1.5- Dienes nitrogen nucleophiles

Additions to l,3-dienes6 (12, 367-368 14, 249-250 15, 245). This reaction can be used to effect intramolecular cyclization of cyclic 1,3-dienes substituted by a suitable nitrogen nucleophile. Thus reaction of the amido diene 1 with lithium acetate catalyzed by Pd(OAc)2 (with benzoquinone as reoxidant) provides the ds-fused heterocycle cis-2, in which the acetoxy group is cis to the ring fusion, formed by an overall trans-1,4-oxyamidation of the diene system. Addition of a trace of LiCl improves the yield and results in an overall cis- 1,4-oxyamidation (equation I). Acetamides and carbamates can also be used in place of amides. 1,4-Chloroamidation can also be effected by use of 2 equiv. of LiCl. 

Conjugated dienes coordinated to palladium(Il) undergo nucleophilic addition of oxygen and nitrogen nucleophiles from the opposite side of the palladium center to give Ti-allylpalladium complexes. Subsequent reaction of the 7C-allyl complexes with another molecule of nucleophile results in the 1.4-addition of two kinds of nucleophiles to dienes. The direction of the second nucleophilic attack is dependent on the nature of the nucleophiles as well as the reaction conditions. Representative examples... 

Diene complexes give allyls on nucleophilic attack. Note how the cisoid conformation of the butadiene in Eq. 8.18 gives rise to an anti methylallyl (in the nomenclature of allyl complexes, a substituent is considered as syn or anti with respect to the central CH proton). Equation 8.19 is interesting in that the amine acts in this case as a carbon, not as a nitrogen nucleophile. ... 

C.ii.b. Intramolecular Attack by Nitrogen Nucleophiles. The nitrogen nncleophiles, which are compatible with the reaction conditions (HOAc and 1,4-benzoquinone), consist of electron-deficient ones such as amides, carbamates, ureas, and sulfonamides. Because of the low nucleophilicity of these, no intermolecular 1,4-additions involving C—bond formation is known. However, if the nitrogen is tethered to the diene, a cyclization takes place in good yields. 

The intramolecular oxidation using nitrogen nucleophiles was developed further by using an amide with the ability to undergo a twofold attack on the diene (Scheme 12). This leads to a bicyclic system and constitutes a useful [4 + 1] intramolecular cycloaddition, which gives access to pyrrolizidine and indolizidine alkaloids. " ... 

Grigg et al. reported a successful four-component domino reaction for the synthesis of functionalized dienes 316 from aryl iodides, allyl amine derivative, allene, and carbon monoxide [110] (Scheme 6.83). Carbon monoxide could insert into the C—Pd bond of arylpalladium(II) iodides to generate a carbonylpalladium species, which is followed by allenylation to form n-allylpalladium species. Finally, the attack of the nitrogen nucleophile produces the product observed. The products of this domino multicomponent reaction could be subjected efficiently to ring-closing metathesis in the presence of Grubbs second-generation catalyst. 

Nitrogen nucleophiles in proximity to (T) -cyclohexa-l,3-diene)iron complexes have been often subjected to oxidative cyclization. Tetrahydro-l -pyrrolo[l,2-o]indoles... 

The steric crowding introduced in the latter by the four ethyl substituents inhibits nucleophilic attack at platinum, so that complexes of this type tend to undergo substitution by a dissociative mechanism [89]. The complex of the more rigid ligand, 2,2, 2"-terpyridyl, Pt(terpy)Cl+, is found to be about 103 to 104 times more reactive to substitution than the dien analogue this is ascribed to steric strain [90], which is reflected in the short Pt—N bond to the central nitrogen (Pt-N some 0.03 A shorter than the other two Pt-N bonds) and N—Pt—N bond angles of 80-82°). 

Table 3.19 lists examples of the preparation of nitrogen-containing heterocycles by RCM. As mentioned in Section 3.2.5.3, free amines can partly deactivate metathesis catalysts. With the highly reactive molybdenum catalyst 1 it is, however, possible to cyclize dienes containing a basic amino group. If the less reactive catalysts 2 or 3 are to be used, protonation or acylation of the amine can be used to reduce their nucleophilicity. This will generally lead to higher yields with smaller amounts of catalyst. 

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