The Allyl Cyanate/Isocyanate Rearrangement: An Efficient Tool for the Stereocontrolled Formation of Allylic C–N Bonds

Abstract

[3,3]‐Sigmatropic rearrangements represent powerful methods in the toolbox of synthetic organic chemists for the stereoselective construction of carbon–carbon as well as carbon–heteroatom bonds. Thus, the allyl cyanate/isocyanate rearrangement, although still underused for the preparation of allylamine derivatives, offers clear advantages over other similar methods. It usually occurs at or below ambient temperature with no need to use any metal catalyst, in a stereospecific way, and with a complete transfer of chirality. Moreover, combined with the high reactivity of the resulting isocyanates towards nucleophiles, this rearrangement gives access to various classes of compounds with wide structural and functional diversity. This microreview provides an overview of synthetic applications of this rearrangement since its discovery, with particular emphasis on its utility for the synthesis of complex nitrogen‐containing molecules such as natural products.

[3,3]‐Sigmatropic Rearrangement of Cyclopropenylcarbinyl Cyanates: Access to Alkylidene(aminocyclopropane) Derivatives

“…As an alternative to the Overman rearrangement of trichloro‐acetimidates, the [3,3]‐sigmatropic rearrangement of allyl cyanates into the corresponding isocyanates has emerged as a powerful tool for the stereocontrolled synthesis of allylic amine derivatives . With the aim of evaluating the feasibility of the [3,3]‐sigmatropic rearrangement of cyclopropenylcarbinyl cyanates as a route toward derivatives of alkylidene (amino‐cyclopropanes), cyclopropenylcarbinol 1 a was selected as the test substrate.…”

“…As an alternative to the Overman rearrangemento ft richloroacetimidates, the [3,3]-sigmatropic rearrangement of allyl cyanates into the corresponding isocyanates hase merged as a powerful toolf or the stereocontrolled synthesis of allylic amine derivatives. [30][31][32][33] With the aim of evaluating the feasibility of the [3,3]-sigmatropic rearrangemento fc yclopropenylcarbinyl cyanates as ar oute towardd erivatives of alkylidene( amino-cyclopropanes), cyclopropenylcarbinol 1a was selected as the test substrate. Alcohol 1a was condensed with trichloroacetyl isocyanate (CH 2 Cl 2 ,08C) and the resulting N-trichloroacetyl carbamate 2a was treated under alkalinec onditions [K 2 CO 3 ,H 2 O/ MeOH (1:1),R T] [34] to afford carbamate 3a (87 %, two steps from 1a).…”

“…Alcohol 1a was condensed with trichloroacetyl isocyanate (CH 2 Cl 2 ,08C) and the resulting N-trichloroacetyl carbamate 2a was treated under alkalinec onditions [K 2 CO 3 ,H 2 O/ MeOH (1:1),R T] [34] to afford carbamate 3a (87 %, two steps from 1a). Amongt he differentr eportedp rocedures to achieve the dehydration of carbamates into cyanates and trigger their subsequent [ 3,3]-sigmatropic rearrangement, [30][31][32][33] the use of trifluoroacetic anhydride( TFAA) in the presence of triethylamine was selected. [32a] Thus, carbamate 3a was treated with TFAA (1.2 equiv) and Et 3 N( 3equiv) in CH 2 Cl 2 at À78 8Ct og enerate the corresponding cyanate 4a in situ and after 1h at À78 8C, the formation of an ew (less polar) product, tentatively assigned as isocyanate 5a,w as observed by analysis of the reaction mixture by thin layer chromatography.H owever,a ttempts to isolate this latter labile compound wereu nsuccessful.…”

Allyl Cyanate/Isocyanate Rearrangement in Glycals: Stereoselective Synthesis of 1-Amino and Diamino Sugar Derivatives

“…In order to synthesize allyl carbamates of simple d -glycals, 4,6- O -protected d -glucal 5a and d -galactal 5b ( 25 ) were reacted with trichloroacetyl isocyanate followed by potassium carbonate to give 6a and 6b in quantitative yield ( Scheme 2 ). Their transformation to the desired products involves three steps, 16 which are usually performed in one-pot. Initial dehydration of the carbamate to the corresponding elusive cyanate 7 ( 26 ) is followed by spontaneous [3,3]-sigmatropic rearrangement to the isocyanate 8 , which is conveniently trapped with a nucleophile to afford the final products 9 .…”

“…All products 10 – 18a/b were obtained as single isomers, assumed to be the β-anomers in consideration of the concerted mechanism of the [3,3]-sigmatropic rearrangement through the cyclic TS 19 occurring with complete 1,3-chirality transfer ( Scheme 3 ). 16 , 26 , 27 However, formation of the α-anomer which may experience anomeric effect 2b , 9a , 28 consequent to a different mechanism, e.g., a Ferrier-type, could not be ruled out. Then, single crystals of products 18a from d -gluco and 10b from d -galacto series were subjected to X-ray structural determination ( SI ), which confirmed the N -glycosides β-configuration.…”