Synthesis of Alkenes Major approaches to the synthesis of alkenes: Dehydrohalogenation of Alkyl Halides E2 mechanism – most useful E1 mechanism Dehalogenation of Vicinal Dibromides Dehydration of Alcohols

Synthesis of Alkenes Dehydrohalogenation can occur via either an E2 or E1 mechanism. Loss of H+ and X- ions from adjacent carbons, forming a new pi bond NaOH D

Synthesis of Alkenes The most synthetically useful dehydrohalogenation reactions occur under E2 reaction conditions. 3o or bulky 2o alkyl halide strong bases strong bulky bases are best when using 2o alkyl halides less likely to undergo substitution reactions

Synthesis of Alkenes Common strong bulky bases triethylamine diisopropylamine t-butoxide ion 2,6-dimethylpyridine

Synthesis of Alkenes Mechanism of E2 Dehydrohalogenation concerted reaction anti-coplanar transition state

Synthesis of Alkenes E2 elimination reactions can take place in cyclohexanes only when proton and leaving group can get into a trans-diaxial arrangement corresponds to anti-coplanar

Synthesis of Alkenes Strong, less hindered bases (MeO-, EtO-, etc) generally give the most substituted alkene (Saytzeff’s rule) as the major product.

Synthesis of Alkenes Strong, bulky bases usually give the Hoffmann product (least highly substituted alkene) as the major product bulky bases often abstract a proton from a less hindered carbon

Synthesis of Alkenes Example: Predict all elimination product(s) of the following reactions. Which one is the major product?

Synthesis of Alkenes Example: Predict all possible elimination products for the following reaction. Which one will be the major product?

Synthesis of Alkenes Dehalogenation of Vicinal Dibromides two possible reagents NaI (E2 mechanism) Zn/HOAc (redox reaction)

Anti-coplanar conformation required Synthesis of Alkenes Dehalogenation using I- takes place via a concerted, stereospecific E2 mechanism Anti-coplanar conformation required Trans-diaxial conformation required for cycloalkanes

Synthesis of Alkenes Example: Predict the major elimination product formed in the following reactions.

Synthesis of Alkenes Dehydration of Alcohols removal of water equilibrium process drive reaction to completion by removing alkene as formed (LeChatelier’s Principle) H2SO4 D

Synthesis of Alkenes Typical reaction conditions alcohol substrate Order of reactivity: 3o > 2o > 1o alcohol acid catalyst conc. H2SO4 conc. H3PO4 heat

Synthesis of Alkenes Mechanism of Dehydration (E1) Step 1: Protonation of the hydroxyl group (fast) Step 2: Ionization (RDS) +

Synthesis of Alkenes Step 3: Proton abstraction (fast) Rearrangements to form more stable carbonium ions are common in dehydration reactions. Saytzeff’s product preferred.

Synthesis of Alkenes Example: Propose a mechanism for the following reaction. C

Synthesis of Alkenes Step 1: Protonation of OH group Step 2: Ionization with Methyl Shift

Synthesis of Alkenes Step 3: Abstraction of proton

Synthesis of Alkenes Example: Predict the major product formed in the following reaction.

Reactions of Alkenes The most common reactions of alkenes are addition reactions: the addition of a reagent to the pi bond with subsequent formation of new sigma bonds number of elements of unsaturation decreases

Reactions of Alkenes The electrons in the p bond of C=C are delocalized above and below the sigma bond more loosely held In the presence of a strong electrophile, the double bond acts as a nucleophile, donating the p electrons to the electrophile and forming a new s bond.

Reactions of Alkenes Most reactions of alkenes are electrophilic addition reactions. Step 1: Attack of electrophile on pi bond forming a carbonium ion: Step 2: Nucleophile attacks carbonium ion giving product.

Reactions of Alkenes Addition of H-X to Alkenes

Reactions of Alkenes In the previous example, the proton added to the secondary carbon, forming the most stable carbonium ion. Markovnikov’s Rule: Asymmetric reagents such as H-X add to a C=C so that the proton adds to the carbon (in the double bond) that already has the greater number of hydrogen atoms. “The rich get richer”

Reactions of Alkenes Markovnikov’s Rule (extended): In an electrophilic addition to an alkene, the electrophile adds in such a way as to give the most stable intermediate.

Reactions of Alkenes Example: Predict the product formed in each of the following reactions.

Reactions of Alkenes Anti-Markovnikov Addition of HBr In the presence of peroxides, HBr adds to C=C via a free radical mechanism giving the “Anti-Markovnikov” product. Works only with HBr (not HCl or HI) due to relative bond strengths.

Reactions of Alkenes Benzoyl peroxide Acetyl peroxide Some common peroxides: Benzoyl peroxide Acetyl peroxide Di-t-butyl peroxide Diethyl peroxide

Reactions of Alkenes HBr Example: Predict the product of the following reaction. HBr