Conjugate Addition of Amidoalkyl Zinc-Copper Reagents to a Propyne Iminium Triflate

Abstract

Zinc-copper reagents of the type IZnCu(CN)-(CH 2 ) n -NR 1 R 2 , obtained from N -(2-iodoethyl)phthalimide, N -(2-iodopropyl)phthalimide, and N -(2-iodoethyl)benzamide, undergo conjugate addition to propyne iminium triflate 1 . After hydrolytic workup, the β -amidoalkyl-α , β -unsaturated ketones 6a , b and 9 are obtained in moderate yield. The iodoalanine derived zinc-copper reagent IZnCu(CN)-Boc-L -Ala-OBn (11) reacts with 1 analogously and furnishes after hydrolytic work-up both N -Boc-α -amino acid ester 12 and 5-aminocyclopent-2-en-1-one 13 .Conjugate nucleophilic addition to the triple bond of propyne iminium triflates represents a versatile approach to aminoallenes and amino-1,3-dienes. Carbon nucleophiles which serve this purpose are typically supplied as organocuprates 1-3 and other organocopper reagents. 1 The shortcoming of these reagents, namely not to be compatible with most of the polar functional groups, can be overcome by the use of zinc-copper organometallic compounds which tolerate many organic functional groups. 4 In fact, we have successfully transferred cyano-and alkoxycarbonyl-substituted carbon nucleophiles via the zinc-copper reagents 2 [R c = -(CH 2 ) 2 -, -(CH 2 ) 3 -, -C 6 H 4 -, FG = CN, COOEt] to propyne iminium salts such as 1 (Scheme 1); the resulting functionalized morpholinoallenes 3 underwent further reactions such as tautomerization to form morpholino-1,3-dienes and cyclization, or were transformed into α , β -unsaturated ketones during hydrolytic workup. 5In this communication, we report that zinc-copper reagents 2 , in which FG is an amido group, also react with salt 1 to give β -( ω -aminoalkyl ) -α , β -unsaturated ketones after hydrolytic workup.Zinc-copper reagents 5a , b were prepared according to a procedure published for 5b , 6 i.e. by reaction of alkyl iodides 4a , b with activated zinc, followed by transmetalation of the organozinc iodide so formed with the THF-soluble salt CuCN • 2 LiCl.In a modification of the literature procedure, we used granulated zinc rather than zinc foil or zinc dust, and completed the activation (1,2-dibromoethane, then Me 3 SiCl) by ultrasonication for 15 minutes. While the zinc insertion into the carbon-iodine bond is usually monitored by GC analysis of a hydrolyzed aliquot of the reaction mixture, we found it convenient to follow the progress of this transformation by direct 1 H NMR control. The addition of CDCl 3 or CD 3 CN as a lock substance to the NMR sample led to the destruction of the organozinc compound, but the use of DMSO-d 6 (water content < 0.005%) 7 allowed observation of the signal of the Zn-CH 2 protons as part of an AA'XX' system at δ = 0.2-0.4 [with δ (DMSO) = 2.49], as well as the disappearance of the starting material. For 4b , zinc insertion was complete after 4 hours, while 4a had been consumed only after 24 hours.Reaction of zinc-copper reagents 5a , b with propyne iminium salt 1 in THF/dichloromethane, followed by hydrolytic workup and chromatographic separation, furnished α , β -unsaturated ketones 6a,b in moderate ...

3-Trifloxypropene iminium and propyne iminium salts derived fromN-Allyl-,N-Homoallyl-, and N-benzyl-substituted semicyclic enaminones

“…As the internal reference, Me 4 Si was used for the proton spectra, and the solvent signal for the 13 C NMR spectra [δ (CDCl 3 ) = 77.0 ppm, δ (CD 3 CN) = 1.3 ppm]. IR spectra were recorded on a Perkin Elmer IR 883 spectrometer.…”

“…Most importantly, they can be transformed into functionalized and highly substituted propargylamines, aminoallenes, and amino-1,3-butadienes [1][2][3][4]. In earlier papers [5 -7], we have described that propyne iminium salts III are easily available by O-sulfonylation of enaminoketones I with triflic anhydride (Tf 2 O), followed by elimination of triflic acid (HOTf) from the resulting 3-trifloxypropene iminium triflates II (Scheme 1).…”

Imines, enamines and oximes

“…113 Amidoalkyl zinc-copper reagents have been shown to undergo conjugate additions to propyne iminium salts. 114 Preformed iminium salts 50 with SbCl 6 Ϫ as the counter-ion react with (1,1-dimethylallyl)trimethylsilane 51 in dichloromethane to give pyrrolidinium salts 52 in 85-95% yields (Scheme 18). 115 Cyclic iminium salts (fluoroborate or bisulfate adducts) have been treated with an iridium catalyst incorporating chiral amidophosphine-phosphinites in a hydrogen atmosphere such that an asymmetric hydrogenation occurred to give the corresponding cyclic secondary amines in up to 86% ee.…”

Orthoamides and iminium salts, LXXXIX. Reactions of N,N,N′,N′,N″,N″,N′″,N′″-octamethyl-acetylene-bis(carboxamidinium) tetrafluoroborate with nucleophilic reagents – new methods for the preparation of amidinium salts and ketene aminalsa

“…Brought to you by | Purdue University Libraries Authenticated Download Date | 5/30/15 5:54 AM A number of chemical reactions have been performed with propyne iminium salts 1 [4,5,8,[21][22][23][24][25][26][27][28][29][30][31][32][33][34]. In contrast, only few reactions of propiolamidinium salts 3 are known.…”