Aminodienes

Barluenga et al. have described novel vinylcarbene complexes containing a cyclic BF2 chelated structure which temporarily fixes the s-cis conformation of the exocyclic C=C and Cr=C double bonds. These boroxycarbene complexes behave as dienophiles with 2-amino-l,3-butadienes in a remarkably regio- and exo-selective way. Moreover, high degrees of enantioselectivity are reached by the use of chiral 2-aminodienes derived from (S)-methoxymethylpyrrolidine [101] (Scheme 54). 

Helmchen and coworkers employed a,co-amino-1,3-dienes as substrates [51]. By using palladium complexes with chiral phosphino-oxazolines L as catalysts, an enantiomeric excess of up to 80 % was achieved. In a typical experiment, a suspension of Pd(OAc)2, the chiral ligand L, the aminodiene 6/1-90 and an aryltriflate in dimethylformamide (DMF) was heated at 100 °C for 10 days. Via the chiral palladium complex 6/1-91, the resulting cyclic amine derivative 6/1-92 was obtained in 47% yield and 80% ee (Scheme 6/1.23). Using aryliodides the reaction time is shorter, and the yield higher (61 %), but the enantiomeric excess is lower (67% ee). With BINAP as a chiral ligand for the Pd°-catalyzed transformation of 6/1-90 and aryliodide, an ee-value of only 12% was obtained. 

We became particularly interested in strychnine when we noticed that the tetracycle 21 (Scheme 4.6), which might be readily available by an intramolecular Diels-Alder cycloaddition of a tryptamine-derived aminodiene, contains much of the complexity of this popular alkaloid target. In fact, this tetracycle is common to many indole monoterpene alkaloids including members of the Strychnos, Aspidosperma, and... 

Experimental Procedure 2.2.9. [4 + 3] Cycloaddition of a Chromium Carbene Complex to a 2-Aminodiene 6-(2-Furyl)bicyclo[5.4.0]undecan-2,4-dione [264]... 

Because a comprehensive discussion of the transition state of hydrogen-bond catalysis will be presented by Berkessel in Chapter 3, the hydrogen bond catalyzed hetero Diels-Alder reaction of butadiene with carbonyl compounds will be discussed briefly here. Huang and Rawal reported that the hetero Diels-Alder reaction of aminodiene with aldehyde exhibited significant solvent effects (Scheme 2.7) [15]. The reaction in CHCfi was accelerated 30 times in comparison with that in THF, while that in i-PrOH was accelerated 630 times. They proposed that the Diels-Alder reaction was promoted by the hydrogen-bond activation of aldehyde. This finding resulted in the development of TADDOL catalyst [3]. 

Domingo and Andres reported a DFT study of the hetero Diels-Alder reaction of aminodiene with acetone in CHCfi (Scheme 2.8) [16]. The transition state structure clearly shows that OH distance is 1.837 A (Figure 2.5), which is in the range... 

Vinylation of dienes in the presence of piperidine or morpholine yields aminodienes as major products. Sometimes trienes are minor products. The reaction is believed to proceed by way of a ir-allylpal-ladium complex formed by addition of the vinylpalladium halide to the least-substituted diene double bond. Nucleophilic attack of the amine upon the ir-allylic complex gives the aminodienes, while hydridopalladium halide elimination yields trienes (Scheme 6).97... 

Cazes et al. reported the Pd-catalyzed intermolecular hydroamination of substituted allenes using aliphatic amines in the presence of triethylammonium iodide leading to allylic amines [19]. In a way similar to the Pd-catalyzed hydrocarbona-tion reactions we reported that the hydroamination of allenes [20], enynes [21], methylenecyclopropanes [22], and cyclopropene [10] proceeds most probably via oxidative addition of an N-H bond under neutral or acidic conditions to give allylic amines. The presence of benzoic acid as an additive promotes the Pd-medi-ated inter- and intramolecular hydroamination of internal alkynes [23]. Intramolecular hydroamination has attracted more attention in recent years, because of its importance in the synthesis of a variety of nitrogen-containing heterocycles found in many biologically important compounds. The metal-catalyzed intramolecular hydroamination/cyclization of aminoalkenes, aminodienes, aminoallenes, and aminoalkynes has been abundantly documented [23]. 

A sequence of aminodiene Diels-AIder reactions of amidofurans provided tricyclic ketones, analogues of Komfeld s ketone, which will serve as the intermediates in the synthesis of ergot alkaloids <02OL4135>. 

Nugent s catalyst, however, failed to effect the cyclization of the aminodiene 106, that was cyclized to the pyrroline 107 either by Grubbs ruthenium alkylidene catalyst, PhCH=Ru(PCy3)2Cl2, in 77% yield or by Schrock s catalyst, PhC(Me)2CH=Mo=N[2,6-(iPr)2C5H3] [OCMe(CF3)2]2 in 60% yield (Equation (123)).149... 

Barluenga J, Tomas M, Suarez-Sobrino A, L6pez LA (1995) ] Chem Soc Chem Comm 1785 for an analogous transformation with an achiral aminodiene see Barluenga J, Aznar F, Fernandez M (1995) Tetrahedron Lett 36 6551... 

Water-soluble dienes are also used in Diels-Alder reactions in water and they too work very well. Sodium salts of carboxylic acids and protonated amines both behave well under these conditions. Presumably, the soluble tail is in the water but the diene itself is inside the oily drops with the dienophile. In this example an aminodiene reacts with a quinone dienophile. 

Both [2 + 2] and [4 + 2] cycloadditions have been observed in the reaction of dienamines with sulfenes. For example, reaction of cross-conjugated dienamine 202 with sulfene afforded a mixture of 203 and 204 (equation 44)111. Also, enamines of 1-tetralone (205, 206) can react as enamines or as aminodienes with phenylsulphene giving 207-209 (equation 45)112. 

The carbon-carbon unsaturated substrates have now expanded from aminoalkenes to aminoalkynes, aminoallenes, and aminodienes, and the hydroamination/cyclization reactions of these substrates have produced functionalized nitrogen-containing heterocycles. It is worth noting that the aminoallene hydroamination/cyclization reactions are highly diastereoselective, and can provide concise routes to the synthesis of some natural products (Figure 8.38) [126]. 

Rare-earth metal complexes have proven to be very efficient catalysts for intramolecular hydroamination reactions involving aminoalkenes, aminoalkynes, aminoallenes, and conjugated aminodienes [88, 97]. They are significantly less efficient in intermolecular hydroamination reactions and only a limited number of examples are known [98-102]. The difficulties in intermolecular hydroamination reactions originate primarily from inefficient competition between strongly binding amines and weakly binding alkenes for vacant coordination sites at the catalytically active metal center. 

Fig. 12 Thermodynamics of the elementary steps in rare-earth metal-catalyzed hydroamina-tion/cyclization of aminoalkenes (a), aminoalkynes (b), aminoallenes (c), and aminodienes (d) n = 1-3) [103-108]...

The rare-earth metal-catalyzed cyclization of aminoalkenes, aminoalkynes and aminodienes generally produces exclusively the exocyclic hydroamination products. The only exception was found in the cyclization of homopropargylamines leading to the formation of the endocyclic enamine product via a 5-endo-dig hydroamination/cyclization (32) [142], most likely due to steric strain in a potential four-membered ring exocyclic hydroamination product. Interestingly, the 5-endo-dig cyclization is still preferred even in the presence of an alkene group that would lead to a 6-exo hydroamination product [142]. 

Scheme 8 Synthesis of (+)-coniine-HCl via enantioselective aminodiene hydroamination/ cyclization...

Cbz-protected vinylpiperidine (Scheme8) [108]. Cyclization of aminodienes followed by hydrogenation constitutes an alternative to the less facile direct hydroamination of a 1,2-disubstituted aminoalkene (see Sect. 6.1.1). 

Scheme 11.20 Stereomodel for the lanthanocene catalyzed hydroamination/cyclization of aminodienes. The silicon linker bridging the two cyclopentadienyl ligands was omitted for the sake of clarity.

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