Organic 7

What is a chemoselective reaction?

one in which 1 fg reacts in preference to another

What is the regioselective reaction?

one that leads to selective formation of one structural isomer (regioisomer)

what is a stereoselective reaction

one in which one enantiomer, one diastereomer, or one double bond isomer is formed selectively over others.

what is a protecting group

converts a reactive fg into an unreactive form such that after desired transformation(s) the original fg can be regenerated

what is a common protecting groups for aldehydes and ketones?

acetals

what are common protecting groups for alcohols

Silyl ethers

what are common protecting groups for amines

Carbamates

what are common protecting groups for carboxylic acids

esters

what is the target molecule

the molecule to be synthesised

what is a retro synthetic arrow

an open-ended arrow used to indicate reverse of a synthetic reaction

what is fg interconversion

converting one fg into another by substitution, addition, elimination, reduction or oxidation

What are synthons?

idealised fragments resulting from a disconnection

what do you draw if a double bond/2 single bonds are broken

precursors

key disconnections?

1) disconnect rings from chains
2) disconnect at a branch point
3) disconnect to form 2 equal sized pieces

conditions for aromatic bromination

Br2/FeBr3

conditions for aromatic nitration

HNO3/H2SO4

conditions for adding SO3H to benzene

H2SO4/SO3

conditions for aromatic friedyl-crafts acylation

RCOCl/AlCl3

how do you form aryl grignargs (ArMgX)

react aryl halides (ArX, X=Cl,Br,I) w Mg in dry diethyl ether or tetrahydrofuran

why are aryl grignards useful

strong nucleophiles (much stronger than benzene) and react w range of electrophiles to form C-C bonds

what are stabilised ylides

ones where the substituent stabilises the adjacent neg. charge

what are unstabilised ylides

ones where the substituent cannot stabilise the adjacent neg charge

how do you prepare stabilised ylides

deprotonation of a phosphonium salt, Ph3P+EWG (EWG= elec withdrawing group) using a relatively weak base

what do stabilised ylides react with

aldehydes but generally unreactive w ketones

what alkenes do stabilised ylides form

they react w aldehydes to give mainly E alkenes

how are non-stabilised ylides prepared

deprotonation of a phosphonium salt, Ph3P+CH2EDG (EDG=elec donating gr) using a strong base

what do non-stabilised ylides react w

both ketones and aldehydes

what alkenes do unstabilised ylides form

give mainly z alkenes

how do you form E alkenes from ketones

\-stabilised ylides unreactive w ketones

* Horner-Wadsworth-Emmons reaction used
* uses deprotonated phosphonate ester (neg changed rather than neutral) so more reactivate to c=o
* MUST USE A STABILISED ONE

conditions to form E/Z alkenes from alkynes

E: Na/Nh3
Z: H2/Lindlars catalyst

what reaction type is the Heck reaction

a C-C bond forming reaction

what can the Heck reaction be used for

to form a disubstituted alkene from a terminal alkene and an aryl halide (ArX) or a vinyl halide (C=CX)

regioselectivity of the heck reaction

R group is introduced at the least hindered end of the C=C bond

stereoselectivity of heck reaction

the more stable E- alkene is formed

what attack are α,β-unsaturated carbonyls susceptible to

attack by nucleophiles at both the 2- and 4- positions

what is attack at the 2 position of a α,β-unsaturated carbonyl called

1,2-addition

what is attack at the 4 position of a α,β-unsaturated carbonyl called

1,4- addition or conjugate addition or Michael addition

examples of factors that affect whether the 2 or 4 position of an α,β-unsaturated carbonyl is attacked

steric effects, type of organometallic

where do grignards usually attack a α,β-unsaturated carbonyl

the C=O bond

what is addition to a α,β-unsaturated carbonyl at the 2 position described as being and why

under kinetic control as stronger C=O bond is broken and weaker C=C bond is retained

what is an example of something that attacks at 4 position of α,β-unsaturated carbonyl

Organocopper reagents (RCu) and cuprates (R2CuLi)

what is addition to a α,β-unsaturated carbonyl at the4 position described as being and why

under thermodynamic control as the stronger C=O bond is retained and the weaker C=C bond is broken (i.e. more stable product is formed)

What is a hard nucleophile?

high δ- density - small nucleophile, charge on highly electroneg atom

What is a soft nucleophile?

low δ- density - large delocalised nucleophile w charge spread out (eg. w resonance over to C=O groups) i

reactants/conditions needed for alkene to halogenoalkane

HX

reactants/conditions needed for terminal alkene to terminal alcohol

1) BH3
2) H2O2, HO-

reactants/conditions needed for terminal alkyne to aldehyde

1) BH3
2) H2O2, HO-

reactants/conditions needed for alkene to trans diol

1) RCO3H
2) H2O/H+ or H2O/HO-

reactants/conditions needed for alkene to cis-diol

KMnO4, HO-/H2O
low temp

reactants/conditions needed for ArNO2 to ArNH2

Sn, HCl

reactants/conditions needed for ArNH2 to ArNHCOR

RCOCL, base

reactants/conditions needed for ArSO3H to Ar

dilute H2SO4

hard nucleophile examples

OH-
Grignard

reactants/ conditions needed for ketone to tertiary alcohol

1)RLi or RMgBr
2) H+

reactants/ conditions needed for ketone to alkene

Ph3P=CHR

reactants/ conditions needed for ketone to diether

2 ROH
H+ (catalyst)

reactants/ conditions needed for aldehyde to enone (HCOCH=CHCH3)

2x aldehyde
OH- heat

precursors for witting

ketone and Ph3P=R

precursors for imine

ketone and primary amine

precursors for acetal

diol and ketone

precursors for epoxide

H2C=CHR (RCO3H used)

precursors for cis-diol

z alkene

common synthon for R+ (R=alkyl not aryl)

R-I, R-Br, R-OSO2Me (R-OMs) , R-OTs (add LH to C)

common synthon for RC+OH(R/H)

ketone or aldehyde

common synthon for RCHOHR+

epoxide

common synthon for RC+=O

carboxylic acid derivatives

common synthon for RC=OCH2CH2+

an alpha-beta unsaturated carbonyl RCH=OCH=CH2

common synthon for R-

R-MgX, R-Li, R2CuLi

common synthon for Ar-

ArH, Ar-MgX, Ar-Li, Ar2CuLi

common synthon for RC=OCH2-

RCH=OCH3 + base

common synthon for ROC=OCH3-

ROC=OCH3 + base

reactants/conditions needed for FGI: secondary alcohol to ketone

CrO3, H+

reactants/conditions needed for FGI: primary alcohol to aldehyde

CrO3, H+, distillation

or milder oxidising agent e.g. PCC

reactants/conditions needed for FGI: primary alcohol to carboxylic acid

CrO3, H+

reactants/conditions needed for FGI: terminal alkene to epoxide

RCO3H (Peracid)

reactants/conditions needed for FGI: terminal alkene to cis diol

aq OsO4

reactants/conditions needed for FGI: ketone to secondary alcohol

NaBH4/LiAlH4 then H+

reactants/conditions needed for FGI: carboxylic acid to primary alcohol

LiAlH4 then H+

reactants/conditions needed for FGI: imine to secondary amine

NaBH4 then H+

reactants/conditions needed for FGI: ArNO2 to ArNH2

Sn, HCl

reactants/conditions needed for FGI: alkyne to z-alkene

H2, Lindlars catalyst

reactants/conditions needed for FGI: alkene to alkane

H2, Pd/C

reactants/conditions needed for FGI: secondary alcohol to secondary halogenoalkane

PX3

reactants/conditions needed for FGI: carboxylic acid to acyl chloride

SOCl2

reactants/conditions needed for FGI: acyl chloride to amide

RNH2, base

reactants/conditions needed for FGI: carboxylic acid to ester

ROH, H+

reactants/conditions needed for FGI: halogenoalkane to alkene

base e.g. tBuO-

reactants/conditions needed for FGI: alkene to halogenoalkane

HX

reactants/conditions needed for FGI: ArNH2 to ArOH

NaNO2, HCl then H2O heat

examples of small molecule RASM (that may not be listed in a q)

CO2, MeBr, MeCOCl, MeCO2H ...

what reagents are needed in the forward steps of a Heck reaction

Pd(0) catalyst, base

alkene + HBr, ROOR/heat =

anti-markovnikov addition- Br adds to least substituted end of C=C

what is a carbamate, how do you turn an amine into one and how do you deprotect at the end?

RNHCOOR

react amine w e.g. BOC (tertbutoxy carbonyl)

to deprotect react w TFA (acid)

reactants/conditions needed for dialkyl ether to carboxylic acid

H2O

reactants/conditions needed for dialkyl ether to ester

react w ROH then remove RCO2H

reactants/conditions needed for R-C(tb)N to amide

H2O, H+

reactants/conditions needed for ester to amide

NH3

reactants/conditions needed for ester to tertiary alcohol

2 RMgX then H+

reactants/conditions needed for acyl chloride to amide

NH3

acetal to alcohol

H+, H2O