Chapter 12 - Electrophilic Addition to Nonpolar Pi Bonds 2: Reactions Involving Cyclic Transition States

chloronium ion intermediate

- Cl2 also undergoes addition to alkenes to produce vicinal (i.e., 1,2) dichlorides. - as in the addition of Br2, Cl2 adds in an anti fashion to the double bond. - the mechanism is similar, proceeding through a chloronium ion intermediate to avoid breaking the C atom's octet.

electrophilic addition of carbenes

- a carbene is a species containing a carbon atom that possesses two bonds and a lone pair of electrons. - like a carbocation, a carbene has a C atom that lacks an octet and is generally highly electron poor. - unlike a carbocation, however, the electron-poor C atom of a carbene has a formal charge of 0. - most carbenes are highly reactive, so they typically have very short lifetimes and cannot be isolated. - in these cases, we cannot simply add a carbene as a reagent. - highly reactive carbenes must be generated in situ (i.e., "on site") from precursors that can be added as reagents.

synthesis of halohydrins

- a vicinal dibromide is produced if an alkene reacts with Br2 in a carbon tetrachloride. - if the same reaction is carried out in water, then a bromohydrin is produced instead.

avoiding the mixture of products

- chemists avoid this problem of product mixture by using a bulky dialkylborane, such as disiamylborane, (C5H11)2BH instead of BH3. - disiamylborane reacts with an alkyne in the usual way, with the R2B group adding to the less sterically hindered C atom. - with the bulky R2B group attached to the alkene, a second addition of disiamylborane does not occur, so hydroboration stops at the alkene stage. - oxidation then produces an enol, which tautomerizes to the keto form.

dichlorocarbene

- chloroform (CHCl3) is another precursor that can be used to generate a carbene. - the carbene that is generated from chloroform must be dichloromethylene (Cl2C:), also called dichlorocarbene, which is different from the Cl2C generated from diazomethane.

electrophilic addition via a three-membered ring

- if the electrophilic atom on the electrophile has a lone pair of electrons, then addition can take place in a way that avoids losing an octet. - two new E-C bonds are formed simultaneously to produce a three-membered ring.

ketones from alkynes

- internal alkynes can also be converted to ketones - a mixture of isomeric ketones will be produced > hydration of an internal alkyne leads to a mixture of isomeric ketones

addition of Br2 to alkynes

- oct-1-yne reacts with one equivalent of Br2 to yield 1,2-dibromooct-1-ene. - a mixture of both E and Z isomers is formed. - reaction with excess Br2 yields the tetrabromide.

oxymercuration-reduction: addition of water

- recall that H2O can add across a C=C double bond in the presence of a strong Bronsted acid catalyst. - an alternate method to add water across a double bond is oxymercuration-reduction (also called oxymercuration-demercuration). - water undergoes markovnikov addition across the C=C bond with no rearrangement. - the alkene is first treated with mercury(II) acetate, Hg(OAc)2, in a water-tetrahydrofuran (THF) solution,and that is followed by a reduction with sodium borohydride. > the product of oxymercuration-reduction is the one expected from markovnikov's rule--that is, the OH group forms a bond to the carbon atom that can better stabilize a positive charge. > no rearrangement takes place with oxymercuration-reduction.

alkynes and oxymercuration-reduction continued...

- reduction with NaBH4 is not required to remove the mercury(II) substituent. - the mercurinium ion intermediate opens to produce a mercuric enol, which tautomerizes to a mercuric ketone. this is then hydrolyzed by water to produce the enol.

halohydrins and regioselectivity

- regiochemistry becomes an issue with halohydrin formation if the alkene reactant is unsymmetrical. - with distinct alkene carbon atoms, two possible constitutional isomers can be produced.

epoxide formation using peroxyacids continued...

- synthesizing epoxides in this way is advantageous because the reaction conditions are relatively mild and many alkenes and common or easily synthesized - the mechanism takes place in a single step, (i.e., concerted). - the stereochemistry is conserved in this reaction.

oxymercuration-reduction, markovnikov's rule, and rearrangements

- the addition of H2O follows Markovnikov's rule, because the C atom that is attacked by water in step 2 is on the side of the ring that can accommodate more of the positive charge that appears on the Hg atom. . in oxymercuration-reduction, no carbocation intermediate is ever formed, therefore no carbocation rearrangements occur.

oxymercuration-reduction mechanistic steps

- the first three steps of the mechanism are identical to those in the formation of a halohydrin. - in step 1, the Hg atom is electron poor, given that it is bonded to two highly electronegative O atoms. - Hg is attacked by the electron rich double bond, and simultaneously a lone pair of electrons on Hg forms a bond to C to produce the three-membered ring. - the result is a mercurinium ion intermediate. - in step 2 of the mechanism, H2O acts as a nucleophile to open the three-membered ring, and in step 3, the positively charged O atom is deprotonated. - reduction with sodium borohydride (NaBH4) replaces the Hg-containing substituent with H.

mechanism for the addition of Br2: the bromonium ion intermediate

- the mechanism must not proceed through a carbocation intermediate. otherwise, both syn and anti addition would take place. - the mechanism proceeds through a bromonium ion intermediate.

synthesis of 1,2-dihalides [ why is this video 15 minutes long? no <3 ]

- when cyclohexene is treated with molecular bromine (Br2) in tetrachloromethane (CCl4), a racemic mixture of trans-1,2-dibromocyclohexane is produced.

stereochemistry is conserved in such reactions because both C-E bonds are formed simultaneously

> The cis/trans relationship is conserved for the groups attached to the alkene carbons in Equation 12-2. Groups that are on the same side of the double bond in the reactant must end up on the same side of the plane of the three-membered ring in the product (and vice versa). > if the cyclic product in Equation 12-2 is chiral, then a mixture of stereo-isomers is produced--a racemic mixture of enantiomers if the original alkene and other reagents are achiral, or an unequal mixture of diastereomers if otherwise.

hydroboration: regioselectivity and stereoselectivity.

addition of OH is favored at the alkene C atom that can least stabilize a positive charge. - hydroboration-oxidation adds H and OH to an alkene with anti-markovnikov regiochemistry. - in hydrboration-oxidation, an alkene undergoes syn addition of H and OH

oxidation of the trialkylborane

after an alkene has undergone hydroboration, treatment with a basic solution of H2O2 produces the alcohol. > each C-B bond is replaced by a C-OH bond. > three equivalents of the alcohol are produced.

epoxide formation using peroxyacids

an epoxide can be produced from an alkeneusing a peroxyacid (RCO3H), also called a peracid, such as meta-chloroperbenzoic acid, MCPBA.

diazomethane mechanism

diazomethane is explosive and requires extreme caution in the laboratory

cyclopropanes from diazomethane

diazomethane, CH2N2, is one precursor from which a carbene can be made.

halohydrin formation mechanism

even though Br- is present, H2O is the dominant nucleophile because, being the solvent, H2O is so much more abundant.

syn and anti addition

even though oxymercuration takes place with anti addition, any stereochemistry set up by oxymercuration is scrambled during the reduction step, giving a mixture of both syn and anti addition of water. > reduction with NaBH4 scrambles the stereochemistry.

hex-1-yne hydroboration-oxidation example

hex-1-yne with disiamylborane for hydroboration.

alkynes and oxymercuration-reduction

hydration of an alkyne leads to an initial enol, which tautomerizes into the more stable keto form. - alkynes can also undergo markovnikov addition of water via oxymercuration. - an unstable enol is produced initially, so subsequent tautomerization converts the enol into the more stable keto form.

hydrboration: BH3

hydroboration is a very useful reaction because it is the starting point for a variety of overall reactions. - borane (BH3) is the reactive species in the hydroboration of an alkene. - borane is highly unstable, however, because the central B atom does not have an octet. - BH3 cannot be isolated; instead in its pure form it exists as a gaseous dimer, diborane (B2H6), in which each of two H atoms constitutes a bridge between the B atoms. - those H atoms are involved in what are called three-center, two-electron bonds.

regioselectivity of hydroboration

hydroboration is also regioselective. - the H atom primarily adds to the C with the greater number of alkyl groups, whereas the BH2 group adds to the C with the fewer number of alkyl groups. > when BH3 adds to an alkene, steric repulsion directs the larger group, BH2, to the carbon atom with the fewer number of alkyl groups. (imagine steric strain, bulky atoms, etc. Bh2 is larger and therefore goes where it's less crowded.)

hydroboration-oxidation reaction

hydroboration-oxidation provides a third reaction in which there is a net addition of water across a nonpolar pi bond. - the alkene first undergoes hydroboration, in which borane, BH3 (from either BH3•THF or B2H6), adds across the double bond. - the product is then oxidized with a basic solution of hydrogen peroxide H2O2.

another halohydrin example

in the formation of a halohydrin from an alkene, the OH group and the halogen atom add anti to each other.

production of a trialkylborane

in turn, the dialkylborane product adds across yet another equivalent of the unreacted alkene to produce a trialkylborane, R3B.

MCPBA mechanism

meta-chloroperbenzoic acid the O-O single bond is very easy to break so it doesn't take much energy to break; if you can form stronger bonds it makes the reaction have a net gain of stability.

oxidation mechanism

oxidation of a trialkylborane in basic solution of hydrogen peroxide three rounds of coordination and 1,2-alkyl shift turn trialkylborane into a borate ester, then coordination, heterolysis, and proton transfer (3x each in order to form 3 equivalents of the syn-addition of water in an anti-markovnikov fashion across a double bond, the mono-alkyl alcohol)

cis-trans stereochemistry

stereochemistry is conserved because both C-E bonds are formed simultaneously.

production of a dialkylborane

that alkylborane can therefore react with an additional unreacted alkene. - that is, RHB-H adds across the double bond of the alkene to produce dialkylborane, R2B-H.

hydroboration-oxidation of alkynes

the addition of BH3 to an alkyne takes place in much the same way as it does to an alkene, with BH2 adding to the less sterically hindered carbon and H adding to the more sterically hindered one. - an alkene is produced, which itself can undergo hydroboration. - as a result, such a reaction would lead to a mixture of products, making it a fairly useless reaction.

dichlorocarbene mechanism

the carbene (Cl2C:) and the alkene react to produce the cyclopropane ring

partial hydroboration mechanism

the mechanism is driven primarily by the flow of electrons from the electron-rich pi bond to the electron-poor boron atom of BH3. > in the transition state, a partial positive charge is better stabilized on this C atom because it is more highly alkyl substituted. > H and BH2 add to the double bond in a syn fashion.

oxymercuration-reduction mechanism

the mercurinium ion intermediate is analagousto the bromonium (or chloronium) ion intermediate. > the side of the ring bears the larger positive charge > sodium borohydride reduces the C atom, replacing the Hg group with an H atom.

production of an alkylborane

the product of hydroboration is an alkylborane, R-BH2, which has two B-H bonds remaining.

more halohydrins and regioselectivity

the specific isomer that is formed is dictated by step 2 of the mechanism

mechanism explained

this reaction avoids the formation of a highly unstable carbocation by simultaneously forming a bond back to the second C atom of the double bond. - in hydroboration the bond comes from electrons originally part of a B-H bond in BH3. - overall, then, two bonds are broken and two bonds are formed in a concerted fashion--that is, without the formation of intermediates. > hydroboration is stereospecific, with the H and BH2 groups adding to the alkene in a syn fashion.