Reductive cyclizations

KAGAN-MOLANDER Samanum reagent Lanthanide reagents, speoflcally samanum, lor generation of free radicals useful in cyclizations, reductions... 

Anionic domino processes are the most often encountered domino reactions in the chemical literature. The well-known Robinson annulation, double Michael reaction, Pictet-Spengler cyclization, reductive amination, etc., all fall into this category. The primary step in this process is the attack of either an anion (e. g., a carban-ion, an enolate, or an alkoxide) or a pseudo anion as an uncharged nucleophile (e. g., an amine, or an alcohol) onto an electrophilic center. A bond formation takes place with the creation of a new real or pseudo-anionic functionality, which can undergo further transformations. The sequence can then be terminated either by the addition of a proton or by the elimination of an X group. 

As can be seen in the scheme below, insertion reactions of aldehydes to the C-H bond of aromatic ketimines by using a rhenium catalyst provided benzo[c]furans via a mechanism involving consecutive steps of C-H bond activation, insertion of aldehyde, intramolecular nucleophilic cyclization, reductive elimination, and elimination of aniline <06JA12376>. 

Cyclization, reductive, aromatic nitro compounds to heterocyclic compounds, 48,115... 

Demethoxycarbonyldihydrogambirtannine (71) was synthesized several times (189-191) before its isolation as a natural product from Ochrosia lifuana Guill. as well as Ochrosia miana H.Bn. ex Guill. (65). In the last decade, ( )-71 was elegantly synthesized by Wilcock and Winterfeldt (792) from an appropriately substituted cyclohexadienyltetrahydronorharmane derivative 349 via the Cope rearrangement, cyclization, reduction, and acid-treatment sequence. 

Recent work by Newcomb has resulted in the emergence of a second method for the cyclizations of amminium radical cations that shows good synthetic potential.175-176 As illustrated in Scheme 42, AMiy-droxypyridine-2-thione carbamates can be generated and cyclized by analogy to the Barton method (which uses thione esters). In Scheme 42, the preparation of the precursors and two variants on the cyclization, reductive trapping and thiopyridyl trapping are illustrated. 

Phosphorylation Photochemical cyclization Reductions acid to alcohol DIBAL... 

A synthesis of tetrahydrogroenlandicine (83) from the N-formyl compound (84) has been achieved by cyclization, reduction, debenzylation, and reductive elimination of the bromine.94... 

Intramolecular cyclization. Reduction of a 2-(3-aminopropyl)isoquinolinium salt (1, n = 2) with lithium aluminum hydride in ether gives the new heterocycle... 

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... 

Scheme 82. Heterocyclization of Alkynylamines, Amides, Alcohols, and Carboxylic Acids via (a) Cyclization-Protonolysis, (b) Cyclocarbonylation, (c) Cyclization-Esterification, and (d) Cyclization—Reductive Elimination3...

Alternatively, a radical cyclization/reduction can be followed by a )9-elimination, resulting in the synthesis of unsaturated ring systems [24a]. This process has been utilized to access 3a,8a-dihydrofuro[2,3-f)]benzofurans, a key structural component of the aflatoxins (Eq. 22) [26],... 

A three-step protocol for al volves two (first and third > re heterocycle with ketones is foil Cyclizations. Reductive c are remarkably efficient. 

Cyclizations. Reductive cyclization that leads to cyclopropanes- and cyclobutanes are remarkably efficient. 

Treatment of 106 or 107 with formic acid at room temperature leads to the corresponding 1-substituted oxazolo[4,3- ]isoquinoline 108 or 109, where the absolute configuration of the a-substitutent of the intermediate iminium carbon does not suffer racemization during the cyclization. Reduction of the isoquinoline with lithium aluminum hydride yields the appropriate l-(a-hydroxy-a-phenyl)-l,2,3,4-tetrahydroisoquinoline (110 or 111) (Scheme 23) [34]. 

Two variations have been introduced by lida et al. 30, 59, 60) in order to synthesize several cularine alkaloids. After cyclization, reduction, and N-meth-ylation, the dibrominated amide 70 affords the 7,8-substituted isoquinoline 71, whose bromine at C-2 is needed for the subsequent Ullmann cyclization. The protective group and the second bromine are removed after ring closure. 

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