Exo-methylene-substituted

Alkylidene-phosphapyrazolines 98-101 are much more thermally stable than their relatives 88, which do not possess the exo-methylene substitution. Dediazo-niation of 98 required heating in toluene at 110°C and gave one or more of the following products, probably via intermediate diphenylmethylene(vinylidene)phos-phoranes methylenephosphiranes, (2-siloxyvinyl)phosphanes, 2//-l,3-oxaphos-pholes, and l-alkylidene-2,3-dihydro-l//-benzo[c]phospholes (169). Thermolysis of 100 ( R = t-Bu, 1-adamantyl) afforded isolable 2-phosphabutadienes (169). The photochemical elimination of N2 from 98 generated cyclic azomethine imine dipoles 104 (Scheme 8.24), which rearrange to compounds 105 and 106 that could be further trapped with DMAD to form 107 (170). 

High diastereoselectivity is found in the reaction of the racemic exo-methylene substituted 3-azabicyclo[3.3.0]octane 4 with bis(AM-toluencsulfonyl)sulfodiimide52. The tosylamide 5 is obtained in 81 % yield. 

In the above example, the enophile is tethered to the terminal carbon atom of the ene component and this leads to a 1,2-disubstituted cyclic product. If the enophile is tethered to the central carbon atom of the allyl metal, then the ene reaction gives an exo-methylene-substituted cyclic product. A key step in a synthesis of khusimone involved the metallo-ene reaction of the allyl Grignard 251, followed by trapping with carbon dioxide and hydrolysis to give the carboxylic acid 252 (3.162). 

When an aUcyl substituent such as Me group is in the terminal position of allyUc side chain, the oxypalladation intermediate has two possibilities of /3-Pd—elimination. This intermediate generally produces the energetically favorable vinyl substituent rather than the exo-methylene substitution (Scheme 5). 

The study on 2,7-di-rerf-butylthiepin has recently been extended to explore more simply substituted thiepins 58). The palladium-catalyzed reaction of the diazo compound 107 lacking a 4-methyl substituent gives exclusively the exo-methylene compound 108 whereas the acid-catalyzed reaction of the same precursor 107 resulted in the formation of 2,7-di-/er/-butyl-4-ethoxycarbonylthiepin (109)58). Due to the substantial thermal stability of 109 it is possible to transform the ethoxy-carbonyl group into the hydroxymethyl (110), trimethylsilyloxymethyl (111) and formyl group (112)58). 

The substitution of the exo-methylene hydrogen atoms of MCP with halogens seems to favor the [2 + 2] cycloaddition reaction by stabilizing the intermediate diradical. Indeed, chloromethylenecyclopropane (96) reacts with acrylonitrile (519) to give a diastereomeric mixture of spirohexanes in good yield (Table 41, entry 2) [27], but was unreactive towards styrene and ds-stilbene. Anyway, it reacted with dienes (2,3-dimethylbutadiene, cyclopentadiene, cyc-lohexadiene, furan) exclusively in a [4 + 2] fashion (see Sect. 2.1.1) [27], while its... 

The key reaction in Jung et al. s proposed assembly of Plaunol B (81a) and C (81b) was an intermolecular Diels-Alder reaction between a diene and an allenic lactone that should give the exo-methylene group in the natural product (Scheme 19.16) [20], The phenyl-substituted lactone 83 was prepared as a model for the eventual furan lactone of the plaunols. Cydoaddition of 82 possessing a TBS enol ether and... 

Figure SAO), fluorometholone, which is 6a-Me-substituted, and fluprednidene, substituted in C-16 with an exo-methylene (Figure 8.43). 

Dimethyl substitution at C-l is achieved bv a Simmon s-Smith cy-clopropanation and subsequent reductive nng opening. The lust step to (-)-A9 -capnellene (1) is a mild selenium oxide elimination, through which the exo-methylene group at C-9 is obtained... 

The substituted homoallylic alcohols 181 were then transformed into the desired exo-methylene derivatives 182 by the addition of an aldehyde 6 in the presence of Et2OBF3 (Scheme 13.64). In general, good to excellent yields of heterocydes 182, in which the robust TBDMS group has been retained, were obtained. In all cases, the substituents around the ring occupy equatorial positions, according to the suggested chair-like transition state 178. It is noteworthy that the reaction conditions... 

The array of dienophiles amenable to these hetero Diels-Alder reactions is not limited to enol ethers and enamines since allylsilanes and simple alkenes have also been successfully employed [370, 371]. More recently, it has been shown that methoxy allenes such as 4-41 undergo formation of 6H-l,2-oxazines 4-43 upon cycloaddition to nitrosoalkenes such as 4-34 and subsequent tauto-merisation of the intermediate exo-methylene compound 4-42 (Fig. 4-9) [372, 373]. In these studies, 4-43 proved to be a versatile synthetical intermediate allowing oxidative demethylation or reductive removal of the methoxy group as well as nucleophilic substitutions after the generation of an azapyrylium ion [372 - 374]. Furthermore, ring contraction reactions of these oxazines leading to pyrroles [373] and y-lactames [375] are known. 

In a similar way, also the cycloaddition of 8-14 to substituted enol ethers has been analysed [547]. In these investigations the correlation between steric hindrance and pressure induced diastereoselectivity is not so clear cut. However, an interesting result is the cycloaddition of 8-14b to 8-17 to give the spiro-compo-und 8-18 as the major adduct, indicating that 8-17 isomerises intermediately to the exo-methylene enol ether which reacts faster than 8-17. But as expected,... 

In addition to the compounds described by Suffness and Cordell in their 1985 review, the principal structures of which will be mentioned here, many new taxane-type substances have been discovered in extracts of yew since 1968. Each of these compounds may be classed as a particular type of taxane derivative characterized either by substitutions on certain carbon atoms (C-1, C-7, C-13) or by a particular functionality at C-20 (exo methylene, epoxide, oxetane, or direct linkage to C-2). 

The preferred synthetic route to these important intermediates is the Mannich reaction (Chapter 27). The compound is stored as the stable Mannich base and the imstable enone released by elimination of a tertiary amine with mild base. The same conditions are right for this elimination and for conjugate addition. Thus the exo-methylene compounds can be formed in the flask for immediate reaction with the enol(ate) nucleophile. The overall reaction from P-amino carbonyl to 1,5-dicarbonyl appears to be a substitution but the actual mechanism involves elimination and conjugate addition. 

The reaction of the dioxide 106 with a-toluenethiolate in DMF affords a substitution product 107 by an addition-elimination mechanism (Scheme 63) [185]. Meanwhile, the reaction in refluxing ethanol gives a mixture of compounds 108 and 109 through addition of the thiolate to two exo-methylene isomers of 106, followed by reaction with ethanol. 

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