Allylamine cyclization

Allylamines cyclize readily with a dicobalt octacarbonyl catalyst (equation 55).1,2 Rhodium catalysis generally allows the carbonylative cyclization to be carried out under milder conditions.86 Application of this reaction to unsaturated amides yields the corresponding imides, the best yields arising when R1 = H and R2 = allyl (equation 56).I>2... 

The diazo compound (181a), prepared from the nitrosamine, cyclized to a pyrrolopyrazoline in 80% yield.98 The diazo compound (181b), prepared from diethyl diazomalonate and allylamine, cyclized similarly but at a much more rapid rate. This is consistent with the lowered LUMO of the dipole of (181b), substituted with an ester group here the dipole LUMO-dipolarophile HOMO is the likely dominant interaction. The N—N double bond of the pyrrolopyrazoline products was readily isomerized to afford A2-isomers. 

Radical cyclization is compatible with the presence of other functional groups. Treatment of XCH2CON(R)-C(R )=CH2 derivatives (X = Cl, Br, 1) with Ph3SnH and AIBN led to formation of a lactam via radical cyclization. " Cyclization of N-iodoethyl-5-vinyl-2-pyrrolidinone led to the corresponding bicyclic lactam, " and there are other examples of radical cyclization with molecules containing a lactam unit " or an amide unit. Radical cyclization occurs with enamines as well. Photochemical irradiation of A,A-dialIyl acrylamide leads to formation of a lactam ring, and in this case thiophenol was added to generate the phenylthio derivative. Phenylseleno N-allylamines lead to cyclic amines. co-Iodo acrylate esters cyclize to form lactones. " ... 

Nucleophilic addition of primary o.-R -allylamine to nitrone followed by a reverse Cope cyclization and Meisenheimer rearrangement gives the oxadiazi-nanes (426a-h) (Scheme 2.198). These reactions have found use for the preparation of oxadiazines, vicinal aminohydroxylamines, and diamines the latter are of particular interest as chiral ligands (683, 684). 

Optically active iV-unprotected-2-pyrrolidinones 194 were obtained from selenocarboxylate or allylamine via radical cyclization and subsequent one-step cleavage of the C-O and C-N bond of the inseparable mixture of the two bicyclic oxyoxazolidinones 192 and 193 with -Bu4NF. The initial radical reaction is highly stereoselective. Products were obtained with ee up to 90%. The mandelic acid 195, which served as the chiral auxiliary in this method, was recovered with no loss of optical activity (Equation 33) <2003T6291>. 

A-allylamine 23 (obtained by standard transformations of 6-iodogluco-side 22) underwent cyclization into the monocycle 24. However, when the amine was in situ protected as a Boc derivative it could be subjected to the RCM process. The products were further converted into the bicyclic aza sugar 26.19 A similar approach to eight-membered ring aza sugars was recently reported (Fig. 9).20... 

Consecutive condensations of 2-naphthol, allylamine, and dibromomethane comprised another route to naphthalene-condensed 1,3-oxazines. A preheated mixture of allylamine and dibromomethane was reacted with 2-naphthol 152 to yield the aminophenol intermediate 520, which was cyclized with the salt formed in the reaction of dibromomethane and diethylamine to give 3-allyl-3,4-dihydro-2//-naphth[l,2-< ][l,3]oxazine 521 on further reaction (Scheme 98) <2004SC2253>. 

The cyclization of carbamate derivatives of unsaturated amines has proven synthetically useful. Cyclizations of carbamates of allylamines containing a terminal vinyl group give oxazolidinone products (equation 60 and Table 17, entries 1 and 2).99,161 Bromocyclizations of systems with a di- or tri-sub-stituted alkene often give mixtures of oxazolidinones and tetrahydrooxazinones,163 while cyclization of an A -cinnamyl carbamate with phenylsulfenyl chloride gave only the oxazolidinone product.163b,163c The stereochemistry of the cyclization of primary carbamates of either allylic or homoallylic amines is low... 

Cyclizations of urea derivatives of allylamines with selenium reagents have been examined recently (equation 62 and Table 18).98 Cyclization of the allylic ureas produces franj-2-oxazoline derivatives with high stereoselectivity when the double bond is internal (Table 18, entry 2). Although O-methylisourea derivatives can be cyclized to dihydroimidazoles [see Section 1.9.3.2.2(ii)], cyclization with phenylsel-enenyl trifluoromethanesulfonate and trifluoromethanesulfonic acid produces 5,6-dihydro-1,3-oxazines (6-endo products), even when the double bond is monosubstituted (entry 3). 

Allylamines may be converted directly to oxazolidinones through condensation with CO2, to form carbamate salts, and treatment with iodine (equation 64 and Table 20).166 High stereoselectivity was obtained only in cases where the a-substituent was hydroxymethyl (entry 5) or the amine was secondary and the substituent was phenoxymethyl (entry 4). The results with primaiy amines are comparable to those for amide cyclizations shown in equation (57). 

TABLE 4.6. Zr-Catalyzed Enantioselective Cyclization of Dienes Containing Allylamine Moieties Induced by n-BuMgCl... 

In the presence of molecular iodine, the C-C double bond of allylamines and homoallylamines can be activated towards nucleophilic attack by carbamate anion. Accordingly, iodoalkyloxazolidinones and iodoalkyloxazinanones have been prepared under mild conditions (ambient temperature, atmospheric C02 pressure) by the reaction of allylamines and homoallylamines with C02 and iodine via intramolecular cyclization [88],... 

The six-membered ring 85 is obtained from the allylamine 84 [31]. The sulfur-containing ring 87 was obtained from 86 using the Mo catalyst. The Ru catalyst is not active for this reaction [32]. The (S, f )-chromene derivative 89 was obtained in 97% yield by the Mo-catalysed intramolecular metathesis of (S,f )-cycloheptenyl styrenyl ether 88 under an atmosphere of ethylene. In the absence of ethylene, 89 and its dimer were obtained. The enantioselective total synthesis of (.S, / ,/ , / )-ncbivoIoI (90) has been carried out from 89 [33]. No cyclization of the cyclopentene 91 was observed, because the highly strained cyclobutane intermediate 92 is difficult to form. 

In this context we have recently reported that A-2-bromoallyl-iV-(3-functionalized) allylamines 315 undergo, after formation of the corresponding vinyllithiums, intramolecular carbolithiation processes giving rise to functionalized methylenepyrrolidines 316 in good yields. We have shown that a moderately activating group at the terminal position of the double bond favours the cyclization reaction and we have presented the first... 

The addition of allylamine to the benzaldehyde nitrone 17 gave mainly the //wi.v-3,6-disubs tituted 1,2,5-oxadiazinane 20 via the cyclization of the ci.y-unsaturated hydroxylamine 18 to give the pyrrolidine A-oxide 19, and a final rearrangement step77. The product 20 was relatively sensitive to chromatographic purification, but could be converted to the more stable A -Boc and iV-(4-ni-trobenzoyl) derivatives (X-ray). 

Like the cycloisomerization of propargylamine amides, allylamine amides such as 181 undergo 5-i 3cti-cyclization in NaOH to give phosphine oxide-substituted oxazoles 182 (Equation 11) <2004T8937>. 

Heterocyclization. Formation of A-tosyl-2-iodomethylaziridine from A-tosyl-allylamine requires iodine and NaH, whereas Ij-LiAl(OBu ) mediates cyclization of allyl A-acylcarbamates." A route to 4-iodo-2,3-dihydropyrroles by iodine-induced cyclization of homopropargylic sulfonamides involves a 5-endo-dig cyclization. ... 

Reaction of 5-substituted isatoic anhydride with allylamines gave 2-amino-5-substituted-jV-alkyl-A -(2-propenyl)benzamides which were subjected to diazotization followed by subsequent nucleophilic substitution and cyclization to give 2-methyl-l,4-benzodiazepin-5-ones. A non-covalent DNA-binding agent like pyrrolo[2,l-c][l,4]benzodiazepine-5,ll-dione has been synthesized. 

A regioselective synthesis of alkylpyrazines (155) starts with condensation of a-oximino carbonyl compounds with allylamines (Scheme 38). The imine intermediates are isomerized in the presence of potassium r-butoxide to the corresponding 1-hydroxy-1,4-diazahexatrienes. Thermal cyclization-aromatization to pyrazines is best performed after 0-acylation of the oximes with methyl chloro-formate <91JOC2605>. 

A related cyclization was recently reported by Jia et al. [14] with allylamine 20 immobilized on poly styrene-Wang resin. The reaction was monitored by acetylation and cleavage to yield 21, as a mixture of free and Boc-protected amines. This solid-phase synthesis of. seco-CBI (21, R = H), related to the pharmacophore of the CC-1065 and duocarmycin class of cyclopropylindole antitumor antibiotics, has potential for the preparation of analogue libraries, and an example of further transformation of resin-bound 21 to a polyamide was presented. 

Allyl ethers and allylamines undergo dimerization, whereas 1,6-dienes are cyclized regioselectively according to the titanium complexes used. ... 

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