Alkenes with Water 1 O + O S O 32 (catalyst) ether 2 O 33 O A number of different acids can be used. Rather than the strongly oxidizing sulfuric acid p-toluenesulfonic acid (32, TsO) is more commonly used because it is not oxidizing and generally soluble in organic solvents. In effect, tosic acid is an organic acid. This variation is illustrated by the reaction of cyclohexene with water in the presence of a catalytic amount of tosic acid, generating cyclohexanol, 33. Note also that alkenes are often insoluble in water, so a co-solvent such as acetone or ether is normally used, as shown.
What is the major product? 2 O O cat + 2 O cat + O Careful! Remember rearrangement. 2 O O cat +
Alkenes with Alcohols 3 cat. + 34 O O - + 35 36 O Once the carbocation is formed, it will react with the most readily available nucleophile, which in the case of water, leads to the oxonium ion and then to the alcohol. If the same reaction is done in methanol rather than water, the nucleophile will be the oxygen atom of methanol. The reaction of a carbocation with an alcohol will also generate an oxonium ion, but loss of a proton leads to an ether. The reaction of cyclohexene and methanol in the presence of an acid catalyst, for example, initially gives the expected carbocation (34), but in the methanol solvent the nucleophilic is the oxygen atom of methanol. Note the use of + in the mechanism rather than TsO. When the proton of the acidic oxonium ion is lost to methanol or cyclohexene in an acid-base reaction, the product is an ether, 36 (methoxycyclohexane; also known as cyclohexyl methyl ether).
Alkenes as Lewis Bases: With Dihalogens 4 37!+! C 4 38 When cyclohexene is mixed with elemental bromine, in carbon tetrachloride as a solvent, the product is trans-1,2- dibromocyclohexane (38) isolated in 57% yield. omine is certainly not a ønsted-lowry acid, but can diatomic bromine be categorized as a Lewis acid? omine, and indeed all of the diatomic halogens are polarizable. This means that covalent bond will become polarized with a δ+ and a δ when brought into proximity of an electron rich species.
Polarizable Dihalogens 5 37!+! C 4 38 Diatomic halogens such as chlorine ( ), bromine ( ) and iodine (I-I) are highly polarizable. In the absence of another molecule, there is no difference in electronegativity between the atoms in - and -, or I I. When the halogen is in close proximity to an electron rich atom or group, the halogen atom closest to the electron source becomes δ+ while the other becomes δ. This means that the atoms are polarized via an induced dipole. In the case of cyclohexene, the electron source is the π-bond and if it donates electrons to the positive halogen, the C=C unit reacts as a Lewis base.
Fluorine 6 For many years, elemental fluorine was thought to be too reactive and too dangerous for reaction with alkenes. To avoid such problems, fluorine is typically mixed with an inert gas such as nitrogen or argon. Diluted in this manner, fluorine does react with alkenes, but the yields are often poor, and in some cases solvents for the alkene, such as methanol, participate in the reaction. 1-Phenylpropene (PhC=C 2 ), for example reacted with fluorine in methanol to give 51% of the corresponding difluoride, along with 49% of 2-fluoro-1-methoxy-1-phenylpropane. Because of problems associated with fluorine, this chapter will report alkene reactions only for chlorine, bromine or iodine and not fluorine.
alonium Ions 7 induced dipole!+!"!!+!!! C 4!+ 39 40 38 transition state In the transition state for this reaction (39), the second carbon of the alkene π-bond develops positive character as the π-electrons are transferred to bromine. In principle, this process would lead to the usual secondary carbocation, but this positive charge develops on carbon in the presence of the bromine atom, with has unshared electron pairs. The bromine donates two electrons to that positive carbon (called back donation) to form a second C- bond in 40 and a three-membered ring with a formal charge of +1, with a bromide ion as the counterion. Cation 40 is the experimentally detected cation intermediate mentioned above. The product is not the carbocation (with the positive charge on carbon) but rather the three-membered ring cation 40 called a bromonium ion (one type of halonium ion), with the positive charge on bromine.
alonium Ions 8 induced dipole!+!"!!+!!! C 4!+ 39 40 38 transition state In reactions with alkenes, bromine gives a bromonium ion, chlorine gives a chloronium ion, iodine gives an iodonium ion, and generically a halogen gives a halonium ion. It is important to understand that 40 is generated in this nonpolar solvent because it is more stable than the carbocation intermediate.
trans-dihalides 9 In 40, the large bromine atom must reside on one side of the cyclohexane ring, or the other, due to the nature of the three-membered ring and the inability to undergo C C bond rotation. As drawn, the bromine atom is on the "top" as the molecule in 40. The sidedness is clearer in the molecular model 40A, and particularly obvious in the space-filling model 40B. When bromide ion attacks an electrophilic carbon atom of the three-membered ring, it must do so from the sterically less hindered side opposite the first bromine atom (as in 40C) leading to formation of a new C bond, with cleavage of the threemembered ring to form the trans dibromide. Note that the other diastereomer (the cis-dibromide) is not formed in this reaction. 40A 40B 40C
trans-dihalides 10 Only the trans diastereomer formed, so this reaction is diastereospecific. If cyclohexene is viewed from the "side", as in 41, it is clear that the initial reaction with bromine must deliver the of the bromonium ion to one on side of the ring or the other. The may be on either the "top" or the "bottom" since there is no facial bias in the C=C unit of cyclohexene. If bromine is arbitrarily drawn on the "bottom," as in 42 (compare this structure with 40C with the bromine on the top ), nucleophilic attack by the bromide ion will occur from the opposite "top" face since that is less sterically hindered. This backside attack leads to the trans stereochemistry in 43. Note that attack from the top or bottom can occur with equal facility, but a transdibromide is produced in both cases. Attack from the top face leads to one enantiomer and attack from the bottom face leads to the other enantiomer, and attack from either face occurs with equal facility. The reaction must produce a racemic mixture. 41 42 43
The Reaction with Acyclic Alkenes is Diastereospecific In cis-2-butene, the two methyl groups are "locked" on one side of the C=C unit since there is no rotation around those carbon atoms. The key to the stereoselectivty is the fact that the stereochemical relationship of the groups on the C=C unit is retained in the transition state that leads to the bromonium ion, in the bromonium ion and in the final product. When cis-2-butene reacts with bromine, bromonium ion 46 is formed, which is arbitrarily drawn with the bromine on the "right," although there is nothing to distinguish one side from another (to be discussed below). If the two methyl groups are locked on one side in the alkene), they will also be "locked" in position in the transition state and in the bromonium ion product, 46 (because the three-membered ring prevents rotation. reacts with 46 via backside (anti) attack at carbon, on the face opposite the bromine atom in 46, which fixes the stereochemistry of the two bromine atoms as anti. If the stereochemistry of the methyl groups is fixed in the transition state leading to the bromonium ion, and anti-attack fixes the stereochemical relationship of the two bromine atoms, the stereochemistry at each new stereogenic center must be fixed in the dibromide product as shown. In this case, it is (2S,3S), 44A. 11 (Z) - (R) 46 rotate 60 44A rotate 60
Diastereospecific but Racemic Imagine that diatomic bromine reacts with cis-2-butene to give bromonium ion 47. Subsequent attack of the bromonium ion from the face opposite the bromine atom will generate the (2R,3R) diastereomer (i.e. 44B), which is the enantiomer of 44A generated from bromonium ion 46 in which bromine was on the "right". The bromine may add to either face of the alkene with equal facility. A mixture of enantiomers is formed; a racemic mixture. A racemic mixture is formed when there is no facial selectivity, but the reaction is still diastereospecific since only one diastereomer is formed. (R) (Z) (R) (R) (Z) - (R) 46 47 rotate 60 44A 44B rotate 60 12
Diastereospecific but Racemic 13 The E isomer reacts similarly, but gives the diastereomer, 2R,3S (E) (R) (R) (R)
Alkenes with ypohalous Acids It is known that dissolving chlorine in water leads to a solution that contains hypochlorous acid (O) and bromine dissolved in water contains hypobromous acid (O). In one experiment, 1-pentene is mixed with chlorine and water (O in aqueous media), and the major product is 1-chloro-2-pentanol (48), in 43% isolated yield. The polarization of O is O δ δ+, where chlorine is the electrophilic atom. The π-bond of an alkene should react with the positive chlorine atom, and cleavage of the bond will give hydroxide ion, which is a nucleophile in this reaction. If the reaction is done in water, the oxygen atom is also a nucleophile. A nucleophile attacks a halonium ion at the less substituted carbon. If chloronium ion 49 forms in this particular reaction, attack by the nucleophilic hydroxide ion at the less hindered carbon of 49 gives 2-chloro-1-pentanol. owever, the isolated product is 48 (1-chloro-2-pentanol), and formation of 48 must result from attack at the more substituted carbon atom of 49.!+! O 2 O O 48 43% + 14 O 2 O 2 O 49 O 50
Alkenes with ypohalous Acids The major product is not consistent with nucleophilic attack with chloronium ion 49. In the reaction with 1-pentene, formation of 48 is only consistent with formation of a secondary carbocation such as 50 rather than 49. Carbocation 50 may react with hydroxide to give 48 directly, but it is more likely that it will react with water to give an intermediate that leads to 48. Carbocation 50 forms in water, with some back donation by chlorine. Water not only generates O, but it also separates charge and stabilizes charge by solvation. Since O is generated in the presence of water, it is anticipated that 50 is more stable in the aqueous medium than 49, and attack by hydroxide at the positive carbon gives 48. Note that in a large excess of water (water is the solvent), 50 can also be attacked by water, and loss of a proton from the oxonium ion (hydroxide or water can function as the base in this reaction) also gives 48. 15!+! O 2 O O 48 43% + O 2 O 2 O 49 O 50
ydroboration. erbert C. own Boron trifluoride (BF 3 ) is a classic Lewis acid. Borane, B 3, also functions as a Lewis acid in the presence of a suitable electron donating species. Borane is a reactive species that is usually written as B 3, but it is actually a dimeric species called diborane (51) that has hydrido bridges (bridging hydrogen atoms). There is an equilibrium between borane and 51, but the monomeric species (B 3 ) and the dimeric species B 2 6 are used interchangeably. NaB 4 + BF 3 B B 51 B 16 1912-2004. Nobel Laureate
ydroboration 17 1-exene reacts with borane to give a new product known as an alkylborane, which is listed as unknown for the moment. The alkylborane product is treated with NaO and 2 O 2 in a second chemical reaction and the major product obtained after this two-reaction process (two-step process) is 1- hexanol (52), isolated in 81% yield. The second reaction with hydroxide and peroxide reacts with the new borane product of the first reaction to give the alcohol. In effect, O replaces the boron unit. The remainder of the 100% is alcohol 53 as a minor product, and this will be explained later. Bu NaB 4 alkylborane NaO BF 3 OEt 2 product 2 O 2 Bu O O + Bu 52 53