Preparation of Aryldiazoalkanes from 2,4,6-Triisopropylbenzenesulphonyl Hydrazones

Dudman, Christopher C.; Reese, Colin B.

doi:10.1055/s-1982-29821

Cited by 34 publications

(17 citation statements)

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“…These observations are in complete accord with the previous work of Reese et al [19] who reported that the rate of base-mediated decomposition of arylsulfonylhydrazones into the corresponding diazo compounds increases with increasing steric bulk on the aryl portion (particularly of the ortho substituents) of the arylsulfonylhydrazone. In general, the flow conditions are tolerant of a useful range of a-substituents (e.g., aryl, alkyl, and trifluoromethyl), and a diverse array of ester groups is also compatible with the conditions.…”

supporting

confidence: 92%

“…[15] We therefore concluded that there would be significant safety benefits in adapting the Bamford-Stevens reaction for use in-flow to produce diazoesters, which in turn could be utilized immediately in subsequent transformations without needing to be isolated or purified. Reassured by these data, a wider range of arylsulfonylhydrazones 1 a-i was readily prepared from simple and inexpensive starting materials [17][18][19] Our initial efforts to develop an in-flow diazoester synthesis focused upon studying the conversion of tosylhydrazone 1 a into the corresponding diazo compound 2 a under flow conditions (Scheme 3). To this end, a solution of the tosylhydrazone 1 a (0.125 m in dichloromethane) was injected into one of the sample loops of the R2 + unit of a Vapourtec R2 + /R4 reactor.…”

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confidence: 99%

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Rapid Access to α‐Alkoxy and α‐Amino Acid Derivatives through Safe Continuous‐Flow Generation of Diazoesters

Bartrum

Blakemore

Moody

et al. 2011

Chemistry A European J

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Despite the wide synthetic potential of diazo compounds (XÀH insertion, ylide formation, cyclopropanation, cycloaddition etc.), [1] concerns over the hazards associated with their preparation, isolation, and use have hindered their full exploitation in both academic and industrial laboratories. A few diazo compounds are commercially available (e.g. ethyl and butyl diazoacetate, TMS-diazomethane and diazodimedone), [2] but safe and convenient access to a wider range of useful functionalized diazo species is still desirable.[3] Diazo transfer can be used to access a-diazocarbonyls, but this only partially addresses the safety concerns associated with the diazo species, as the use of equally hazardous azidebased diazo-transfer reagents is still required.[4] Ideally, it would be beneficial if the diazo species could be generated and consumed in situ so that handling of the hazardous diazo compound is avoided altogether.Recent work by Ley, [5] Jamison, [6] Kappe, [7] and others [4,[8][9][10] has shown that highly reactive diazo and azido compounds can be used in lab-scale continuous-flow reactors to achieve a number of very useful synthetic transformations, and indeed work from our own laboratory has shown that ethyl diazoacetate can be used in-flow to access b-keto esters.[11] We therefore wondered if it was possible to actually generate a-diazocarbonyl compounds under flow conditions and then use these materials directly in further synthetic manipulations, thus minimizing exposure to any potentially hazardous material. In effect, could we develop a continuous-flow diazo generator and then demonstrate its use to prepare a range of useful a-alkoxy (3 a-i) and aamino acid (4 a-i) derivatives through O À H and N À H insertion (Scheme 1)?At the outset we were aware that in order to provide an acceptable solution to the problem, we needed to identify a way to access the diazo compounds of interest (2 a-i) from starting materials that showed an acceptable safety profile, that is, the precursor molecules and reagents should be safer to prepare and handle than the diazocarbonyl compounds being produced. Of the methods available for the generation of a-diazocarbonyl compounds, we were particularly attracted to the Bamford-Stevens reaction as it uses readily accessible arylsulfonylhydrazones (e.g., 1 a-i) as starting materials, with the corresponding diazocarbonyls being generated upon exposure to relatively weak base at moderate reaction temperatures. [12][13][14] Thermal stability studies (DSC and TGA) were conducted on the tosylhydrazone 1 b and its corresponding methyl diazoester 2 b [15,16] in order to determine if a safe window of operation could be identified for the continuous-flow process (see the Supporting Information). The results clearly show that the rate of initial mass loss from diazoester 2 b peaks at 125 8C, which corresponds to a significant exotherm. In comparison tosylhydrazone 1 b has a rate of mass loss which peaks at 221 8C, indicating that it is substantially more thermally stable.[15] We therefore co...

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confidence: 92%

mentioning

confidence: 99%

Rapid Access to α‐Alkoxy and α‐Amino Acid Derivatives through Safe Continuous‐Flow Generation of Diazoesters

Bartrum

Blakemore

Moody

et al. 2011

Chemistry A European J

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“…Thel ower reaction temperature may be attributed to steric hindrance of the bulky substitution, which facilitates the decomposition of N-2,4,6-triisopropylbenzenesulfonyl hydrazone to adiazo compound. [14] Since N-arenesulfonylhydrazones can be readily prepared simply by mixing carbonyl compounds and arenesulfonyl hydrazide,w ee xamined the [Co(F 20 -TPP)]-catalyzed cyclo- Thea so btained cyclopropanation products could be converted into ar ange of N-heterocycles of interest in medicinal chemistry.F or example, 4i readily underwent cyclopropane ring opening by treatment with K 2 CO 3 in DMF at 90 8 8Ct og enerate the 5,7a-dihydro-3H-pyrrolizine 5 in 91 %y ield, and then hydrogenation of 5 gave the polysubstituted pyrrolizidine 6 in 90 %y ield (Scheme 3). Thep resent catalysis thus facilitates rapid construction of polysubstituted pyrrolizidines which are commonly found in naturally occurring pyrrolizidine alkaloids possessing aw ealth of bioactivities.…”

Section: Angewandte Chemiementioning

confidence: 99%

Cobalt(II) Porphyrin‐Catalyzed Intramolecular Cyclopropanation of N‐Alkyl Indoles/Pyrroles with Alkylcarbene: Efficient Synthesis of Polycyclic N‐Heterocycles

Reddy

Hao

et al. 2015

Angew Chem Int Ed

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A protocol on chemoselective cobalt(II) porphyrin-catalyzed intramolecular cyclopropanation of N-alkyl indoles/pyrroles with alkylcarbenes has been developed. The reaction enables the rapid construction of a range of nitrogen-containing polycyclic compounds in moderate to high yields from readily accessible materials. These N-containing polycyclic compounds can be converted into a variety of N-heterocycles with potential synthetic and biological interest. Compared to their N-tosylhydrazone counterparts, the use of bulky N-2,4,6-triisopropylbenzenesulfonyl hydrazones as carbene precursors allows cyclopropanation to occur under milder reaction conditions.

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“…Use of phenyldiazomethane for this purpose is uncommon, but has been reported. 15 Formation of 6 using phenyldiazomethane generated as described by Dudman and Reeze 16 proved successful. Gratifyingly, in contrast to the corresponding methyl ester, 6 was stable under the conditions required for silica gel chromatography and was purified as a clear oil (84% yield).…”

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confidence: 97%

A simple route for synthesis of 4-phospho-d-erythronate

Novikov

Copley

Eaton

2011

Tetrahedron Letters

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4-Phospho-D-erythronate is an intermediate in synthesis of pyridoxal 5′-phosphate in some bacteria and an inhibitor of ribose 5-phosphate isomerase. Previous synthetic schemes for the preparation of 4-phospho-D-erythronate required expensive precursors and typically gave low yields. We report a straightforward synthesis of 4-phospho-D-erythronate from the inexpensive precursor D-erythronolactone in 5 steps with a preparatively useful yield of 22%.

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Preparation of Aryldiazoalkanes from 2,4,6-Triisopropylbenzenesulphonyl Hydrazones

Cited by 34 publications

References 0 publications

Rapid Access to α‐Alkoxy and α‐Amino Acid Derivatives through Safe Continuous‐Flow Generation of Diazoesters

Rapid Access to α‐Alkoxy and α‐Amino Acid Derivatives through Safe Continuous‐Flow Generation of Diazoesters

Cobalt(II) Porphyrin‐Catalyzed Intramolecular Cyclopropanation of N‐Alkyl Indoles/Pyrroles with Alkylcarbene: Efficient Synthesis of Polycyclic N‐Heterocycles

A simple route for synthesis of 4-phospho-d-erythronate

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