Imines, reduction reductive cyclization

One of the interesting application of 12 (R= allyl, X=Br) will be the synthesis of cyclic amino acid, (S)-pipecolic acid, as its tert-butyl ester 271251 Monoalkylation of the O Donnell imine 23 with l-chloro-4-iodobutane afforded the alkylated product 26 with 99 % ee. The conversion of 26 to the tert-butyl ester of pipecolic acid 27 was achieved in high yield by the sequence imine reduction, cyclization, and hydrogenolytic removal, as shown in Scheme 8. 

Beyond palladium, it has recently been shown that isoelectronic metal complexes based on nickel and platinum are active catalysts for diyne reductive cyclization. While the stoichiometric reaction of nickel(O) complexes with non-conjugated diynes represents a robust area of research,8 only one example of nickel-catalyzed diyne reductive cyclization, which involves the hydrosilylative cyclization of 1,7-diynes to afford 1,2-dialkylidenecyclohexanes appears in the literature.7 The reductive cyclization of unsubstituted 1,7-diyne 53a illustrates the ability of this catalyst system to deliver cyclic Z-vinylsilanes in good yield with excellent control of alkene geometry. Cationic platinum catalysts, generated in situ from (phen)Pt(Me)2 and B(C6F5)3, are also excellent catalysts for highly Z-selective reductive cyclization of 1,6-diynes, as demonstrated by the cyclization of 1,6-diyne 54a.72 The related platinum bis(imine) complex [PhN=C(Me)C(Me)N=Ph]2Pt(Me)2 also catalyzes diyne hydrosilylation-cyclization (Scheme 35).72a... 

The cyclization of (3-haloamines is the Gabriel synthesis of aziridines (B-83MI101-01, 84CHEC-(7)47). Imines with halogen-containing side chains on the nitrogen atom have been reductively cyclized via the (3-haloamines, as shown in Scheme 14 (94SL287). 

Gronowitz found the Pictet-Spengler reaction a convenient route for the preparation of (259 equation 22) (70AK(32)217). Thiophene-3-carbaldehyde was condensed with nitromethane to give w-nitrovinylthiophene. Reduction of the nitro derivative with LAH afforded the /3-(thienyl)ethylamine. The condensation of this amine with formaldehyde to the corresponding imine followed by cyclization with hydrochloric acid proceeded very smoothly and in high yield. The aromatization was achieved with potassium ferricyanide in an alkaline dioxane-water mixture. 

Imines have been employed as radical acceptors in the preparation of nitrogen heterocycles [95AJC291]. A highly selective 6-endo-trig radical cyclization onto a chiral aldehyde imine has been developed by Werstiuk et al. Reductive cyclization of 218 provides a 3.8 1 diastereomeric mixture of the tetrahydroisoquinoline 219. A minor amount of 220, a product arising from a 5-exo cyclization is also produced. 

The conjugate addition of iV-sulfinyl metalloeneamines to enones gave 19, which is converted in a facile manner to the corresponding piperidine in good diastereoselectivity after sequential stereoselective reduction, N-deprotection, cyclization, and imine reduction (Equation 35) <2005JOC7342>. 

Deoxygenation of a nitrone. Some years ago Todd and co-workers noted that 1-pyrroline-1-oxides can be obtained by reductive cyclization of a y-nitro ketone. This reaction was used recently in a synthesis of chlonns related to vitamin B,. Thus the nitro ketone 1 on reduction with zinc and acetic acid gives the pyrroline N-oxide 2 in high yield. The N-oxide is stable to triphenylphosphiue or trimethyl phosphite, but is reduced to the imine 3 in high yield by TiCl,. 

Using the Birth modification (57) of the Cranwell-Saxton (55) methodology, Narasimhan and Dhavale (97) have described a synthesis of 6-methyl-11-de-methylellipticine (171) (Scheme 29). Carbazole aldehyde 167 underwent the usual condensation to give imine 168. Direct cyclization of 168 with phosphoric acid gave a mixture of 171 and 172, although only the former could be obtained in pure form (by repeated crystallization). However, reduction of 168 to 169, followed by tosylation and cyclization, gave 171 exclusively. 

In contrast to ammonia, primary, secondary, and tertiary amines can add to aldehydes and ketones to give different kinds of products. Primary amines give imi-nes and secondary amines gives enamines (10-69). This section will focus on imines. Reduction of co-azido ketones leads to the amino-ketones, which cyclizes to form a 2-substituted pyrroline. Reduction of nitro-ketones in the presence... 

Cyclic imines. co-Azido carbonyl compounds undergo reductive cyclization (6... 

Other synthetic applications derive from various cyclizations that occur during reduction of the substrates that contain a reactive function at a specific position. These cyclizations proceed through the intermediate imine or amine to the cyclic amine. Various functional units such as olefins, heterocyclic rings, ketones, acids, amides, amines, nitrile, and nitro have been involved. Palladium, Rh, and finely divided Ni (Raney Ni) under more vigorous conditions are commonly used. Reductive cyclization of ketonitrile 1 over Raney Ni gives myosmine 2 along with some nomicotine 3 as overreduced product ... 

Chiral hydrazones derived from SAMP or RAMP are used in the asymmetric synthesis of 4,5,6-trisubstituted and 6-substituted piperidinones <97LA1115>. Chiral 2-substituted piperidines are prepared by the addition of Grignard reagents to chiral imines followed by oxidation of the terminal double bond and reductive cyclization <97JOC746>. 

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