Asymmetric 1,3-dipolar cycloadditions to 5-(R)-menthyloxy-2(5H)-furanone

Abstract

Abstract:Various diazo compounds, nitrile oxides, nitrones and azomethine ylides were examined in 1,3-dipolar cycloadditions to enantiomerically pure 5-(R)-menthyloxy-2(5H)-furanone 1a. Pyrazoline 9 was obtained in 100% c.y. as a mixture of 2 diastereoisomers in ratios up to 72 : 28, whereas pyrazoline 16 was obtained in 100 % c.y. as a single enantiomer. Photochemically pyrazolines 9 and 10 have been converted to cyclopropanes 11 and 13. Under thermal conditions pyrazoline 9 is converted to 4-methyl-5-menthyloxy-2(5H)-furanone. Isoxazoles 21a-24a were obtained enantiomerically pure via nitrile oxide addition to 1a in 64-67% yield. Nitrone addition afforded isoxazolidines 27, 28 and 34 with complete anti-facial-and regiochemistry, but with endo-exo selectivities up to 76%. Enantiomerically pure isoxazolidines were obtained in 25-75% yield. Pyrrolidine 36 was obtained diastereomerically pure in 81% c.y. Pyrrolidines 42 and 45, however, were obtained as diastereomeric mixtures in 37% resp. 6% yield. IntroductionCycloadditions are undoubtedly a cornerstone in synthetic methodology. In order to control the absolute stereochemistry of the ring systems which are formed, regio-, facial-, and endo/exo-selectivity are decisive factors. Therefore it is not surprising that a variety of asymmetric Diels-Alder reactions and 1,3-dipolar cycloadditions have been developed in the last decade.1,2 The 1,3-dipolar cycloaddition reactions of nitrones and nitrile oxides to alkenes have been extensively used for the preparation of isoxazolidines and isoxazoles.3 Further transformations offer access to a variety of functional intermediates for synthesis, in many cases with multiple stereogenic centers introduced during the cycloaddition

A “Chiral Aldehyde” Equivalent as a Building Block Towards Biologically Active Targets

“…The corresponding reaction of the menthoxy acceptor is reported to provide a selectivity of 3:1 in 55 % yield. [15] The stereochemistry of addition was assigned by comparison to similar systems and by use of the Karplus relationship, which indicates that the coupling constant between the protons should be less than 2.0 Hz for the anti addition product while the syn addition product should have a coupling constant between 8.0 and 11.0 Hz. The observed signal for the g-lactone proton of the major cycloadduct 16 at d = 5.77 ppm appeared as a doublet, J = 1.5 Hz, consistent with the assigned stereochemistry.…”

“…The previously described cyclopentene 23 a was oxidatively cleaved in a one-pot protocol with catalytic osmium tetroxide and sodium periodate [26] to give a 92 % yield of ketone 41 [Eq. (15)]. The crude adduct was sufficiently pure for use in subsequent transformations without further purification.…”

One-pot catalyst-free synthesis of down- and upconversion fluorescent oligopyrazolines from diazoacetates and maleic anhydride

“…However, this reaction is rarely used in the synthesis of polymers, especially in the field of fluorescent polymers. To the best of our knowledge, only structure-analogues of MA, like maleimide 26 and furanone, 27 were exploited to react with diazocompounds leading to pyrazolines. Importantly, the resulting oligomer shows a 100-fold higher fluorescent emission compared with the monomer.…”

A Synthesis of (-)-cis-2-Aminomethylcyclopropanecarboxylic Acid [(-)-CAMP]

“…In 1994, Feringa's group reported the diastereoselective synthesis of cyclopropane (enantiomer of 2, see Scheme 1) using Lmenthol as a chiral auxiliary. 8 However, they did not isolate the cyclopropane ent-2, and synthetic details were not described in the paper probably due to the lability of ent-2 and/or the diazene precursor (see below), which causes poor reproducibility. In the present study, we reinvestigated the synthesis of the cyclopropane 2 (Scheme 1) and successfully established the isolation procedure.…”

“…The major isomer 4 was then subjected to photoirradiation (high- pressure mercury lamp, benzophenone, benzene) to induce cyclopropane formation with concomitant elimination of nitrogen. While small amounts of by-products such as undesired 3-methylbutenolide (structure not shown) 8 were observed, the desired cyclopropane 2 11 was cleanly provided in 71% yield. Scheme 2 Ten-step enantioselective synthesis of (-)-CAMP (1) With cyclopropane 2 in hand, we then investigated the introduction of nitrogen functionality.…”