Synthesis of Substituted Benzhydrylamines

Dejaegher, Yves; Mangelinckx, Sven; Kimpe, Norbert De

doi:10.1055/s-2002-19328

Cited by 18 publications

(24 citation statements)

References 8 publications

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“…At first, reduction was attempted using sodium borohydride in methanol, since the diphenylmethylidenamino moiety normally is reduced under these conditions. 37 However, refluxing cyclopropane 4a in methanol with one molar equivalent of sodium borohydride resulted in an almost 1:1 mixture of starting material and 1-pyrroline 8 (entry 1). Apparently, heating of cyclopropane 4a with sodium borohydride lead to formation of 1-pyrroline 8, while sodium borohydride is not a strong enough reducing agent in this case, confirmed by the absence of reaction at room temperature (entry 2).…”

Section: Methodsmentioning

confidence: 99%

Synthesis of N-Protected β-Aminocyclopropanedicarboxylates and Their Ring Transformation to N-Benzhydryl-3-alkoxycarbonyl-4,4-dialkylpyrrolidin-2-ones

Mangelinckx¹,

Kimpe²

2005

Synlett

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An easy and short synthesis of new N-protected b-aminocyclopropanedicarboxylates, a rather unexplored class of highly activated conformationally constrained b-amino acid derivatives, is described. Michael-induced ring closure (MIRC) of diphenylmethylidenamine to 2-bromoalkylidenemalonates leads to 3,3-dialkyl-2-(diphenylmethylidenamino)cyclopropane-1,1-dicarboxylates, the reactivity of which with hydrides was investigated, yielding 3-(alkoxycarbonyl)pyrrolidin-2-ones.One of the most conformationally constrained classes of b-amino acids are 2-aminocyclopropanecarboxylic acids (b-ACCs) 1, which readily undergo ring opening to goxo-carboxylates 2, due to the 1,2-push-pull substitution on the cyclopropane ring (Scheme 1). 1 Therefore, an appropriate N-protecting group has to be introduced during the synthesis of b-aminocyclopropanecarboxylic acid derivatives, and special procedures are necessary to incorporate these donor-acceptor cyclopropanes (D-A cyclopropanes) into b-peptide structures, which has limited their use. 2 Besides their incorporation in b-peptide structures, it can be envisioned that the intrinsic characteristic of b-ACCs to ring open could be used as an advantage in the synthesis of N-heterocyclic compounds under appropriate conditions. However, contrary to D-A cyclopropanes with an oxygen substituent as donor, 1a only relatively few examples of the heterocyclic synthetic use of ring-opening of b-ACCs are known. Moreover, often further functionalisation in the b-ACC structure is required to make the synthesis of the N-heterocycle possible. These examples include hydrolysis of a cyclopropanated enaminocarboxanilide to a pyrrolidone, 3 transformation of ring-opened 3-acyl-2-aminocyclopropane-1-carboxylates to tetrahydrocyclopenta[b]pyrroles and tetrahydroindoles, 4 electrocyclic ring enlargement of cyclopropanated uridines to 1,3-diazepinediones, 5 ring transformation of b-ACC derivatives during the synthesis of the alkaloid (±)-eburnamonine, 6,7 thermal rearrangement of 6-ethyl 2-methyl 2-azabicyclo[3.1.0]hex-3-ene-2,6-dicarboxylate in the presence of CuBr to ethyl Nmethoxycarbonylpyrrole-2-acetate or gas pyrolysis to 2-ethyl 1-methyl pyridine-1,2(2H)-dicarboxylate, 8 and the photochemical rearrangement of 2-diphenylmethylidenamino-2-methylcyclopropane-1-carboxylates to the corresponding 1-pyrrolines. 9In the present article results are disclosed on the synthesis of N-protected 2-aminocyclopropane-1,1-dicarboxylates, a class of highly activated b-ACCs, of which only few related compounds have been synthesised, i.e. b-purinyl, 10 b-imidazolyl, 11 b-nitro, 12 and b-N,N-(bistrimethylsilyloxy)aminocyclopropanedicarboxylates. 13 Furthermore, the synthetic use of the newly prepared b-aminocyclopropanedicarboxylates as interesting building blocks for functionalised g-lactams is described. 3-(Alkoxycarbonyl)pyrrolidin-2-ones are highly desirable targets in organic synthesis, as they exhibit physiological activities, e.g. scytalone dehydratase inhibition. 14 Moreover, they also have been used in the synthesis o...

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Section: Methodsmentioning

confidence: 99%

Synthesis of N-Protected β-Aminocyclopropanedicarboxylates and Their Ring Transformation to N-Benzhydryl-3-alkoxycarbonyl-4,4-dialkylpyrrolidin-2-ones

Mangelinckx¹,

Kimpe²

2005

Synlett

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“…19 F NMR were recorded at 25 °C on 470 MHz spectrometer by using (trifluoromethyl)benzene (δ −63.2) as external standard. Data for 1 H, 13 C, and 19 F were recorded as follows: chemical shift (δ, ppm), multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, dd = doublet of doublets). High-resolution mass spectra (HRMS) were obtained using a microTOF II focus spectrometer (SI).…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

“…1 H NMR (500 MHz, DMSO) δ 10.85 (s, 1H), 7.77 (d, J = 8.0 Hz, 2H), 7.56 (d, J = 8.0 Hz, 2H), 7.41 (d, J = 8.0 Hz, 2H), 7.38 (d, J = 7.5 Hz, 2H). 13 C NMR (125 MHz, DMSO) δ 173.5, 150. 6, 150.0, 138.5, 137.6, 131.1 (2C), 130.2 (2C), 121.2 (2C), 120.9 (2C), 120.7 (q, J = 255.0 Hz, 2C 3, 122.1, 121.4, 119.8, 118.5, 115.9, 115.3, 114.1, 113.6, 113.0, 55 (4-Fluorophenyl)(4-methoxyphenyl)methanimine (1q).…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

“…1 H NMR (500 MHz, DMSO) δ 10.26 (s, 1H), 7.56 (s, 2H), 7.49 (s, 2H), 7.23 (t, J = 9.0 Hz, 2H), 6.97 (d, J = 9.0 Hz, 2H), 3.79 (s, 3H). 13 C NMR (125 MHz, DMSO) δ 174.4, 163.5 (d, J = 247.2 Hz), 161. 3, 136.3, 131.5, 130.9, 130.2 115.6, 115.4, 114.1 (4C), 55.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

“…1 H NMR (500 MHz, CDCl 3 ) δ 7.71 (d, J = 7.5 Hz, 2H), 7.54−7.43 (m, 4 H), 7.38 (t, J = 7.5 Hz, 2H), 7.26 (d, J = 7.5 Hz, 2H). 13 C NMR (125 MHz, CDCl 3 ) δ 179.0 (q, J = 8.0 Hz, 1C), 137.7, 135.8, 133.0, 130.3 (2C), 129.6, 128.3 (2C), 127.9 (2C), 127.3 (d, J = 1.4 Hz, 2C), 123.7 (q, J = 261.9 Hz, 1C). 19 F NMR (470 MHz, CDCl 3) δ −56.0 (s, 3F).…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

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