Tosylhydrazones synthesis

Of course, the key limitation of the ylide-mediated methods discussed so far is the use of stoichiometric amounts of the chiral reagent. Building on their success with catalytic asymmetric ylide-mediated epoxidation (see Section 1.2.1.2), Aggarwal and co-workers have reported an aza version that provides a highly efficient catalytic asymmetric synthesis of trans-aziridines from imines and diazo compounds or the corresponding tosylhydrazone salts (Scheme 1.43) [68-70]. 

An unusual synthesis of the l,6-dihydro-l,2,3-triazine system 8 involves the Bamford-Stevens reaction of cis-aziridinylketone tosylhydrazones 7 in the presence of a "slight excess" of sodium hydride or sodium ethoxide. If a large excess of sodium ethoxide is used then isopropylamino-3,5-diaiylpyrazoles are formed <%H(43)1759>. 

On the other hand, ( )-corynantheine was achieved from key intermediate 301, used previously in the synthesis of ajmaline (167). The fra/u-tosylhydrazone derivative 302 afforded the desired vinyl-substituted indolo[2,3-o]quinolizine 304 in moderate yield along with the corresponding ethylidene-substituted isomer. Formylation and methylation of 304 afforded finally ( )-corynantheine (164). 

A disadvantage of the traditional synthesis of A -alkyl-A -tosylhydrazones, particularly in the reaction of the tosylhydrazine with weakly electrophilic carbonyl compounds, is the instability of the hydrazine under the reaction conditions. However, A -alkylation of the tosylhydrazone (Table 5.23) under weakly basic condi-... 

Synthesis of novel bicyclic heterocyclic systems involving aziiidine ring formation has been described. The sodium salts of tosylhydrazones 11 decomposed by heating in benzene and gave aziridinopyrroloindoles 12 in yields up to 73% (equation 5) . Intramolecular cyclization of oxime ether 13 in the presence of base (for example, DBU) in acetonitrile afforded aziridinopyrrolidine 14 in yields up to 51% (equation 6) °. 

A variant on this synthesis uses the tosylhydrazones 14, which on treatment with a base (aqueous alkali,18 morpholine19 or sodium ethoxide20) give the triazolopyridines 15, often in excellent yield. Heating or irradiating such tosylhydrazones in basic media can give triazolopyridines.21... 

Bamford-Stevens reaction of the tosylhydrazones of the readily available tetrahydrofuran-3-ones provides a useful synthesis of 2,3-dihydrofurans which may be dehydrogenated to furans with 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (66CJC1083). Tetrahydrofuran-2-ones (y-butyrolactones) may be alkylated in the 3-position with LDA and an alkyl halide. The products on reaction with phenyl selenylchloride and LDA, and subsequent oxidation, yield 3-alkylfuran-2(5//)-ones reducible with DIBAL to furans (75JOC542). 

A 2-cyclohexenone derivative can be transformed into the corresponding epoxy tosyl-hydrazone by sequential treatment with peracid and tosylhydrazine. The elimination of nitrogen and p-toluenesulfinate and fragmentation after rearrangement to the 3-tosylazo allylic alcohol may occur under mild conditions. Carbonyl compounds with 5,6-triple bonds are formed in high yields (J. Schreiber, 1967 M. Tanabe, 1967). If one applies this reaction to a 9,10-epoxy-1-decalone, a ten-membered 5-cyclodecyn-l-one ring is formed (D. Felix, 1971). This product is an important intermediate in the perfume industry and has been used on a large scale. For this purpose Eschenmoser developed a synthesis in which the readily removed styrene was split off instead of a sulfmic acid. Thus a l-amino-2-phenylaziridine hydrazone was used instead of a tosylhydrazone (D. Felix, 1968). ... 

The first synthesis of the parent compound (1) was reported in i963,14 the best route starting from 2,3-dihydropyrrolizin-l-one (3a), which was transformed to the corresponding tosylhydrazone (182). Compound 1 was obtained from 182 in 29% yield, using Huang-Minion conditions. 

The method using the cyclization of the tosylhydrazone 40, however, gave diazepine 41 in moderate yield (9%) along with the formation of tetrahydropentalene 42 (in 40% yield) (Scheme 9). The tosylhydrazone 40 was made in a four-step synthesis sequence in moderate yield from cyclopentanone. Benzoannulated, polycyclic and the partly saturated systems are known and have been obtained, for example, the benzo[c]cyclopenta[i ]-l,2-diazepine 43 <2001TH1>. 

Pyrolysis of the sodium salt of the tosylhydrazone of 10-bicyclo[5.2.1 ]deca-none provides a remarkably easy synthesis of tricyclo [5.2.1.0 4>10] decane... 

Alkene synthesis. A modified version of an earlier synthesis of alkenes from the tosylhydrazones of aldehydes and certain alkyllithium reagents (9, 472-473) employs the N-r-butyldimethylsilyl derivatives (1) of tosylhydrazones of a,f)-enals, which undergo only 1,2-addition of an alkyllithium at - 78°. The adducts (2) decom-... 

Tosylhydrazones can be silylated with (fert-bufyldimethylsilyl)trifluoromethanesulfonate (Me2teriBuSi03SCF3) on the sulfonamide nitrogen. This is how the starting material for a broadly applicable alkane synthesis is produced ( Figure 1.49). Due to their ability to undergo reductive cyanization (Figure 17.69) mesitylene sulfonyl hydrazones allow for a two-step synthesis of nitriles from ketones. 

Scheme VIII/14. Synthesis of ( )-muscone (VIII/48) using the tosylhydrazone approach of the a,/ -epoxyketone - alkynone fragmentation [38].

Some 2-deoxy-analogues of rubrosterone have been reported.73 The synthesis commenced with a Bamford-Stevens reaction upon 3/3,17/3-diacetoxyandrost-5-en-7-one tosylhydrazone to yield the corresponding 5,7-diene. Successive chromic acid and selenium dioxide oxidation of this diene furnished the 2-deoxyrubrosterones (177 R1 = OAc, R2 = H, R3 = OH, X= 17/3-0Ac,H 5a-H) and (177 R = OAc, R2 = R3 = H, X = 17/3-OAc,H 5a-H) respectively. Alkaline hydrolysis of the latter derivative afforded an A-homo-B-nor-steroid (178). The rubrosterone (177 R1 = R2 = R3 = OH, X = O 5/3-H), which possesses antidiabetic activity, has been prepared by oxidative degradation of the cholestene (179), itself obtained from ecdy-sterone.74... 

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