Orthoacylimines:  A New Class of Chiral Auxiliaries for Nucleophilic Addition of Organolithium Reagents to Imines

Abstract

A new class of orthoacylimine-derived chiral auxiliaries has been synthesized and tested in the nucleophilic addition of organolithium reagents to imines. The precursors can be prepared by an aza-Wittig reaction between the corresponding orthoacyl azide and a variety of aldehydes in the presence of trialkylphosphines. The nucleophilic addition of organolithium reagents led to the addition products in good yields and with good to excellent diastereoselectivities (from 85:15 to 99:1). The chiral, nonracemic secondary amines could be readily obtained under mild hydrolytic condition. Furthermore, the chiral auxiliary can be recovered in quantitative yield and reconverted to the starting orthoacyl azide precursor. This method was applied to the synthesis of (S)-t-leucine.

Alkylation of Aryl N‐(2‐Pyridylsulfonyl)aldimines with Organozinc Halides: Conciliation of Reactivity and Chemoselectivity

“…Interestingly, the (3-pyridylsulfonyl)imine 1 g, an isomer of 1 f, proved to be unreactive under the optimized reaction conditions (Table 1, entry 7), which suggests that a chelating interaction of the heteroaryl moiety with the metal center may be responsible for the dramatic increase in reactivity observed with imines 1 e and 1 f. Next, the influence of catalyst loading was investigated for the addition of the secondary alkyl zinc reagent 2-pentylzinc bromide to 1 f ( Table 2). The addition was equally effective with 5 mol % ( Table 2, entry 1) and 1 mol % (entry 2) of Cu(OTf) 2 : In both cases the product 3 f was formed in over 90 % yield in less than 15 min. [18] As a further demonstration of the potential of this method, the addition of 2-pentylzinc bromide to imine 1 f on a gram scale (4 mmol) in the presence of 0.1 mol % of Cu(OTf) 2 (molar ratio S/C = 1000) led to 3 f in 77 % yield after 75 min at room temperature ( Table 2, entry 3).…”

“…[1] Consequently, a number of synthetically useful addition reactions for the formation of carbon-carbon bonds have been developed with organolithium, [2] Grignard, [3] dialkyl zinc, [4] alkenyl zirconium, [5] aryl tin, [6] aryl titanium, [7] and aryl boron [8] reagents as nucleophiles, including some very efficient catalytic enantioselective procedures. [9] Despite this great progress, limitations in the scope of this reaction remain, especially with regard to functional-group compatibility.…”

“…[14d] and (2-pyridylsulfonyl)imine 1 f [14a, b] underwent smooth addition reactions under the catalysis of Cu(OTf) 2 [17] (10 mol %) to afford the corresponding adducts 2 e and 2 f in 80 and 97 % yield, respectively, in 15 min or less (Table 1, entries 5 and 6). Imine 1 f underwent addition with N-hexylzinc bromide even in the absence of a copper salt, although the reaction became much slower (8 h at room temperature), and the yield of 2 f Table 1: Influence of the N-sulfonyl group on the reactivity of the imine.…”

Syntheses and applications of C2-symmetric chiral diols

“…87 The same group also provided an explanation for the asymmetric induction. As depicted in Figure 17 88 The main advantage of their method was the ease of recovery of the chiral auxiliary (Scheme 38).…”

Trimethylphosphine

“…15 (12) In this context, the use of Me 3 P increases the reactivity of the iminophosphorane reagent. For instance, Charette and co-workers 16 (13) Iminophosphoranes derived from Me 3 P react with ketenes to give ketenimines (eq 14). 17 The addition of different nucleophilic reagents to the central sp carbon and the cycloaddition reactions of these compounds, studied in detail by Alajarin and co-workers, 18 have attracted attention in recent years.…”