ADDITION

Many reagents add to the alkene bond. The reactions are called electrophilic additions and thus a carbocation is formed on a carbon atom. The reaction is regioselective as controled by the formation of the more stable carbocation. The reactions follow somewhat complex kinetic expressions showing that a simple mechanism is not being followed. For example, below possibly two molecules of the reagent are reacting with the substrate in the rate determining step.

X-Y X C=C C-C Y X-C-C-Y

rate = k [alkene][XY] + k[alkene][XY][Y-] + k[alkene][XY]2

X-Y C=C

X-Y Additions of HCl, HBr

The ionic addition of HX produces the more stable carbocation which then reacts with the bromide ion. The result is that the bromide is attached to the more substituted part of the alkene. This stereoselective reaction is called Markovnikov addition.

Br HBr H Br- H

or HBr

HBr Br OAc HOAc H H HBr H

CH3 CH3 Br

H CH3 HBr Br H C=C H CH3 Ph H Ph H

The addition of HBr in the presence of a radical iniatiator such as a peroxide follows a regioselective results which is opposite to the ionic addition. The two reactions are referred to as Markovnikov and anti-Markovnikov additions but result because of the operation of two entirely different mechanisms. The ionic mechanism (Markovnikov) produces the more stable carbocation which reacts with bromide. The radical mechanism (anti-Markovnikov) adds the Br radical first to give the more stable radical which reacts with HBr to abstract a hydrogen atom.

Br HBr

Markovnikov ROOR 2 OR peroxide

HBr + OR Br + HOR H H HBr Br Br Br

anti-Markovnikov

Additions of Halogens and pseudohalogens.

Halogenation of organic compounds occurs readily with halogens (X2), mixed halogens (X-Y) and pseudohalogens (X-function). The reaction kinetics contain higher level terms just as addition of HX and thus may have more than one molecule of halogen in the rate controlling step. The possible stereochemical result of halogenation is shown in the mechanism below. Most electrophilic halogenations occur through the path involving a halonium ion to give anti addition, but syn addition is also observed as well as non stereoselective addition.

+

+ X2 X X X X syn-addition Sigma complex

+ X + X X Halonium ion carbocation

X X

X X non-stereoselective anti-addition

In the bromination of an adamantyl alkene a stable bromonium ion has been isolated. Br +

The reactivity of alkyl substituted alkenes is shown below. The order reflects the nucleophility of the alkene for the electrophilic halogen. CH CH CH3 CH3 CH3 3 3 CH3 CH3

CH3 CH3 CH3 1 61 2600 10,000 2 x 106

The amount of syn addition increases with phenyl subsituted alkenes. This is a result of the increased stability of the intermediate benzylic cations..

Br H Br Br Br2 CH3 H H Ph CH3 H Ph Br Ph CH3 anti syn anti:syn ratios Ph

H C Ph 3 CH3 Ph H3C CH3 100:1 1.9:1 2:1 100:1

Fluorinated aliphatic alkenes also show a preference for anti addition as shown below, but fluorinated styrenes show high levels of syn addition. Br H Br Br Br2 CH3 H H F CH3 H Ph Br Ph CH3 anti syn 97 % 3 % Fluorinated styrenes, as well as other halogenated styrenes, give an increased amount of syn addition. Sometimes the syn addition product is the major product. In these cases, less halonium ion is formed because the fluorine atom and the phenyl ring stabilize the cation.

F Ph Br Ph Br Br Br2 F Ph Cl F F F Cl Br Cl F anti syn 64 % 35 % A few representative examples of halogen addition `are shown below.

COO- COOH I2 O O NaHCO3 I I

OH OH Cl2 , NaOH CH3 CH3 CH3 ( Cl - OH) Cl Cl

Pseudo halogens are composed of compounds such as I-NCO and I-N3 . These reagents add with the halogen positive followed by the negative functional part. The function allows for further organic transformations.

NCO INCO I

Mixed halogens can be added to alkenes. While addition of F2 is usually a hazardous proposition, the use of BrF or IF proceed smoothly. IF can be produced in situ from the reaction of xenon difluoride and iodine. In the example shown the F anion adds at the site of the more stable cation. CH F H3C 3 H C CH3 XeF2 / I2 3 H C 3 H H3C H I Addition of Boranes (Hydroboration)

Alkenes react with BH3 ( a commerical reagent is a comples with Me2S) followed by oxidation with peroxide and base to give alcohols. The reaction is very selective and subject to steric effects. It is not an ionic addition , but is nearly a four-center addition with the boron atom going to the less substituted carbon atom. H H H B H H B H H BH2 R R R

H B -OOH H OH

R 3 R

The regio and stereoselectivity are show in the examples below.

1) BH3 H 2) HOO- , -OH OH

1) BH3 OH 2) HOO- , -OH

The highly sensitive regioselective nature of hydroboration may be expanded to larger borane reagents that add almost exclusively to the least substituted carbon atom. Three reagents are compard below. A 6 94 A 43 57 B 1 99 B 3 97 C 99.9 C 99.8

B2H6 = H-B-H A H3C CH3 H H3C 2 H B BH B

C

Epoxidation and Hydroxylation

Alkenes undergo addition of peroxy reagents to produce alkenes as shown below. The reaction occurs through a concerted addition of an oxygen atom to the alkene.

O O PhC-OOH + O + PhC-OH

O H Ph-C O O

A procedure known as Sharpless epoxidation allows the preparation of chiral epoxides by using chiral oxidation agents. O HO CO Et O 2 t-BuOOH O + O Ti(OiPr)4 HO CO2Et O OH mol sieves OH (+)-diethyltartrate

Alkenes also add hydroxyl groups to produce glyclols on reaction with cold potassium permanganage.

KmnO 4 OH OH A single hydroxyl function is added in a process called oxy-mercuration- demercuration. In this reation, mercuric acetate reacts with the alkene to produce an intermediate three membered ring similar to that seen in halogenation, called a mercurinimium ion. Nucleophilic solvent present such as water, alcohol, or acetate can open the ring to give an oxygenated mericury compound. Reaction of the intermediate with sodium borohydride reduced the C-Hg bond to a C-H bond.

Hg(OAc)2 OH H2O

H2O

Hg(OAc)2 HgOAc

OH OH

NaBH4

HgOAc

The nucleophilic solvent, water in this case, attacks the carbocation at the more stable tertiary position. After reduction the tertiary alcohol is formed. This is the same regioselectivity observed in acid-catalyzed hydration but the mercuration reaction proceeds much cleaner except for the presence of mercury compounds. Hydroboration-oxidation gives the the reverse selectivity shown below. Thus for synthetic purposes the processes compliment each other.

1) BH3 - 2) OOH OH

Alkenes also undergo addition of carbon units. The addition of divalent carbon, carbenes or carbenoids, produce three membered rings. A very useful method for making difluorocylopropanes comes from treatment of the trimethylsilyl ester below with catalytic fluoride. Several products occur including the difluorocarbene which reacts immediately with any alkene present.

- F SO2CF2-CO2SiMe3 + F Me3SiF + CO2 + SO2 + CF2

- F SO2CF2-CO2SiMe3 + F

F2 C CF2

79 %

Dichlorocarbene can be easily generated and captured by an alkene as shown.

HCCl3 CCl2 CCl2 carbene KOH The addition of dienes in the Diels-Alder reaction provides six membered rings.

O O

+ O O Diels-Alder

O O Carbene addition and the Diels-Alder reaction are coverend in more detail in the chapter on orbital symmetry. Addition of Fluorine to Unsaturated compounds

From Hudlicky book Purrington Some reagents ArIF2, CsOso4F XeF2 HF, Cf3of Feiring Addition of HF to alkenes and to acetylenes, Halogen Fluoride addition, OF reagents FCLO3,. Sf, NOF,