Chapter 7: Alkene reactions conversion to new functional groups

Transcription

1 hapter 7: Alkene reactions conversion to new functional groups Preparation of alkenes: two common elimination reactions 1. Dehydration of alcohols Dehydration is a common biochemical reaction in carbohydrate and fatty acid metabolism and terpene biosynthesis it s catalyzed in vivo by specific enzymes. In the lab, dehydration is an acid-catalyzed elimination reaction. The mechanism involves formation of a carbocation intermediate (more on eliminations in h. 11) Example: Formation of 2-butene from 2-butanol S 4 heat The regiochemistry of elimination leads to the most substituted alkene possible = Zaitsev s rule 2. Dehydrohalogenation of alkyl halides Alkyl halides also undergo elimination to produce alkenes: What s the major alkene product of this elimination, based on Zaitsev s rule? eat

2 Addition Reactions of Alkenes A. Additions to produce alkyl halides and halohydrins 1. From h. 6, Alkene + X alkyl halide 2. alogenation: Br 2 and l 2 can add to alkenes just like Br, l and 2! Note: Similar reactions do not take place with F 2 and I 2 Br Br Br 3 Product is a vicinal" dibromide Where's the electrophile? Br 2 makes both electrophile (Br + ) and nucleophile (Br - ) Mechanism is a little different: the intermediate is a cyclic cation Br Br Br Br 3 Br Br Br- "bromonium ion" *Rearrangements do not occur with the cyclic cation mechanism!* Solvent effects: When planning a synthetic reaction in the lab, solvent should be chosen carefully For halogenation reactions, solvents such as 2 l 2 & l 4 do not interfere 3. alohydrins: Use of a nucleophilic solvent like 2 alters the outcome of the reaction, because both the halogen + water react with the alkene l l l 3 a halohydrin ow would the product change if an alcohol was the solvent?

3 Stereochemistry of halogenations: Use of NBS to provide a bromine: Some key points about this reaction: 1) Br 2 furnished by NBS is the electrophile, water is the nucleophile 2) The organic solvent used (DMS) doesn t take part in the reaction 3) The benzene double bonds don t react: Aromatic = do NT undergo electrophilic addition like alkene =!

4 B. More addition on the "Markovnikov" theme: Alcohol formation rxns 1. Acid-atalyzed ydration: Alkene Alcohol R R R R 2 + R R R R Mechanism: similar to addition of - X: Same rules apply as for addition of - X: 1) The bond is attracted to an electrophile and a new σ bond forms 2) The intermediate is the most stable carbocation 3) The nucleophile reacts with the carbocation to form another new σ bond 4) Markovnikov's rule is obeyed and the group ends up on the most substituted. Rearrangements can occur: mostly Another variation on this theme: alkenes ethers when alcohols are present, they become the nucleophile and add a -R group to the molecule: In summary: an ether Alkenes + - X Alkyl halides Alkenes + X, 2 alohydrin Alkenes + 2, + Alcohols Alkenes + R, + Ethers

5 2. xymercuration-demercuration: Metal complexes in organic reactions Some organic reactants are sensitive to harsh reagents (can cause decomposition!) ow do we avoid this in the case of hydration? A milder reagent for hydration: Mercuric acetate in TF & water A two-step synthetic procedure: 3 1) g(ac) 2, 2, TF ) NaB 4,- TF (tetrahydrofuran) is a cyclic ether; a moderately polar solvent Ac = 3 - No rearrangements occur with this process due to cyclic cation intermediate: Ac g g(ac) Ac 3 gac + Ac Demercuration step: NaB 4 provides a hydride ion, - gac NaB Na + g + -Ac A similar reaction, alkoxymercuration: Using R instead of 2 produces ethers Advantages of this procedure over hydration: 1) No rearrangements can occur 2) onditions for reaction are less harsh

6 ow would you prepare each of these alcohols?

7 3. 1 o alcohols by ydroboration-xidation ( Anti-Markovinikov orientation ) 3 = 2 1) B 3 2) -, 2 2, What s new about this reaction: 1. The electrophile is a Lewis acid, B 3 2. The nucleophile is a hydride (-) from the borane watch this: 3 = B 2 B 2 alkylborane 3. It s a concerted reaction (one step, no intermediate) and pericyclic 4. yclic transition state means no rearrangements 5. Product has Anti-Markovnikov orientation but it only APPEARS to violate Markovnikov s rule the nucleophile (-) still ends up on the most substituted, because this gives the more stable transition state: Figure from p. 153 here What happens next: The alkylborane reacts with 2 more moles of alkene to produce a trialkylborane. Steric hindrance of alkyl groups promotes further addition to less-substituted : 3 -= 2 3 -= B 2 ( ) 2 B ( ) 3 B Trialkylborane The trialkylborane reacts with peroxide and hydroxide ion to release 3 moles of alcohol: ( ) 3 B 2 2, -, B 3- Summary: ydroboration is an effective route to 1 o alcohols

8 . Alkanes by atalytic ydrogenation (the "risco" reaction) Suppose you want to prepare alkanes from alkenes? An example from real life: Vegetable oil Semi-solid shortening Addition of 2 is catalyzed by Pt or Pd on charcoal, Pt 2, or Ni (heterogeneous catalysts): R R Pt/ R R R R R R 2 The - bond is particularly strong; requires a catalyst to help bond break. Addition occurs on one side of the molecule (syn addition) see WL tutorial 2 adsorbs on the catalyst surface and the reaction occurs there. D. yclopropanation by using arbenes: carbon adds to the = in a stereospecific way arbenes are an electron-deficient, sp 2 -hybridized species with formula (R) 2 : These are reactive species generated in situ by deprotonation of chloroform: l 3 + K -:l 3 -:l 2 + l- r generated from similar reagents: Simmons-Smith reaction Zn/u 2 I 2 : 2 Ether As electrophiles, carbenes can react with = to form a cyclopropane ring: 2 = 2 + :l 2 l l Stereospecific: the original arrangement of groups around = bond is retained. 2I Zn/u/ether 3 3 2

9 E. xidation of = bonds to produce oxygenated functional groups xidation: Reaction resulting in an increased number of bonds from carbon to oxygen, and a decrease in bonds to hydrogen Increasingly oxidized functional groups R R R 1 R 2 R R 2 R 1 alkanes alkenes alcohols ketones acids alkynes aldehydes esters xidation of - pi bonds is a versatile way to introduce new functional groups to molecules containing the alkene group. 1. ydroxylation of alkenes: diol preparation Alkenes can be oxidized by transition metal oxides with a high metal oxidation state cold KMn 4, -, s , NaS 3 Stereospecific syn addition occurs to produce vicinal diols The positive charge on the metal attracts electrons and sets a pericyclic reaction in motion; π electrons form σ bonds As the organic functional group gets oxidized, the inorganic reagent gets reduced (by products: Mn 2 or s 3 ) KMn 4 is cheaper but harsher (can completely oxidize =, see next page) s 4 is expensive, highly toxic

10 2. xidative leavage of alkenes: produces carbonyl compounds by breaking both σ and π bonds The 1,2-diols produced by oxidation of alkenes can be further oxidized to carbonyl compounds by a second pericyclic reaction: 3 3 I I Products may be aldehydes or ketones depending on structure at diol carbons Significant reaction because - bonds are not broken easily A similar reaction occurs when KMn 4 is used under acid conditions or heat: R 1 R 1 R 3 KMn 4 + or heat R 2 R 2 + R 3 A disubstituted = (two R groups attached) becomes a ketone carbon A monosubstituted = (one attached) becomes fully oxidized to a carboxylic acid (no aldehydes are produced under these conditions) A = 2 from a terminal alkene becomes 2 instead of a carboxylic acid: xidation of cyclic alkenes opens up the ring resulting in a diacid or a diketone: KMn 4, 3 + KMn 4, 3 +

11 3. zonolysis: A milder, more efficient, "greener" (?) way to do oxidative cleavage! Problems with transition metal-mediated oxidations: Reagents form toxic metal compounds as by-products (hazardous waste!) onditions may be rather harsh, require heat, acids, bases Side reactions: KMn 4 will oxidize any or = groups in the molecule too The solution: zone! ycloaddition of ozone to = produces a molozonide which rearranges to an ozonide. leavage under oxidizing or reducing conditions to yield different products as shown: R 1 R 3 R 2 3 R 1 R 3 R 2 R 1 R 3 R 2 Zn, R 1 R 3 R 2 + R 1 R 3 R 2 A bearing a single R group yields an aldehyde under reducing cond. Terminal alkenes form formaldehyde or 2 as the second product Tetra-substituted alkenes form only ketones under any conditions

12 zonolysis is a useful way to determine the structure of an unknown alkene: React the unknown with ozone under controlled conditions Determine the identity of the oxidative cleavage products (the simpler the molecule, the easier it is to determine structure!) Figure out how the pieces would fit together Road map problems! Goal: Piece together information from reactions to figure out structures of unknown compounds. You are given some key pieces of information to help you figure out what is happening to the molecule in each step. Example: ompound A has the formula n catalytic hydrogenation over palladium ( 2, Pd) it reacts with only one molar equivalent of 2. ompound A also undergoes reaction with ozone ( 3 ), followed by zinc treatment (Zn, 3 + ) to yield a symmetrical diketone, B which has formula ( ). Propose plausible structures for A and B.

13 What reagents would be best to carry out these reactions? (f) KMn 4? 3 +

14 2, + or 1.g(Ac) 2 2.NaB 4 l 2 or Br 2, 2 1.B 3 /TF , - 2 /catalyst 1.s 4, 2.NaS 3, 2 l 2 or Br 2, 2 l 2 Br or l 3 KMn 4, 3 + or Zn, 3 + or I 2, Zn(u), ether Alkene + X Alkyl halide Alkene + X 2 (Br 2, l 2 ) Alkyl dihalide Alkene + X 2, 2 alohydrin Alkene + +, 2 Alcohol (Markovnikov) Alkene + g(ac) 2, NaB 4 Alcohol (Markovnikov) Alkene + B 3 /TF, 2 2, - Alcohol (Non-Markovnikov) Alkene + 2 / Pd, Pt or Ni catalyst Alkane Alkene + 2 I 2, Zn/u yclopropyl alkane Alkene + s 4, 2, NaS 3 diol + I 4 aldehydes & ketones Alkene + KMn 4, 3 +, heat carboxylic acids & ketones Alkene + 3, Zn, 3 + aldehydes & ketones