Stereoselective Complete Reduction of α-Alkyl-β-ketonitriles toanti γ-Amino Alcohols

Nino, Antonio De; Dalpozzo, Renato; Cupone, Giovanna; Maiuolo, Loredana; Procopio, Antonio; Tagarelli, Antonio; Bartoli, Giuseppe

doi:10.1002/1099-0690(200209)2002:17<2924::aid-ejoc2924>3.0.co;2-5

Cited by 7 publications

(4 citation statements)

References 23 publications

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“…1,3-Amino alcohols are common structural motifs in many biologically active compounds − and are extensively used in asymmetric synthesis as both chiral ligands and auxiliaries . Many methods for the synthesis of enantio- and diastereoenriched 1,3-disubstituted-1,3-amino alcohols are available. − In contrast, the stereoselective synthesis 1,2-disubstituted-1,3-amino alcohols remains a significant challenge. ,− The best approach to enantioenriched 1,2-disubstituted-1,3-amino alcohols is addition of lithium arylacetonitriles to aldehydes, which leads to β-hydroxy nitriles with moderate enantio- and diastereoselectivities. This method employs greater than stoichiometric amounts of chiral ligand.…”

Section: Resultsmentioning

confidence: 99%

“…[109][110][111][112][113] In contrast, the stereoselective synthesis 1,2-disubstituted-1,3-amino alcohols remains a significant challenge. 6,[114][115][116][117][118][119][120][121][122] The best approach to enantioenriched 1,2-disubstituted-1,3-amino alcohols is addition of lithium arylacetonitriles to aldehydes, 123 which leads to β-hydroxy nitriles with moderate enantio-and diastereoselectivities. This method employs greater than stoichiometric amounts of chiral ligand.…”

Section: Tandem Asymmetric β-Aminovinylation Of Aldehydes/mentioning

confidence: 99%

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Stereoselective Synthesis of β-Hydroxy Enamines, Aminocyclopropanes, and 1,3-Amino Alcohols via Asymmetric Catalysis

2010

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Tandem methods for the catalytic asymmetric preparation of enantioenriched β-hydroxy (E)-enamines and cyclopropylamines are presented. The diastereoselective hydrogenation of enantioenriched (E)-trisubstituted hydroxy enamines to generate 1,2-disubstituted 1,3-amino alcohols is also outlined. These methods are initiated by highly regioselective hydroboration of N-tosyl substituted ynamides with diethylborane to generate β-amino alkenyl boranes. In situ boron to zinc transmetalation generates β-amino alkenyl zinc reagents. These functionalized vinylzinc intermediates were subsequently added to aldehydes in the presence of catalyst derived from an enantioenriched amino alcohol (morpholino isoborneol, MIB). The catalyst promotes highly enantioselective C–C bond-formation to provide β-hydroxy enamines in good isolated yields (68–86%) with 54–98% enantioselectivity. The intermediate zinc β-alkoxy enamines can be subjected to a tandem cyclopropanation to afford amino cyclopropyl carbinols with three continuous stereocenters in a one-pot procedure with good yields (72–82%), enantioselectivities of 76–94% and diastereomeric ratios >20:1. Diastereoselective hydrogenation of isolated enantioenriched β-hydroxy enamines over Pd/C furnished syn-1,2-disubstituted-1,3-amino alcohols with high yields (82–90%) and moderate to excellent diastereoselectivities. These methods were used in an efficient preparation of the enantioenriched precursor to PRC200-SS derivatives, which are potent serotonin-norepinephrine-dopamine reuptake inhibitors.

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Section: Resultsmentioning

confidence: 99%

Section: Tandem Asymmetric β-Aminovinylation Of Aldehydes/mentioning

confidence: 99%

Stereoselective Synthesis of β-Hydroxy Enamines, Aminocyclopropanes, and 1,3-Amino Alcohols via Asymmetric Catalysis

2010

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“…Reactions were conducted using 30 mol% of the catalyst and BH 3 · SMe 2 as the reducing agent of choice, where this methodology was used successfully to generate the antidepressant drugs ( R ) -fl uoxetine and ( R ) -duloxetine (Scheme 12.22 ). Likewise, reduction of α -alkyl -β -keto nitriles to anti -γ -amino alcohols was also reported using BH 3 · SMe 2 and cerium chloride as the Lewis acid catalyst [107] . Scheme 12.20 Synthesis of fullerene -based amino acid derivatives.…”

Section: Catalyzed Reactionsmentioning

confidence: 99%

Hydroboration and Diboration of Imines

Westcott

Baker

2008

Modern Reduction Methods

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“…83 CO (21) Another example of the sensitivity of nitrile transformation to methylene amines, relative to other adjacent functional groups such as ketone and ester, is reported by Almqvist and co-workers in the reduction of 14. 86 Nitro ketones undergo enantioselective reduction with 1.2 equiv of BMS in the presence of CBS catalyst, without affecting the nitro group, to afford chiral 1,2-nitro alcohols (ee = 49-94%). 86 Nitro ketones undergo enantioselective reduction with 1.2 equiv of BMS in the presence of CBS catalyst, without affecting the nitro group, to afford chiral 1,2-nitro alcohols (ee = 49-94%).…”

Section: Phosphate-boranesmentioning

confidence: 99%