The Mitsunobu reaction in the chemistry of nitrogen-containing heterocyclic compounds. The formation of heterocyclic systems (review)

Abstract

Methods for the design of nitrogen-containing heterocyclic systems involving the formation of C-N bonds under the conditions of the Mitsunobu reaction are discussed.The Mitsunobu reaction [1][2][3][4] is the reaction of compounds containing a mobile hydrogen atom HX with alcohols in the presence of a reagent system consisting of an azodicarboxylic ester and a phosphine PR 1 3 . This reaction results in the formation of an alkylation product RX accompanied by oxidation of the phosphine PR 1 3 to phosphine oxide R 1 3 P=O and reduction of the azodicarboxylic ester to the corresponding hydrazine.The reaction takes place under very mild conditions and usually at room temperature. If a chiral secondary alcohol ROH is used, the reaction is usually stereospecific and is accompanied by inversion of the configuration at the asymmetric carbon atom of the alcohol [1-3].From the moment of the first report [5] the Mitsunobu reaction became a powerful tool in synthetic organic chemistry and found widespread use in the synthesis of various heterocyclic compounds, optically active substances, steroids, alkaloids, carbohydrates, and nucleosides [1][2][3][4]6]. In particular, in a number of cases the Mitsunobu reaction has made it possible to synthesize new physiologically active compounds or to put forward new highly effective approaches to synthesis. Several reviews have been devoted to the Mitsunobu reaction [1-4, 6, 7]. Data on the use of the Mitsunobu reaction in the synthesis of alkaloids were reviewed in [6]. Various experimental techniques that make it possible to simplify the isolation of the products of the Mitsunobu reaction RX from the reaction mixture, including the use of reagents attached to a polymer support, were discussed in [7]. _______ * Dedicated to Afanasi Andreevich Akhrem on his 95th birthday. _________________________________________________________________________________________

Unified Total Syntheses of Fawcettimine Class Alkaloids: Fawcettimine, Fawcettidine, Lycoflexine, and Lycoposerramine B

“…With diol 31 in hand, the hurdle remaining for the synthesis of fawcettimine ( 1 ) was the formation of the 9-membered azonine ring . Guided by the elegant synthesis of (−)-strychnine by the Fukuyama group as well as our own experience with the synthesis of FR900482, we decided to employ a double (inter- then intramolecular) Fukuyama–Mitsunobu reaction to construct the medium-ring N -heterocycle.…”

Regioselective O-Alkylations of Indazolinone Using (Cyanomethylene)triphenylphosphorane

“…pK a of nucleophile must be less then 11 to allow deprotonation step to occur CMMP is the most common trialkylphosphorane found in the literature, and it has been used successfully on indazoles, 11 activated methylenes, 12 and secondary amines. 13 Unfortunately CMMP is very air and moisture sensitive and is currently not commercially available. Tsunoda et al cited a single example of the use of (Cyanomethylene)triphenylphosphorane (CMPP), 14 and the yield obtained was comparable to CMMP.…”

“…) 13. C NMR (400 MHz, CDCl 3 ): d = 24.2, 33.2, 81.5, 109.8, 113.6, 119.8, 120.3, 127.9, 142.7, 157.3.…”

A gram-scale synthesis of a macrocyclic amidinourea with strong antifungal activity through a Fukuyama tri-protected polyamine intermediate

“…Hence, many scientists devoted part of their work to the analysis of protecting group strategies, as testified by the remarkable work done in late 1990s/early 2000s by Fukuyama and co-workers, [8][9][10][11][12] as well as by many others. [13][14][15][16][17][18][19][20][21][22][23] In the last years, our research group focused its efforts on the preparation of a series of compounds bearing interesting antifungal properties, as we reported in previous works, [24][25][26][27][28][29][30][31][32] well represented by compound 1 (Figure 1). These compounds showed good activities against various Candida strains, most notably albicans, guillermondii, kefyr, glabrata.…”