Catalyst‐Free Synthesis of 2,3‐Benzodiazepines via Tetrahydrodiazirino[3,1‐a]isoquinoline Reacts with Sulfonyl Chlorides

Abstract

An unexpected process from tetrahydrodiazirino[3,1‐a]isoquinolines and diversified sulfonyl chlorides RSO2Cl (R=aryl, alkyl) to deliver highly yields 4,5‐dihydro‐3H‐benzo[d][1,2]diazepine skeleton compounds was disclosed via N‐insertion ring‐opening reaction. The structural framework of 2,3‐benzodiazepines is unambiguously confirmed by single‐crystal X‐ray crystallographic analysis. The present protocol features mild reaction conditions, high yields and feasibility of large‐scale synthesis and catalyst‐free access to benzo[2,3]diazepines skeleton. In contrast, azomethine imines were produced by employing tetrahydrodiazirino[3,1‐a]isoquinoline reacts with aroyl chlorides under the same conditions.

Asymmetric Synthesis of Tetrahydroisoquinoline Derivatives through 1,3-Dipolar Cycloaddition of C,N-Cyclic Azomethine Imines with Allyl Alkyl Ketones

“…The 1,3-dipoles of 1 [ 43 ], 2 [ 44 ], 3 [ 45 ] and 4 [ 46 , 47 , 48 , 49 , 50 , 51 ] were synthesized according to the literature methods. The substrates 5a−h were prepared according to the literature procedures [ 36 , 52 , 53 , 54 , 55 , 56 , 57 ].…”

1,3‐Dipolar versus Nucleophilic Reactivity of Diaziridines Based on 3,4‐Dihydroisoquinoline toward Aryl Iso(thio)cyanates

“…[2g,10] Diaziridine 1 has been found to react with arylsulfonyl chlorides to produce 3arylsulfonyl-4,5-dihydro-3H-benzo[2,3]diazepines in high yields via an N-insertion ring-opening process (Scheme 1). [10] The alkylation of diaziridine 1 by trimethyloxonium tetrafluoroborate has led to the isolation of a diaziridinium ion, which on heating transformed into 3-methyl-4,5-dihydro-3Hbenzo[2,3]diazepine (Scheme 1). [11] In this work, we set out to investigate reactions of two diaziridines -1, 3,4,8b-tetrahydrodiazirino[3,1-a]isoquinoline (1) and 1-methyl-1, 3,4,8b-tetrahydrodiazirino[3,1-a]isoquinoline (2) -with aryl iso(thio)cyanates in order to distinguish between the two reactivity modes possible for these transformations.…”

“…N ‐Aroyl‐substituted azomethine imines are obtained by the action of aroyl chlorides on 1,3,4,8b‐tetrahydrodiazirino[3,1‐ a ]isoquinoline ( 1 ) in the presence of a base (Scheme 1). [2g,10] Diaziridine 1 has been found to react with arylsulfonyl chlorides to produce 3‐arylsulfonyl‐4,5‐dihydro‐3 H ‐benzo[2,3]diazepines in high yields via an N ‐insertion ring‐opening process (Scheme 1). [10] The alkylation of diaziridine 1 by trimethyloxonium tetrafluoroborate has led to the isolation of a diaziridinium ion, which on heating transformed into 3‐methyl‐4,5‐dihydro‐3 H ‐benzo[2,3]diazepine (Scheme 1).…”

Asymmetric Synthesis of Multifunctionalized 2,3-Benzodiazepines by a One-Pot N-heterocyclic Carbene/Chiral Palladium Sequential Catalysis

“…One of the most frequently used strategies to synthesize 2,3-benzodiazepine, dihydro- and tetrahydro-2,3-benzodiazepine, 2,3-benzodiazepin-4-one and 2,3-benzodiazepin-1,4-dione compounds is to construct the 2,3-benzodiazepine ring by means of the condensation reaction between a hydrazine or substituted hydrazines with the carbonyl compound including 1-( o -acyl)­aryl-2-ketones, , 2-( o -acyl)­arylacetic acids and esters, , and 2-( o -carboxy)­arylacetic acid anhydride . Other methods such as the Rh-catalyzed coupling reaction between N -boc hydrazones and diazoketoesters followed by intramolecular condensation, the ring expansion reaction of tetrahydrodiazirino­[3,1- a ]­isoquinoline with sulfonyl chlorides, and the reaction of hydrazine with 2-benzopyrylium or 2-benzoselenopyrylium salts have also been reported. Although most of the bioactive 2,3-benzodiazepine derivatives contain a stereogenic center, and different enantiomers have considerably different bioactivities on the physiologic system, − surprisingly, the asymmetric synthesis of chiral 2,3-benzodiazepine derivatives remains largely unexplored.…”