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Organic Tutorials 3rd Year MT01 Stereochemistry and Conformational Analysis: References: OUP Primers 36 (Kirby), 54 (Grossel), 63 (Proctor) and 88 (Robinson). Bassindale, The third dimension in Chemistry Buxton & Roberts, Guide to Organic Stereochemistry. Eames & Peach, Stereochemistry at a Glance Mackie, Smith & Aitken, Guidebook for Organic synthesis And finally: Eliel, Wilen & Mander, Stereochemistry of Organic compounds (for stereochemistry, the equivalent of March for reactions, but not always the easiest read). ************ USE A SET OF MOLECULAR MODELS! ************** Revision topics: Stereochemical terms Drawing diagrams for ring compounds, e.g. cis-decalins Synthesis and properties of alicyclic compounds Trends in properties with change in ring size Conformational analysis and the stereochemical requirements of common reactions Stereoselective synthesis Stereoelectronic effects on reactivity Problems - General Paper Questions – attached: 1998 I Q4, Q8 1999 II Q5, Q7 2000 I Q5 2001 I Q7 2003 I Q1 2004 I Q2

GOI 98

6

(a)

O

H

O

H

H

OH

HOH

BUT

MeMgBr

MeMgBr

(b)AcO

AcOOBs

+AcOH

(c)

O

Br

O

O

LDA, Et2O

BUT

BrLDA, Et2O

O

(d)

OMeOMe

OMeOMe O

HO

HO

OH

OMe

OH O

OOH

O

OMe

OHOMe

OMe

+TsOH,

MeOH

Question continues

7

(e)

TsON

O

H

NCCO2Et

NEtO

O

H

+

NaOEt, EtOH

(f)

Me2ButSiOO OSiButMe2OO

OO

OHO

OEt

TsOH, MeOH

Turn over

10

7. Answer ALL parts of this question.

(a) How would you predict, in principle, whether a molecular compound is chiraland can be resolved into enantiomers. Illustrate your answer by considering allfour of the following compounds. [ 4 ]

(ii)

(iv)(iii)

(i) N C NN

N

O

O

H

H

HO2CCO2H

OH

OH

OHOH

(b) Illustrate the Cahn-Ingold-Prelog R/S system by drawing the R enantiomer ofboth the following molecules. [ 4 ]

HO OOH

(ii)(i) HSCO2H

NH2

(c) Predict the stereochemistry of the main product of each of the following threereactions, and explain your answer by considering the reaction mechanism. [ 3 x 4 ]

(i)

(ii)

OH

O

OH

Ot-Bu OHt-Bu(iii)

PhCO3H

I2, AgOAc

Al(i-PrO)3

i-PrOH

benzene

HO OAc

HOAc, H2O

5 . Answer all parts of this question.

A synthesis of the insect pheromone multistriatin is shown:

Note you are NOT asked about STEP 3

OH O OPO(OEt)2

STEP 1 STEP 2 STEP 3O

OH OH

OOAc

O

O

OO

OH

STEP 4

STEP 5STEP 6STEP 7

multistriatin

(a) The reagents used to accomplish STEP 2 were:

(i) (Me2CH)2NLi (ii) (EtO)2POCl (iii) Me2CuLi [4 marks]

Suggest a mechanism for this transformation and draw the structures of any intermediates.

(b) Suggest suitable reagents for carrying out each of the following, commenting on anypoints of stereoselectivity [more than one stage may be required for each step]:

[16 marks]

(i) STEP 1(ii) STEP 4(iii) STEP 5(iv) STEP 6(v) STEP 7

Turn over

DCHA 2703 7

2703 DCHA 8

(a) Predict the structure of the products in THREE of the following reactions, withparticular attention to stereochemistry. In each case write a mechanism to explainyour answer. [ 3 x 4 ]

O

OPh

Ot-Bu

OTs

OH

BuLi(i)

Ph i-PrMgCl

(ii)

Ph

O(iv)

(iii)

Al(i-PrO)3

i-PrOH

t-BuOK

C10H14O

C8H14

C10H20O

C11H18O

C11H14+ +

single enantiomer

( IR (KBr): ν = 1715 cm–1 )

single enantiomer (R-)

(b) Explain the stereochemistry of TWO of the following reactions. [ 2 x 4 ]

N

t-Bu

i-Pr(i)

(ii)

N

t-Bu

NaHCO3 (aq.)

i-Pr

100 °C

N

t-Bu

i-PrLDAthen MeI

Br

H

H

HO(iii)

then MeILDA

OO

OPh3PEt Br, NaNH2

−+

Turn over

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1. Answer both part A and part B.

Part A.

Draw diagrams to show all the stereoisomers of dimethylcyclohexane. State which existas enantiomers, and draw the R,R stereoisomer of one pair of enantiomers. [8]

Part B.

Explain what is meant by the following pairs of terms. Give examples to illustrate youranswers. [3 x 4]

(a) regioselective and stereoselective;

(b) resolution and racemisation;

(c) enantiomeric excess and diastereomeric excess.