Methyl Carbamate and tert butyl ester in the synthesis of (-) kainic acid

Amine as methyl carbamate:  T. Fukuyama's group converted an acid into a methyl carbamate protected amine by using a Curtius rearramgement. 
Installation: DPPA, NEt3, toluene, reflux then MeOH, reflux, 78% yield

Survived: Base (LiHMDS at -78 C), Zn/AcOH, LiAlH(Ot-Bu)3, TMSCN with BF3.OEt2
Removal: aq. NaOH, reflux , 70% yield
Reference: Organic Letters, 2011, 13, 2068.

Acid as tert-butyl ester: T. Fukuyama's group used a tert-butyl ester which came from commercially available tert-butyl bromoacetate.
Installation: Commercially available tert-butyl bromoacetate
Survived: Zn/AcOH, LiAlH(Ot-Bu)3, TMSCN with BF3.OEt2
Removal: aq. NaOH, reflux , 70% yield
Reference: Organic Letters, 2011, 13, 2068.

April 25, 2011

I will post examples of protecting groups in organic synthesis.  In my experience in organic and medicinal chemistry the proper choice, instllation, and removal of protecting groups is of paramount importance to the success of a synthetic scheme.  Anybody who embarks on a synthesis of a complex organic molecule encounters difficulties with protecting groups - on most occassions installation is relatively easy but removal difficult.  In my own case, my PhD got delayed by almost 6 months, because of an error in removing a trityl group from the imidazole ring of Histidine.  The choice of the reagent wasn't at fault - rather the work-up was wrong.  On the other hand, the success of my post-doc rested largely on an extremely efficient protocol for deprotecting a TBS ether using HF.pyridine in pyridine to stablize the acid-sensitive final product.

My aim is to highlight the (often overlooked) protection and deprotection strategies as they continue to evolve in organic synthesis.