Step 1
TBDMSCl |
|
CH2Cl2 |
TMS(CH2)2OH |
|
CH2Cl2 |
Bu4NF |
|
THF |
Alcohol 2 |
|
DCC, DMAP, CH2Cl2 |
Bu4NF/THF |
|
Lactonize |
3D |
|
This first step was required to make the macrocyclopropane reagent for later in the synthesis (designated alcohol 2 reagent in step 4). Quinquecyclopropane was the starting reagent and was protected with TBDMS by the application of TBDMSCl with imidazole in CH2Cl2.
The starting reagent for this step was isophthaloyl chloride which was esterified with 2-trimethylsilylethanol to give the resulting fully protected diester.
The diester was half deprotected utilizing 1 equivalent of Bu4 in THF. Because only 1 equivalent was used all the reagent would deprotect one ester, leaving the second protected.
Alcohol 2 from the first step was utilized to carry out an esterification following the Steglich-esterification procedure. This used alcohol 2 with DCC, DMAP, and CH2Cl2 to form an unsymmetrical diester.
Double deprotection was achieved by using an excess of Bu4 in THF. Lactonization was achieved by Yamaguchi conditions to obtain the coronane 23. Interestingly, the yield was in the 90% range, suggesting macrocyclization was a favored stable conformation. Recrystallization yielded crystals suitable for X-ray crystallography. Identification was determined mainly by IR and NMR. If you proceed to the next step, I've constructed an interactive Chime 3D model of coronane 23.
Click here to view a Large Image of the model. If you don't have the plug-in goto http://www.mdlchime.com/chime/ and download the free Chime plug-in.