Reactions aminoallylation

Yamamoto and coworkers developed cycloadditions between activated olefins and vinylaziridines 253 with the aid of a palladium(O) catalyst (Scheme 2.63) [94], based on their three-component aminoallylation reaction. The corresponding 4-vi-nylpyrrolidines 255 were obtained as mixtures of diastereomers (ds trans= 55 45 to 23 77). 

The stereochemistry of the alkylation reaction of chiral 1-aminoallyl metallics can be rationalized by supposing (S,S)-9 to be the reacting species. In the case of bulky, poorly complexing solvents, such as tm-butyl methyl ether, metalloinversive Re attack on a tight ion pair from the less-hindered allyl face is favored. With better complexing and smaller solvents, such as THF, a looser ion pair reacts by a metalloretentive mode on the Si-side which now becomes more reactive. 

The transcription reaction is performed using T7 RNA polymerase according to the general protocol of Milligan et al. (1987), using a DNA template strand that incorporates 2 -OMe modifications at each of the first two nucleotides at the 5 -end to suppress formation of n + 1 transcription products (Kao et al., 1999). The sequence of the 19-mer unlabeled tagging RNA is 5 -GCaaAAGAGAUGGUGAUGGGA-3, where Caa denotes 5-aminoallyl-C. 

In the indirect labeling method, amine modified cDNA is first synthesised by incorporating aminoallyl-modified nucleotides in first strand cDNA by a reverse transcriptase. After hydrolysis of the RNA template, and purification of the amine-modified cDNA, chemical labeling with N-hydroxyl succinimidyl-ester derivative of the Cy dye is performed. A high excess of Cy dye NHS-ester is needed for an efficient reaction. The Cy dye-cDNA is then purified to remove Cy dye that is not incorporated into labeled cDNA. 

The three component aminoallylation reaction of the activated olefins 4 was also reported by us (Scheme 7) [39]. The palladium catalyzed reaction between phthalimid 10, olefins 4 and allyl chloride 11 proceeded well in the presence of CS2CO3 to give the corresponding aminoallylation products 12 in high yields. Likewise, cyanoallylation of activated olefins was also reported (Scheme 8) [40]. In both cases only aryl substituded and f-bulyl substituded olefins are proved good substrates. The mechanism of these reactions is presumably similar to that of hydroalkoxylation reaction (see Scheme 5). 

Ab initio calculations indicated that the cyclopropiminium ion is more stable than the 2-aminoallyl cation.As allyl cations can be generated from the reaction of allylic halides with silver salts, ° reactions of a-haloenamines with these salts have been investigated in order to increase the yield and chemoselectivity of the formation of bicyclo[3.1.0]hexan-6-one aminals. ° ... 

Among fhe known [4 + 3] cycloaddition protocols examined, only the Schmid2 and Fohlisch4.10 procedures were found to afford the [4 + 3] cycloadducts in synthetically useful yields. Schmid s rarely-used aminoallyl reaction appears to be most effective, particularly when sterically demanding 1,3-dienes [e.g., spiro[2.4]hepta-4,6-diene] or otherwise recalcitrant N-acylpyrroles are required for the cycloadditions. On the other hand, with sterically unencumbered 1,3-dienes and also with furans, the Fohlisch reaction has emerged as the method of choice in view of the practical aspects of simple and convenient execution. 

Two Pd-catalyzed cyclizations were used for the enantioselective synthesis of (—)-cephalotoxine [109]. One-pot Pd-catalyzed domino reactions, namely intramolecular allylation of amine and HR of 256, seem to be the best path for the desired synthesis. However, attempted direct conversion of 256 to 258 with the Herrmaim complex was unsuccessful. Then selective intramolecular aminoallylation with the chiral cyclopentyl acetate occurred smoothly to give the Spiro amine 257 in 88 % yield when Pd(PPh3)4 and TMG (tetramethylguanidine) as a base were used. The cyclization proceeded with retention of stereochemistry without racemization. The next HR reaction of 257 gave the seven-membered compound 258 in 81% yield under Jeffery s conditions using the Herrmann complex as a catalyst. No transformation of 257 to 258 occurred when Pd(PPh3)4 was used. The results show that the best catalysts for the allylation and HR are different. 

Morken and coworkers extended their previously developed palladium-catalyzed asymmetric diboration of prochiral allenes [54] to the subsequent a-aminoallylation of the in situ generated allyl and vinylboronate 62, as versatile intermediate for allylation reactions (Scheme 4.30) [55]. 

J. Org. Chem. 2(X)4, 69,4(X)5—4(X)6. Iodine as a very powerful catalyst for three-component synthesis of protected homoal-lylic amines, (c) J.-R. Ella-Menye, W. Dobbs, M. BUlet, P. Klotz, A. Mann, Tetrahedron Lett. 2005, 46, 1897-19(X). Unexpected 1,2 syn diastereoselectivity in the three-component aza Sakurai-Hosomi reaction, (d) M. Sugiura, K. Hirano, S. Kobayashi, J. Am. Chem. Soc. 2004, 126, 7182-7183. a-Aminoallylation of aldehydes with ammonia stereoselective synthesis of homoallylic primary amines, (e) M. BiUet, P Klotz, A. Mann, Tetrahedron Lett. 2(X)1,42, 631-634. Syn diastereoselectivity in the synthesis of homoallylamine using crotylsilane in the three-component reaction, (f) L. Niimi,... 

Shipman and coworkers have shown that coordination of Bp3 OEt2 to 2-methylene aziridines (21) lead to an alternative precursor to 2-aminoallyl cations, which can be trapped with an appended 1,3-diene to effect an intramolecular [4 + 3] cycloaddition reaction that generates seven-membered ring systems such as (22) (Equation 16) [22]. 

Later on, Ren and Wulff [53] reported that a combination of the chiral catalyst VANOL-B3 29, derived from the reaction of binaphthol derivative VANOL with triphenyl-borate, also afforded good results in the asymmetric catalytic aminoallylation of a series of aromatic, aliphatic, and a,P-unsaturated aldehydes. Catalytic amounts of benzoic acid were required to ensure the formation of the intermediate imines, and the rearranged imines were hydrolyzed in situ to afford the homoaUylic amines (Scheme 40.44). 

An extensive review of the synthesis of a wide variety of five-membered heterocyclic compounds, via the formal 3-1-2-cycloaddition reactions of aziridines with alkenes, alkynes, nitriles, carbonyl groups, and heterocumulenes, has been presented." Supercritical CO2 has been used as the solvent in the formal 3-1-2-cycloaddition reactions of A-benzyl- and A-cyclohexyl-2-benzoyl-3-phenylaziridines with allenoates to yield pyrrole derivatives." The Lewis acid-catalysed intramolecular formal 3-1-2-cycloaddition reactions of 2-methyleneaziridines with tethered alkenes or alkynes (23) yielded cw-octahydrocyclopenta[c]pyrroles (24) after reductive workup. The reaction mechanism proceeds in a stepwise manner via a 2-aminoallyl cation (Scheme The Cu(I)/DTBM-Segphos-catalysed 1,3-dipolar cycloaddition reactions of a-silylimines and activated alkenes yielded highly enriched 5-unsubstituted a-quaternary proline cycloadducts with excellent diastereo- and enantio-selectivities (73-99% The... 

---