Cycloadditions oxabicyclo octanes

Cycloadditions and Rearrangements. The addition of 2-oxyallyl cations to furan provides a route to oxabicyclo[3,2,l]octanes complementary to the cycloaddition of cyclopropanones to furan. Careful experimental studies have led to yields of preparative importance both with furan and with cyclopentadiene. Following the route to azabicyclo-octanes, dipolar addition to the pyrylium betaine (99) affords oxa-analogues (Scheme 23). Also reported are the addition of fiiran to 1-cyanonaphthalene, the formation of various cycloadducts of tropone and tropolone (Scheme 24), and the phototransformations of (100) (Scheme 25) and (101) (Scheme 26). Thermal addition gives (102) from (103) and similarly other 8-oxabicyclo-octanes are prepared from acyclic precursors. ... 

Tlie thermal reaction of dithiiranes is of particular interest in relation with the dithiirane/thioketone 5-sulfide manifold. Heating 5-oxodithiiranes (4) in solution led to both isomerization to 6,7-dithia-8-oxabicyclo[3.2.1]-octanes 74 and desulfurization to 5-oxothiones 75, the ratio of which was dependent on the reaction conditions employed. The intramolecular [3 + 2] cycloaddition of the thioketone 5-sulfide 76, generated by ring-opening, provides a straightforward explanation for the formation of 74. Meanwhile, 75 is probably formed by a nucleophilic attack on the sulfur atom by another molecule of 4 and/or by elemental sulfur formed during the reaction. 

Lewis acid catalyzed reaction of oximes 172 (equation 113) with divinyl ketone (173) provided l-aza-7-oxabicyclo[3.2.1]octan-4-ones 174 through a sequential Michael addition and [3 + 2] cycloaddition. The reaction occurred with complete stereoselectivity giving the same product with both cis- and frawi-oximes . 

The addition of ZnBi 2 to die tandem 1,3-azaprotio cyclotransfer-cycloaddition of a ketoxime with divinyl ketone results in rate enhancement and the exclusive formation of l-aza-7-oxabicyclo[3.2.1]octan-3-ones.79 The 1,3-dipolar cycloaddition of 1-aza-l-cyclooctene 1-oxide with alkenes produces the corresponding isoxazolidines in high yields with a minimum of polymeric material.80 The cycloaddition of thiophene-2 -carbaldehyde oxime with acetonitrile and methyl acrylate produces the 1,3-dipolar adduct, substituted isoxazolidines, and not the previously reported 4 + 2-adducts.81 Density functional theory and semi-empirical methods have been used to investigate the 3 + 2-cycloaddition of azoxides with alkenes to produce 1,2,3-oxadiazolidines.82 The 3 + 2-cycloaddition of a-nitrosostyrenes (62) with 1,3-diazabuta-l,3-dienes (63) and imines produces functionalized cyclic nitrones (64) regioselectively (Scheme 22).83... 

The 1,3-dipolar cycloaddition of the carbonyl ylide (31) to the aldimine (32) produces the adduct (33), which has been used to synthesize the taxol C(13) side-chain (34), which is known to be required for the antitumour activity of taxol (Scheme 9).35 The dirhodium tetraacetate-catalysed decomposition of l-diazo-5-phenylpentane-2,5-dione (35) yields the carbonyl ylide (36), which cycloadds to methylenecyclopropanes (37) to produce spirocyclopropanated 8-oxabicyclo[3.2.1]octan-2-ones [(38)-(40)] in 6-75% yields (Scheme 10).36 The 1,3-dipolar cycloadditions of aliphatic or alicyclic thiocarbonyl ylides with thiobenzophenone produce both regioisomeric 1,3-dithiolanes as expected. However, in the case of highly sterically hindered thiocarbonyl ylides, methylene transfer leads to the formation of 4,4,5,5-tetraphenyl-l,3-dithiolane.37,38... 

Danishefsky prepared the furanophane 184 and converted it to hydropyrone 185 through a directed epoxidation with DMDO. Diastereoselective addition of methyllithium was followed by an acid catalyzed isomerization to the furanoside 186. Vinylogous aldol addition of a silyloxy furan to an imine gave 189 that was easily isomerized to the azacycle 190. Another general strategy to prepare pyran derivatives is a cycloaddition/fragmentation route involving an oxabicyclo[3.2.1]octane intermediate (Scheme 24). 

When a substrate with a diazo functionality at the 5-position to the carbonyl group, e.g. 44, is reacted with an appropriate transition metal catalyst, a cyclic six-membered ring carbonyl ylide 45 is formed as a transient species via transannular cyclization onto the 5-positioned carbonyl oxygen. These transient species 45 readily engage in inter- or intramolecular [3+2]-cycloadditions with a variety of dipolarophiles to furnish oxabicyclo[3.2.1]-octan-2-ones 46 (Scheme 13). 

The synthesis of the oxabicyclo[3.2.1]octan-2-one ring system was successfully accompUshed via the 1,3-dipolar cycloaddition of 6-membered ring carbonyl yUdes. hi a reactivity profile similar to that of the five-membered carbonyl yhdes (see Schemes 14,15), the carbonyl ylide derived from 1-diazo-... 

Malonate-substituted cyclopropanes are often considered as synthetic building blocks due to the specific reactivity of their carbocyclic ring systems. For instance, total synthesis of ( )-bruguierol A was achieved in several steps that involved cyclopropanation of 2-(2-ally 1-4-methoxyphenyl)-2-methyl-1,3-dioxolane with dimethyl diazomalonate and [Rh2(esp)2] as catalyst (eq 44). The characteristic 2,3-benzofused 8-oxabicyclo-[3.2.1]octane core of bruguierol was constructed via a Sc(OTf)3-catalyzed intramolecular [3+2] cycloaddition of the cor-... 

Thus, a concise and direct formal asymmetric total synthesis of platensi-mycin based on the key use of a furan-TBCP cycloaddition reaction has been described. Two sequential annulations on the oxabicyclo[3.2.1]octane core established the hydrophobic cage domain found in the natural product. 

Recently, the first example of organocatalyzed asymmetric [5+2] dipolar cycloaddition of oxidopyrylium ylides was achieved by the same research group, leading to structurally diverse 8-oxabicyclo[3.2.1]octane derivatives 306 in good yield and stereoselectivity (Scheme 2.83). The combination of a chiral primary aminothiourea 140 m and a second achiral thiourea 305 offered an optimal dual-catalysis system to promote the formation of oxidopyrylium ylides from acetoxypyranones 304 and subsequent intramolecular cycloaddition [115]. 

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