Chem 232 Lecture 12

Home , Borane

CHEM 232 University of Illinois Organic Chemistry I at Chicago UIC

Lecture 12 Organic Chemistry 1

Professor Duncan Wardrop February 18, 2010

1 Self Test Question

Which of the following reactions proceeds through a carbocation intermediate? HCl A HO

HBr Br Br B Br H Br H peroxides

Br CH3ONa

H Br C CH3OH Br Br Br + Br

HBr Br D E H2, Pd/C

University of Slide CHEM 232, Spring 2010 2 Illinois at Chicago UIC Lecture 12: February 18 2 CHEM 232 University of Illinois Organic Chemistry I at Chicago UIC

Hydroboration–Oxidation

Section 6.12-6.14

3 Addition of B-H Bonds to Alkenes

addition C C + X Y X C C Y

hydroboration C C + H BH2 H C C BH2

alkene borane alkyl borane

oxidation oxidation is a separate step and requires a separate set of conditions and reagents H C C OH

alcohol University of Illinois Slide 4 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 4 Boranes - Structure & Electronics

• boron is exception to octet rule • sp2-hybridized (only 3 valence e-s) H B H • contains an empty p-orbital H • strong Lewis acid (electron pair acceptor) • forms 3-bonds (neutral) & 4-bonds (-/ve)

“Free” borane (BH3) only exists in gas phase, otherwise undergoes dimerization to diborane (B2H6) dimerization

2 x BH3 B2H6

borane diborane

University of Illinois Slide 5 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 5 Conditions: Hydroboration

“Free” borane (BH3) only exists in gas phase, otherwise undergoes dimerization to diborane (B2H6)

H H dimerization H H H B + B B B H H H H H H H

borane diborane

University of Illinois Slide 6 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 6 Conditions: Hydroboration

“Free” borane (BH3) only exists in gas phase, otherwise undergoes dimerization to diborane (B2H6)

H H H dimerization B B H H H

borane diborane University of Illinois Slide 7 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 7 Stoichiometry of Hydroboration

B2H6 2 x 6 x B diglyme

1-butene tributylborane

• diglyme is a common solvent H C O CH 3 O O 3 • hydroborations typically at room temp. diglyme: diethylene glycol dimethyl ether • generally very fast reactions

University of Illinois Slide 8 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 8 Borane is a Lewis Acid & Reducing Agent!

Other hydroborating reagents with different reactivities may be prepared by adding Lewis bases to diborane (B2H6)

O H3B O B2H6 + diborane tetrahydrofuran (THF) H3B•THF

CH3 S H3B S B2H6 + H3C CH3 diborane CH3 dimethyl sulfide (DMS) H3B•DMS

N B H H3B N(CH2CH3)3 2 6 + diborane }

triethylamine (TEA) H3B•TEA Lewis Complexes Acid-Base

University of Illinois Slide 9 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 9 Oxidation Step

H H

hydroboration BH2 oxidation OH

B H 2 6 H2O2 diglyme NaOH (aq)

carried out in the same reaction vessel (boranes are reactive)

oxidation using I will not ask you to boron is replaced by • • • peroxide (H O ) & learn the mechanism more electronegative 2 2 hydroxide (OH–); added for this step; for the atom (O); therefore: immediately after curious, see textbook oxidation hydroboration page 250

University of Illinois Slide 10 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 10 Hydroboration-Oxidation is Regioselective

1. B2H6, diglyme OH • usually written as a two-

2. H2O2, NaOH step process

• works with diborane (B2H6) OH or a borane complex with CH CH 3 1. H3B•S(CH3)2 3 another Lewis base

2. H2O2, NaOH • diglyme is a common solvent • aﬀords alcohol products; 1. H3B•THF similar to hydration (H2O/ + 2. H2O2, NaOH H3O ) OH

University of Illinois Slide 11 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 11 Which carbon of the alkene becomes bonded to the -OH group? Do you see a pattern here? Regioselectivity Determined During Hydroboration

– O H3B•THF O BH2 H2O2/OH O OH

compare to . . .

OSO3H OH O O H2SO4 H2O/heat O

• boron atom is added to least substituted carbon atom, hydrogen atom is added to most substituted • after oxidation, gives the least substituted product • opposite regioselectivity of Markovnikov addition

University of Illinois Slide 12 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 12 Mechanism of Hydroboration

H2B H CH3 CH3 H2B H CH3 H2B CH3

Why this regioselectivity? not H2B CH3 • Syn Addition: B and H atoms add to same side (face) of C-C double bond at same time • hydride (H:) adds to most substituted carbon • boron adds to least substituted carbon • this is NOT a PROTONATION

University of Illinois Slide 13 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 13 Note that although the borane generated upon monohydroboration of methylcyclopentene is itself trans-substituted, the hydroboration remains a syn-addition. In other words, it is the BH2 group and beta-hydrogen on the carbon bearing the methyl group which are in a syn relationship. Regioselectivity - 1st Rationale

Steric Eﬀects Control Regioselectivity. . . boron is larger than hydrogen; it prefers to add to the less sterically hindered side of the double bond, which is the least substituted side.

H H B H H B H H H H BH2 H2B H CH C H 3 CH CH3 X H 3

Steric strain in transition state raises Eact for this pathway - slower reaction

University of Illinois Slide 14 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 14 Regioselectivity - 2nd Rationale

Electronic Eﬀects Control Regioselectivity. . . both carbons in alkene develop partial positive charge in transition state; more substituted = more partially positively charged = hydride (H:) transfer preferred (faster) to that carbon atom. Lewis acid

Lewis base

π-complex π-complex rearranged π-complex most substituted = most partially positively charged = most electrophilic carbon atom = want electrons from a nucleophile most

University of Illinois Slide 15 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 15 Self Test Question

What is the product of the following reaction sequence? HO A.

1. Br2, CH2Cl2, hv B. 2. NaOC(CH3)2, DMSO ? HO 3. B2H6, diglyme 4. H2O2, NaOH (aq) C.

D. HO

Br E. HO

University of Slide CHEM 232, Spring 2010 Illinois at Chicago UIC Lecture 12: February 18 16 CHEM 232 University of Illinois Organic Chemistry I at Chicago UIC

Halide Addition to Alkenes

Section 6.15-6.18

17 Alkene-Halogen Addition

addition C C + X Y X C C Y

halide C C + Br Br addition Br C C Br

vicinal dibromide halide addition C C + Cl Cl Cl C C Cl

vicinal dichloride halide C C + I I addition I C C I

vicinal diiodide

University of Illinois Slide 18 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 18 Typical Reaction Conditions for Halogen Addition

• only bromine (Br2) and chlorine (Cl2) undergo this reaction

• typically use a halogenated solvent like chloroform (CHCl3) • low temperature (0 ºC) • no light (avoid radical halogenation at saturated carbons)

University of Illinois Slide 19 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 19 Halogenation is Stereospeci!c

• anti addition of Br2 or Cl2 across double bonds • two halogen atoms are trans to each other in rings

University of Illinois Slide 20 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 20 Stereospeci"c Reactions?

stereospeciﬁcity is the property of a reaction mechanism that leads to different stereoisomeric reaction products from different stereoisomeric reactants, or which operates on only one (or a subset) of the stereoisomers

University of Illinois Slide 21 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 21 Stereospeci"c Reactions

Stereospeci"c In stereospeci"c reactions, the con"guration of the product is directly related to the con"guration of the reactant and is determined by the reaction mechanism. Stereoisomeric reactants will give diﬀerent, stereoisomeric products.

CHEM 232 Deﬁnition, 2009

Br Br2 Me Me Me Me CHCl stereoisomeric different 3 Br geometrical products resulting Br from anti-halide isomers Br 2 Me addition Me Me Me CHCl3 Br

University of Illinois Slide 22 CHEM 232, Spring 2010 at Chicago UIC Lecture 10: February 11 22 Halogen Addition Does Not Involve Syn Addition

• concerted process would require syn addition of two halogen atoms • therefore mechanism is not concerted.

University of Illinois Slide 23 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 23 Halogen Addition Does Not Involve Free Carbocations

H CH2Br H

• carbocation intermediate are planar (#at) • addition of second halide could approach either lobe of empty p-orbital on carbocation • therefore this mechanism is not possible because it would not be stereoselective

University of Illinois Slide 24 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 24 Halogen Addition Does Involve Halonium Ions

H C 3 Br Br Br H3C Br H Br H H3C H H3C H H3C H H3C H Br Br Br H3C H H3C H

• electron pair in π-bond form new bond to bromine atom as Br-Br bond breaks • lone pair of electrons on bromine form new bond to alkene carbon losing a bond at the same time (concerted) • halonium ions (three-membered rings with one halogen) are intermediates; no carbocation intermediates

University of Illinois Slide 25 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 25 Anti Addition

.... –– :: BrBr :: ...... BrBr ...... :: BrBr :: ....

attack of bromide (Br–) from opposite side C-Br bond that .... is breaking gives anti product ::

University of Illinois Slide 26 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 26 Hyperconjugation (σC-H→πC=C) Increases Rate of Halogenation

alkene relative rate (krel) H H H σ➞∏ 1 H H

donation H3C H 61 C H H

C C H H3C H H 5400 H3C H

H3C CH3 920,000 H3C CH3

• more alkyl groups attached to double bond ➡ • more σ➞π orbital donation/overlap ➡ • double bond has more electron density ➡ • double bond is a stronger nucleophile (Lewis base) ➡ • reacts faster with electrophiles like Br-Br

University of Illinois Slide 27 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 27 Halogen Addition Modi"cation: Aqueous Solutions Give Halohydrins

bromohydrin

• if the solvent for the reaction is changed to water, halohydrins are formed • since water is much more concentrated, it will add to halonium ion intermediate faster than the halide

University of Illinois Slide 28 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 28 Ring Opening of Halonium Ions is Regioselective

H C 3 Br H C Br Br 3 Br Br H C H 3 Br HO H H3C OH H3C H H 2 H C H OH H O H3C H 3 H C H 2 H 3 H H Br

H3C H H3C H

• product is most substituted alcohol; least substituted halide • most substituted carbon is most partially positively charged in transition state = strongest electrophile = water most attracted to that carbon

University of Illinois Slide 29 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 29 CHEM 232 University of Illinois Organic Chemistry I at Chicago UIC

Epoxidation & Ozonolysis

Sections 6.19 We will skip epoxide nomenclature for now.

30 Expoxides (a.k.a Alkene oxides)

• three-membered rings containing an oxygen atom • common intermediates in organic synthesis

University of Illinois Slide 31 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 31 Epoxides are Prepared via Alkene Epoxidation

O O O H3C OH H3C O H acetic acid peroxyacetic acid

• peroxyacids are source of electrophilic oxygen atoms • addition of a single oxygen atom across double bond • similar to formation of bromonium ion intermediate • don’t worry about mechanism; for curious see textbook page 257

University of Illinois Slide 32 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 32 Examples

• any peroxyacid will work • more substituted double bonds react faster • because only adding one atom across double bond, must be syn addition

University of Illinois Slide 33 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 33 Alkenes are Cleaved via Ozonolysis

ozone

O O O O syn O R1 R3 addition O O O reduction 1 2 C C R R 1 3 3 R R R1 C C R 4 R2 O O R O C C R2 R4 2 R R4 R2 R3 Alkene Primary (1°) Secondary (2°) Carbonyl ozonide ozonide compounds • ozone adds across double bonds to give ozonides • ozonides react further with reducing agents to provide carbonyl compounds • we will not discuss mechanism for this reaction

University of Illinois Slide 34 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 34 Ozonolyis is a Two Step Process

reducing agents; reduce ozonide intermediate

pattern = alkene is cut in half and replaced by an oxygen atom at each end carbonyl product depends on substitution of alkene

University of Illinois Slide 35 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 35 CHEM 232 University of Illinois Organic Chemistry I at Chicago UIC

Organic Synthesis

Section 6.21 We will not cover section 6.22.

36 Retrosynthetic Analysis

How could you prepare 1-methylcyclohexene from methylcyclohexane? ? CH3 CH3

Step One: Devise a retrosynthesis. Work backwards from the target molecule. Each step backward you should ask, How can I prepare the target functional group.

CH3 CH3 CH3 Br

dehydrohalogenation radical bromination

University of Illinois Slide 37 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 37 Synthetic Route

How could you prepare 1-methylcyclohexene from methylcyclohexane? ? CH3 CH3

Step One: Write the synthesis out in the forward direction including all necessary reagents and conditions.

CH3 CH CH3 Br2, CHCl3 3 NaOCH2CH3 Br light, 60 ºC DMSO, 55 ºC

University of Illinois Slide 38 CHEM 232, Spring 2010 at Chicago UIC Lecture 12: February 18 38 Self Test Question

Which retrosynthetic analysis is correct for the synthesis of 2-bromocyclopentanol?

OH OH Br Br A.

Br2, CHCl3 OH Br Br light, 60 ºC B. Br OH NaOCH CH Br Br 2 3 2 OH OH Br DMSO, 55 ºC H2O/THF C.

OH OH Br D.

University of Slide CHEM 232, Spring 2010 39 Illinois at Chicago UIC Lecture 12: February 18 39 Self Test Question

Devise a retrosynthesis for the synthetic target below.

HCl Cl A. Cl ? B. Cl Cl

1. B2H6, diglyme 2. H2O2, NaOH SOCl C. 2 Cl OH K2CO3

OH O D. Cl

University of Slide CHEM 232, Spring 2010 40 Illinois at Chicago UIC Lecture 12: February 18 40 Self Test Question

What is the product of the following series of reactions?

A. O O

1. Pt/C, H2(g), CH3CH2OH OH OSO H 2. H2SO4 (conc.) B. 3 3. H2O, heat 4. peroxyacetic acid O

C. OH

OSO3H D. O

University of Slide CHEM 232, Spring 2010 41 Illinois at Chicago UIC Lecture 12: February 18 41 Self Test Question

Which starting material could be used to prepare the molecule below? Write out your synthesis. Don’t guess.

O A. D. H H O B. E. Br O O C. H H

University of Slide CHEM 232, Spring 2010 42 Illinois at Chicago UIC Lecture 12: February 18 42 CHEM 232 University of Illinois Organic Chemistry I at Chicago UIC

Next Lecture. . .

Chapter 13: Sections 13.1-13.2 & 13.20-13.22

43 Quiz & Exam Averages

Quiz 1 = 61% Quiz 2 = 61% Quiz 3 = 50% Quiz 4 = 50%

Midterm Exam = 51%

University of Slide CHEM 232, Spring 2010 44 Illinois at Chicago UIC Lecture 12: February 18 44