Asymmetric Induction by a Nitrogen ¹⁴N/¹⁵N Isotopomer in Conjunction with Asymmetric Autocatalysis

Abstract

Chirality arising from isotope substitution, especially with atoms heavier than the hydrogen isotopes,i su sually not considered as ource of chirality in ac hemical reaction. An N 2 ,N 2 ,N 3 ,N 3 -tetramethyl-2,3-butanediamine containing nitrogen ( 14 N/ 15 N) isotope chirality was synthesized and it was revealed that this isotopically chiral diamine compound acts as ac hiral initiator for asymmetric autocatalysis. Most of the chemical elements have stable isotopes.Isotope-substituted compounds (isotopomers) have almost the same chemical reactivity,isotope substitution and isotope effect, therefore they are widely used for studies of reaction mechanisms and tracing compounds.[1] However,i sotope substitution sometimes breaks the molecular symmetry and produces hidden chirality in usually achiral molecules. Usually,this hidden chirality does not receive much attention because the difference between these isotopically chiral compounds is very small and negligible in asymmetric induction. Although the chirality arising from isotope substitution was discussed after the finding of stable isotopomers, [2][3][4] the isotope effect in chirality has mainly been studied on hydrogen isotopes because the almost double relative mass ratio of Ha nd Dp roduces relatively large isotope effects compared with other element isotopomers.[5] Thus,c hirality induction in areaction arising from heavier atoms [6] is ahighly challenging and interesting topic, especially in the study of the origin of homochirality. [7] We have been studying asymmetric autocatalysis of pyrimidyl alkanol, [8] which causes significant amplification of enantiomeric excess (ee)during the progress of areaction. This reaction can recognize the various chiral environments [9] and attracts wide attention from the viewpoint of symmetry breaking [10] and its unique reaction mechanism.[11] Recently, we demonstrated that asubtle difference of isotopic chirality can induce asymmetric induction in an asymmetric autocatalysis reaction.[12] Chiral compounds (as the result of hydrogen (H/D), [13] carbon ( 12 C/ 13 C), [14] and oxygen ( 16 O/ 18 O) [15] isotopes) act as chiral initiators for asymmetric autocatalysis. Herein, we report the first example of asymmetric induction by chiral nitrogen ( 14 N/ 15 N) isotopomers with as maller relative mass difference compared to previously reported isotopomers (Scheme 1).Nitrogen is one of the abundant atoms in the construction of various bioorganic molecules,and the coordinating ability of nitrogen atoms is widely exploited in various ligands. 15 Nis auseful NMR-active isotope and the isotope ratio of 14 N/ 15 N is also used in the study of the origin of meteorites. [16] However,t oo ur knowledge,i sotopically chiral compounds arising from nitrogen isotope ( 14 N/ 15 N) substitution have not been synthesized and studied as achiral initiator.Herein, we demonstrate the synthesis of compounds that are isotopically chiral by nitrogen isotope substitution and their chiral induction of asymmetric autocatalysis (S...

In Situ Mass Spectrometric and Kinetic Investigations of Soai's Asymmetric Autocatalysis

“…Autocatalysis and amplification are also observed in pyridyl-3-carbaldehydes, [12] however the 2-alkynyl substituted pyrimidine analogues are superior in amplification of the ee. Even at race imbalance of chiral molecules [13] such as an extremelyl ow ee of the initial catalysto fo nly~5 10 À5 % [14] or other chiralt riggers like 1 H/ 2 H, [15] 12 C/ 13 C, [16] 14 N/ 15 N [17] and 16 O/ 18 O [18] isotopically labelled cryptochiral compounds, [19] cryptochiral compounds, [20] circularly polarized light, [21] (enantiomorph) crystals [22] and other compounds [23] are able to induce enantioselectivities,t hat lead to an amplification greater than 99.5 % ee in af ew cycles. A highly interesting feature of the reaction is, that spontaneous symmetry breaking with stochastic distribution of the final (R)-1 or (S)-1 product is possible, even when no chiral additive is employed.…”

Demystifying the asymmetry-amplifying, autocatalytic behaviour of the Soai reaction through structural, mechanistic and computational studies

“… 3 In the absence of added catalyst, symmetry breaking can yield non-racemic products, 4 – 7 thus categorizing the transformation as an example of spontaneous absolute asymmetric synthesis. 8 A large variety of chiral additives 2 , 9 – 15 and even circularly polarized light 16 and isotopic chirality 17 – 19 can influence the outcome of the reaction by biasing an initial imbalance toward one of the enantiomers. Soai’s seminal discoveries have received widespread attention in diverse chemical fields and have revived discussions regarding absolute asymmetric synthesis, chiral symmetry breaking, and the origin of biological homochirality.…”

Asymmetric autocatalysis. Chiral symmetry breaking and the origins of homochirality of organic molecules

“…By contrast, the chiral trigger [ 15 N]( S )-diamine 14 afforded ( S )-alkanol 1c with >99.5% ee. 105) It was also found that oxygen ( 18 O/ 16 O) isotopomers of 1,2-diphenyl-1,2-ethanediol 15 and glycerin acted as chiral triggers of asymmetric autocatalysis. 106,107)…”