Selective Oxidations SUBSTRATE REAGENT. Non-activated Carbon Atoms. Bugs, enzymes. X 2 / hv. X 2 / hv or ArICl 2

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1 Selective xidations SUBSTATE EAGET on-activated Carbon Atoms Bugs, enzymes X X 2 / hv X 2 / hv or ArICl 2 Activated on-functionalized Carbon Atoms Se 2 Se 2, PDC Se 2 K t Bu / (Et) 3 P / 2 or LDA / Mo(VI)( 2 ) 2 / MPA / py (MoP) Z Carbon Atoms of C-C Double Bonds Z Se 2 or (i) LDA / PhSeBr (ii) 2 2 /ai 4 (i) X (ii) - or C()- trans (i) C()- (ii) - or (i) AgAc / I 2 (ii) - or LA

2 cis (i) AgAc / I 2 / 2 / Ac (ii) - or LA or s 4 X X or (i) (i) C() (ii) X X Cr 2 Cl 2 X X X 2 X = Cl, Br, I (i) B 2 6 (ii) 2, - Carbon Atoms of C-C TripleBonds (i) 2 B (ii) 2 2 / - g(ii) / / 2 ' ' KMn 4 or u 4 C KMn 4 or u 4 2

3 xygen Containing Functional Groups PDC or PCC or 2 C / Al(iPr) 3 or DMS E E = DCC or Ac 2 or S 3 or P 4 0 or CCl 2 or (CCl) 2 Ag 2 C 3 or Pb(Ac) 4 ' C ' Most strong [] u 4 Mn 2 or DDQ Cu(Ac) 2 earrangements & Cleavages C() (i) 2 (ii) Cr 3 or KMn 4 or (i) Se 2 (ii) I 4 3

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5 Prof Ben Davis TID YEA GAIC CEMISTY - EVISI CUSE Lecture 4 MLECULA EACTIVITY 3: BITAL SYMMETY AD PEICYCLIC EACTIS Books: Carey and Sundberg, Part A, Ch 0. Lowry and ichardson, " chanism and Theory in rganic Chemistry", Ch 0 and. Fleming CP 67 Fleming, "Frontier rbitals and rganic Chemical eactions", Sections 2. and 2.2. Gilchrist and Storr, "rganic eactions and rbital Symmetry", Ch 2, and sections in Ch 4, 5, 6, 7. Morrison and Boyd, rganic Chemistry, 6th Edn, Ch 28.. MLECULA BITALS Ms for extended -systems by Linear Combination of Atomic rbitals ( LCA). ethene ( and *), butadiene (, 2, 3, 4), hexatriene (, 2, 3, 4, 5, 6 ): Ethene Butadiene exatriene B: (i) The nth orbital has n- nodes symmetrically distributed around the midpoint; (ii) The orbitals are alternately symmetric and antisymmetric with regard to a mirror plane at the midpoint; (iii) The orbitals are alternately antisymmetric and symmetric with regard to a two-fold rotational axis of symmetry at the midpoint; This analysis is applicable to systems with odd numbers of atoms: here one M is nonbonding (i.e. energetically neutral), and has nodes at the nuclei (this is why electron deficiency or electron density lies at the end of the molecule), e.g. allyl and pentadienyl systems (cation, radical and anion)

6 5 4 Allyl Cation adical Anion Pentadienyl Cation adical Anion The Frontier Molecular rbital Approach (FM): considers the interactions of M (electron donor) and LUM (electron acceptor)(bonding arises only when orbitals of the same phase overlap) to determine the feasibility of any given reaction. The easiest path (i.e. lowest E act ) for a reaction is one which maximises the bonding during the reaction process; since bonding results from orbital overlap, we require maximum overlap which can only be achieved when orbitals are of the same phase. Thus, concerted reactions can either be symmetry allowed or symmetry forbidden. This can easily be decided by a consideration of the Frontier Molecular rbitals, which contain the "valence electrons" of the molecules. 2. PEICYCLIC EACTIS - a concerted reaction that proceeds via a cyclic TS (concerted = simultaneous bond making/breaking) - characteristics: * S <<0 * highly stereospecific * reversible A) Electrocyclic eactions - a pericyclic reaction that involves ring opening or ring closure, by bond formation/cleavage between the ends of a linear system of electrons But the reaction is of much greater interest when there are substituents on the polyene termini: we can understand the mode of ring closure (conrotatory or disrotatory) by a consideration of the FM, in particular the M of the polyene; ring closure is symmetry allowed only when orbital overlap of the same phase. 2

7 (i) Butadiene Cyclobutene (4 e - in diene) con con trans-, transcis cis-, trans- trans via T thermal = conrotatory photochemical = disrotatory (ii) exatriene Cyclohexadiene (6 e - in triene) dis dis trans-, cis-, cis- trans-, cis-, transtrans cis via T thermal = disrotatory photochemical = conrotatory These results are generalised in the following Selection ules: o. of e - in ring closure eaction Photochemical Thermal n Dis Con 4n2 Con Dis B) Cycloaddition eactions - a reaction in which two unsaturated molecules react to form a cyclic compound; the electrons are used to form two new bonds. [42] equire * s-cis conformation of the diene * addition is stereospecifically syn -with respect to the alkene dienophile (suprafacial) 3

8 endo- exo- * endo- additions is kinetically preferred, due to secondary orbital interactions * FM analysis permits either a) M( diene)-lum( * dienophile) This is promoted by EG substituents on diene and EWG ( -M type) on dienophile Diels-Alder Inverse Demand Diels Alder b) LUM( diene)-m( dienophile) Inverse demand D-A; This is promoted by EWG substituents on diene and EG on dienophile * reversible, and this can lead to equilibration of product mixtures [22] * Favoured only under photochemical conditions, by supra-supra overlap * Irradiation excites an electron from M of the ground state, and then FM analysis permits M( * excited ene)-lum( * ground state ene) LUM (ground state) M (excited) Woodward-ofmann ules for the Facial Selectivity of [ij] Cycloadditions ij Thermal Photochemical 4n s,a (or a,s) s,s (or a,a) 4n2 s,s (or a,a) s,a (or a,s) [32],3-Dipolar Cycloadditions - FM description of cycloadditions of,3- dipoles to double bonds (called the "dipolarophile"). Examples of,3-dipoles, their synthesis and synthetic utility: 4

9 Some useful types of 32:. Diazomethane -----> pyrazolines 2. Azides -----> triazoles 3. itrile oxides -----> isoxazolines 4. zone -----> molozonides (primary ozonides) C) Sigmatropic eactions - a migration, in an uncatalysed intramolecular process, of a -bond, adjacent to one or more systems, to a new position in the molecule, with the -system reorganised in the process - the process is given an [i,j] descriptor, with each terminus of the bond being broken given the number, thus: G G [,3] 2 3 [3,3] Cope earrangement - the FM approach treats the reaction formally as a radical process, and uses the singly occupied non-bonding orbital of the allyl/pentadienyl/etc system: G G G allyl pentadienyl heptatrienyl 4 5

10 (i) [i,j] Sigmatropic migrations. YDGE SIFTS: here we consider overlap with s - [,3] are thermally allowed (antarafacial) but sterically impossible - [,5] are thermally allowed (suprafacial) since the s can overlap simultaneously with the end orbitals of 3, which are of the same phase - [,7] are thermally allowed (antarafacial), e.g. in the Vitamin D series. 2. CAB SIFTS: here we consider overlap with C 2p (much more complex than for ) - [,3] are thermally allowed (suprafacial) - [,5] are thermally allowed (suprafacial) (ii) [i,j] Sigmatropic rearrangements * Cope earrangement (see above) * Claisen earrangement Consider as i.e. D) Cheletropic eactions - reactions in which 2 bonds that terminate at a single atom are made or broken in concert. S S 2 S 2 S E) Group Transfer - reactions in which one is used to form one new bonds. e.g. ene 6