A Route to Carbasugar Analogues - Jonathan Clayden - The ...
A Route to Carbasugar Analogues - Jonathan Clayden - The ... A Route to Carbasugar Analogues - Jonathan Clayden - The ...
Chapter 4 – Synthesis of carbasugars Ph Ph Ph Ph O NMe O NMe HO HO OH 311 OH (CO 2 H) 2 THF/H 2 O rt or 50 °C no isolable products HO HO O 319 OH (CO 2 H) 2 THF/H 2 O 50 °C 95:5 dr α-L-Altrose analogue Scheme 4.40 – dihydroxylation of allylic alcohol (route C) Pleasingly, the dihydroxylation proceeded cleanly with no other diastereomers observed in the crude NMR or upon purification. Optimisation of this step was deemed unnecessary since it completed the five step synthesis from diene 102b in 45.3% yield. An overview of the synthesis is given in Scheme 4.58 at the end of the chapter. 163
4.5 – Mannose synthesis 4.5 Synthesis of a Mannose Analogue Hydrolysis of the known epoxide 309 (section 4.2.8) would give an epimer of the altrose analogue synthesised above. Regioselectivity of nucleophilic attack on oxiranes can often be predicted by considering stabilisation of a developing charge and torsional strain in the transition state. If we consider the opening of epoxide 309 (Scheme 4.41) there is little stabilisation of a developing charge at either juncture but clear differences when we consider torsional strain in the transition states. Nucleophilic attack of cyclohexene oxides generally proceeds through a chair-like trans-diaxial transition state, 200 whereas the regiomeric opening requires the carbocycle to go through a strained twist-boat. HO HO O H 2 O Me HO R O OH 2 321 twist-boat OH OH HO HO OH OH α-L-Idose analogue 322 OH OH 309 H 2 O R = i-Pr Me HO R OH 2 O OH 323 trans-diaxial & neopentyllic OH HO HO HO OH OH α-L-Mannose analogue 324 Scheme 4.41 – hydrolysis of cyclohexane epoxide 309 However, the example above is complicated by the presence of a quaternary centre hindering the approach of the nucleophile in the diaxial transition state 323. These conflicting strains make it hard to predict the preferred product, and the likely result would be poor regioselectivity, as was seen in the work of Gonzalez in the synthesis of cyclitols from (–)-quinic acid. 201 164
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4.5 – Mannose synthesis<br />
4.5 Synthesis of a Mannose Analogue<br />
Hydrolysis of the known epoxide 309 (section 4.2.8) would give an epimer of the<br />
altrose analogue synthesised above. Regioselectivity of nucleophilic attack on<br />
oxiranes can often be predicted by considering stabilisation of a developing charge and<br />
<strong>to</strong>rsional strain in the transition state.<br />
If we consider the opening of epoxide 309 (Scheme 4.41) there is little stabilisation of<br />
a developing charge at either juncture but clear differences when we consider <strong>to</strong>rsional<br />
strain in the transition states. Nucleophilic attack of cyclohexene oxides generally<br />
proceeds through a chair-like trans-diaxial transition state, 200 whereas the regiomeric<br />
opening requires the carbocycle <strong>to</strong> go through a strained twist-boat.<br />
HO<br />
HO<br />
O<br />
H 2 O<br />
Me<br />
HO<br />
R<br />
O<br />
OH 2<br />
321<br />
twist-boat<br />
OH OH<br />
HO<br />
HO OH<br />
OH<br />
α-L-Idose<br />
analogue<br />
322<br />
OH<br />
OH<br />
309<br />
H 2 O<br />
R = i-Pr<br />
Me<br />
HO<br />
R<br />
OH 2<br />
O<br />
OH<br />
323<br />
trans-diaxial &<br />
neopentyllic<br />
OH<br />
HO<br />
HO<br />
HO OH<br />
OH<br />
α-L-Mannose<br />
analogue<br />
324<br />
Scheme 4.41 – hydrolysis of cyclohexane epoxide 309<br />
However, the example above is complicated by the presence of a quaternary centre<br />
hindering the approach of the nucleophile in the diaxial transition state 323. <strong>The</strong>se<br />
conflicting strains make it hard <strong>to</strong> predict the preferred product, and the likely result<br />
would be poor regioselectivity, as was seen in the work of Gonzalez in the synthesis of<br />
cycli<strong>to</strong>ls from (–)-quinic acid. 201<br />
164
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