Reductive Ring Contraction

after an initial reductive ring-opening step, the cycloalkane ring is constructed on subsequent in situ annulation of the electrophilic carbonyl and a newly formed nucleophilic organometalic site. 

SCHEME 3.27 Mechanism for the formation of l-nitro-6-hexenes 76 and 1-bromo-l-nilro-6-hexene 77 from 5-iodo-ribofuranoside 3. 

SCHEME 3 9 Reagents and conditions (i) Smij, HMPA, THF, reflnx, 70%. 

Similarly, Chiara et al. reported a cascade reaction of 6-deoxy-6-iodohexopyranosides promoted by samarium diiodide [69]. A series of 6-deoxy-6-iodohexopyranosides with different configurations and substitution patterns was treated with Sml2 in THF/HMPA to give the desired cyclopentanols. For example. 

SCHEME 3.32 Proposed mechanism for the reductive ring opening and intramolecular radical trapping to produce 83. 

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DIlVIETHirLCYCLOBUTENES BY REDUCTIVE RING-CONTRACTION OF SULFOLANES cw-7,8-DIMETHYLBICYCLO-[4.2.0] OCT-7-ENE... 

Such reductive ring contractions of sulfones are formally similar to two other methods capable of supplanting a sulfur atom by a carbon-carbon double bond the Ramberg-Backlundand Stevens rearrangements. The distinguishing feature of this novel approach to cyclobutenes consists in the resultant higher level of alkyl substitution at the sp -hybridized centers. 

REDUCTIVE RING CONTRACTION OF , DISUBSTITUTED SULFOLANE ANIONS WITH LITHIUM ALUMINUM HYDRIDE... 

Boger et al. reported the first total synthesis of ningaline D (282) starting from the diphenylacetylene 1092 and dimethyl l,2,3,4-tetrazine-3,6-dicarboxylate (1093) (687). In this synthesis, the key step is the formation of the fully substituted pyrrole core using an inverse electron demand heterocyclic azadiene Diels-Alder reaction followed by a reductive ring contraction of the resultant 1,2-diazine. 

Boger has reported efficient total syntheses of the marine alkaloids ningalin A, lamellarin O, lukianol A, and stomiamide A each of which possess a common 3,4-diaryl-substituted pyrrole nucleus bearing 2- or 2,5-carboxylates <99JA54>. A key step in each of these syntheses utilized a zinc mediated reductive ring contraction of 1,2-diazines such as 29 to pyrrole 30, a precursor in... 

Apreparation of pyrrolo[3,4-3]indoles 495 from pyridazino[4,5- ]indoles 494 using aZn/AcOH reductive ring contraction has been described <1997TL8611>. Since 494 are easily prepared from the inverse electron demand cycloaddition of indoles 492 with tetrazine 493, this represents a simple, two-step sequence to prepare the pyrro-loindoles 495 (Scheme 62). 

Quinoline 1-oxides can be rearranged photochemically into indoles (103 — 104 — 105) or N-hydroxyindoles (106 — 107). Cinnolines are reductively ring-contracted into indoles (Section 3.2.1.6.9.ii). 

Reductive ring contraction of the 1,2-dithiine skeleton was applied in the formation of the thiophene ring. Thieno[3,4-h]thiophenes 148 were prepared from thiophen-3-yl-substituted [l,3]dithiol-2-ones 144 in good yields [39], The photochemical irradiation of 144 leads to thieno[3,4-c]dithiines 145 via a unique ring cleavage reaction, and subsequent reductive treatment of dithiines 145 proceeds to give 2,3-dihydroth-ieno[3,4-h]thiophenes 146 and 147. Heating of 147 in the presence of further iodomethane leads to the formation of the thieno[ 3,4-/ ] thiophenes 148 (Scheme 27). 

Cyclic nitrones generated by [4+ 2]-cycloaddition of nitroalkenes undergo various, synthetically very valuable reactions. Thus, Denmark et al. have developed an elegant access to different enantiopure, 3- and 3,4-substituted pyrrolidine derivatives by reductive ring contraction of the cyclic nitrone resulting from a hetero Diels-Alder reaction [389,390]. Upon reaction of -2-nitrostyrene 4-51 with the chiral enol ether 4-52 in the presence of the bulky Lewis acid MAPh (4-53), three diastereomeric cycloadducts 4-54, 4-55 and 4-56 were formed. Hydrogenolysis of the main product 4-54 yielded the desired pyrrolidine 4-57 in excellent optical purity and allowed nearly quantitative recovery of the chiral auxiliary (Fig. 4-12) [391]. It is noteworthy that the nature of the Lewis acid catalyst, especially its steric demand, decisively influences the stereochemical course of such cycloadditions [392]. 

It is noteworthy that both components are highly reactive and both required an in situ generation. The cycloadduct 7-56 was then subjected to a reductive ring contraction, acetylation, and a highly diastereoselective bishydroxylation to yield 7-58 which upon several protecting group transformations gave man-nostatin A 7-57 in enantiomerically pure form (Fig. 7-13). 

Rearrangement of a pyridazine into a pyrrole has been found when 3-anilinopyridazine is heated in the presence of Raney nickel 2-anilino-2-pyrroline is formed in this reductive ring contraction. Similarly, 2,3,4-triphenylpyrrole is obtained from 4,5,6-triphenyl-3(2H)-pyridazinethione by reductive desulfurization with Raney nickel. A mechanism suggested for similar ring contractions of cinno-lines into indoles may be operating also in this case. Another... 

The acetylene 24 was allowed to react with 1,2,4,5-tetrazine 25 to give the desired pyridazine 26 in excellent yield. Zinc reductive ring contraction followed by A-alkylation of... 

When the dihydro-1,2,4-triazinone 76 is heated at 180°C with red phosphorus and hydroiodic acid, there is rupture of the 1,2-bond and subsequent ring closure to give 4,5-diphenylimidazolin-2-one (77) (see Scheme 17) and reductive ring contractions to imidazoles (81) have also been reported " in the 1,3,5-triazine series. A further interesting ring contraction is that which occurs when 4H-l,3,5-thiadiazines (78) are treated with aliphatic amines at room temperature. The triarylimidazoles (81) may be formed by initial formation of the 1,3,5-thiadiazine anion (79) which probably loses sulfur... 

Such 1,2-diazines can be transformed to the corresponding substituted pyrroles in a reductive ring contraction employing zinc in either acetic acid or trifluoroacetic acid. This reductive ring-contraction reaction presumably proceeds via the reduction of 1,2-diazine 6 to the corresponding 1,4-dihydro-1,2-diazine 10, which is subsequently reduced to intermediate 11. Then, 11 undergoes an intramolecular cycli-zation providing the tetrasubstituted pyrrole 5," ... 

Similar ring contractions in which the nitrogen-nitrogen bond is cleaved are found in the reductive ring contractions of pyridazines to pyrroles [148, 149], phthalazines to isoindoles [150], 5,6-diphenyl-1,2,4-triazinones to imidazolones [151], benzo-l,2,4-triazines to benzimidazoles [71], benzo-l,2,3-triazinone to indazolone [la, 152], benzo-l,2,3-triazin-3-oxide to indazole [la], benzo-2,3-diazepines to isoquinolines [153], benzo-l-pyrano-[4,3-e ]-as-triazin-3-one to benzopyranoimidazolone [154], and 2-methyl-4,5-dihydropyridazin-3-ones to pyrrolin-2-ones [155]. 

The reductive ring contraction of 2-phenylpyrimidines to 2-phenylpyrroles involves a cleavage of a carbon-nitrogen bond, followed by attack by a carbanion on an azomethine group [158]. 

Both 1,4- [340-342] and 1,5-benzodiazepines [343] are polarographically reducible the latter is somewhat unstable in aqueous solution, which complicates the investigations. 1,4-Benzodiazepines like 7-chloro-2-methylamino-5-phenyl-3i7-l,4-diazepine-4-oxide are reducible in acid solution in three steps. The first two steps, the reduction of the A -oxide and the saturation of the benzophenone imine, are straightforward. The mechanism of the third step, a reductive ring contraction to 6-chloro-2-methyl-4-phenyl-3,4-dihydroquina-zoline, is more controversial [51, 157]. 

With hydrogen sulhde in the presence of a base, dihydrothiazines undergo reductive ring contraction to give thiazolidines, usually in good yield for example, 2,2-diethyIthiazolidine was formed from the compound 60a. S-Labeling experiments are consistent with the pathway outlined in Scheme... 

Reductive Ring Contraction of Substituted Dimethyi 1,2-Diazine-3,6-dlcaiboxyiates Pyrrole Introduction ... 

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