Reduction cyclic imines

In contrast, the enantioselectivity of cyclic imine reduction is independent of hydrogen pressure. 

The asymmetric hydrogenation of acyclic imines with the ansa-titanocene catalyst 102 gives the chiral amines in up to 92% ee.684,685 This same system applied to cyclic imines produces the chiral amines with >97% ee values.684,685 The mechanism of these reductions has been studied 686... 

The preparation of chiral isoquinoline derivatives continued to be investigated. Sulfanamide 59 was prepared by addition of a lateral lithiated o-toluonitrile with the corresponding sulfinimine. Treatment of 59 with MeLi followed by acidification afforded cyclic imine 60. Reduction of imine 60 with liAlHi/MejAl afforded the trans-1,3 derivative, and... 

The reduction of imines and iminium salts present a particular difficulty in that those which are N-substituted can exist in different geometrical isomers that are reduced at different rates and with different selectivities. One way to overcome this problem is to use cyclic imines that can exist only as cis isomers. Although these are good substrates, this is not a general solution. The cyclic amines produced by transfer hydrogenation, together with best reported enantiomeric excesses, are listed in Table 35.6. Primary amines are difficult to pre-... 

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. 

Several characterized NRPSs utilize alternative methods for chain termination. In some synthetases, the TE domain of the final module is replaced by an NAD(P)H-dependent reductase domain. Reduction of a peptidyl-S-PCP substrate through a two-electron reaction leads to the formation of a transient aldehyde, which is subsequently converted into a cyclic imine or hemiaminal through intramolecular cyclization. This two-electron reaction is utilized in the biosynthesis of nostocyclopeptides, the saframycins, ° and anthramycin. Alternatively, a four-electron reduction to the primary alcohol is observed in the biosynthesis of mycobacterial peptidolipids, linear gramicidin," " the myxalamides, lyngbyatoxin, " and myxochelin A 75,76 alternative four-electron reduction pathway involving aldehyde formation, transamination, and reduction to a primary amine occurs in the biosynthesis of myxochelin B. ... 

Another field where ATH catalysts have made an industrial impact is in the area of chiral amine synthesis by stereocontrolled reduction of imines. First demonstrated by Uematsu et the reduction of cyclic imines to yield chiral amines... 

A RhCp complex (S,S)-6 (Cp =pentamethylcyclopentadienyl), which is iso-lobal with Ru(rj6-arene) complex (S,S)-5 (Scheme 13), effected the transfer hydrogenation of a cyclic imine substituted by an isopropyl group with an S/C of 200 in the presence of a 5 2 mixture of formic acid and triethylamine to give the R amine in 99% ee (Scheme 13) [31]. When the reaction was performed with an S/C of 1,000, the optical yield decreased to 93%. The methyl imine was reduced with a 91% optical yield. Reduction of a cyclic sulfonimide resulted in the R sul-tam in 81% ee. 

Chiral sodium acyloxy borohydride 554 prepared from NaBH4 and AyV-phthaloyl amino acid reduced cyclic imines in good enantioselectivity. Thiazazincolidine complex 555 was shown to be an excellent catalyst for the catalytic reduction of dihydroisoquinolines with BH3-THF (Equation (265)).1132-1134... 

The heterocyclic hemi-aminal 44 was formed as a model for the synthesis of the marine alkaloids zoanthamine and zoanthenol and is derived from the cyclic imine formed by the reduction of an appropriated substituted azide <07H(72)213>. A pyrrolidine-fused azepine has been isolated from the venom of the ant Myrmicaria melanogaster and assigned as 45 based upon GC and FT-IR comparison with synthetic material <07JNP160>. The axially chiral doubly bridged biphenyl azepine 46 has been synthesised and used with oxone as an epoxidation catalyst in a biphasic system <070BC501>. 

Asymmetric reduction of cyclic imines. (Df a series of chiral sodium acyloxybo-rohydrides obtained from various chiral N-acyl-a amino acids, 1 affords the highest optical yields (70-86% ee) in the reduction of cyclic imines. 

While the. V-hydroxypyrrolidine 1 was obtained as a mixture of isomers, the /V-hydroxypipc-ridine 2 was obtained predominantly as the trans-isomer. However, these intermediates were not isolated and the observed ratio of trans- and d.v-l-acetyl-2,5-dimethylpyrrolidine does not necessarily reflect the composition of the intermediate cyclic hydroxylamine as the cyclic imine is probably formed as the initial step in the reduction. 

The reduction of cyclic imines with this system was found to proceed under much milder conditions. For example, 2-phenylpyrroline was reduced at 80 psi of hydrogen to afford 2-phenylpyrrolidine in good yield and excellent enantiomeric excess (eq 4). 

The (S)-prolinate-borane complex (5)-(22) reduces ketones to the corresponding alcohols with optical yields up to 50%. The asymmetric reduction of cyclic imines (24) with chiral sodium triacyloxyborohydride (S)-(23) was utilized to prepare optically active alkaloids (25) with optical yields up to 86% (eq 9). ... 

Systematic investigations of the stereochemical outcomes of reductions of cyclic oximes and their derivatives have been sparse the available information suggests that results sometimes parallel those obtained in other imine reductions (Sections 1.2.2.2.3, 1.2.2.3.3 and 1.2.2.4.2), but differences are also noted. A collection of examples in which the stereochemistry was determined is presented in Table 15. Thus, with cyclohexyl systems enhanced equatorial attack (compared to ketones) leading to axial amines... 

We reported a new general method for an extremely short chiral synthesis of the bicyclic alkaloids having a nitrogen atom ring juncture utilizing a highly diastereoselective alkylation to the cyclic acylimines, followed by reductive annulation of the resultant cyclic imines (88JA289). 

Cyclic imines will not be dealt with in this review as the conversion is often simply achieved. Mention will be made to the stereoselective reduction involved in the preparation of Solenopsin A and B (131), two naturally occurring piperidine alkaloids isolated from the venom of the fire ant. The desired trans isomer 131 was obtained with > 95% selectivity, using LAH (7 equiv) and trimethylaluminum (7 equiv) in THF. This selectivity could be reversed by using LAH (7 equiv) and NaOMe (14 equiv). °... 

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

Many cyclic amines are prepared by reduction of cyclic imines (see Section 1.20.3), or amides (see Section 1.20.4). Nitro-, amine- and carboxyl-substituted cyclic amines are formed by Mannich condensations (see Section 1.20.6). 

---