Title: ETH_Sem5 / OCIII

Q: H - H eclipsing interaction energetic cost:
A: + 4.2 kJ/mol

Q: H - Me eclipsing interaction energetic cost:
A: + 5.9 kJ/mol

Q: Me - Me eclipsing interaction energetic cost:
A: + 13.0 kJ/mol

Q: Cl - Cl eclipsing interaction energetic cost:
A: + 15.1 kJ/mol

Q: Me - Me gauche energetic cost:
A: + 3.8 kJ/mol

Q: Double gauche pentane and the energetic cost:
A: 23.1 kJ/mol

Allylic 1,2-strain:

Q: Allylic 1,3-strain:
A: Allylic 1,3-strain is an important controlling factor in stereoselective transformations.

Cyclohexane: different conformations and relative energies

1,3-diaxial interaction:

Q: 1,3-diaxial interactions energetic cost Me/H:
A: + 3.8 kJ/mol

Q: 1,3-diaxial interactions energetic cost Me/Me:
A: + 15.5 kJ/mol

Q: 1,3-diaxial interactions energetic cost Me/OH:
A: + 10 kJ/mol

Q: 1,3-diaxial interactions energetic cost OH/OH:
A: + 8 kJ/mol

Q: 1,3-diaxial interactions energetic cost OAc/OAc:
A: + 8.4 kJ/mol

Definition of an A-value:

Q: A value of Me in kJ/mol:
A: 7.6

Q: A value of CH_2CH_3 in kJ/mol:
A: 7.6

Q: A value of CH(CH_3)_2 in kJ/mol:
A: 8.8

Q: A value of C(CH_3)_3 in kJ/mol:
A: 19.7

Q: A value of CH_2OH in kJ/mol:
A: 7.1

Q: A value of CO_2Et in kJ/mol:
A: 5

Q: A value of CN in kJ/mol:
A: 0.8

Q: A value of CC-H in kJ/mol:
A: 1.7

Q: A value of CH=CH_2 in kJ/mol:
A: 6.7

Q: A value of C_6H_5 in kJ/mol:
A: 11.8

Q: A value of Si(CH_3)_3 in kJ/mol:
A: 10.5

Q: A value of Sn(CH_3)_3 in kJ/mol:
A: 4.2

Q: A value of O_2CCH_3 in kJ/mol:
A: 2.9

Q: A value of OMe in kJ/mol:
A: 2.5

Q: A value of N_3 in kJ/mol:
A: 2.1

Q: A value of F in kJ/mol:
A: 1.2

Q: A value of Cl in kJ/mol:
A: 2.6

Q: A value of Br in kJ/mol:
A: 2.5

Q: A value of I in kJ/mol:
A: 2.1

Q: A values of OR dependence of R:
A: A values of OR change little as a function of R

Q: How do sp^2 hybridised groups orient themselves on a cyclohexane ring?
A: They orient themselves in such a way that the flat face confronts the ring. For axial phenyl groups, this preference imposes steric crowding of ortho hydrogen atoms with both adjacent equatorial hydrogen atoms of the cyclohexane ring. For equatorial phenyl groups, the most stable conformer bisects the plane of the cyclohexane chain. This avoids unfavourable interactions with equatorial hydrogens.

Q: How do branched alkyl group substituent on a cyclohexane ring behave?
A: The rotate about the axial C-C bond so as to avoid unfavourable interactions that result by having the side chain over the ring. This is reflected in the entropy of the free energy of the system.

Q: How can A values be treated with several substituents?
A: Energetic interactions can be used in an additive fashion except for geminally substituted systems!

Why do isopropyl groups in cyclohexanol behave as if it were larger than in cyclohexane:

Q: Do axial and equatorial substituent exhibit different reactivity?
A: Yes! However, which one is faster depends on the reaction taking place.

Q: Bond length C-C:
A: 1.54 A

Q: Bond length C-C_sp^2:
A: 1.51 A

Q: Bond length C=C:
A: 1.32 A

Q: Bond length C-H:
A: 1.1 A

Q: Bond length C-O:
A: 1.43 A

Q: Bond length C-N:
A: 1.47 A

Q: Bond length C-S:
A: 1.82 A

Q: Bond length C-Cl:
A: 1.8 A

Q: Bond length C-Br:
A: 1.9 A

Q: Bond length C-I:
A: 2.1 A

Interaction of axial methyl with C=O:

1,3-Dioxanes and A values:

A values in 1,3-dithianes:

Q: Is cyclopentane more or less flexible compared to cyclohexane?
A: It is more flexible since the energy barriers between the different conformations are not as high.

What are the most stable positions for methyl or carbonyl substituents on a cyclopentane ring?

Gauche effect and preferred conformation if an extended acetal:

Preferred conformations of esters and diazines:

Which lone pair of the carbonyl is protonated « more easily » in an ester?

Are lactones or open esters more reactive?

Explanation for acidity of amides:

Anomeric effect:

Reverse anomeric effect:

Explanations for the anomeric effect (4 points):

Q: Bohlmann bands:
A: Shift in IR frequencies due to the anomeric effect:

Bicyclic ketals, which structure is preferred:

Endo vs. exo anomeric effect:

Beta-silyl effect:

Aryl silanes substitutions:

Beta silyl effect and use for alkene synthesis:

Baldwin rules:

Enamine formation of alpha substituted cyclohexanones:

Q: Stereoelectronic vs. diaxial interactions:
A: Steric diaxial interactions can override stereoelectronic effects:

Q: exo-Enolate alkylation in cyclohexane derivatives:
A: Equatorial attack is favored

Q: What if a ring contains more than two sp^2 centers?
A: The system is rigidified and can be considered as nearly flat for  analysis.

Cyclisation:

Q: Exceptions to Baldwins rules (two):
A: 1. 3rd row elements
2. Charged intermediates

Considerations for transition state for [3,3] sigmatropic rearrangements:

Oxy-cope rearrangement stereoselectivity considerations:

Q: Chair vs. Boat transitions states on cyclic substrates for sigmatropic rearrangements:
A: F. ex. Boat can be preferred if it leads to the avoidance of a double gauche pentane

Problems of sigmatropic RAR and how to solve them (2 problems and 5 solutions)

How to form an enolate selectively depending on the solvent used:

Metal assisted sigmatropic rearrangements and its consequences:

[2,3]-Sigmatropic rearrangements and selectivity:

The Wittig RAR:

Release of ring strain as a driving force!

Hydroboration general:

Hydrozirconation general:

Houk’s rule:

Rules and procedure for Felkin-Ahn model:

Felkin-Anh with boranes:

Polar Felkin-Anh model:

Chelate effects on Felkin-Anh model:

Factors favoring chelation for the Felkin-Anh model:

Q: Models for selectivity if a beta-heteroatom is present in carbonyl addition:
A: 1. Chelate model
2. Dipolar model

Chelate model for heteroatom in beta position for carbonyl addition:

Dipolar model for the carbonyl addition in case of a beta-heteroatom:

Catalysts for homogeneous catalytic hydrogenation:

Reductions with HB(OAc)_3^- with alcohol in beta position:

Enolate selectivity for monosubstituted amides:

Generation of enolates for monosubstituted esters: On what does it depend?

Alkylation of carboxamides: What are the desireable characteristics?

Name and draw six chiral auxiliaries for monosubstituted enolate alkylation:

Draw Evans' auxiliary and explain how it works:

How is the substrate with Evans' auxiliary prepared?

How is Evans' auxiliary cleaved? (four possible ways)

Oppolzer's Camphor Sultam Auxiliary and its selectivity:

Meyers' chiral Oxazolines and how they work (pioneering studies):

Modern variant of Meyers' chiral oxazolines: What are they and how are they used?

Evans' prolinol-based auxiliary: How does it look and how does it work?

Meyers' pseudoephedrine auxiliary: Structure and selectivity:

Different cleavage conditions and products from Myers' pseudoephedrine auxiliary:

Q: Seebach's self-regeneration of stereocenters:
A: Can be f.ex. employed for the synthesis of AA.

Enders' SAMP/RAMP hydrazones: What are they and how are they used?

How to draw 5- and 7-membered transition states:

What characterises allylation reactions type I?

Allylation type I!

Allylation type I with reagent stereocontrol.

Favoured transition state for Roush's tartrate allyl boronates:

Q: Allylation reactions type II general properties:
A: Models for type II reactions: no clear explanation for observed preference for syn products.

Characteristics of allylation type III reactions:

Q: What is the usual model for an aldol reaction with chelation?
A: Zimmerman-Traxler:

Boat vs. chair in aldol additions:

Aldol with Evans auxiliary coordinating only two oxygens:
What is minimised here?

Q: Crimmins modification of Evans aldol:
What is here the most important interaction?
A: Chelation to all "carbobnyls":

Q: What is the difference between these two reactions in terms of metals?
A: Tin only coordinated twice and the main factor the is dipole minimisation. Titanium choordinates to three carbonyl groups and this results in chelation control.

Q: Which auxiliary does not work for acetate aldols?
A: Evan's auxiliary!

Q: Why can external chiral centers be veryuseful for example for aldol addition reactions?
A: Because they can lead to double asymmetric induction and products with increased selectivities.

Q: What do you have to look out for when you are working with chiral aldehydes in an Aldol addition?
A: Double gauche pentane interactions! Sometimes this can then favour anti-Felkin Ahn products:

Mukayama Aldol: General reaction and selectivity

What is minimised in aldol reactions with chiral enamines?

Q: What determines in many cases the regioselectivity of hydroboration reactions?
A: Inductive effects

Q: What factors lead to higher facial selectivity in hydroboration, but what are the drawbacks?
A: Both larger protecting groups and larger boranes give higher facial selectivity, but lead to reduced regioselectivity.

Q: Draw 9-BBN and explain what it is used for:
A: A bulky hydroboration agent.

Catechol borane:

Q: Metal mediated vs. metal-free hydroboration:
A: Metal mediated and metal free processes have complemetary regioselectivity.

What is 1,2-allylic stereocontrol and how can it be analysed for hydroborations?

What is the differenct between hydroboration with BH_3 or alkyl boranes?

What has to be analysed in addition to conformational analysis of substrates?

Small effects that lead to homoallylic stereocontrol in hydroboration with beta stereocenters?

What are important features of Rhodium catalysed hydroboration reactions?

What is the difference in reactivity/selectivity of E vs. Z alkenes in hydroboration reactions?

What influences the rate of dihhydroxylation with OsO_4?

What is the most common way of dihydroxylation and what are the aspects?

Q: What type of compounds are used for enantioselective stoichiometric dihydroxylations?
A: Chiral diamines.

What are the two possible mechanisms for dihydroxylation reactions with OsO_4?

What are the three proposed models for dihydroxylation with OsO_4 considerinh how the reagent and substrates approach each other?

Q: What seems to be reeeally important for dihydroxylation reactions in terms of minimisation?
A: 1,3-allylic interactions

Q: Very general, which type of interactions seem to clearly dominate when it comes to dihydroxylation by OsO_4?
A: Steric interactions!

Sharpless dihydroxylation:

Bartlett's Butterfly mechanism for epoxidation with mCPBA:

How does Sharpless' proposal for a transition state of epoxidation with mCPBA look like and what are the consequences?

How can the amount of epoxide opening for epoxidation with mCPBA be diminished?

Q: How can the selectivity of the syn-isomer for cyclic allylic alcohols in epoxidation be enhanced?
A: Metal-mediated epoxidation!

What happens here?

What happens in this case?

What are two typical metal-catalysed epoxidation reactions? Which system is more reactive towards allylic alcohols?

Mechanism of the epoxidation reaction of allylic alcohols with VO(acac)_2 and TBHP:

Why?

Sharpless asymmetric epoxidation:

What is the Peterson olefination?

Q: How do we get Evans' syn product?
A: Use B(Bu)_2OTf --> Dipole control

Q: How do we get non Evans' syn product?
A: Use TiCl_4 --> chelation control as Ti can expand the coordination sphere

How to draw the following TS?

How to apply Felkin-Anh to a six-membered ring:

Q: What happens here in the very first step?
A: Afterwards we have allylation, but not with chelation. Open TS.

Q: What is a crucial interaction in the following reaction?
A: We can form an intramolecular H-bond:

Q: What is very important to remember about the type II allylation reactions?
A: F.ex. Bu_3Sn-Allyl