Study of chiral auxiliaries for the intramolecular [2+2] cycloaddition of a keteniminium salt to an olefinic double bond. A new asymmetric synthesis of cyclobutanones.

Chen, Lian-Yong; Ghosez, Léon

doi:10.1016/s0040-4039(00)97650-0

Cited by 82 publications

(29 citation statements)

References 6 publications

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“…Indeed, when the sterically hindered proton scavenger 2,6-ditert-butylpyridine (DTBP) was applied, a base that is most likely unable to deprotonate the α-methine of the activated amide under these conditions, the yield increased considerably (Entry 5). This is consistent with the fact that DTBP was only observed to promote keteniminium formation when less sterically hindered αmethylene protons were abstracted, [30] although the temperature might also play a decisive role. [31] Concluding on the experiments of Table 1, the reaction might not need a base that directly participates in the formation of the product.…”

Section: Resultssupporting

confidence: 82%

A Novel Class of 7‐Membered Heterocyclic Compounds

2020

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The work presented herein describes the synthesis of a formerly inaccessible class of heterocyclic compounds. The reaction relies on α‐phthalimido‐amides, which are readily prepared from amino acids in 2 simple reactions steps. Under amide activation conditions in which classical keteniminium ions are not formed, the nitrile solvent is incorporated into the new fused 7‐membered ring system. Due to the absence of a keteniminium intermediate, the stereogenic information in the α‐position is fully retained.

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Section: Resultssupporting

confidence: 82%

A Novel Class of 7‐Membered Heterocyclic Compounds

2020

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“…After stirring for 45 min, EtMgBr (3.0 equiv) was added, and the mixture was stirred at RT for 3 h. The results are summarized in Table 1. As can be seen from Table 1, among the bases tested (triethylamine, Hünig base, pyridine, 2,6‐lutidine, 2‐chloropyridine, 2‐fluropyridine, and 2,6‐di‐ tert ‐butyl‐4‐methylpyridine (DTBMP),22d, 24 DTBMP afforded the best result, providing the desired 2,2‐diethylpyrrolidine 10 a in 87 % yield (Table 1, entry 7). The success with DTBMP may be attributed to the appropriate basicity and low nucleophilicity of DTBMP as well as the low electrophilicity of the plausible pyridinium ion intermediate.…”

Section: Resultsmentioning

confidence: 99%

General One‐Pot Reductive gem‐Bis‐Alkylation of Tertiary Lactams/Amides: Rapid Construction of 1‐Azaspirocycles and Formal Total Synthesis of (±)‐Cephalotaxine

Xiao

Luo

Xia

et al. 2013

Chemistry A European J

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Amides are a class of highly stable and readily available compounds. The amide functional group constitutes a class of powerful directing/activating and protecting group for C-C bond formation. Tertiary tert-alkylamine, including 1-azaspirocycle is a key structural feature found in many bioactive natural products and pharmaceuticals. The transformation of amides into tert-alkylamines generally requires several steps. In this paper, we report the full details of the first general method for the direct transformation of tertiary lactams/amides into tert-alkylamines. The method is based on in situ activation of amide with triflic anhydride/2,6-di-tert-butyl-4-methylpyridine (DTBMP), followed by successive addition of two organometallic reagents of the same or different kinds to form two C-C bonds. Both alkyl and functionalized organometallic reagents and enolates can be used as the nucleophiles. The method displayed excellent 1,2- and good 1,3-asymmetric induction. Construction of 1-azaspirocycles from lactams required only two steps or even one-step by direct spiroannelation of lactams. The power of the method was demonstrated by a concise formal total synthesis of racemic cephalotaxine.

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“…The benzyl ester was hydrolyzed and the intermediate acid was activated and condensed with a C ‐2 symmetric pyrrolidine‐derived chiral auxiliary to give amide 46 . Following the pioneering work of Ghosez, treatment of 46 with triflic anhydride initiated a stereoselective intramolecular [2+2] cycloaddition reaction, which proceeded via the ketene‐iminium intermediate 47 , to form tricyclic iminium species 48 . Hydrolysis gave cyclobutanone 49 , which underwent ring expansion via a regioselective Baeyer–Villiger oxidation to give the tricyclic lactone 50 with excellent enantiomeric excess (91 %).…”

Section: Accessing Single Enantiomer Strigolactonesmentioning

confidence: 99%