Imines boron trifluoride etherate

Hydrogenation of imines, e.g. 45-48, with a chiral titanocene catalyst at 2000 psig gave the corresponding optically active secondary amines in high enantiomeric excess74. Imines are reduced to amines by trichlorosilane/boron trifluoride etherate in benzene75. 

Allyltributyltin, 10 Boron trifluoride etherate, 43 Di-jjL-carbonylhexacarbonyldicobalt, 99 Grignard reagents, 138 Ketenylidenetriphenvlphosphorane, 154 Methoxyamine, 177 Reformatsky reagent, 346 Tin(IV) chloride, 300 Tributylcrotyltin, 10 Aldol reactions General considerations, 202 Directed aldols using imines Norephedrine, 200... 

Imines may be activated by complexation with Lewis acids, but this also increases the acidity of a-hydrogen atoms. A combination of copper(i) halide and boron trifluoride etherate is a possible solution to the problem [6, 7]. Activation by trimethylsilyl triflate is also effective with aldimines (though not with ketimines) [7, 8]. 

Analogous to epoxides, aziridines can be prepared by the methylenation of imines. In this case, ethyl diazoacetate is the most common source of carbenes. For example, the imine derived from p-chlorobenzaldehyde 148 is converted to the c/j-aziridinyl ester 149 upon treatment with ethyl diazoacetate in the presence of lithium perchlorate <03TL5275>. These conditions have also been applied to a reaction medium of the ionic liquid l-n-butyl-3-methylimidazolium hexafluorophosphate (bmimPFe) with excellent results <03TL2409>. An interesting enantioselective twist to this protocol has been reported, in which a diazoacetate derived from (TJ)-pantolactone 150 is used. This system was applied to the aziridination of trifluoromethyl-substituted aldimines, which were prepared in situ from the corresponding aminals under the catalysis of boron trifluoride etherate <03TL4011>. 

Recently, Sisko and Weinreb have developed a new, in situ procedure for effecting A -sulfonyl imine Diels-Alder reactions. The method consists of treating an aldehyde with an A -sulfinyl sulfon-amide/boron trifluoride etherate in the presence of a diene (Scheme 3). Under these conditions the IV-sul-finyl sulfonamide reacts with the aldehyde to produce an /V-sulfonyl imine. This reaction, developed by Kresze, has been used previously for preparing imines from simple, non-enolizable aldehydes (c/. 1,2), but had not been applied to more complex aldehydes. As can be seen from the scheme, the cycload-... 

Ugi with imine (Scheme 87) [349] Synthesis of N-(4-methoxyphenyl)-(R,S)-valine methylester iso-Butyraldehyde (0.044 mL, 0.48 mmol) and 60 mg p-anisidine (0.48 mmol) were dissolved in 2 mL dry dichloromethane and 50 mg molecular sieve (0.4 nm) was added. The reaction mixture was stirred at r. t. for 1 h. The molecular sieve was filtered off and 0.195 mL dry CH3OH (4.8 mmol), 0.183 mL boron trifluoride etherate (1.44 mmol), and 400 mg isocyanomethyl polystyrene (0.24 mmol) were added together -with 2 mL dry CH2CI2. The reaction mixture was shaken at r.t. for 2 h. The resin was filtered off and washed twice with dry CH2CI2 and dry acetone. 

More recently, in a series of papers Weinreb and coworkers have found that N-sulfonyl aldimines can in fact be rapidly produced in situ from aliphatic aldehydes using N-sulfinyl sulfonamides and boron trifluoride etherate as catalyst at low temperature [11-15] [Eq. (6)]. Similarly, aliphatic aldehydes can be converted to the N-sulfonyl imines in the absence of a Lewis acid at room temperature or above, but more slowly. The former procedure also works well for aromatic aldehydes, whereas the reaction is too slow to be useful if a Lewis acid is not used. The N-sulfonyl imines generated in this manner can be utilized in a number of transformations (vide infra). However, except in rare cases [16], AT-sul-fonyl ketimines cannot be formed by this methodology. 

Weinreb and Sisko have reported the first examples of Diels-Alder reactions of Af-tosyl imines derived from enolizable aldehydes [12]. The imines were generated in situ from the aldehyde, N-sulfinyl-p-toluenesulfonamide and boron trifluoride etherate. Two examples of these cycloadditions are shown in Egs. (50) and (51). It was also possible to effect the cycloaddition intramolecularly [Eq. 

Reactions of free ketones with imines are far more restricted than those with preformed iminium salts. Examples of ketone-imine condensations are included in several reviews - and are limited to the use of arylimines, mainly benzylideneaniline. Blatt and Gross have noted that the reproducibility of uncatalyzed additions of ketones to Schiff bases is poor but can be improved by the addition of small amounts of hydrochloric acid. The highest yields of 3-amino ketones are obtained using 10 mol % of concentrated hydrochloric acid and 95% ethanol as solvent, and by performing the reaction at room temperature. The reaction, however, is of limited applicability, as it is restricted to methyl ketones and cycloalkanones. Deamination leading to unsaturated ketones is a major side reaction. In addition to hydrochloric acid, boron trifluoride etherate has been used as a catalyst in reactions of aromatic imines with methyl ketones, cyclic ketones and an epoxy ketone. ... 

Furthermore, pyrazol-3-ones have been oxidized by a variety of oxidizing agents such as ozone in oxygen, hydrogen peroxide solution, 3-chloroperbenzoic acid, aqueous sodium periodate, lead(IV) acetate with boron trifluoride etherate, or atmospheric oxidation. The reactions lead mainly to epoxidation of an alkene or imine functionality and cleavage of the pyrazol-3-one ring. 

Nucleophilic addition of lithium alkynides to Af-[bis(tri-methylsilyl)methyl] aldimines mediated by boron trifluoride etherate afforded )V-[bis(trimethylsilyl)methyl] propargylamines in moderate to good yields (eq 7). For example, imine (12, R = n-Pr) reacted with lithium phenylethynide to give propar-gylamine (13, R = n-Pr, R = Ph) in 81% yield. 

Alternative routes to pyrimidines, that avoid the later hydrogenation steps, were developed at Hoffmann-La Roche [46]. This alternative synthetic strategy is shown in Fig. 36. An amino-imine can be prepared in the same way, but this time it is not reacted with a substituted phenylmalonate. Instead an alkoxybenzaldehyde is subjected to a Wittig reaction with the phosphorus ylide of chloromethoxymethane to yield l-(4-al-koxyphenyl)-2-methoxyethane. Treatment with triethoxymethane in the presence of a Lewis acid such as boron trifluoride ether-ate gives the tetraethoxy derivative. Hydrolysis produces 2-(4-alkoxyphenyl)-3-me-thoxypropenal, reaction of this material with the imine results in the pyrimidine being formed directly. 

An interesting example from carbohydrate chemistry is the boron trifluoride-diethyl ether complex catalyzed nucleophilic addition of silyl enol ethers to chiral imines (from n-glyceralde-hyde or D-serinal)22. This reaction yields unsaturated y-butyrolactones with predominantly the D-arabino configuration (and almost complete Cram-type erythro selectivity). 

An approach to the preparation of asymmetrically 1,2-disubstituted 1,2-diamines has been reported the zinc-copper-promoted reductive coupling of two different N-(4-substituted)phenyl aromatic imines, one bearing a 4-methoxy and the other a 4-chloro substituent, in the presence of either boron trifluoride or methyltrichlorosilane, gave a mixture of the three possible 1,2-diamines, where the mixed one predominated [31 ]. Low degrees of asymmetric induction were observed using 1-phenylethylamine, phenylglycinol and its 0-methyl ether, and several a-amino acid esters as the chiral auxiharies meanwhile the homocoupling process was not avoided (M.Shimizu, personal communication). 

While aromatic aldimines of amino acid esters are readily accessible from benzaldehyde or related derivatives and amino acid esters with concomitant removal of water,the corresponding ketimines require harsher reaction conditions, e.g. the benzophenone imine of glycine methyl ester is formed in boiling xylene in the presence of boron trifluoride-diethyl ether complex as a Lewis acid in 82% yield.P l These or similar reaction conditions lead also to piperazine-2,5-dione (DKP) formation therefore milder reaction conditions have been developed such as the transimination with benzophenone imine in dichloromethane, which occurs at room temperature overnight in 80-95% yield (Scheme The N -diphen-... 

Phosphorus Compounds. - The synthesis of the chiral phosphate (494) has been described. The silyl ether ds-Me3SiOCMe=CMeOSiMe3 reacts with Me0P(0)p3 to yield the dioxaphospholen (495). Treatment of the tetramer (496) with boron trifluoride affords the di-co-ordinated phosphorus compound (497). The imines (499) are obtained when the 1,2,3-diaza-phospholine (498) is heated with aryl azides. The oxazaphospholine (500) decomposes to trimethyl phosphate and the nitrile ylide (CF3)2C-N=CPh. ... 

An analogous transformation with A-tosyl aziridines produces A/-tosyl imines When aziridine 15 was treated with boron trifluoride-diethyl etherate in the presence of 2,3-dimethylbutadiene, amine 17 was produced via imine 16. 

The addition of lithiated ynol ethers to chiral A-sulfinyl imines proceeds in high yield and diastereoselectivity dr > 95 5)." The selectivity was completely reversed by the addition of boron trifluoride (Scheme 2). 

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