Title: ETH_Sem4 / OCII / OCII Concepts & things to know

Front: DEAD
Back: - Used as H acceptor and activator of PPh3 in Mitsunobu reaction
- Has high lying LUMO, so acts as dienophile

Front: DIAD
Back: - Used as H acceptor and activator of PPh3 in Mitsunobu reaction
- Has high lying LUMO, so acts as dienophile

Front: DCC
Back: - Coupling reagent, activates carboxylic acids to form good LG
- Also used in Moffatt oxidation

Front: DIC
Back: - Activates carboxylic acids towards substitution

Front: Electrocyclic ring opening general rules
Back: 4n electrons:
- Thermal -> conrotatory
- Photochemical -> disrotatory
4n + 2 electrons
- Thermal -> disrotatory
- Photochemical -> conrotatory

Front: Sigmatropic rearrangement nomenclature
Back: [m,n]
m and n are the number of atoms between the two fragments  at which the bonds break

Front: DPPA
Back: - N3 donor for mitsunobu reaction

Front: DCE/ EDC
Back: - Chlorinated solvent

Front: CDI
Back: - Used to activate carboxylic acids (Imidazole replaces OH)

Front: How can carboxylic acids be activated?

Back: - Diels Alder
- Ring-closing metathesis/ Olefin metathesis

Back: Favorksii

Back: Henry reaction, then reduction

Back: HWE/ Wittig with stabilized ylid

Back: Still-Gennari modification

Back: Hunsdiecker or Appel

Back: Knoevenagel.
Base often amine

Back: Mannich

Back: Michael addition, eg. Rauhut Currier

Front: EDCI
Back: Used to activate carboxylic acids

Front: How to synthesize allylic alcohols?
Back: - Wharton reaction from alpha-beta epoxy ketone/aldehyde
- Selenoxide oxidation, ene reaction with SeO2 and allylic H

Front: PyBop
Back: Coupling reagent, to activate carboxylic acids

Front: Difference singlet vs triplet carbenes

Front: Generation of triplet carbenes

Front: Generation of singlet carbenes

Front: Reactivity of triplet carbenes

Front: Singlet carbene reactivity

Front: Generation of carbenes by alpha elimination
Back: E.g.:

Front: How to generate carbenes from diazo compounds

Front: C-H insertion using carbenoids

Front: Carbenoid generation

Front: N-H insertion using carbenes

Front: O-H insertion using carbenes

Front: Ylide formation using carbenes

Front: In which direction does transmetallation proceed?
Back: - R group is transferred from the more electropositive metal to the more electronegative one!
- E.g. from Li or Mg to Cu!

Front: Schlenk equilibrium

Front: Why should tBuLi never be used with THF?
Back: - TBuLi is basic enough to deprotonate THF!

Front: Why are ether solvents usually used for Li or Mg compounds?
Back: - Coordinate metal, so break up polymers -> making the metal more reactive

Front: TMEDA
Back: - Additive to break uop Organolithium or grignard clusters into monomers

Front: Reactivity of R-Li reagents
Back: - Proportional to pKa of "protonated species"
- tBuLi e.g. most reactive,
also in general sp less reactive, sp2 more and sp3 least

Front: Synthesis of organolithium reagents
Back: - Through oxidative insertion into C-X bond
- Through metal-halogen exchange and transmetallation, esp. if sp2 nucleophiles are needed

Front: Synthesis of Grignard reagents
Back: - Oxidative addition of Mg(0) into C-X bond to form Mg(II)
- Proceeds via radical mechanism

Front: Metal-halogen exchange
Back: - R-Li bonds transmetallate to form more stable R-Li bonds
- Direction of exchange depends on stability of theoretical carbanion
- Also with Grignards

Front: Turbo Grignard
Back: - Very reactive combination of Grignard and LiCl.
- LiCl breaks uo Grignard aggregates and makes it more reactive.

Front: Directed ortho-lithiation
Back: - Aromatic C-H bonds can be deprotonated by R-Li, such as BuLi. -> rules according to aromatic substitution?
-  Using NON-DEPTROTONATABLE directing group, such as ethers or tertiary amines/amides, only ortholithiation due to complexation

Front: Synthesis of organocuprates
Back: Synthesized through transmetallation from organolithium or grignards

Front: Reactivity of organocuprates
Back: - Soft nucleophiles! Do Sn2 reactions and 1,4 conjugate additions instead of 1,2

Front: Structure of organocuprate
Back: R: group to be transferred
CN: dummy ligand, which isn't transferred ( so only 1 eq of R is used)

Front: Why can sp3 carbons not be cross-coupled?
Back: Transmetallation is slower than beta-hydride elimination, so alkene is eliminated before it can be coupled (Pd takes H from beta-carbon, releasing alkene)

Front: Which cross-coupling uses Mg?
Back: Kumada

Front: Which cross-coupling uses organozinc compounds?
Back: Negishi

Front: Which cross-coupling uses organostannanes?
Back: Stille

Front: Which cross-coupling uses boranes?
Back: Suzuki

Front: Which cross-coupling uses organosilicon?
Back: Hiyama

Front: What extra step is required in the Suzuki coupling?
Back: Activation of borane to boric acid, so it's no longer electrophilic -> Is done with a base

Front: How are organostannanes for Stille and organoboric acids for Suzuki couplings generally synthesized?
Back: - From organolithiums, formed from organobromides

Front: SPhos
Back: - Ligand for Pd cat. reactions, phosphine derivative

Front: Why do silanes need to be activated for cross-coupling?
Back: Organosilanes transmetallate fairly slowly, so are activated using Fluoride ions to form silicates that transmetallate fast.
- TBAF and CsF may be used for this.
Alternatively, organosilicates can be added to the reaction as they are, instead of in situ activation

Front: Side reaction of Suzuki Cross-coupling
Back: Protodeborylation of Boric acid, to form B(OH)3.

Front: HBpin
Back: Boron reagent.
Reacts with alkynes and alkenes, esp. under transition metal catalysis

Front: Regioselectivity of Heck reaction
Back: R group generally terminal, since EWG stabilizes "carbanion" from Pd
- Unless strongly EDG

Front: Regioselectivity of intramolecular Heck
Back: - Exo product favoured for most rings (due strain), so for rings smaller than 13 Cs, exo product

Front: Beta-hydride elimination in Heck reaction
Back: - Syn elimination of Beta hydride.
- Depending on structure of double bond,cis or trans double bond results
- Terminal alkenes: Always E selective

Front: Schwartz reagent
Back: Used in Hydrozirconation

Front: How to form organoboron reagents for Suzuki?
Back: 5 Ways:
- Nucleophilic substitution of e.g. grignard to Boron reagent
- Miyaura Arylboronic cross coupling
- Hydroboration (antimarkovnikov)
- Transition metal catalyzed hydroboration
(markovnikov)
- Hydrozirconation then transmetallation with Boron

Front: How to form stannanes for Stille Cross-coupling
Back: - S\(_N\)2 of ClSnBu3 by Grignard or organolithium
- Stille Cross coupling of Sn-Sn reagents
- Hydrostannation using AiBN
- Transition metal catalyzed hydrostannation using Alkynes and Pd0
- Hydrozirconation and then cross-coupling with Sn

Front: Grubbs catalysts features:
Back: - d6 Ru(II) complexes
- Less reactive than W and Mo based analogues
- Better functional group tolerance

Back: From alpha,beta + beta/gamma unsat ether

Back: From allylic ester

Back: MISSING R GROUP

Front: How do substituents at conjugated systems affect the FMOs of the molecules?
Back: - Pi acceptor: Increases coefficient of LUMO, lowers HOMO
- Pi donor: Increases HOMO, decreases LUMO coefficient
-> At the atom where the charged resonance structure is!

Front: When are [2+2] cycloadditions allowed thermally?
Back: When the double bond is part of a ketene-like system, i.e. carries a second double bond on the same carbon!

Front: How to determine "direction" of electrocyclic ring opening
Back: - Look at the "target molecule" orbitals, i.e. the system that should be after the ring opening! Then, see which way the bond needs to open to get that HOMO