Bicyclic stereoselective formation

Another interesting example of a photochemi-cally induced domino process is the combination of the photocyclization of aryl vinyl sulfides with an intramolecular addition as described by Dittami et al. [901 as intermediate a thiocarbonyl ylide can be assumed. The domino-Norrish I-Knoevenagel-allyl-silane cyclization developed by us allows the efficient stereoselective formation of 1,2-trans-subsituted five- and six-membered carbocycles.1911 A photochemical cycloaddition of enamino-aldehydes and enamino-ketones with the intermediate formation of an iminium salt followed by addition to allylsilanes gives access to novel bicyclic heterocy-des. New examples of photochemically induced... 

Wender et al. s [5 + 2] metal-catalyzed annulation strategy has also been applied to the total synthesis of (+)-aphanamol I (154) [34]. The scope of this method was expanded by using a tetrasubstituted allene that resulted in the stereoselective formation of an angular methyl group. The reaction of allene 149 with 0.5 mol% of rhodium biscarbonyl choride dimer afforded the fused bicyclic product 152 in 93% yield with complete exo/endo and diastereoselectivity (Scheme 19.28). The stereoselectivity of this process was attributed to a preference for formation of the cis-fused metallo-... 

Scheme 7.22 Stereoselective formation of bicyclic oxetanes in the PB reaction of 1,3-dioxol derivatives.

Several triflates and metal salt hydrates were tested as Lewis acid catalysts (each 10 mol%) and the best results were obtained using Yb(OTf or Ni(C104)2-6H20. The stereoselective formation of bicyclic y-lactones (7) could be obtained from bicyclic nitronate (9) via the hydrolytic process by the action of a strong acid generated from Lewis acid with a small amount of water in both nitroalkene (5) and the Lewis acid. This new methodology of one-pot reaction also involves a new type of intramolecular HAD reaction of nitroalkenes as heterodienes, which provides stereochemically defined bicyclic nitronates. 

The stereoselective formation of cw-fused dihydropyrans and the steric requirements for the reaction of the norbornenyl examples support a concerted mechanism. However, boron trifluoride catalyzed rearrangements of mixtures of endo- and exo-compounds to bicyclic pyrans, i.e., stepwise reactions through cationic intermediates, are also possible38. 

Nishitani, K., Nakamura, Y, Orii, R., Aral, C., and Yamakawa, K., Studies on the terpenoids and related alicyclic compounds. Part 43. Stereoselective intramolecular cyclization of P-alkoxycarbonyl-CO-formylallylsilanes into bicyclic a-methylene-y-lactones, Chem. Pharm. Bull., 41, 822, 1993. Kuroda, C., Ohnishi, Y, and Satoh, J.Y, Intramolecular cyclization of P-(aIkoxycarbonyl)allylsilane with conjugated ketone. A new entry to bicyclo[4.3.0]nonane. Tetrahedron Lett., 34, 2613, 1993. Kuroda, C., Inoue, S., Takemura, R., and Satoh, J.Y, Intramolecular cyclization of allylsilanes in the synthesis of guaian-8,12-olide. Stereoselective formation of trans- and cw-fused methylenelactones, 7. Chem. Soc., Perkin Trans. 1, 521, 1994. 

Radical cyclization reactions have proven to be a very efficient approach for polycyclic natural product synthesis. In many cases, the last step involves a reduction of a cyclic radical with formation of a new stereogenic center. Very good stereochemical control has been achieved with such polycyclic radicals. For example, Beckwith has reported a highly stereoselective formation of a quinolizidine ring (Scheme 19, Eq. 19.1) [41b]. This process is the key reaction in a four-step synthesis of epilupinine and the stereochemical outcome results from a stereoselective axial reduction by tin hydride of a bicyclic radical. In a related process, Tsai has prepared silylated hydroxyquinolizidine by radical cyclization to an acylsilane followed by a radical-Brook rearrangement (Scheme 19, Eq. 19.2) [42]. 

A combination of palladium-ene cyclization with carbonylation reactions is particularly attractive since it permits the stereoselective formation of four carbon-carbon bonds in a single process. In this reaction, 7r-allylpalladium complex 47 (Scheme 11) is formed from allyl carbonate 46 and Pd(0), and it is then converted into vinylpalladium complex 48 via palladium-ene cyclization. Carbonylation of 48 gives bicyclic compound 49, which is further reacted with carbon monoxide to give carboxylic acid 50. 

An alternative route has been developed in Marquez laboratory to prepare the methano-carbocyclic thymidine 127 (see Vol.28, p.286). A key step involved the highly stereoselective formation of 126 by addition of diazomethane to the a,P unsaturated nitrile, itself accessible from a known intermediate in two steps. Photochemical loss of nitrogen from 126 was followed by a Curtius sequence to establish an amine from which the thymine ring was formed. The aristeromycin analogue 128 has also been prepared, using chemistry reminiscent of earlier work on analogues of this type (Vol.28, p.285-6), and bicyclic compounds of type 129 have been prepared as racemates. ... 

Stirring a solution of acetonide 256 in a 1 1 mixture of dichloromethane and trifluoroacetic acid for 15 min at room temperature resulted in the stereoselective formation of cycloadduct 260 as a single stereoisomer in approximately 60% yield. The product contains the 5,7-bicyclic carbon skeleton of rameswaralide 255. Presumably, the reaction proceeded by hydrolysis of the acetonide to give diol 257, which then underwent ionization to afford the furfurylic cation 258. This cation can then undergo [4-1-3] cycloaddition, either in a concerted or stepwise manner, with the internal diene, resulting in cation 259. Lastly, rearoma-tization followed by proton loss would afford cycloadduct 260. This is a unique and rare example in which a furfuryl cation participates in [4-1-3] cycloaddition processes and is also completely stereoselective [126]. 

Strained bicyclic sulfonium salts are important reactive intermediates and undergo subsequent transformations often with high levels of regio- and stereoselectivity. Various research groups have reported evidence for the formation of [4.1.0] 7, [3.2.0] 8, [3.1.0] 9, and [2.2.1] 10 bicyclic sulfonium salts as reactive intermediates. 

Conversion of silylenynes 102 [6] into the corresponding SnMe3 derivatives 103, followed by a Zr-promoted bicyclization, leads to the gem-stanniozirconocene derivatives 104. Car-bonylation gives 105, and subsequent iodinolysis of 105 gives 106 in good yield (Scheme 7.30). The formation of 106 proceeds with >98% stereoselectivity, thus allowing the synthesis of carbacyclin 107 [170,171]. 

Hsung and co-workers described the first epoxidation of 1-amidoallenes leading to highly reactive intermediate 292 (Scheme 8.76) [159]. Formation of bicyclic products 291 occurs via iminium enolate 293, which was trapped by cyclopentadiene 290 (X = CH2) or furan 290 (X = 0). [4+3] Cycloaddition of the intermediate 293furnished 291 in good yield as a mixture of mdo-diastereoisomers (-75 25). The best dia-stereoselectivity was found when the reaction was performed in the presence of 2 equiv. of zinc chloride (>96 4). 

---