Chiral lithium amide base-mediated rearrangement of meso-cyclohexene oxides: asymmetric synthesis of amino- and aziridinocyclohexenols

O’Brien, Peter; Pilgram, Christopher D.

doi:10.1039/b210608f

Cited by 32 publications

(12 citation statements)

References 73 publications

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“…During some of the runs, a mixture of aziridine and cyclohexene oxide was used, and the epoxide rearranged successfully, showing that active LDA was in fact present. This finding is consistent with O'Brien's observation that N ‐tosyl aziridines are substantially less reactive than epoxides to lithium amide bases 25. Because the calculations predicted so convincingly that the sulfonylated aziridines would react even more favorably than epoxides, the apparent inertness of the aziridines was surprising.…”

Section: Resultssupporting

confidence: 84%

β‐Elimination of an aziridine to an allylic amine: a mechanistic study

Morgan

Brown

Pichon

et al. 2011

J of Physical Organic Chem

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The base-induced rearrangement of aziridines has been examined using a combination of calculations and experiment. The calculations show that the substituent on nitrogen is a critical feature that greatly affects the favorability of both α-deprotonation, and β-elimination to form an allylic amine. Experiments were carried out to determine whether E2-like rearrangement to the allylic amine with lithium diisopropyl amide (LDA) is possible. N-Tosyl aziridines were found to deprotonate on the tosyl group, preventing further reaction. A variety of N-benzenesulfonyl aziridines having both α- and β-protons decomposed when treated with LDA in either tetrahydrofuran or hexamethylphosphoramide. However, when α-protons were not present, allylic amine was formed, presumably via β-elimination.

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Section: Resultssupporting

confidence: 84%

β‐Elimination of an aziridine to an allylic amine: a mechanistic study

Morgan

Brown

Pichon

et al. 2011

J of Physical Organic Chem

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“…Deprotonation reactions involving a stoichiometric (or more) amount of CLA, and thus in the absence of an achiral amide, continued to be explored in the same period (Scheme 10.2). Some of the reactions studied in this context include the rearrangements of (i) bis-protected meso-4,5-dihydroxycyclohexene oxides 110 (using CLAs 18b, 41-47, 56a,c, 58 or 69, 2 equiv, ee up to 95%), precursors of conduritol derivatives known for their antibiotic and antileukemic activity (Scheme 10.2, first line) [4d]; (ii) spiro epoxide fused cis-bicyclo [3.3.0]octanes 111 (using CLAs 4b, 18a, or 58, 2 equiv, ee up to 80%) (Scheme 10.2, second line) [15]; (iii) meso-aziridinocyclohexene oxides 112 (using CLAs 46a, 56a, 58, 60, or 69, 1.2 equiv, ee up to 68%) (Scheme 10.2, third line) [16]; and (iv) substituted cyclopentene oxides 113 (using CLAs 5a, 18a, 21, 22a, 24a, 25, 26, 27, 46a, 56, or 69, 2-3 equiv, ee up to 93%) (Scheme 10.2, fourth line) [17,18]. Working with solid-phase supported CLAs (99 and 100) on cyclohexene oxide also proved to be successful (ee up to 91%) [19].…”

Section: Enantioselective Conversion Of Epoxides Into Allylic Alcoholsmentioning

confidence: 99%

Advances in the Chemistry of Chiral Lithium Amides

Harrison‐Marchand

Maddaluno

2014

Lithium Compounds in Organic Synthesis

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“…7,8 Alternatively, different iodinanes PhI=NSO 2 R in combination with Cu(I) or Cu(II) salts can be used in the direct aziridination of alkenes, 9 and we have exploited this in previous studies. 8,10,11 Some different iodinanes were prepared by Andersson and co-workers 12 and Protasiewicz and co-workers; 13 the iodinanes can also be generated in situ, as reported by Dauban and Dodd. 14 In addition, N-SES-protected (SES: trimethylsilylethylsulfonyl) aziridines have been prepared using this approach.…”

Section: Figurementioning

confidence: 99%

Two-Step Synthesis ofN-Sulfonyl Aziridines from Epoxides

Huang¹,

O’Brien²

2006

Synthesis

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A convenient and high-yielding two-step synthesis of Nsulfonyl aziridines starting from epoxides is described. The method, which involves epoxide ring opening with sulfonamides and subsequent mesylation-cyclisation, is particularly suitable for variation of the N-sulfonyl substituent; 18 examples are presented.Aziridines have an ever-improving reputation as useful intermediates in synthetic organic chemistry. 1 As such, several different approaches and methodologies have been developed for the synthesis of aziridines. 1-3 With reference to the preparation of N-sulfonyl aziridines, close inspection of the different approaches reveals that they mostly generate N-toluenesulfonyl (N-tosyl) aziridines. Methodology for the synthesis of 'non-tosyl' aziridines is far less developed and/or typically low yielding. We are interested in developing new organolithium-mediated reactions of aziridines and our previous work has focused on the use of N-tosyl aziridines. 4,5 With a view to investigating other N-sulfonyl aziridines in the organolithium chemistry, we needed a reliable, high yielding and simple route to a range of N-sulfonyl aziridines 1 and 2 ( Figure 1). Figure 1The most straightforward route to N-sulfonyl aziridines 1 and 2 would be sulfonylation of the NH aziridine, which can be produced by Staudinger reduction of the azido alcohol (generated by ring opening of the corresponding epoxide). 6 In our hands, this three-step route is often lowyielding. 7,8 Alternatively, different iodinanes PhI=NSO 2 R in combination with Cu(I) or Cu(II) salts can be used in the direct aziridination of alkenes, 9 and we have exploited this in previous studies. 8,10,11 Some different iodinanes were prepared by Andersson and co-workers 12 and Protasiewicz and co-workers; 13 the iodinanes can also be generated in situ, as reported by Dauban and Dodd. 14 In addition, N-SES-protected (SES: trimethylsilylethylsulfonyl) aziridines have been prepared using this approach. 15 Overall, however, the iodinane methodology mostly employs PhI=NTs, is generally moderate to low yielding, and often works best with an excess of the alkene. N-Sulfonyl aziridines can also be prepared from alkenes using electrophilic Br + and N-chloramine sulfonamide salts (RSO 2 NCl -Na + ), as pioneered by Sharpless 16 and Komatsu. 17 These reactions almost always use commercially available chloramine-T 4,5,7,16-18 (introduction of an N-tosyl group), but Sharpless and co-workers have also used tBuSO 2 NCl -Na + . 19 Finally, three-step routes from epoxides to N-sulfonyl aziridines via epoxide ring opening using sulfonamides, activation, and cyclisation have been reported by Albanese 20 and Jacobsen. 21 Although both routes had not varied the sulfonamide significantly, the Albanese route appeared ideal for our purposes of generating a range of N-sulfonyl aziridines 1 and 2 from the corresponding epoxides. 22,23 The general approach we have optimised is summarised in Scheme 1. In particular, we have streamlined this approach into a two-step synthesis by cyclising the crude a...

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Chiral lithium amide base-mediated rearrangement of meso-cyclohexene oxides: asymmetric synthesis of amino- and aziridinocyclohexenols

Cited by 32 publications

References 73 publications

β‐Elimination of an aziridine to an allylic amine: a mechanistic study

β‐Elimination of an aziridine to an allylic amine: a mechanistic study

Advances in the Chemistry of Chiral Lithium Amides

Two-Step Synthesis ofN-Sulfonyl Aziridines from Epoxides

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