- Antonio Guarna added an answer:DOSdiversity oriented synthesis(DOS) is an emerging area in creating a small molecule libraries. Since it is since still in its infacy, there is a great opportunity to the synthetic chemists to discover novel lead molecules by putting efforts in this field in comig days. Till now there is no much rational efforts in this field.Hi
to have a complete picture of the potentiality of DOS , I may suggest you to read the book edited by Andrea Trabocchi, recently published by Wiley. https://www.researchgate.net/publication/249011185_Diversity-Oriented_Synthesis_Basics_and_Applications_in_Organic_Synthesis_Drug_Discovery_and_Chemical_BiologyFollowing
- Pierre-André Fournier added an answer:Does the synthetic scheme attached herewith have any faults?We are working on the synthesis of a HIV NRTI. We want to protect the -OH end of the starting element with TMS-Cl. What would be the best reagent to deprotect TMS-Cl in case of this reaction? Will it be done by any acid, NaF or tetra-n-butylammonium fluoride? Which one will be better in this case? Please give your views on any other issues with thissynthetic scheme?Cyclopropyl bromide is a terrible electrophile. The cyclopropanes have a strong sp2 character (the bonds are actually "bend" to accommodate the 60° angle of triangles and the 109 angles of sp3 bonds). I would look at a Chan-Lam coupling with the cyclopropyl boronic acid (copper promoted cross coupling between amines, most commonly anilines, and boronic acids). Mono-coupling is not an issue in these cases.
Chemical Communications (Cambridge, United Kingdom), 46(19), 3393-3395; 2010.
Also, as Mr. Dera stated, alkylation of amines is a greatly over-rated reaction as the overalkylation problem is very common. Reductive amination or cross-coupling are far better alternatives. And as for a TMS-deprotection of a primary alcohol, some 1N HCl in THF should do the job instantly as TMS is very easy to remove (maybe too easy for a Chan-Lam coupling...). I don't think a primary alcohol is incompatible with most cross-coupling, so I'd first try a direct reaction.Following
About Diversity Oriented Synthesis
design and synthesis of skeletally diversified library of molecules from privilized structures