Ugi Multicomponent Reaction Followed by an Intramolecular Nucleophilic Substitution:  Convergent Multicomponent Synthesis of 1-Sulfonyl 1,4-Diazepan-5-ones and of Their Benzo-Fused Derivatives

Abstract

A short, two-step approach to the synthesis of diazepane or diazocane systems, based on a Ugi multicomponent reaction followed by a subsequent intramolecular SN2 reaction was studied. 1-sulfonyl tetrahydrobenzo[e]-1,4-diazepin-1-ones 1 were obtained in very high yield through a Ugi multicomponent reaction followed by Mitsunobu cyclization. On the other hand, aliphatic 1-sulfonyl 1,4-diazepan-5-ones 2 could be obtained employing different cyclization conditions (sulfuryl diimidazole). A similar approach toward diazocane rings using hydroxamates as nucleophiles was less successful, affording only O-cyclized adducts or unexpected side products. A mechanistic explanation of the observed outcomes is proposed.

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

“…It was also shown [80] that the cyclization of the sulfonylamide 105 under analogous conditions takes place in a more complicated manner. The diazepanone 106 is formed with a yield of only 32%, while the main product is the bicyclic compound 107 in the form of a mixture of diastereomers in a ratio of 15 The synthesis of tetrahydrodiazepinopurines, which are analogs of the marine alkaloids asmarines and have antitumor activity, was reported [18].…”

“…The Synthesis of 1,4-Perhydro-1,4-diazepin-2-ones by the Mitsunobu Method -carboxylic acid derivative 101 was obtained in a solid-phase version of the cyclization of p-nosylamide 102 attached to a polymer support[66].An intramolecular Mitsunobu reaction involving the tosylamino group was used in the synthesis of 2,3,4,5-tetrahydrobenzo[e]-1,4-diazepines and 2,3,4,5-tetrahydrobenzo[f]-1,4-thiazepines[79].A synthesis scheme involving a combination of the Ugi reaction with subsequent intramolecular Mitsunobu reaction with the participation of the sulfonyl groups was proposed for the production of derivatives of 2,3,4,5-tetrahydrobenzo[e]-1,4-diazepine 103(Table 13)[80].…”

Base-catalyzed cyclization of Ugi-adducts to substituted indolyl based γ-lactams

“…Using this method, Bruttomesso et al [16] prepared highly stereoselective steroidal 2,5-diketopiperazines. In this context, the Ugi multicomponent reaction, followed by intramolecular Mitsunobu cyclization, resulted in diazepane or diazocane systems [17,18]. Benzolactames were isolated from the cyclization of an Ugi adduct in the presence of Cs 2 CO 3 under microwave conditions [19].…”

Tandem Ugi MCR/Mitsunobu Cyclization as a Short, Protecting‐Group‐Free Route to Benzoxazinones with Four Diversity Points

“…We have already reported the application of this approach to short syntheses of 3,4-dihydrobenzo[f] [1,4]oxazepin-5-ones, [19][20][21] 1-sulfonyl-3,4-dihydrobenzo[e] [1,4]diazepin-5-ones, [20,22] 1-sulfonyl-1,4-diazepan-5-ones, [22] benzo[e] [1,3]oxazin-4-ones [23] and 3-aminoisochromenes. [24] In these syntheses the additional alcohol moiety was always implanted into the amine or the carbonyl component.…”