Allyl amines cyclization

Allylic oxidation of cyclohexene and related alkenes can be achieved with catalytic amounts of palladium(II) acetate, Cu(OAc)2, hydroquinone, and O2 as oxidant in AcOH, leading to allylic acetates.Methyl glyoxylate adducts of A-Boc-protected allylic amines cyclize, in the presence of catalytic Pd(OAc)2 and an excess of Cu(OAc)2 in DMSO at 70 °C, to 5-(l-alkenyl)-2-(methoxycarbonyl)oxazolidines (eq 7). ... 

The reductive coupling of of dienes containing amine groups in the backbones allows for the production of alkaloid skeletons in relatively few steps [36,46,47]. Epilupinine 80 was formed in 51% yield after oxidation by treatment of the tertiary amine 81 with PhMeSiEh in the presence of catalytic 70 [46]. Notably, none of the trans isomer was observed in the product mixture (Eq. 11). The Cp fuMcTIIF was found to catalyze cyclization of unsubstituted allyl amine 82 to provide 83. This reaction proceeded in shorter time and with increased yield relative to the same reaction with 70 (Eq. 12) [47]. Substitution of either alkene prevented cyclization, possibly due to competitive intramolecular stabilization of the metal by nitrogen preventing coordination of the substituted olefin, and resulted in hydrosilylation of the less substituted olefin. 

Allylic amination is important for the solid-phase organic synthesis.15 The solid-phase allylic aminations are devised into the G-N bond formation on solid support and the deprotection of allyl ethers. As a novel deprotection method, the palladium-catalyzed cyclization-cleavage strategy was reported by Brown et al. (Equation (4)).15a,15b The solid-phase synthesis of several pyrrolidines 70 was achieved by using palladium-catalyzed nucleophilic cleavage of allylic linkages of 69. 

A novel procedure for the synthesis of an indole skeleton 81 was developed by Mori s group (Scheme 13).16e,16f Enantioselective allylic amination of 78 with A-sulfonated < r/ < -bromoaniline 79 followed by Heck cyclization of 80 provided chiral indoline 81. The treatment of a cyclohexenol derivative 78 with 79 in the presence of Pd2(dba)3-GHGl3 and ( )-BINAPO gave compound 80 with 84% ee in 75% yield. Total syntheses of (—)-tubifoline, (—)-dehydrotubifoline, and (—)-strychnine were achieved from compound 80. 

Isomerization of allylic amines is another example of the application of the BINAP complex. Rh BINAP complex catalyzes the isomerization of N,N-diethylnerylamine 40 generated from myrcene 39 with 76-96% optical yield. Compound (R)-citronellal (R)-42. prepared through hydrolysis of (R)-41, is then cyclized by zinc bromide treatment.49 Catalytic hydrogenation then completes the synthesis of (—)-menthol. This enantioselective catalysis allows the annual production of about 1500 tons of menthol and other terpenic substances by Takasago International Corporation.50... 

Radical cyclization of N-alkenylamino acid derivatives Proline derivatives can be obtained by cyclization of N-alkenyl amino acid derivatives. Thus the (3-iodo allylic amine 2, prepared in 54% yield from threonine, cyclizes in the presence... 

The combination of allylic amination, ring-closing metathesis, and a free radical cyclization provides a convenient approach to the dihydrobenzo[b]indoline skeleton, as illustrated in Scheme 10.10. The rhodium-catalyzed aUylic amination of 43 with the lithium anion of 2-iodo-(N-4-methoxybenzenesulfonyl)arrihne furnished the corresponding N-(arylsulfonyl)aniline 44. The diene 44 was then subjected to ring-closing metathesis and subsequently treated with tris(trimethylsilyl)silane and triethylborane to afford the dihydrobenzojhjindole derivative 46a in 85% yield [14, 43]. 

Dihydropyrroles have recently become readily available by ring-closing metathesis. For this purpose, N-acylated or N-sulfonylated bis(allyl)amines are treated with catalytic amounts of a ruthenium carbene complex, whereupon cyclization to the dihydropyrrole occurs (Entries 6 and 7, Table 15.3 [30,31]). Catalysis by carbene complexes is most efficient in aprotic, non-nucleophilic solvents, and can also be conducted on hydrophobic supports such as cross-linked polystyrene. Free amines or other soft nucleophiles might, however, compete with the alkene for electrophilic attack by the catalyst, and should therefore be avoided. 

Some other rhodium-catalyzed reactions of CO are collected here. The cyclization of allyl amine to y-butyrolactone (equation 97) is catalyzed by the complexes RhCl3, [Rh(acac)3], [Rh2Cl2(C2H4)4], [RhCl(PPh3)3] (23) and [RhCl(CO)(PPh3)2] (71). If allyl chloride or iodide is used together with ammonia or a primary amine, analogous cyclizations occur.461... 

Table 18 0-Cyclization of Urea Derivatives of Acyclic Allylic Amines.

Table 20 Cyclization to 2-Oxazolidinones from Allylic Amines and Carbon Dioxide (Equation 64)...

Methyl glyoxylate adducts of N-BOC-protected allylic amines 321 have been utilized to construct a new C—O bond by an intramolecular, Pd(II)-catalysed reaction436. In analogy, lactones 324a437 and cyclic ethers 324b438 can be prepared by the Pd(II)-catalysed cyclization of the suitable precursors 322a and 322b, respectively. 

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]. 

Further functionality (i.e., 4-oxo) has been introduced by the cyclization of a-allyloxy-carbonylnitrones, which have traditionally been problematic to obtain. Tamura and co-workers have reported that simple alkoxycarbonylnitrones (e.g., (243)) undergo transesterification and cyclization with various allylic alcohols in the presence of titanium isopropoxide (Scheme 43) <95T107, 95T119). Alternatively, allyl a-oximinocarboxylates (246) are converted in situ to nitrones (247) and further cyclized to the bicyclic heterocycles (248) (Scheme 44) <91T4495>. Tetrahydro-1 //-pyrrolo[3,4-c]isoxazoles (250) have been prepared by the condensation of C-acylnitrones with allyl amines <78AJC2013> further reduction of the bicycles (250) with sodium borohydride affords the 3-oxa-2,7-diazabicyclo[3.3.0]octane (251) (Scheme 45). 

A chemoselective addition of allylic alcohols (82) to 3-halogenovinyl sulfones (81) has been accomplished using KF-basic alumina as the basic medium.55 The resulting adducts (83) can be stereoselectively cyclized by a radical process, affording 2,4-disubstituted tetrahydrofurans (84) (Scheme 22, Eq. 1). The same group has recently reported an analogous protocol using allylic amines (85) for the synthesis of 2,4-disubstituted pyrrolidines (87) (Scheme 22, Eq. 2)56... 

In a similar way, 2-oxazolidinones and tetrahydro-2//-l, 3-oxazin-2-ones have been prepared by the reaction of primary allyl amines and homoallyl amines10, respectively, with carbon dioxide and iodine in methanol via an intramolecular cyclization. Prolonged reaction for a week in the presence of cesium carbonate increases the yield to 70-90%. This reaction has a large applicability and the ease of the method makes it useful in organic synthesis. 

Benzamidines and trichloroacetamidines, readily prepared from allylic amines and benzonitdle or trichloroacetonitrile, cyclized on treatment with A-iodosuccinimide or iodine in tetrahydro-furan to give the corresponding 4,5-dihydroimidazoles 1 and 2. The successive hydrolysis gave diamines166. 

Vinyl halides add to allylic amines in the presence of Ni(cod)2 where cod=l, 5-cyclooctodine, followed by reduction with sodium borohydride. Aryl iodides add to alkynes using a platinum complex in conjunction with a palladium catalyst. A palladium catalyst has been used alone for the same purpose, and the intramolecular addition of a arene to an aUcene was accomplished with a palladium or a GaCl3 catalyst, " AUcyl iodides add intramolecularly to aUcenes with a titanium catalyst, or to alkynes using indium metal and additives. The latter cyclization of aryl iodides to alkenes was accomplished with indium and iodine or with Sml2. " ... 

The reaction can be modihed to give additional products, as with the reaction of o-hydroxybenzaldehyde and methyl vinyl ketone with DABCO, where the initial Baylis-Hillman product cyclized via conjugate addition of the phenolic oxygen to the conjugated ketone (15-31). ° Aldehydes and conjugated esters can be coupled with a sulfonamide to give an allylic amine. 

M.G. Finn and co-workers developed a procedure for the preparation of 2/-/-chromene derivatives that includes a Petasis three-component reaction between salicylaldehyde, vinylic- and aromatic boronic acids, and dibenzylamine. The hydroxyl group of the salicylic aldehyde is essential for the activation of the boronic acid. The initially formed allylic amine undergoes a cyclization upon ejecting the dibenzylamine, thus rendering the process catalytic in the amine. 

Our first approach to 1 is based on a retrosynthetic analysis depicted in Fig (8). The crucial step to construct the cw-fused bicyclic ring skeleton of 1 is the intramolecular allylic amination of a cw-allylic carbonate 25. The paUadium-catalyzed allylation takes place with retention of the configuration [76] and requires the c/s-isomer 25 for the ring closure. Compound 25 may be derived from keto acid 24 through a sequence of reactions including esterification, O-methoxycarbonylation, removal of the Boc and benzylidene groups, dehydrative cyclization, reductive alkylation and ureido formation. The last five transformations are to be conducted in a successive manner, i.e., without isolation of the intermediates. The 4-carboxybutyl chain of 1 may be installed by the reaction of O-trimethylsilyl (TMS) cyanohydrin 23 with a di-Grignard... 

---