Reactants and Products for Synthesis

started from chapter 7, all the way to 11

S_N2

use nucleophile and 1^o or 2^o alkyl halide

form alkane with nucleophile attached, and X^-

better in polar aprotic solvent

remember to invert stereocenter; back-side attack

E2

use 3^o or 2^o alkyl halide and strong base

form alkene and halogen

remember Zaitsev and Hofmann (Zaitsev for non-bulky base, Hofmann for bulky base)

trans usually favored over cis

remember anti-periplanar arrangement of leaving group and hydrogen

S_N1

use 3^o alkyl halide and solvent acting as weak nucleophile

form alkane with nucleophile, and X^-

remember methyl and hydride shifts

better in polar protic solvent

produces a mix of products; not very useful for synthesis

E1

use alkyl halide and solvent acting as a weak base

form alkane with nucleophile and conjugate acid

produces a mix of products; not very useful for synthesis

always Zaitsev over Hofmann, usually trans and E over Z

hydrohalogenation of alkenes

use alkene and HX

form alkane

if alkene is asymmetrical, H usually goes to the C with more Hs already there

Markovnikov: X goes to the more substituted C

anti-Markovnikov: X goes to the less substituted C. Occurs when ROOR is added

if 1 new chiral center is formed, 2 enantiomers are formed, racemic

acid-catalyzed hydration of alkenes

use alkene and H₃O⁺ (may have H₂SO₄ listed as a reagent)

form alkane with H and OH attached

usually Markovnikov

racemic mixture of enantiomers is expected

oxymercuration-demurcuration

use alkene and mercuric acetate, Nu-H, and NaBH₄

form alkane with nucleophile and H

nucleophile goes to the more substituted C, H goes to the less substituted C (more Hs attached)

hydroboration-oxidation of alkenes

use alkene and borane

form anti-Markovnikov with added H2O

OH goes to less substituted position

syn addition, not anti

catalytic hydrogenation of alkenes

use alkene and H₂(g) with metal catalyst (Ni, Pd, Pt)

form alkane

if 0 chiral centers are formed, only 1 product

is 1 chiral center is formed, enantiomers formed

if 2 chiral centers are formed, syn

halogenation of alkenes

use alkene and Br₂ or Cl₂

form alkane with 2 halogen groups

anti addition across a cis alkene → enantiomers

anti addition across a trans alkene → meso compound

halohydrin formation for alkenes

use alkene and halogen (Br2 or Cl2)

form alkane with 1 halogen and OH, + enantiomer

usually OH goes to the more substituted position

anti dihydroxylation for alkenes

use alkene and peroxy acid (RCO₃H)

turns into epoxide, then into diol (2 OHs)

OHs are anti, on opposite sides of the alkane

syn dihydroxylation for alkenes

use alkene and osmium tetroxide (OsO₄)

form diol

osmium tetroxide acts concerted

oxidative cleavage (ozonolysis) of alkenes

use alkene and ozone with DMS

break C=C bond, form 2 C=O bonds

other parts of the molecule aside from the double bond remain as they were

no issues with stereochemistry or regiochemistry

substitution (in general)

turn one group into another

elimination (in general)

turn alkyl halide into alkene

addition (in general)

take alkene, add two groups across the double bond and turn it into an alkane

how to change the position of a group

elimination, then addition

how to change the position of a pi bond

addition, then elimination

how to form an acetylide ion

treat acetylene with a strong base, e.g. NaNH₂

how to form an alkynide ion

treat a terminal alkyne with a very strong base, e.g. NaNH₂

catalytic hydrogenation of alkynes

use alkyne and 2 equivalents of H₂

form trans alkane, unless poisoned (e.g. by Lindlar’s catalyst or Ni₂B), then cis alkene

syn addition

dissolving metal reduction

use internal alkyne and sodium metal dissolved in liquid NH₃ at low temperature

form trans alkene

cannot reduce a terminal alkyne

how to produce an alkane

use an alkyne with H₂ with Ni, Pd, or Pt as a catalyst (no poison)

how to produce a cis alkene

use alkyne with H₂(g) with Lindlar’s catalyst or Ni₂B

how to produce a trans alkene

use an internal alkyne with Na(s) in NH₃(l)

hydrohalogenation of alkynes

use alkyne + HX, form Markovnikov alkene

use alkyne + excess HX, form geminal dihalide (2 addition reactions)

radical hydrohalogenation

use terminal alkyne, HBr, and peroxide

form anti-Markovnikov alkene, mixture of 2 different shapes

how to make an alkyne

use a dihalide with excess HX

how to form a dihalide

use an alkyne with excess NaNH₂ in NH₃, then H₂O

acid-catalyzed hydration of alkynes

use alkyne and H₂SO₄ and H₂O (faster if catalyzed in HgSO₄)

form enol, which tautomerizes into ketone

hydroboration-oxidation of alkynes

use terminal alkyne and BH₃ and THF, then H2O2 and NaOH

form enol, which tautomerizes into aldehyde

anti-Markovnikov

halogenation of alkynes

use internal alkyne and excess X₂ in CCl₄

form tetrahalide (alkane)

use internal alkyne and 1 equivalent of X₂

form E (major) and Z (minor) alkenes

ozonolysis of alkynes

use alkyne and O₃ and H₂O

oxidative cleavage

form 2 carboxylic acids

if a terminal alkyne is used, the terminal C becomes CO₂

alkylation

use a terminal alkyne and alkyl halide

deprotonate alkyne with strong base

treat with alkyl halide (S_N2), attach alkyl group to alkyne

only works with methyl and 1^o alkyl halides

how to go from an alkyne to an alkene

start with alkyne

use H₂ with Lindlar’s catalyst, or use Na(s) dissolved in NH₃(l)

how to go from an alkyne to an alkane

start with alkyne

use H₂(g) in metal catalyst, proton transfer

how to go from an alkene to an alkane

start with alkene

use H2(g) in metal catalyst, proton transfer

how to go from an alkene to an alkane

start with alkene

bromination (Br₂ in CCl₄), then elimination (first excess NaNH₂, then H₂O)