Formals, bicyclic

Unfortunately the only known X-ray structure of a lithiocarbon is that of lithium carbide 15 c Interestingly the elementary cell is built up by formally bicyclic... 

Tlie existence of the ylide 19, which can formally be interpreted as the deprotonation product from the corresponding salt 7a, has been claimed by trapping chlorocarbene with pyridine during the laser-flash photolysis of e do-7-chlorodibenzo[n,c]bicyclo[4.1.0]heptane (18) (96JPC18426). Bromination of l-vinyl-2-pyridone (20) yields the bicyclic pyridinium bro-... 

The -elimination of a thiyl radical (RS ) terminated a remarkably productive tandem radical bicyclization in Parker s formal total syntheses of ( )-codeine and ( )-morphine (see Scheme 14).29 Subjection of aryl bromide 72 to the conditions indicated generates transient aryl radical 73, an intermediate which engages the substi-... 

Formal hydration of the double bond appeared by the hydroboration-oxidation sequence. Desymmetrization reactions with catalytic asymmetric hydroboration are not restricted to norbornene or nonfunctionalized substrates and can be successfully applied to meso bicyclic hydrazines. In the case of 157, hydroxy derivative 158 is formed with only moderate enantioselectivity both using Rh or Ir precatalysts. Interestingly, a reversal of enantioselectivity is observed for the catalytic desymmetrization reaction by exchanging these two transition metals. Rh-catalyzed hydroboration involves a metal-H insertion, and a boryl migration is involved when using an Ir precatalyst (Equation 17) <2002JA12098, 2002JOC3522>. 

Ring transposition processes are well established in six-membered heteroaromatic systems. Recent studies have centered on perfluoro systems in which bicyclic and tricyclic intermediates are sufficiently stable to permit isolation or at least detection. Thus, on irradiation in CF2C1CFC12, the perfluoropyridine 207 is converted into the azabicyclo[2.2.0]hexa-2,5-diene 208 and the two azaprismanes 209 and 210.154 An azabicyclo[2.2.0]hexa-2,5-diene has also been shown to be an intermediate in the photorearrangement of substituted 2-methylpyridines to o-substituted anilines.155 Diaza-bicyclo[2.2.0]hexa-2,5-dienes have similarly been shown to be intermediates in the conversion of fluorinated pyridazines (211) into the corresponding pyrazines (212)156 the proposed pathway is outlined in Scheme 7. Photoproducts which are formally dimers of intermediate azetes have been obtained when analogous reactions are carried out in a flow system.157... 

Nucleophilic substitution at the a-carbon atom does not occur in the case of the most studied and stable bicyclic disulfonium dications.96 Although the reaction of dication 34 with bromide ions formally leads to the S C bond cleavage, the reaction mechanism involves initial nucleophilic attack at the sulfonium atom by the bromide anion. The bromosulfonium salt intermediate... 

Mason and coworkers10 studied the chiral bicyclic derivatives 2, 3, 33 and 34, having known absolute configuration. These molecules possess a planar s-cis diene chromophore and formally their chirality is due to the presence of the D or CH3 substituents, which rule out all the symmetry planes. However, it is interesting to point out a peculiar structural... 

An intramolecular palladium-catalyzed tandem cyclization of dienamides 67 in which the amide nucleophile adds twice has been developed (equation 29)60. This reaction constitutes a formal [4+1] cycloaddition and provides a new route to pyrrolizidine and indolizidine alkaloids. Reaction of dienamides 67 in the presence of catalytic amounts of Pd(OAc)2 and CUCI2/O2 as the oxidant afforded bicyclic compounds 68 in good yields. The pyrrolizidine derivative 68 (R = Me, n = 1) was transformed to the alkaloid ( )-heliotridane. 

For the depiction of structural formulas of hexofuranoses, a combination of a three-dimensional, Haworth-perspective tetrahydrofuran ring with a Fischer projection of the C-5-C-6 side-chain is commonly used, as exemplified by formulas 3 and 6. With the formal closure of the second ring and formation of a 2,6-dioxabicyclo[3.3.0]octane system, however, the depiction of the C-6-C-3 ring, as in formula 7, also assumes three-dimensional geometry, and this does not correspond to the Fischer projection rule.11 Consequently, structural representations of such bicyclic molecules should be as close as possible to the actual steric situation, as shown by structures 4 and 8. 

These studies paved the way for numerous synthetic applications, in particular total syntheses. Thus, the low-tech PtCl2, PtCl4, or PtBr4 systems, as named by Fiirstner, proved superior and more reliable compared to Trost s TCPCtfe system288 for the reactions of the cyclooctene substrate as shown in Scheme 81.300 These reactions, which could be run in a multi-gram scale, proved useful, for instance, for the formal total synthesis of streptorubine B. Similarly, a formal total synthesis of roseophilin was devised, based on a nearly quantitative transformation of an enyne moiety into a bicyclic diene system (Scheme 81).301... 

The formal total synthesis of racemic guanacastepene (rac-187) from Snider and co-workers (Fig. 20) was submitted six months later than the completed synthesis of Danishefsky s group [116-118]. The shortest sequence developed by the Snider group utilized the sequential cuprate addition/enolate alkylation of 2-methylcyclopent-2-enone 90 previously exploited by Piers, Williams and Danishefsky (Schemes 15 and 31). As outlined in Figs. 19 and 20, the strategies of Danishefsky and Snider are closely related. Both rely on stepwise annulations to build up the tricyclic ring system. They differ only in respect to the particular reactions that converted the monocyclic starting material (90) via bicyclic hydroazulenes (207 vs 227) into the desired tricyclic 5-7-6-system (224). 

In extending this concept to transformations that formally deliver Diels-Alder products, a one-pot three-component Mannich/Michael reaction pathway was developed in which simple cyclic enones, formaldehyde, and aryl amines were treated with catalytic amounts of proline (2) to provide regio-, diastereo-, and enantioselective bicyclic compounds in high yields (Scheme ll.lOb). Multicomponent domino... 

Tertiary N-butynylamine 48 when oxidized generates an N-oxide intermediate that is cyclized in situ via gold catalysis to give bicyclic piperidone 49 (09JA8394). As amine 48 can be prepared readily, the overall transformation constitutes a formal [4+2] synthesis. 

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Compounds 99a and 99b were smoothly converted to the penultimate intermediate 68 in 92% and 90% yields (Scheme 4.17). First, 99a and 99b were treated with potassium hydroxide in tetrahydrofuran (THF) to deliver the intermediate bicycle 100. Addition of aqueous KOH to 100 and then refluxing the reaction gave 68 in 92% and 90% yields, respectively, to complete a formal total synthesis of levofloxacin (1). 

Similar to their reaction with phosphaalkenes, l-diazo-2-(oxoalkyl)silanes 29 react with various heterophospholes by [3 + 2] cycloaddition of the diazocumulene system 30 (which is in equilibrium with 29) across the P=C bond. With 2-acyl-1,2,3-diazaphospholes 119 (R = Ac, Bz no reaction with R = Me, Ph up to 60 °C), the expected cycloaddition products 120 (Scheme 8.27) could be isolated (186). Elimination of N2 from these bicyclic A -pyrazolines occurred upon heating at 100 °C and furnished the tricyclic systems 122 when SiRs was a trialkylsilyl group. Apparently, the thermolysis of 120 generates the 5-aIkenylidene-l,2,5-diazaphosphole 121 (by N2 extrusion) as well as diazaphosphole 119 (by a [3 + 2] cycloreversion process), which recombine in an intermolecular cycloaddition to furnish 122. When SiRa = SiPhaf-Bu, a formal intramolecular [3 + 2] cycloaddition of the C=P=C unit with an aromatic C=C bond occurs and the polycyclic compound 123 is obtained (187). 

This strategy is a powerful route to bicyclic pyridones and their transformation products. Thus, these workers (40,41) applied this methodology to formal syntheses of the lupinine alkaloids ( )-lupinine and ( )-anagyrine (89) (Scheme 10.14). Imidosulfoxide (82) is converted to the corresponding isomiinchnone that is trapped with methyl acrylate to give 85. Oxidation, ring opening, and triflate formation... 

A formal 13+2 -cycloaddi lion can be accomplished by adding bis(2-carbethoxyethyl) zinc to acetylenic esters . This reaction allows the construction of complex cyclopen-tenones, such as 388, which is a precursor of ( )-bilobalide (Scheme 101) . The allylzincation of tiimethylsilylacetylenes can be performed intramolecularly providing a functionalized alkenylzinc which cyclizes in the presence of Pd(PPh3)4 at 25 "C within 3.5 h, leading to the bicyclic product 389 in 84% yield (Scheme 102). The addition of allylic zinc halides to various alkynes occurs in the absence of copper salts. The related... 

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