Bnding, Cycladditins, and Terpene chanisms Paul Bracher Chem 30 ectin 2 ectin genda 1) andm tuff, Decide n Better Time fr ffice urs 2) eturn Prblem et 1 3) andut: w t Win Chem 30 4) andut: ectin 2 (this ne) 5) andut: ectin 2 Practice Prblem et nnuncements New ffice urs Thursdays, 3-4PM and 8-9PM in the Bauer Lbby Crrectin In the ectin 1 handut distributed last week, there is an errr in the sectin n the anmeric effect. The 3D Lewis structures (chair drawings) were mismatched with their 2D cunterparts (hexagns with dashes and wedges). If yu catch any typs r errrs, drp me an e-mail s I can stp errr prliferatin by psting crrected versins f the handuts n the curse Web site. Unlike hw yu re taught in Chem 27, d nt draw verly abbreviated mechanisms. When a reactin ccurs stepwise, yu shuld draw ut the expected intermediates and indicate any imprtant cnsideratins which factr int the mechanism (such as resnance structures f reactive intermediates). GD Prblem et 1 Fallut nilines are basic (pka fr cnj. acid. = 4), s in acidic slutins, these cmpunds will be prtnated. While nitrgen substituents generally activate an armatic ring by a resnance effect, they are deactivating when prtnated. N 2 N 3 Cl Cl NT GD rth-/paradirecting metadirecting Prblem sets are graded in whle pints, s small/stupid/careless errrs will cst yu big time. imple prtn transfers are fast cmpared t electrphilic armatic substitutin reactins. In general, prtn transfers are amng the fastest reactins. 1
Building Mlecular rbitals (Ms) I m bumping this up frm material that appears later in the semester (pericyclic reactins) because yu re getting Ms crammed dwn yur thrats nw. This is a little shrter versin f last week s handut and includes a pictrial example n the next page. imple ules tmic rbitals must ve rlap if they are t interact t frm a set f mlecular rbitals. There are n exceptins rthgnal rbitals will nt interact. Yu will get n mlecular rbitals (Ms) fr every n atmic rbitals (s) that interact. The mst stable Ms have the mst bnding character. The highest energy Ms have the mst antibnding character. In the same π system, the energy f an M is directly prprtinal t the number f ndes. Thus, as the number f ndes increases, the antibnding character increases and the rbital lies higher-in-energy. The electrn density at an atm is equal t the square f the M s cefficient at that atm. Lcatins with bigger cefficients are depicted by drawing bigger rbital lbes. The and designatins, als shwn as green and blue, have nthing t d with charge. They are designatins fr the sign f that rbital s wavefunctin. When rbitals f the same wavesign interact, there is cnstructive interference resulting in a bnding interactin. When rbitals f the ppsite wavesign interact, there is destructive interference resulting in an antibnding interactin. Ndes are lcatins in the system where the bnding interactins are cmpletely cancelled by antibnding interactins. Mlecular rbitals have zer electrn density at ndes. eactins will nt ccur at these lcatins. Mlecular rbitals fr equivalent atms are symmetric. Nte hw the Ms belw either have a mirrr plane f symmetry (a symmetric M = ) r a C 2 axis f symmetry (an antisymmetric M = ). Nte patterns in M diagrams t help yu draw them and t figure ut shrtcuts in prblem slving In the lwest energy M, all f the wavesigns are the same In the highest energy M, all f the wavesigns alternate The termini alternate between having the same wavesign and ppsite wavesigns The number f ndes increases by ne as yu climb higher in energy Fr linear systems with an dd number f s, sme ndes will lie at atms in the chain Electrnic Perturbatins f Mlecular rbitals Placing electrn dnating grups (EDGs) r electrn withdrawing grups (EWGs) n a π system will shift r perturb the relative energies f the mlecular rbitals. EDGs will push mre electrn density int the π system and will crrespndingly raise the energies f the mlecular rbitals EWGs will pull electrn density ut f the π system and will crrespndingly lwer the energies f the mlecular rbitals Lewis acids that cmplex with extended π systems als lwer the energies f the Ms. These metals typically serve as catalysts by lwering the energy f a reactive LUM such that it is mre accessible. Determining which atms will becme enriched r depleted in electrn density can be accmplished by using an electrn pushing mdel. 2
Graphical Depictins f Mlecular rbitals Linear ystems Cyclic ystems Frst Circles Frst circles are the fastest methd t arrive at the mlecular rbitals fr cnjugated cyclic systems. Yu simply inscribe the plygn in a circle vertex dwn, such that ne f the crners tuches the bttm f the circle. Each vertex f the plygn represents the energy level f a mlecular rbital. Fr Chem 30, yu need nly wrry abut the relative psitin f the Ms and nt the quantitative energy difference between the Ms. wever, the reasn Frst circles are s pwerful is that they can be used t get these energies. 3
Cycladditin eactins In a cycladditin reactin, tw π systems react such that fur π electrns g int frming tw σ bnds t jin the termini f the systems. The reactin will nly prceed if the wavesigns match at the termini f the π systems Prblem-lving pprach 1) Identify the tw π systems (can be intramlecular) 2) ketch ut the mlecular rbitals fr the systems 3) Chse which system will serve as the M and LUM 4) egichemistry and terechemistry: analyze bth substitutent perturbatin and secndary interactins diene dienephile [42] majr prduct methyl grups hinder access t the tp face f the diene, frcing the dienephile t apprach frm the bttm face, as drawn the "end" rule secndary rbital interactin (invlving carbnyl π rbitals nt shwn) is respnsible fr the end transitin state Φ 4 Φ 3 Φ 2 Φ 1 1 2 3 4 electrn dnating alkyl substituents push up the energies f the Ms relative t butadiene M-LUM interactin 5 6 Φ 2 Φ 1 electrn withdrawing carbnyl substituents pull dwn the energies f the Ms relative t ethene Cycladditins will prceed nly if the symmetries f the M and LUM are the same s discussed previusly, substituents and Lewis acids catalysts will change the energies f the Ms. nytime the relative energy f the M and LUM are changed, the reactin rate will als change. The clser they becme in energy, the faster the reactin. The M typically has electrn dnating substituents; the LUM typically has electrn withdrawing substituents. End selectivity can lead t the mre sterically crwded prduct: [42] majr minr 4
Terpenid/Carbcatin earrangement chanisms General Ntes I tk this frm a Chem 27 handut. me f the material yu dn t knw (yet). But, a fair amunt f this stuff is applicable t this week s prblem set. Enzymes ften cntrl the sterechemistry f these steps in a way that cannt be predicted n paper. If faced with tw plausible mechanisms, chse the alternative with the mst stable intermediates and the fewest steps Cmmn chanistic teps 1) Inizatin PP alkyl pyrphsphate carbcatin PP Pyrphsphate ( - PP) is a gd leaving grup Lss f - PP results in the frmatin f a reactive carbcatin 2) Deprtnatin 3 C 3 C 3 C 3 C C 2 3 C prtnated 2 C 3 C deprtnated (new duble bnd) Lss f a prtn adjacent t a carbcatin generates a duble bnd lways shw prtns being remved by a base (unlike the example abve). 3) lefin ttack f a Carbcatin The π bnd is the nuclephile, while the carbcatin (empty p rbital) is the electrphile Nte that yu are left with a new carbcatin; the charge is cnserved Mre ften than nt yu attack with the less substituted carbn s that yu generate the mre substituted/stable carbcatin 5
4) N 2 eactin PP PP alkyl pyrphsphate carbcatin The bttm π bnd is the nuclephile, while the 3-carbn allyl system is the electrphile 5) lkyl hift alkyl shift 2 carbcatin 3 carbcatin alkyl shift 5-membered ring 6-membered ring lkyl shifts are typically driven by the frmatin f a mre stable catin ecall, carbcatins are stabilized by greater alkyl substitutin There is less ring strain in a six membered ring vs. a five membered ring 6) ydride hifts hydride shift 2 carbcatin 3 carbcatin ydride shifts are als driven by the frmatin f a mre stable catin 7) llyl-phsphate earrangement P i P P i P This is a [3,3] sigmatrpic shift, just like the Claisen rearrangement This is a key step in cases where, prir t phsphate rearrangement, the duble bnd is nt psitined crrectly t lead t a stable prduct (e.g., trans gemetry) 6