Asymmetric synthesis of the cis- and trans-stereoisomers of 4-aminopyrrolidine-3-carboxylic acid and 4-aminotetrahydrofuran-3-carboxylic acid

The diastereoselective conjugate addition of lithium (S)-N-benzyl-N-[small alpha]-methylbenzylamide has been successfully applied to the first asymmetric syntheses of cis-(3S,4R)- and trans-(3R,4R)-4-aminotetrahydrofuran-3-carboxylic acids (26% and 25% overall yield respectively, >98% d.e. and >97% e.e. in each case). Furthermore, the most efficient asymmetric synthesis to date of cis-(3R,4R)- and trans-(3R,4S)-4-aminopyrrolidine carboxylic acids is delineated: for cis-(3R,4R), four steps, >98% d.e., 52% overall yield; for trans-(3R,4S), five steps, >98% d.e., 50% overall yield.     

Parallel kinetic resolution of tert-butyl (RS)-3-oxy-substituted cyclopent-1-ene-carboxylates for the asymmetric synthesis of 3-oxy-substituted cispentacin and transpentacin derivatives

tert-Butyl (RS)-3-methoxy- and (RS)-3-tert-butyldiphenylsilyloxy-cyclopent-1-ene-carboxylates display excellent levels of enantiorecognition in mutual kinetic resolutions with both lithium (RS)-N-benzyl-N-(alpha-methylbenzyl)amide and lithium (RS)-N-3,4-dimethoxybenzyl-N-(alpha-methylbenzyl)amide. A 50 : 50 pseudoenantiomeric mixture of lithium (S)-N-benzyl-N-(alpha-methylbenzyl)amide and lithium (R)-N-3,4-dimethoxybenzyl-N-(alpha-methylbenzyl)amide allows for the efficient parallel kinetic resolution of the tert-butyl (RS)-3-oxy-substituted cyclopent-1-ene-carboxylates, affording differentially protected 3-oxy-substituted cispentacin derivatives in high yield and >98% de. Subsequent N-deprotection and hydrolysis provides access to 3-oxy-substituted cispentacin derivatives in good yield, and in >98% de and >98% ee, while stereoselective epimerisation and subsequent deprotection affords the corresponding transpentacin analogues in good yield, and in >98% de and >98% ee.     

Asymmetric synthesis of substituted 1-aminocyclopropane-1-carboxylic acids via diketopiperazine methodology

Diketopiperazinespirocyclopropane 12 is prepared in > 98% d.e. via the conjugate addition of a phosphorus ylide to (6S)-N,N'-bis(p-methoxybenzyl)-3-methylenepiperazine-2,5-dione 2. Deprotection and hydrolysis of adduct 12 and subsequent peptide coupling demonstrate the applicability of this methodology to the asymmetric synthesis of 1-aminocyclopropane-1-carboxylic acids for incorporation into novel peptides. A model for the high level of diastereofacial selectivity observed in the cyclopropanation reaction is presented. A highly selective asymmetric approach (> 98% d.e.) to (S)-[2,2-(2)H2]-1-aminocyclopropane-1-carboxylic acid 29 is also reported via a deuterated sulfur ylide addition to acceptor 2.     

Inside Back Cover: Cu(II)‐Catalyzed Ligand‐Free Oxidation of Diarylmethanes and Second Alcohols in Water (Chin. J. Chem. 9/2017)

The inside back cover picture shows a simple and efficient Cu(II )‐catalyzed ligand‐free oxidation of diarylmethanes and secondary alcohols using 70% TBHP in water. A series of diarylmethanes were directly oxidized into diaryl ketones in 67%–98% yields. Additionally, various secondary alcohols were also transformed into the desired products in 48%–98% yields. Importantly, the catalytic system in the absence of any organic solvent, surfactant, or phase transfer agent, had a wide substrate scope and a high tolerance for various functional groups. More details are discussed in the article by Liu et al. on page 1391–1395.

     

Triclorosilane-mediated stereoselective synthesis of β-amino esters and their conversion to highly enantiomerically enriched β-lactams

A highly stereoselective trichlorosilane-mediated reduction of N-benzyl enamines was developed; the combination of a low cost, easy to make metal-free catalyst and an inexpensive chiral auxiliary allowed to perform the reaction on substrates with different structural features often with total control of the stereoselectivity. By easy deprotection through hydrogenolysis followed by conversion of β-aminoester to 2-azetidinones, the synthesis of enantiomerically pure β-lactams (>98% e.e.) was successfully accomplished.     

Organocatalytic asymmetric vinylogous addition to quinones - formation of optically active alpha-aryl ketones

The first organocatalytic addition of dicyanoalkylidenes to quinones catalyzed by Cinchona alkaloids leading to formation of 1,4-diketone derivatives with high diastereomeric ratios (up to >98 : <2 dr) and enantioselectivities (up to 99% ee) has been developed; the optically active compounds obtained are useful for a number of transformations, e.g. the synthesis of optically active alpha-aryl ketones.     

A mild protocol for allylation and highly diastereoselective syn or anti crotylation of aldehydes in biphasic and aqueous media utilizing potassium allyl- and crotyltrifluoroborates

[formula: see text] Potassium allyl- and crotyltrifluoroborates undergo addition to aldehydes in biphasic media as well as water to provide the corresponding homoallylic alcohols in high yields (> or = 94%), excellent diastereoselectivity (dr > or = 98:2), and without the necessity of any subsequent purification. The presence of a phase transfer catalyst (e.g., nBu4NI) significantly accelerates the rate of reaction, whereas added fluoride ion retards the reaction.     

Bond length alternation in ground and HOMO→LUMO excited states in polyenes. Dynamic Stokes shift?

Complete-active-space self-consistent-field calculation of the reorganisation energy, , corresponding to the strongly allowed HOMOLUMO transition in planar polyenes in the trans form (C _{2 h} symmetry), gives >0.5 eV. This large depends on the fact that the short and long bond lengths of the excited ¹B _u (or ³B _u ) state compared to the ¹A _g ground state are almost cancelled. The emission redshift (Stokes shift) in molecules with the same type of system is quite small, however, which suggests that the Stokes shift may be dynamic, owing to the presence of another excited state at lower or about the same energy. Acknowledgement.We congratulate Björn on his birthday and at the same time thank him for the CASSCF method and for many years of collaboration and help from him and his collaborators to make this wonderful method work in our laboratory.Contribution to the Björn Roos Honorary Issue     

A Stereoselective Synthesis of the Bromopyrrole Natural Product (−)‐Agelastatin A

Weaving an intricate web : A stereoselective synthesis of (?)‐agelastatin A has been developed, which requires 11 steps from commercially available starting material. The application of a Rh‐catalyzed intramolecular olefin aziridination reaction and the subsequent manipulation of the resulting tricyclic intermediate (see scheme) punctuate this study.

     

Enzyme‐Catalyzed Preparation of Aliphatic Polythioester by Direct Polycondensation of Diacid Diester and Dithiol

Summary: Aliphatic dithiol‐diacid type polythioesters were first enzymatically prepared by the direct polycondensation of hexane‐1,6‐dithiol and diacid diesters using the immobilized lipase from Candida antarctica (lipase CA). As a typical example, diethyl sebacate and hexane‐1,6‐dithiol were polymerized using lipase CA in bulk in the presence of molecular sieves 4A to produce the corresponding polythioester with an of 10 200 in 90% yield. Both the melting and crystallization temperatures of the produced polythioesters were higher when compared to those of the corresponding polyoxyesters. A higher molecular weight polythioester was produced using lipase in a two‐step procedure, i.e., cyclization with subsequent ring‐opening polymerization.

Preparation of polythioester and melting temperature of various polythioesters and polyoxyesters.     

Organocatalytic enantioselective synthesis of β-blockers: (S)-propranolol and (S)-naftopidil

An efficient enantioselective synthesis of β-adrenergic blockers (S)-propranolol and (S)-naftopidil with >98% ee using an l-proline-catalyzed α-aminoxylation of an aldehyde as a key step is described.     

Closed and Open Clamlike Structures Formed by Hydrogen‐Bonded Pairs of Cyclotricatechylene Anions that Contain Cationic “Meat”

Clamming up : The hexaphenolic compound cyclotricatechylene, which has a bowl‐shaped cavity, forms clamlike pairs that encapsulate cations (see picture). Variable hydrogen bonding allows two linked cyclotricatechylene clamshells to be in a closed arrangement when smaller cations such Rb⁺ or Cs⁺ provide the clam meat, whereas larger cations such as NMe₄⁺ and NEt₄⁺ cause the clam to be partially opened.

     

Band‐gap Modification in a Nanoscale Region of Polyethylene by Fast Electrons

Drastic change: A nanoscale spot of polyethylene (PE) can change its electrical properties dramatically after exposure to fast electrons—from a representative insulator, via a semiconductor, to a hopping conductor (see picture). These modifications of the chemical and energy‐band structures of PE are extremely localized, thus opening a new way to use this conventional polymer in nanotechnology.

     

Gold‐Catalyzed Reactions of 1,5‐ and 1,6‐Enynes with Carbonyl Compounds: Cycloaddition vs. Metathesis

Gold and rings : The gold(I)‐catalyzed addition of aldehydes to 1,6‐enynes gives 1,3‐dienes, by a cycloaddition/fragmentation process. 1,5‐Enynes react with aldehydes and ketones by the 5‐endo‐dig pathway to give the corresponding cycloadducts.

     

Asymmetric synthesis of (1R,2S,3R)-3-methylcispentacin and (1S,2S,3R)-3-methyltranspentacin by kinetic resolution of tert-butyl (+/-)-3-methylcyclopentene-1-carboxylate

Conjugate addition of lithium dibenzylamide to tert-butyl (+/-)-3-methylcyclopentene-1-carboxylate occurs with high levels of stereocontrol, with preferential addition of lithium dibenzylamide to the face of the cyclic alpha,beta-unsaturated acceptor anti- to the 3-methyl substituent. High levels of enantiorecognition are observed between tert-butyl (+/-)-3-methylcyclopentene-1-carboxylate and an excess of lithium (+/-)-N-benzyl-N-alpha-methylbenzylamide (10 eq.) (E > 140) in their mutual kinetic resolution, while the kinetic resolution of tert-butyl (+/-)-3-methylcyclopentene-1-carboxylate with lithium (S)-N-benzyl-N-alpha-methylbenzylamide proceeds to give, at 51% conversion, tert-butyl (1R,2S,3R,alphaS)-3-methyl-2-N-benzyl-N-alpha-methylbenzylaminocyclopentane-1-carboxylate consistent with E > 130, and in 39% yield and 99 +/- 0.5% de after purification. Subsequent deprotection by hydrogenolysis and ester hydrolysis gives (1R,2S,3R)-3-methylcispentacin in > 98% de and 98 +/- 1% ee. Selective epimerisation of tert-butyl (1R,2S,3R,alphaS)-3-methyl-2-N-benzyl-N-alpha-methylbenzylaminocyclopentane-1-carboxylate by treatment with KO'Bu in 'BuOH gives tert-butyl (1S,2S,3R,alphaS)-3-methyl-2-N-benzyl-N-alpha-methylbenzylaminocyclopentane-1-carboxylate in quantitative yield and in > 98% de, with subsequent deprotection by hydrogenolysis and ester hydrolysis giving (1S,2S,3R)-3-methyltranspentacin hydrochloride in > 98% de and 97 +/- 1% ee.