Organoiodine-Catalyzed Enantioselective Intermolecular Oxyamination of Alkenes

Abstract

Metal-free, catalytic enantioselective intermolecular oxyamination of alkenes is realized by use of organoiodine(I/III) chemistry. The protocol is applicable toward aryl-and alkyl-substituted alkenes with high enantioselectivity and electronically controlled regioselectivity. The oxyaminated products can be easily deprotected in one step to reveal free amino alcohols in high yields without loss of enantioselectivity. A key to our success is the discovery of a virtually unexplored chemical entity, N-(fluorosulfonyl)carbamate, as a bifunctional N,O-nucleophile.

Organoiodine-Catalyzed Enantioselective Intramolecular Oxy­aminations of Alkenes with N-(Fluorosulfonyl)carbamate

“…Finally, we demonstrated the feasibility of deprotection of the imide moiety, as an important advantage of our oxyamination (Scheme 5). In contrast to our intermolecular oxyamination products which could be deprotected by simply treating the products with aqueous acid, 39 lactone 3a first required basic hydrolysis of the imide moiety followed by acidic hydrolysis of the corresponding sulfamic acid. The deprotected, intermediate -amino acid was isolated as Boc-protected lactone 9 in 73% overall yield after successive treatment of the amino acid with Boc 2 O and EDC.…”

“…Absolute configurations of 3b-i and 5a-f were tentatively assigned by analogy with 3a. 1 and Scheme 2); General Procedure A Selectfluor (0.15 mmol, 54.8 mg, 97.0%) was added to a stirred solution of benzhydryl ester 2 (100 mol), 1d (15 mol, 8.4 mg), 24 CbzN-HSO 2 F (0.24 mmol, 56.0 mg), 39 and CbzNLiSO 2 F (0.24 mmol, 57.4 mg) 39 in MeCN (200 L) at 10 °C. The mixture was stirred at the same temperature until completion of the reaction.…”

“…43 For this substrate, we decided to resort to a stoichiometric oxyamination by use of a readily available chiral organoiodine(III) reagent (Scheme 4). By use of the reaction conditions optimized for our stoichiometric enantioselective intermolecular oxyamination reported previously, 39 dihydrofuran 8 could be obtained in 58% yield and 37% ee.…”

“…38 Concurrently, we have reported a catalytic enantioselective intermolecular oxyamination, which was realized by the use of benzyl N-(fluorosulfonyl)carbamate as an N,O-bifunctional nucleophile (Scheme 1c). 39 In continuation of this study, we wondered if this reagent could be used just as a nitrogen nucleophile in catalytic intramolecular oxyamination wherein the oxygen nuc-leophile is already set in the alkene substrate (Scheme 1d). We report herein the results of this study, using ,-and ,-unsaturated esters and N-allyl amides as substrates to give enantioenriched lactones and oxazolines bearing an easy-to-deprotect nitrogen functionality.…”

“…30 The initial optimization was implemented using pent-4-enoic acid as the model substrate (Table 1). The catalytic reaction conditions were applied from our previous study, 39 which consists of a mixture of benzyl N-(fluorosulfonyl)carbamate and its lithium salt, Selectfluor as the oxidant, and phenyllactamide-based C2-symmetric chiral organoiodine catalyst 1a. The reaction catalyzed by 1a gave product 3a in good yield, albeit with moderate enantioselectivity (entry 1).…”