Synthesis of alkaloids by a diastereoselective allylation of chiral N-sulfinyl imines

The indium-promoted allylation of chiral N-sulfinyl imines represents a useful and versatile procedure to prepare chiral protected homoallyl amines in a diastereoselective manner. Desulfinylation under acidic conditions liberates easily the corresponding enantioenriched homoallyl amines. This type of compounds can be easily manipulated synthetically in order to prepare a series of natural alkaloids in an enantiopure form, using simple transformations.We thank the continued financial support from our Ministerio de Ciencia e Innovación (MCINN; projects CONSOLIDER INGENIO 2010-CDS2007-00006, CTQ2011-24151, CTQ2011-24165), the Ministerio de Economía y Competitividad (MINECO; projects CTQ2013-43446-P, CTQ2014-51912-REDC, CTQ2014-53695-P), FEDER, the Generalitat Valenciana (PROMETEO 2009/039, PROMETEOII/2014/017) and the University of Alicante

Catalytic Asymmetric Transfer Hydrogenation of Imines: Recent Advances

In this review article recent developments in the asymmetric transfer hydrogenation of imines from 2008 up to today are presented. The main methodology involves either metal-catalyzed procedures in the presence of a chiral ligand or organocatalyzed technologies using a Hantzsch ester and a chiral BINOL-derived phosphoric acid. The most important procedures are collected, paying special attention to the application of this methodology in synthetic organic chemistry.We thank the continued financial support from our Ministerio de Ciencia e Innovación (MICINN; projects CTQ2007-62771/BQU, CTQ2010-20387, CONSOLIDER INGENIO 2010-CDS2007-00006, CTQ2011-24151, CTQ2011-24165), the Ministerio de Economía y Competitividad (MINECO; projects CTQ2013-43446-P, CTQ2014-51912-REDC, CTQ2014-53695-P), FEDER, the Generalitat Valenciana (PROMETEO 2009/039, PROMETEOII/2014/017), and the University of Alicante

Recent advances in the use of chiral aldimines in asymmetric synthesis

Chiral N-(tert-butyl)sulfinyl aldimines easily prepared from commercially available compounds have been used as starting materials for the following processes: (i) hydrogen transfer, (ii) addition of zincates, (iii) In-promoted allylation, and (iv) addition of zinc enolates. In all cases, the final desulfinylation to yield the expected chiral α-substituted primary amines was easily performed with hydrochloric acid in an organic solvent. This methodology has been successfully applied to the preparation of chiral natural products such as alkaloids and amino acids.We thank the continuous financial support from the Ministry of Science and Innovation (Ministerio de Ciencia e Innovación (MICINN), Projects CTQ2007-62771/BQU, CTQ2010-20387, CONSOLIDER INGENIO 2010-CDS2007-00006, CTQ2011-24151, and CTQ20122-24165), the Ministry of Economy and Competitiveness (Ministerio de Economía y Competitividad (MINECO), Projects CTQ2013-43446-P, CTQ2014-51912-REDC, and CTQ2014-53695-P), the Fondo Europeo de Desarrollo Regional (FEDER), the Government of the region of Valencia (Generalitat Valenciana, Project PROME-TEOII/2014/017), and the University of Alicante

Catalytic asymmetric transfer hydrogenation of ketones: recent advances

In this review, we consider the main processes for the asymmetric transfer hydrogenation of ketones from 2008 up today. The most effective organometallic compounds (derived from Ru, Rh, Ir, Fe, Os, Ni, Co, and Re) and chiral ligands (derived from amino alcohols, diamines, sulfur- and phosphorus-containing compounds, as well as heterocyclic systems) will be shown paying special attention to functionalized substrates, tandem reactions, processes under non-conventional conditions, supported catalysts, dynamic kinetic resolutions, the use of water as a green solvent, theoretical and experimental studies on reaction mechanisms, enzymatic processes, and finally applications to the total synthesis of biologically active organic molecules.We thank the continuous financial support from our Ministerio de Ciencia e Innovación (MICINN) (projects CTQ2007-62771/BQU, CTQ2010-20387, CONSOLIDER INGENIO 2010-CDS2007-00006, CTQ2011-24151, CTQ2011-24165), the Ministerio de Economía y Competitividad (MINECO) (projects CTQ2013-43446-P, CTQ2014-51912-REDC, CTQ2014-53695-P), FEDER, the Generalitat Valenciana (PROMETEO 2009/039, PROMETEOII/2014/017), and the University of Alicante

Indium Mediated Allylation of N-tert-Butanesulfinyl Imines with 1,3-Dibromopropene: Stereoselective Synthesis of Aziridines

The reaction of N-tert-butanesulfinyl imines 1 with 1,3-dibromopropene (2), in the presence of indium metal, in saturated aqueous solution of sodium bromide, produced bromohomoallylamine derivatives 3 with total facial diastereoselectivity for the imine addition, and moderate yields. These compounds were easily transformed into the corresponding vinyl aziridines 5 upon deprotonation with KHMDS in THF, the intramolecular cyclization taking place in a stereospecific manner in moderate to high yields.We thank the continued financial support from our Ministerio de Economía y Competitividad (MINECO; project CTQ2014-53695-P, CTQ2014-51912-REDC, CTQ2016-81797-REDC, CTQ2017-85093-P), FEDER, the Generalitat Valenciana (PROMETEOII/2014/017), and the University of Alicante

Enantiodivergent Approach to the Synthesis of Cis-2,6-Disubstituted Piperidin-4-ones

Enantiopure β-amino ketone derivatives were synthesized by decarboxylative Mannich reaction of chiral N-tert-butanesulfinyl imines with β-keto acids and were subsequently transformed into cis-2,6-disubstituted piperidin-4-ones through an organocatalyzed condensation with aldehydes. Both enantiomers were accessible from the same precursors by inverting the order in the reaction sequence of the aldehydes involved in the imine formation and the intramolecular Mannich condensation. The synthesis of the piperidine alkaloids (+)-241D, (−)-epimyrtine, and (−)-lasubine II demonstrated the utility of this methodology.We acknowledge the continued financial support from the Spanish Ministerio de Economía y Competitividad (MINECO; projects CTQ2014-53695-P, CTQ2014-51912-REDC, CTQ2016-81797-REDC, CTQ2017-85093-P), FEDER, the Generalitat Valenciana (PROMETEOII/2014/017), and the University of Alicante

A general protocol to afford enantioenriched linear homoprenylic amines

The reaction of a readily obtained chiral branched homoprenylamonium salt with a range of aldehydes, including aliphatic substrates, affords the corresponding linear isomers in good yields and enantioselectivities.We thank the Spanish Ministerio de Ciencia e Innovación for their financial support (CTQ2011-24165). I. B. acknowledges the Generalitat Valenciana for a predoctoral fellowship (ACIF/2011/159)

Stereoselective Aza-Henry Reaction of Chiral tert-Butanesulfinyl Imines with Methyl or Ethyl 4-Nitrobutanoate: Easy Access to Enantioenriched 6-Substituted Piperidine-2,5-diones

The base-catalyzed addition of 4-nitrobutanoates 6 to N-tert-butanesulfinyl imines 8 under solvent-free reaction conditions proceeded with high face diastereoselectivity. The resulting β-nitroamine derivatives 9 were easily transformed into 6-substituted piperidine-2,5-diones 11 upon removal of the sulfinyl group with concomitant δ-lactam formation and functional group transformation under Nef reaction conditions.This work was generously supported by the Spanish Ministerio de Ciencia e Innovación (Grant Nos. CTQ2011-24165, and Consolider Ingenio 2010-CSD-2007-00006), the Generalitat Valenciana (Grant No. PROMETEO/2009/039 and FEDER) and the University of Alicante. M.J.G.M. thanks the University of Alicante for a predoctoral fellowship

Stereoselective Synthesis of 2-(2-Aminoalkyl)- and 1,3-Disubstituted Tetrahydro-1H-pyrido[4,3-b]- Benzofuran and Indole Derivatives

The addition of an allenyl indium intermediate to chiral N-tert-butanesulfinyl imines 7 proceeds with high levels of diastereocontrol. The resulting homopropargylic amine derivatives 10 were transformed into 2-(2-aminoalkyl)benzofuran and indole derivatives 13 and 19, after Sonogashira coupling with o-iodophenol or o-iodoaniline, followed by formation of the heteroaromatic ring through an intramolecular cyclization. Enantioenriched tetrahydropyrido-benzofuran and indole derivatives 16 and 21 were prepared through a Pictet-Spengler condensation of the free amines derived from compounds 15 and 20, involving the nucleophilic 3-position of the benzofuran or indole moiety.We thank the continued financial support from our Ministerio de Ciencia e Innovación (MCINN; projects CTQ2010-20387, CONSOLIDER INGENIO 2010-CDS2007-00006, CTQ2011-24165), the Ministerio de Economía y Competitividad (MINECO; projects CTQ2014-53695-P, CTQ2014-51912-REDC), FEDER, the Generalitat Valenciana (PROMETEO 2009/039, PROMETEOII/2014/017) and the University of Alicante

Enantioselective Synthesis of Tetrahydroquinoline Alkaloids (-)-Angustureine and (-)-Cuspareine from Chiral tert-Butanesulfinyl Imines

The addition of a Grignard reagent to both enantiomeric N-tert-butanesulfinyl imines derived from 3-(2-bromophenyl)propanal 8 proceeded with high diastereoselectivity. The resulting sulfinamides 9 and 12 were easily transformed into tetrahydroquinoline alkaloids (-)-angustureine (4) and (-)-cuspareine (5) after three steps: N-desulfinylation, intramolecular N-arylation and N-methylation.This work was generously supported by the Spanish Ministerio de Ciencia e Innovación (Grant Nos. CTQ2007-65218 and CTQ2011-24165, and Consolider Ingenio 2010-CSD-2007-00006), the Generalitat Valenciana (Grant No. PROMETEO/2009/039 and FEDER) and the University of Alicante. J.A.S. thanks the Spanish Ministerio de Ciencia e Innovación for a predoctoral fellowship