Stereocontrolled Synthesis of β‐Amino Alcohols from Lithiated Aziridines and Boronic Esters

Abstract

From natural products to ligands for asymmetric catalysis, the b-amino alcohol motif is ubiquitous. [1] The importance of this motif to such a broad spectrum of chemistry has prompted the development of a range of methodologies for its synthesis which include Sharpless aminohydroxylation [2] as well as the addition of nucleophiles to aminocarbonyls, [3] imines, [4] epoxides, and aziridines. [5] We considered a conceptually different route to prepare this class of compound: namely, the lithiation/borylation [6] of aziridines [7] (Scheme 1, pathway a).This route was attractive because: 1) it combines readily available aziridines 1 and boronic esters 2, and creates a C À C bond, 2) high stereoselectivity for the overall process could be expected since lithiation of N-Boc [8] (tert-butoxycarbonyl) and N-Bus [9] (tert-butylsulfonyl) aziridines [10] had been shown to occur trans to the aziridine substituent, and the subsequent steps (3 ! 4 ! 5 ! 6) were expected to be stereospecific, 3) there existed the potential to create quaternary stereogenic centers through lithiation at the internal position. [11] Although most studies have focused on lithiation and trapping of N-sulfonyl aziridines, [9,12] we were attracted to the N-Boc aziridines because: 1) they could be easily prepared in enantiomerically enriched form (either from the corresponding amino acid [13] or by Jacobsens kinetic resolution of terminal epoxides [14] using Boc-NH 2 [15] Scheme 1. Lithiation/borylation of terminal aziridines. LTMP = lithium 2,2,6,6-tetramethylpiperidide, pin = pinacolato.

Investigation of Functionalized α‐Chloroalkyllithiums for a Stereospecific Reagent‐Controlled Homologation Approach to the Analgesic Alkaloid (−)‐Epibatidine

“…The dark-brown residue (ca. 6.4 g) was purified by column chromatography (SiO 2 , eluting with 35-75 % EtOAc in hexanes) to afford sulfoxide (S S )-23 d (24), 100 (32), 73 (60); HRMS (EI +) m/z calcd for C 12 H 16 O 3 S: 240.0820; found: 240.0816. XRD analysis of a recrystallized sample of (R S )-23 d produced in the same fashion using ligand (R)-25 confirmed the stereochemical outcome of this reaction.…”

“…Iteration allows for an “assembly‐line” style synthesis of complex polysubstituted alkyl moieties wherein stereochemical and constitutional features are directly programmed by the carbenoid presentation sequence. Since the first demonstration of StReCH of boronic esters with α‐chloroalkylmagnesium chlorides,6a the concept has been better realized with other carbenoid types, including α‐chloroalkyllithiums,6 α‐[(diisopropylamino)carbonyloxy]alkyllithiums,9 α‐[(2,4,6‐triisopropylbenzoyl)oxy]alkyllithiums,10 oxiranyllithiums,11 aziridinyllithiums,12 and α‐lithiated N ‐Boc amines 13. Of these findings, the fact that StReCH can be effected with species as chemically labile as α‐chloroalkyllithiums is arguably the most surprising result 14.…”

Stereoretentive Addition of N‐tert‐Butylsulfonyl‐α‐Amido Silanes to Aldehydes, Ketones, α,β‐Unsaturated Esters, and Imines

“…[10] One of the diastereomers of 2a (more polar product on silica gel columnc hromatography) derived from benzaldehyde as well as 2c (less polar product on silica gel columnc hromatography) derived from cyclohexanecarboxaldehyde were both (S,S)-syn-diastereomers based on comparison of their NMR spectra and optical rotation values with the reportedd ata ( Figure 6). [17] In addition, the sulfonyl group of the other diaste- www.chemasianj.org reomero f2a was removed according to the reported methods, [10,18] giving the corresponding free amino alcohol 8 in 73 %y ield. Its optical rotationv alue and NMR spectra perfectly matched those of (S,R)-anti-diastereomer.…”