Diastereoselective allylation and crotylation of N-tert-butanesulfinyl imines with allylic alcohols

Abstract

The palladium-catalyzed allylation of N-tert-butanesulfinyl imines with allylic alcohols in the presence of InI as reducing reagent takes place with high diastereoselectivity in reasonable yields. The reaction with crotyl alcohol is totally regioselective, leading to the antidiastereomer as the main reaction product.The stereoselective allylation of imines using organometallic compounds is of great interest in synthetic organic chemistry because the resulting homoallylic amines are valuable building blocks. 1 For instance, the double bond of the allylic moiety can participate in a number of further synthetically useful transformations: hydroboration, hydration, epoxidation, hydroformylation, ozonolysis, olefin metathesis, etc. 2 Among the stereoselective methodologies, the catalytic enantioselective allylations 3 rely on the use of chiral Lewis acids or chiral Lewis bases. In addition, double activation could be also achieved by using chiral bifunctional catalysts 4 by the simultaneous activation of both electrophilic and nucleophilic reaction partners through a cooperative action of different functionalities of the ligand. However, and in spite of the rapid evolution of catalytic methods in recent years, the use of stoichiometric reagents (including substrates and/or allylic organometallic partners) is still the favourite choice of organic chemists in the synthesis of key intermediates of natural products. In these diastereoselective allylations, 5 the stereochemical information can be transferred by substrate control, including chiral auxiliaries, or through the use of chiral reagents (reagent control). Sometimes a double induction could also be involved in the process, a match/mismatch effect being possible. Performing the stereoselective allylation of imine derivatives with allylic halides in the presence of reducing metals under Barbier-type reaction conditions (metalation in the presence of the electrophile) is also of interest, because this strategy circumvents the need of isolating allyl metal species (the real nucleophiles), which usually are sensitive, and in many cases also toxic. The most commonly used metals in these transformations are chromium, 6 indium 7 and zinc. 8 Particularly noteworthy is the use of allylic alcohols as allylating reagents of carbonyl compounds and imines under palladium catalysis in the presence of a reducing reagent. 9 More recently, the use of the Kulinkovich reagent in the coupling of allylic alcohols with aldimines provides an alternative approach to regio-and stereodefined homoallylic amines. 10 On the other hand, in the growing field of the synthetic applications of chiral N-tert-butanesulfinyl derivatives, 11 we reported the diastereoselective allylation 12 of N-tert-butanesulfinyl aldimines 13 and ketimines 14 with in situ generated allylindium reagents, and the first one-pot a-aminoallylation of aldehydes with chiral tert-butanesulfinamide, allylic bromides, and indium, which provides homoallylic amines with high chemoand stereoselectivities. 15 The chiral auxiliar...

Transition-metal-free allylation of 2-azaallyls with allyl ethers through polar and radical mechanisms

“…Economical methods to prepare homoallylic amines remain in demand. The use of allylic alkylations [49][50][51][52][53][54][55][56] or decarboxylative allylic alkylation reactions [56][57][58][59][60][61] to prepare homoallylic amines has been demonstrated with various transition-metal catalysts, including Ni, Pd, Cu, Zn, Ir, Rh, and Yb (Fig. 1a, b).…”

Stereoselective Synthesis of Spiro-α-methylene-γ-lactams via Chiral Quaternary 3-Aminooxindole Adducts Accessed by Zn-Mediated Allylation of Sulfinyl Ketimines

“…obtained by allylation of N-tert-butanesulfinyl aldimines utilizing allylic bromides 7 and alcohols 8 as well as cinnamyl bromide 9 and acetates, 10 reports of allylation of ketimines are limited. A few examples include reaction of various chiral N-tert-butanesulfinyl ketimines by substituted allylic zinc chloride and Zn-promoted aza-Barbier-type reaction with -ethynyl allylic bromide developed by Reddy 11 and Sun, 2e respectively.…”

Asymmetric synthesis of γ-aryl-substituted GABA derivatives via a highly diastereoselective Rh-catalyzed boronic acid addition at room temperature

“…1 GABAergic drugs. † Electronic supplementary information (ESI) available: Synthesis of 1 and additional experimental details, 1 H and 13 C NMR spectra of all products, and 19 F NMR spectra of 2d and 2g. See DOI: 10.1039/c5qo00133a using a sulfinamide via the sequence of sulfinylimine formation and diastereoselective reduction has been reported recently.…”

“…Allylation of these types of inactivated sulfinylimines is known. 19 However, to the best of our knowledge, Rh-catalyzed addition of boronic acids 14 remains a challenge. Herein we describe the successful preparation of the target molecules using the Ellman protocol.…”