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Klimenko, S. K.; Stolbova, T. V.; Макаров, В. В.

doi:10.1023/a:1022605013067

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(2 citation statements)

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“…The synthesis of 13f following GP 1 yielded 1.45 g (32%) of the major diastereomer as a colourless oil; ee >99%; R f = 0. 1, 26.9, 28.9, 30.6, 32.6, 39.1, 47.2, 83.4, 127.5, 128.1, 128.9, 136.6, 137.0, 151.5, 192.0, 195.4 3.42 (ddd,J = 11.5,10.8,2.5 Hz,1 H),3.64 (dd,J = 10.8,3.9 Hz, 1 H), 3.70 (dd, J = 6.9, 3.0 Hz, 1 H), 4.18 (dd, J = 12.1, 11.5 Hz, 1 H), 5.41 (dd, J = 12.1, 6.9 Hz, 1 H), 7.40-7.21 (m, 10 H), 9.68 (d, J = 2.5 Hz, 1 H).…”

Section: Carbaldehyde 13fmentioning

confidence: 99%

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Asymmetric Synthesis of Thiadecalins via an Organocatalytic Triple Cascade/Sulfa-Michael Sequence

Enders¹,

Schmid²,

Erdmann³

et al. 2010

Synthesis

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An efficient two-step asymmetric synthesis of highly substituted cis-configured thiadecalins and the corresponding hexahydrobenzothiophene core is described. Thiadecalin derivatives are known for their widespread biological activities, such as antimicrobial and neurotropic properties. The procedure is based on an organocatalytic triple cascade reaction followed by an intramolecular sulfa-Michael addition. In this manner six consecutive stereocentres are controlled and the target molecules are obtained in moderate yields, with virtually complete enantioselectivitiy (ee >99%) and after recystallisation in diastereomeric ratios of >97:3. The relative and absolute configuration was determined by NMR spectroscopy and X-ray structure analysis.The research field of organocatalysis 1 has developed rapidly since about the turn of the millennium and can now be seen as a third pillar of asymmetric catalysis beside metal and biocatalysis. Numerous basic organocatalytic protocols for very efficient and highly stereoselective carbon-carbon and carbon-heteroatom bond formations are now part of the strategic arsenal of synthetic chemistry and can be used in the asymmetric total synthesis of natural products and bioactive compounds in general.Thiadecalin derivatives have been studied intensively with regard to their antimicrobial and antiphage properties including the treatment of infected wounds. 2 It has also been shown that thiadecalins exhibit neutrotropic activity. 3 The corresponding thiadecalin sulfonium salts showed sedative properties during hexenal-induced sleep. In addition, other thiadecalin derivatives are known to be antigestagens and antiglucocorticoids. 4 These compounds are also mentioned in combination with the treatment of psychosis and addictive behaviour. The antiglucocorticoids can be used to treat spontaneous or narcotic-induced withdrawals, especially from heroin, morphine, methadone, cocaine, and their mixtures. 5Among the various subdisciplines of organocatalysis, domino reactions 6 enabling the highly stereoselective construction of complex molecules in a single operation have been studied intensively in the last few years. 7 In 2006, our group reported an efficient three-component domino reaction leading to tetrasubstituted cyclohexenecarbaldehydes. 8 In order to synthesize the potentially bioactive thiadecalins 1 we envisaged extending the triple cascade method by a subsequent intramolecular sulfaMichael addition 9 via nucleophilic displacement of bromide 3 to form the sulfa-Michael precursor 2 (Scheme 1). Scheme 1 Retrosynthetic analysis of the asymmetric thiadecalin synthesisEmploying 5-bromopentanal (4), readily available through DIBAL-H reduction of the commercially available bromo ester, in the cascade reaction with nitrostyrene (5) and cinnamaldehyde (6) under diphenylprolinol TMSether catalysis 7 gave the desired domino product 8 as a 3.8:1 diastereometric mixture of the a-nitro epimers and with practically complete enantiomeric excess (ee >99%) in 68% yield. The major diastereomer shown could ...

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Section: Carbaldehyde 13fmentioning

confidence: 99%

“…2 It has also been shown that thiadecalins exhibit neutrotropic activity. 3 The corresponding thiadecalin sulfonium salts showed sedative properties during hexenal-induced sleep. In addition, other thiadecalin derivatives are known to be antigestagens and antiglucocorticoids.…”

mentioning

confidence: 99%