Chapter 24, Problem 24.37P

(a)

Interpretation Introduction

Interpretation:

The other products obtained from the highly stereo and regioselective reaction of O-alkylation during the formation of Gilvarin M. has to be interpreted.

Concept introduction:

Regioselectivity:

Regioselectivity is the preference of one direction of chemical bond making or breaking over all other possible directions.

Stereoselectivity:

Stereoselectivity is the property of a chemical reaction in which a single reactant forms an unequal mixture of the stereoisomers during a non-stereospecific creation of a new stereocentre or during a non-stereospecific transformation of a pre-existing one.

Explanation of Solution

The reaction is given as,

The other possibility is,

(b)

Interpretation Introduction

Interpretation:

The structure of the compound C has to be given.

Concept introduction:

Acid-base reaction:

The species that donates proton or accepts lone pair of electrons are called acids and those who accepts proton or donates lone pair of electrons are called base.

$S_{N^2}$ Reaction:

The ${\text{S}}_{{\text{N}}^{\text{2}}}$ reaction is a type of nucleophilic substitution reaction where one bond is broken and one bond is formed simultaneously. Since the two reacting species are involved in the rate determining step hence it is bimolecular also.  The reaction passes through a five co-ordinated intermediate.  The mechanism is as follows,

Explanation of Solution

The pathway of formation of C is,

Here the ${\text{i-Pr}}_{\text{2}}\text{NEt}$ acts as base and takes up the acidic hydrogen from alcohol by simple acid base reaction.  Then the conjugate base formed undergoes ${\text{S}}_{\text{N}}{}^{\text{2}}$ reaction with ${\text{Tf}}_{\text{2}}\text{O}$ and turned into a good leaving group.

(c)

Interpretation Introduction

Interpretation:

The structure of compound D has to be given.

Concept introduction:

Lithium halogen exchange:

Organolithium reagents are characterised by the presence of $\text{C}-\text{Li}$ bond. Due to the high electronegativity difference between carbon and lithium the bond is very much polar and reactive.

The reaction of lithium metal at low temperature with an alkyl halide in a hydrocarbon solvent gives alkyl lithium. The reaction proceeds smoothly in the presence of above $0.02\%$ sodium and the reactivity of alkyl halide is $\text{RI>RBr>RCl}$

  $\text{RX}\text{+}\text{2Li}\stackrel{{\text{-78}}^{\text{ο}}\text{C}}{\to }\text{RLi}\text{+}\text{LiX}$

The same reaction happens with the haloarenes also,

Explanation of Solution

The reaction for the formation of D is as follows,

(d)

Interpretation Introduction

Interpretation:

Structure of E has to be given along with the mechanism of formation of E from D.

Concept introduction:

Benzyne formation:

Benzynes are highly reactive intermediate species that are made from aromatic ring by the removal of two substituients.  Mainly benzynes are ortho benzynes.  The reaction is as follows,

Explanation of Solution

Here benzyne formation occurs due to removal of $\text{Li}$ and $-\text{OTf}$ simultaneously.  Reaction occurs via zwitterion form.

(e)

Interpretation Introduction

Interpretation:

A mechanism for formation of F from E has to be given.

Concept introduction:

Diels Alder reaction:

The Diels-Alder reaction is a chemical reaction between a conjugated diene and a substituted alkene which is called dienophile to form a substituted cyclohexene derivative.  It is one type of pericyclic reaction with a concerted mechanism and more specifically it is thermally allowed $[4+2]$ cycloaddition.  Dienes attached to some electron donating group are good HOMO and dienophile with electron withdrawing group are good LUMO.  The mechanism is as follows,

Explanation of Solution

Here Diels Alder reaction occurs between furan and benzyne.  A new ring is formed.

(f)

Interpretation Introduction

Interpretation:

Mechanism from F to G has to be given.

Concept introduction:

Hydrolysis:

Hydrolysis is any chemical reaction in which a water molecule ruptures one or more chemical bonds.  This is mainly used for substitution, elimination and fragmentation reactions in which water is the nucleophile.  Hydrolysis is reverse of condensation reaction because in this process water is added to beak down.

Explanation of Solution

Here aqueous work up leads to breaking of the bridging oxygen bond by protonating the oxygen.  Thus the angle strain increases as positive charge on electronegative oxygen is tough.  Thus the bond breaks and the charge formed is stabilised by electron donating effect of $-{\text{OCH}}_{\text{3}}$.  Again positive charge on oxygen destabilises and so the ring breaks and carbocation is formed.  Then to again attain the aromaticity

Thus G is formed from F.

(g)

Interpretation Introduction

Interpretation:

The reagents and condition from G to H has to be given.

Concept introduction:

Acid-base reaction:

The species that donates proton or accepts lone pair of electrons are called acids and those who accepts proton or donates lone pair of electrons are called base.

$S_{N^2}$ Reaction:

The ${\text{S}}_{{\text{N}}^{\text{2}}}$ reaction is a type of nucleophilic substitution reaction where one bond is broken and one bond is formed simultaneously. Since the two reacting species are involved in the rate determining step hence it is bimolecular also.  The reaction passes through a five co-ordinated intermediate.  The mechanism is as follows,

Explanation of Solution

Here on giving base the acidic hydrogen from phenol is removed and the new carbanion formed undergoes ${\text{S}}_{\text{N}}{}^{\text{2}}$ with the given anhydride.

Thus H is formed from G.

(h)

Interpretation Introduction

Interpretation:

Reagents and condition for conversion of H to I has to be given.

Concept introduction:

Cross coupling:

A cross coupling reaction is defined as a reaction that creates a $\text{C}-\text{C}$ bond by coupling together two alkyl, aryl, alkenyl or alkynyl groups.  Cross coupling reactions involve a transmetallation step.  A transmetallation is a pairwise interchange of ligands between two different metals or metalloids.

In the case of palladium catalysed cross-coupling reactions the other metal or metalloids are commonly $\text{Zr,}\text{Sn}\text{,}\text{B}\text{,}\text{ZN}\text{,}\text{Cu}\text{,}\text{Mg}$ which are designated as M in the following general example,

$\text{R-Pd}\text{+R'-M}\stackrel{}{\to }\text{R'-Pd}\text{+}\text{R-M}$

Suzuki coupling:

The Suzuki coupling uses a boron compound and an alkenyl, aryl or alkyl halide or triflate as the carbon sources with a palladium salt as a catalyst.  The reaction is mainly used to form biaryls.  The mechanism of the reaction starts with an oxidative addition followed by transmetallation in which the substituent on the borane replaces the ligand on the palladium concluding with the reductive elimination of the palladium to form the new carbon-carbon bond.  The base may serve as a new labile ligand to palladium or it may activate the borane by coordination.

Generalized reaction,

$\text{RX}\text{+}{\text{R'BY}}_{\text{2}}\underset{\text{base}}{\overset{{\text{PdL}}_{\text{4}}}{\to }}\text{R-R'}\text{+}{\text{XBY}}_{\text{2}}$

Oxidative addition and ligand exchange,

$\text{RX}\stackrel{{\text{PdL}}_{\text{n}}}{\to }\text{R-PdX}\stackrel{{\text{RO}}^{\text{-}}}{\to }\text{R-Pd-OR}$

Borane activation

${\text{BY}}_{\text{3}}\stackrel{{\text{RO}}^{\text{-}}}{\to }{\left[{\text{RO-BY}}_{\text{3}}\right]}^{\text{-}}$

Reaction,

$\text{R-Pd-OR}\text{+}{\left[{\text{R'-BY}}_{\text{3}}\right]}^{\text{-}}\stackrel{}{\to }\text{R-Pd-R'}\stackrel{}{\to }\text{R-R'}\text{+}\text{Pd(0)}\text{+}{\left[{\text{RO-BY}}_{\text{3}}\right]}^{\text{-}}$

Explanation of Solution

The reaction is given as,

The reaction proceeds as follows,

1^st boron has to be added so that via transmetallation by intramolecular Suzuki coupling the product can be formed.

(i)

Interpretation Introduction

Interpretation:

Reagent needed to form Gilvocarcin M. from I has to be interpreted.

Concept introduction:

Protection-deprotection:

A protecting group is introduced to a molecule by chemical modification of a functional group to obtain chemoselectivity in a subsequent chemical reaction specially in multistep organic synthesis.

Hydrogenolysis:

Hydrogenolysis is a chemical reaction whereby a carbon carbon bond or carbon heteroatom single bond is cleaved by hydrogen gas catalytically.

Explanation of Solution

The reaction is given as,

Here deprotection is done by hydrogenolysis with the help of palladium and catalytic amount of hydrogen.

(j)

Interpretation Introduction

Interpretation:

Probable source of chiral centres has to be found.

Concept introduction:

Chiral centre:

Chiral centre is defined as an atom bonded to four different chemical species.  It is a stereo centre that holds the atom in such way that the structure may not be superimposable to its mirror image.  They give optical isomerism.

Explanation of Solution

The source of the chiral centre is only the five membered carbohydrate ring attached to the benzene ring as shown below,

The chiral centre is marked with the asterisk.

(k)

Interpretation Introduction

Interpretation:

The need of protection of hydroxyl group has to be stated.

Concept introduction:

Protection-deprotection:

A protecting group is introduced to a molecule by chemical modification of a functional group to obtain chemoselectivity in a subsequent chemical reaction specially in multistep organic synthesis.

Explanation of Solution

If protection has not been done to the hydroxyl groups then there were possibilities of getting so many unwanted products.

During the acid base reaction all the hydroxyl groups could have lost the proton and thus all the substitution could have taken place in different places. The benzyne formation could have hampered and the stereochemistry could have changed.

The process of protection to the hydroxyl group is given by,