atom transfer + Y ' Y + ' ex: equilibrium process favoring stable radical Br Bu 3 Sn, AIB (5%), mechanism: very weak bond! ( - 2 ) + SnBu 3 transfer atom - SnBu 3 + Br Br transfer - Bu 3 Sn Br Bu 3 Sn atom transfer v. stable bond typically, & X transfers are observed (note: also a method of generating new radicals) 128

16 2) Addition to π systems + the most common variant of this reaction is intramolecular: Br Bu 3 Sn, AIB (cat.) Ph, h! 3 mechanism: Br SnBu exo trig 2 SnBu 3 3 Bu 3 Sn radical cyclization: Beckwith, Tetrahedron 1981, 37, 3073 review: urran, Synthesis 1988, 417 & π system can also be radicals most easily detected by electron spin resonance (ES) - they appear as doublets 129

17 adical Anions & ations These species consist of neutral molecules that have gained (. A.) or lost (..) a single electron. 3 (l) ex: "dissolving metal" reduction lithium naphthalide What is meant by the structure? etc. -an extra electron is delocalized throughout the π system (unlike free radicals, no addition/loss of atoms during formation) M description:! " e -! "! 3! 3 extra electron is placed in antibonding M likewise we can place an extra electron in σ* orbital: SPh SPh - PhS very common example: a o a sodium benzophenone ketyl (blue-purple) 130

18 radical cations are somewhat more rare; most commonly encountered when single electron oxidants are used (also in mass spectroscopy) ex: Me e IV 3-2 Me para-methoxybenzyl (PMB) group etc. M description! 1 "! 2 - e -! 1 "! 2 vacant bonding orbital ( hole in π 2 ) adical cations also arise in the oxidations produced by DDQ l l - l (- e - ) l very e - deficient l l + - (- e - ) 131

19 radical ions can also be distonic (Kenttamaa) ex: vs. -differing stabilities, reactivities (these species are very important in mass spectrometry experiments) arbenes - neutral molecules lacking on octet 1 2 divalent carbon with two non-bonded electrons VEY reactive & unstable two different spin states:! 2! 1 vs.! 2! 1 singlet (J = 0) triplet (J = 1) at first approximation, we can consider them as: triplet -behaves as isolated radicals 2 singlet -behaves as zwitterion sp 3 sp

20 structure: much debate on structure of methylene ( 2 ) 136 o triplet 103 o singlet triplet - Wasserman, JAS 1970, 92, 7491 singlet - erzberg, ature 1959, 183, same bent structure holds for most other carbenes stability: methylene ( 2 ) is a ground state triplet (by 8-10 kcal/mol) -normally, carbenes are generated as singlets carbenes are stabilized by resonance: 2 < < < X < X X (X = l, Br) a very stable carbene has been reported: Arduengo, JAS 1991, 113,

21 Methods of Generation 1) α - elimination X base X slow ex: l 3 K 2 35 o l 2 (dichlorocarbene) also: l 3 Me TF -78 o l 2-78 o to 25 o l (chlorocarbene) In many cases, one can get a carbenoid instead: Zn o 2 2 I 2 Zn( 2 I) 2 Zn(2 I) 2 Simmons - Smith reagent stable to α - elimination but behaves like a carbene 2) decomposition of diazo compounds 2 1 h! or " (Δ gives singlet, hν gives excited state) 134

22 mechanism: 1 1-2! - elim. 1 also works with diazirines: h! or " 2-2 most important to synthetic chemists is the metal-catalyzed decomposition: h 2 (Ac) 4 2 " 2 ML n " 1-2 see, e.g.: Doyle, JAS 1996, 118, 8837 stable, but reacts like carbene haracteristic eactions 1) yclopropanation singlet and triplet behave differently : 2 singlet one isomer : 2 triplet + mixture 135

23 singlet reacts in concerted fashion (no intermediate) triplet reacts via diradical intermediate: Skell, JAS 1956, 78, 4496 can rotate can invert more commonly: 2 2 Et h 2 (Ac) 4 2 Et Zn-u, 2 I 2 "Simmons-Smith reaction" [via Zn( 2 I) 2 ] l 3, K 25 l l [via l 2 ] 2) - insertion : 2 3 how? Maybe via 3-center, 2-electron transition state 136

24 for preparative purposes: 2 h 2 (Ac) 4 TF Doyle in omprehensive rganometallic hemistry II, (1995), Vol. 2, h. 5.2 (very powerful transformation stereoselective functionalization of methylene group) this can also be intramolecular: Br K - 30 o Br > 25o - insertion Doering, Tetrahedron 1960, 11, 266 3) earrangements (like carbocations) 1,2 shift Schechter, JAS 1960, 82, 1002 also: 2 h!, " or h 2 (Ac) 4 (- 2 ) (ketene) 2 this is known as the Wolff rearrangement (JAS 1961, 83, 492) when the ketene is trapped by an alcohol, it s the Arndt - Eisnert rxn 137

25 The nitrogen equivalent (nitrenes) are also known: 3 h! or " very reactive they behave similarly to carbenes, but are less stable and more reactive 138