Sulfonyl‐Activated Cyclobutenes as Building Blocks for the Synthesis of Dihydrodiazepines

Abstract

1,2-Bis(phcnylthio)-I-cyclobutcnc (S), prepared in high yield using a modified literature procedure, was oxidized to the corresponding his-sulfone 2. sulfone-sulfoxide 9, bis-sulfoxide 10, or monosulfoxidc 15 by means of hydrogen peroxide or sodium periodate, rcspectivcly. When treated with diazomethane the bis-sulfone 2 and thc sulfonc-sulroxidc 9 yicld thc dihydrodiazcpincs 4 a and 11, rcspcctivcly. Thc rcactivity of thcse cyclobutenes and thc rcgioselectivity of 9 is discussed in terms of the MNDO model.Vinyl sulfoxides and vinyl sulfones are often used as dienophiles because of their high reactivity2). Further activation can be achieved with 1,2-bis(phenylsulfonyl)ethylenes3~. Therefore, these olefins represent useful synthetic equivalents for acetylene4). The activating influence of the sulfonyl group also becomes noticeable in dipolar cycloadditions 5), By inserting a sulfonyl group into the cyclobutene ring a considerable increase of the reactivity of the cyclobutene double bond is achieved. Thiete 1,l-dioxide (1) possesses excellent dienophilic6) and dip~larophilic~) properties. We showed that cycloadducts of cyclobutenes and 1,3-dipoles represent potential precursors to dihydroazepines8) and dih ydrodia~epines~).However, the ring enlargement of dipolar cycloadducts of thiete 1,l-dioxide (1) leading to seven-membered heterocycles has not succeeded yet, Either the adducts eliminate 502'' or the cycloadduct of 1 reacts by splitting the SO2-C bond lo).According to our experience, keto groups in or methoxycarbonyl-and cyano groups at the four-membered ring favour the ring enlargementsx9).In order to examine how much the sulfonyl group facilitates the fission of the central cs bond of the cycloadducts Sulfonyl-aktivierte Cyclobutcne als Synthesebausteine fur die Sjnthese von Dihydrodiampinen " 1,2-Bis(phcnyIthio)-l-cyclobutcn (S), das nach cincm modifizicrtcn Litcraturverfahren in hoher Ausbcutc crhalten wurde, konntc mittels Wasserstoffperoxid byw. Natriumperiodat zum entsprechenden Bis-sulfon 2, Sulfon-sulfoxid 9, Bis-sulfoxid 10 oder Monosulfoxid 15 oxidiert werden. Mit Diazomethan ergeben das Bissulfon 2 und das Sulfon-sulfoxid 9 die Dihydrodiazepine 4a bzw. 11. Die Reaktivitat dicscr Cyclobutcne und die Regiosclcktivitit von 9 wcrdcn im Rahmcn dcs MNDO-Modells diskuticrt.of cyclobutenes (without competing cleavage of an outer bond of the four-membered ring), the preparation of bicyclic pyrazolines 3 with activating phenylsulfonyl substituents and their possible ring enlargement leading to 4 was investigated. We now report on the synthesis of 1,2-bis(phenylsulfony1)-1 -cyclobutene (2) and its reactivity towards diazoalkanes. ResultsThe bis-sulfide 5"), described by Cohen et al., should be a suitable starting material for the sulfone 2. However, the published yield of 70% for 5 could not be reproduced. With sec-butyllithium in THF at -78 "C mixtures of 5 and 8 were obtained (yields: ca. 50% of 5, 30% of 8).We assume that 8 arises from 1,l -bis(phenylthio)ethylene (7) which originates from 6 by Grob fragment...

The Application of Cyclobutane Derivatives in Organic Synthesis

“…Martin et al reported the synthesis of dihydrodiazepines by thermal rearrangement of the cycloadduct of ethyl diazoacetate and a bissulfonyl-activated cyclobutene . For example, the 2,3-diazabicyclo[3.2.0]heptene 507 provided ethyl-4,4-dihydro-3,6-bis(phenylsulfonyl)-1- H -1,2-diazepine-7-carboxylate ( 508 ) in 82% yield.

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“…246 Martin et al reported the synthesis of dihydrodiazepines by thermal rearrangement of the cycloadduct of ethyl diazoacetate and a bissulfonyl-activated cyclobutene. 247 For example, the 2,3-diazabicyclo-[3. During the investigation of [2+2] cycloadditions of cyclic β-alkoxyvinyl phosphonates to activated ketenes, Ruder and Ding reported the fragmentation of the resulting phosphonated 7-oxobicyclo[3.2.0]heptane derivatives, such as 511, to ring-enlarged diketones.…”

Reactions of heterocyclic compounds with nitrilimines and their precursors

“…Ph-C^-N-Ph ecently, it was reported thatiV-acylnitrilimines lm react similarly with maleic anhydride (65) to give the corresponding l-acylfuro[3,2-c]pyrazoline-4,6-diones 67, which underwent dehydrogenation upon treatment with iodine and potassium iodide to give the furopyrazole derivatives 68.79 Such a result should be accepted with some reservations due to the fact that the precursors of lm were not characterized and it is wellknown that nitrilimines of type lm undergo intramolecular cyclization as soon as they are formed to give the corresponding oxdiazole derivatives. [80][81][82][83] The reaction of C-(trifluoromethyl)-./V-phenylnitrilimine (lb) with maleic anhydride yields the dicarboxylic acid 70 directly.…”