Asymmetric Dipolar Cycloadditions of Me<sub>3</sub>SiCHN<sub>2</sub>. Synthesis of a Novel Class of Amino Acids:  Azaprolines

Mish, Michael; Guerra, Francisco M.; Carreira, Erick M.

doi:10.1021/ja971708p

Cited by 97 publications

(50 citation statements)

References 21 publications

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“…[13,14] The latter reactions proceed via pyrazolines, which are further reduced with NaBH 3 CN or LiBEt 3 H. As a potential access to compounds of type C a direct condensation of (+)-pulegone (1) with hydrazines appeared feasible. Precedence for the formation of pyrazolines from hydrazines and a,b-unsaturated carbonyl compounds exists.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, the oxidation product 6 a of octahydroindazole 7 a was obtained as an oily material from the recrystallization attempts. While the air sensitivity of pyrazolidines has been earlier mentioned by others, [13,14,22] we are not aware that this process was further studied. We assumed that pyrazolidine 7 a is capable of reducing oxygen under atmospheric pressure to hydrogen peroxide (Scheme 7) and would therefore be a source of water-free hydrogen peroxide in organic solvents.…”

Section: Entrymentioning

confidence: 88%

“…Common solvents for chromatography [pentane, ethyl www.chemeurj.org tion. 13 C NMR spectra of all new compounds are also presented in the Supporting Information. 3,3a,4,5,6,hexahydroindazole (2 a): (+)-Pulegone (538 mL, 502 mg, 3.30 mmol, 92 %) was dissolved in THF (12 mL).…”

Section: Methodsmentioning

confidence: 99%

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Synthesis and Properties of Chiral Pyrazolidines Derived from (+)‐Pulegone

Jakob

Herdtweck

Bach

2010

Chemistry A European J

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Several enantiomerically pure N(2)-substituted octahydroindazoles were prepared as bicyclic pyrazolidine derivatives of (+)-pulegone. Condensation of pulegone with hydrazine delivered a hexahydroindazole intermediate, which underwent N(2)-substitution with various electrophiles (alkyl halides, acyl chlorides, phenyl isocyanate). The resulting N(2)-substituted hexahydroindazoles could be reduced with LiBEt(3)H in THF to the target compounds. In addition, a N(2)-thiobenzoyl and some N(2)-carbamoyl derivatives as well as a N(1)-substituted octahydroindazole were synthesized. The compounds showed medium activity as iminium ion catalysts promoting quantitatively the Michael addition of nitroethane to cinnamaldehyde in up to 82% ee for the resulting syn-diastereoisomer and 78% ee for the anti-diastereoisomer. Unexpectedly, the N(2)-acyloctahydroindazoles were readily oxidized under aerobic conditions. Moreover, it was shown that an oxidation of methyl phenyl sulfide to the corresponding sulfoxide is promoted by an N(2)-acyloctahydroindazole in deuterochloroform as solvent. It is proposed that the oxidation of N(2)-acyloctahydroindazoles proceeds by in situ generation of hydrogen peroxide, which in turn can act as an oxidant.

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Section: Resultsmentioning

confidence: 99%

Section: Entrymentioning

confidence: 88%

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Synthesis and Properties of Chiral Pyrazolidines Derived from (+)‐Pulegone

Jakob

Herdtweck

Bach

2010

Chemistry A European J

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“…[12][13][14][15][16][17][18][19][20] Nevertheless, most of these asymmetric methods do not lend themselves to a simple synthesis of MS-153 in any obvious way. A notable exception is the asymmetric acylhydrazone-enol ether cycloaddition developed by Kobayashi and co-workers, and indeed as part of that work a synthesis of MS-153 was reported.…”

Section: A C H T U N G T R E N N U N G [3+2]mentioning

confidence: 99%

A Simple, Efficient, and Highly Enantioselective Synthesis of MS‐153 Employing a Chiral Silane Lewis Acid‐Promoted Acylhydrazone‐Enol Ether [3+2] Cycloaddition

Tran¹,

Leighton²

2006

Adv Synth Catal

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Our previously reported chiral silane-promoted enol ether-acylhydrazone [3 + 2] cycloaddition reaction has been applied to a brief and efficient synthesis of the neuroprotective agent MS-153. Unsatisfactory and variable levels of efficiency and enantioselectivity with the requisite acetaldehyde-derived acylhydrazone occasioned a modification to the chiral silane Lewis acid, which led to the key cycloaddition step proceeding with excellent efficiency (85 % yield) and enantioselectivity (! 98 % ee).

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“…Compared to the normal imine C=N double bond, the C=N double bond of 64d ( Figure 24) is more robust as indicated by the fact that no reduction of 64d ( Figure 24) occurred and most of the starting material was recovered in the reduction attempts with sodium cyanoborohydride in acetic acid 163 (Table 6, Entry 5-6).…”

Section: Reductions Of Protected 2-pyrazolinesmentioning

confidence: 99%

Syntheses of aza analogs of kainoids

Di¹

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Asymmetric Dipolar Cycloadditions of Me₃SiCHN₂. Synthesis of a Novel Class of Amino Acids: Azaprolines

Cited by 97 publications

References 21 publications

Synthesis and Properties of Chiral Pyrazolidines Derived from (+)‐Pulegone

Synthesis and Properties of Chiral Pyrazolidines Derived from (+)‐Pulegone

A Simple, Efficient, and Highly Enantioselective Synthesis of MS‐153 Employing a Chiral Silane Lewis Acid‐Promoted Acylhydrazone‐Enol Ether [3+2] Cycloaddition

Syntheses of aza analogs of kainoids

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Asymmetric Dipolar Cycloadditions of Me3SiCHN2. Synthesis of a Novel Class of Amino Acids: Azaprolines

Cited by 97 publications

References 21 publications

Synthesis and Properties of Chiral Pyrazolidines Derived from (+)‐Pulegone

Synthesis and Properties of Chiral Pyrazolidines Derived from (+)‐Pulegone

A Simple, Efficient, and Highly Enantioselective Synthesis of MS‐153 Employing a Chiral Silane Lewis Acid‐Promoted Acylhydrazone‐Enol Ether [3+2] Cycloaddition

Syntheses of aza analogs of kainoids

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Asymmetric Dipolar Cycloadditions of Me₃SiCHN₂. Synthesis of a Novel Class of Amino Acids: Azaprolines