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Review
. 2018 Mar 28;16(12):2006-2027.
doi: 10.1039/c8ob00138c. Epub 2018 Feb 26.

The Curtius Rearrangement: Mechanistic Insight and Recent Applications in Natural Product Syntheses

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Free PMC article
Review

The Curtius Rearrangement: Mechanistic Insight and Recent Applications in Natural Product Syntheses

Arun K Ghosh et al. Org Biomol Chem. .
Free PMC article

Abstract

The Curtius rearrangement is a versatile reaction in which a carboxylic acid can be converted to an isocyanate through an acyl azide intermediate under mild conditions. The resulting stable isocyanate can then be readily transformed into a variety of amines and amine derivatives including urethanes and ureas. There have been wide-ranging applications of the Curtius rearrangement in the synthesis of natural products and their derivatives. Also, this reaction has been extensively utilized in the synthesis and application of a variety of biomolecules. In this review, we present mechanistic studies, chemical methodologies and reagents for the synthesis of isocyanates from carboxylic acids, the conversion of isocyanates to amines and amine derivatives, and their applications in the synthesis of bioactive natural products and their congeners.

Conflict of interest statement

Conflicts of interest

Authors declare no competing interests

Figures

Fig. 1
Fig. 1
The Curtius rearrangement route to isocyanates, amines and amine derivatives.
Fig. 2
Fig. 2
Stieglitz’s mechanism via carbonylnitrene intermediate.
Scheme 1
Scheme 1
Thermal and photochemical decomposition of pivaloyl azide.
Scheme 2
Scheme 2
Concerted thermal Curtius rearrangement mechanism.
Scheme 3
Scheme 3
Photochemical formation of acylnitrenes.
Scheme 4
Scheme 4
Photolysis of alkoxycarbonyl azide.
Scheme 5
Scheme 5
Preparation of acyl azides.
Scheme 6
Scheme 6
Preparation of 8,9,15-trihydroxypentadecylamine using the Naegeli modification.
Scheme 7
Scheme 7
Synthesis of amino acid derivatives from α-cyanoacetic esters.
Scheme 8
Scheme 8
Synthesis of DPPA and modified Curtius rearrangement.
Scheme 9
Scheme 9
Overman procedure for the Curtius rearrangement.
Scheme 10
Scheme 10
General procedure developed by Lebel.
Scheme 11
Scheme 11
Protocol for the Curtius rearrangement by Li and co-workers.
Scheme 12
Scheme 12
Knoechel protocol for quaternary carbon centers.
Scheme 13
Scheme 13
Synthesis of orthogonally protected diaminopropionic acid.
Scheme 14
Scheme 14
Synthesis of optically active cyclopropylamines.
Scheme 15
Scheme 15
Synthesis of a cyclopentano-oxazolidinone.
Scheme 16
Scheme 16
Synthesis of peptidomimetic derivatives.
Scheme 17
Scheme 17
Synthesis of macrocylic derivatives.
Scheme 18
Scheme 18
Synthesis of spirocyclic lactam derivatives.
Scheme 19
Scheme 19
Synthesis of triquinacene.
Scheme 20
Scheme 20
Synthesis of haemanthidine.
Scheme 21
Scheme 21
Synthesis of saxitoxin.
Scheme 22
Scheme 22
Synthesis of colchicine.
Scheme 23
Scheme 23
Synthesis of streptonigrin and streptonigrone.
Scheme 24
Scheme 24
Synthesis of camptothecin.
Scheme 25
Scheme 25
Synthesis of huperzine A.
Scheme 26
Scheme 26
Synthesis of calyculin A.
Scheme 27
Scheme 27
Synthesis of zampanolide.
Scheme 28
Scheme 28
Synthesis of salicylihalamide.
Scheme 29
Scheme 29
Synthesis of gelsemine.
Scheme 30
Scheme 30
Synthesis of methoxatin.
Scheme 31
Scheme 31
Synthesis of sinefungin.
Scheme 32
Scheme 32
Synthesis of AI-77-B.
Scheme 33
Scheme 33
Synthesis of brostallicin.
Scheme 34
Scheme 34
Synthesis of belactosin A.
Scheme 35
Scheme 35
Synthesis of the himandrine skeleton.
Scheme 36
Scheme 36
Synthesis of welwitindolinones.
Scheme 37
Scheme 37
Synthesis of diisocyanoadociane.
Scheme 38
Scheme 38
Synthesis of mycalamide A.
Scheme 39
Scheme 39
Synthesis of altemicidin core.
Scheme 40
Scheme 40
Synthesis of pancratistatin.
Scheme 41
Scheme 41
Synthesis of NP25032.
Scheme 42
Scheme 42
Synthesis of dievodiamine.
Scheme 43
Scheme 43
Synthesis of lyconadin C.
Scheme 44
Scheme 44
Synthesis of lundurine B.
Scheme 45
Scheme 45
Synthesis of axisonitrile and axamide.
Scheme 46
Scheme 46
Synthesis of aspeverin.
Scheme 47
Scheme 47
Synthesis of cyclindricine core.
Scheme 48
Scheme 48
Retrosynthetic approach to cephalotaxine.
Scheme 49
Scheme 49
Synthesis of azaspiro[4.4]nonane-2,6-dione 204.
Scheme 50
Scheme 50
Synthesis of (−)-esermethole.
Scheme 51
Scheme 51
Synthesis of psymberin.
Scheme 52
Scheme 52
Synthesis of the mycalamide nucleus.
Scheme 53
Scheme 53
Synthesis of pederin.
Scheme 54
Scheme 54
Synthesis of mycalamide B.
Scheme 55
Scheme 55
Synthesis of echinocandin C.

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