Heterocyclic Alkenes

To test the effect of a heteroatom, Starokon et al. [175] studied three five-membered heterocycles with a similar molecular structure, containing the oxygen (2,5-dihy-drofuran), nitrogen (3-pyrrole) and sulfur (butadiene sulfone). Only the oxygen-containing cycle was carboxidized selectively, while the others showed a strong tendency towards side reactions resulting in a set of unidentified products. 

The comparison of some oxygen-containing cycles presented in Table 7.11 allows one to reveal a significant effect of the double bond location with respect to the heteroatom. Results with 2,3-dihydrofuran (entry 1) and 3,4-dihydro-2H-pyran (entry 3) show that the double bonds having the nearest location to the oxygen exhibit strong 

In contrast, the carboxidation of 2,5-dihydrofuran (entry 2) and 4,7-dihydro-l,3-dioxepin (entry 4), having a more distant location of the double bonds, proceeds with minor cleavage, leading in both cases to formation of the corresponding ketones with 94% selectivity. 

In conclusion, we can say that the liquid-phase carboxidation of alkanes can be applied to various substrates, induding linear, cyclic, heterocydic alkenes and their derivatives, yielding the corresponding ketones and aldehydes with selectivities in many cases of 90%. 

Recently, this approach was applied to more complex compounds, that is, fatty adds methyl esters and triacylglycerols, resulting in up to 99% selectivity of the ketonization products [177]. 

Entry Substrate Pn20 T Time Conversion Product selectivity 

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Scheme 6.14 Cyclopropanations of heterocyclic alkenes catalysed by Rh2[(-R)-D0SP]4.

These alkylation processes become particularly attractive when used in conjunction with powerful catalytic ring-dosing metathesis protocols [11]. The requisite starting materials can be readily prepared catalytically and in high yields. The examples shown in Scheme 6.3 demonstrate that synthesis of the heterocyclic alkene and subsequent alkylation can be carried out in a single vessel to afford unsaturated alcohols and amides in good yields and with >99% ee (GLC analysis) [12],... 

The high levels of enantioselectivity obtained in the asymmetric catalytic carbomagnesa-tion reactions (Tables 6.1 and 6.2) imply an organized (ebthi)Zr—alkene complex interaction with the heterocyclic alkene substrates. When chiral unsaturated pyrans or furans are employed, the resident center of asymmetry may induce differential rates of reaction, such that after -50 % conversion one enantiomer of the chiral alkene can be recovered in high enantiomeric purity. As an example, molecular models indicate that with a 2-substituted pyran, as shown in Fig. 6.2, the mode of addition labeled as I should be significantly favored over II or III, where unfavorable steric interactions between the (ebthi)Zr complex and the olefmic substrate would lead to significant catalyst—substrate complex destabilization. 

The N-heterocyclic alkenes derived from ring-closing metathesis are useful substrates for further transformation. In a synthesis directed toward the insecticidal cripowellin 12, Dieter Enders of RWTH Aachen has shown (Angew. Chem. Int. Ed. 2005,44, 3766) that the tertiary amide 8 cyclizes efficiently to the nine-membered alkene 9. The vision was that an intramolecular Heck cyclization could then deliver the cripowellin skeleton. Indeed, the Heck did proceed, and, depending on conditions, could be directed toward either 10 or 11. Unfortunately, the conformation of 9 is such that the cyclization proceeded cleanly across the undesired face. Nevertheless, both 10 and 11 appear to be valuable intermediates for further transformation. 

Azine approach. Bicyclic isoxazolines can be prepared by 1,3-dipolar cycloaddition of nitrile oxides to heterocyclic alkenes such as the iV-acetyl tetrahydropyridine (92) (68CPB117). 

J-Heterosubstituted organoboranes, which are highly sensitive to elimination, can be derived from heterocyclic alkenes and are cleanly transformed into the corresponding chiral alcohols of high optical purity (Table 2). 

Figure 2 Asymmetric hydroboration-oxidation of some heterocyclic alkenes with Ipc2BH...

Asymmetric hydroborations of heterocyclic alkenes are highly regio- and enantioselective. For example, hydroboration of 2,3-dihydrofuran with Ipc2BH followed by oxidation provides 3-hydroxyfuran in 83% ee, which can be upgraded to essentially the enantiomerically pure form (>99% ee) (Figure 2). ... 

Asymmetric hydroborations of several heterocyclic alkenes with diisopinocampheylborane appear to be particularly favorable, resulting in products of almost 100% enantiomeric purity (e.g. equation 53). The reagent has also been used in asymmetric syntheses of a number of complex molecules. Discussion is beyond the present scope but a single example is given as an illustration (equation 54). °... 

Use SpartanView to compare electrostatic potential maps of styrene + hydride anion, 2-vinyJpyridine + hydride anion, and 3-vinylfuran + hydride anion. Are either of the two heterocycles as effective as styrene at delocalizing the developing negative charge during anionic polymerization Next, compare electrostatic potential maps of neutral styrene, 2-% inylpyridine, and 3-vinylfuran. Why don t the heterocyclic alkenes lend themselves to cationic polymerization ... 

Importantly, a similar result was obtained with heterocyclic alkenes such as 2,5-dihydrofuran and N-Boc-pyrroline which were converted to the corresponding 3-aldehyde. It must be noted that the P[0(2,4-di-/BuC6H3)]3 rhodium-based catalyst, which is one of the most active catalyst for this type of transformation, also furnished the 2-aldehyde derivative resulting from the hydroformylation of the 2,3-dihydroheterocyclopentenes (Scheme 34). 

Studies relating to the stereoselective hydroboration of polyfunctional alkenes continue to appear. Various vinyl substituted pyridines, thiophenes and furans have been reacted with representative hydroborating agents,11" and further aspects of the hydroboration of cyclic dienes have been disclosed.11 The asymmetric hydroboration of cyclic enol ethers and enamines (heterocyclic alkenes) provides access... 

Additional general reactions are the synthesis of 11 -acyldipyridoimidazolium salts such as (174 R = Ac, Bz) by condensation of l-acylmethyl-2-chloropyridinium salts with pyridine and substituted pyridines under mild conditions <76CB3646, 77LA1692), and a 1,3-dipolar cycloaddition of a nitrone (196) with heterocyclic alkenes. A derivative (198) of the parent system (35) has been obtained by the reaction of (196) with 5,6-dihydro-2-pyranone (197) (Equation (10)) <93T3857>. A similar reaction occurs with 2,3-dihydropyran yields (172), a perhydro derivative of the parent system (34) <82JOC230, 90JCS(P1)2593>. 

Tanaka et al. established the chemistry of using the bromoallene moiety as the equivalent of allyl dications.This dication can react with an intermolecular nucleophile (MeOH) and an intramolecular nucleophile to form heterocyclic alkenes (Scheme 26) [19]. The PdCl2-catalyzed reaction of 2,3-allenoic acids 58 with allylic halides in DMA at 50 °C afforded 4-allylic-substituted 2(5Tf)-fura-nones 59 in moderate to excellent yields (Scheme 27) [20]. 

A in the equation represents a substituted aldehyde. An electron withdrawing group can activate the double bond and its the electron-withdrawing capability is related to the produced electronegativity, which are usually believed that nitro is the strongest followed by sulfonic acid group [20]. The double bond is between the substituted a, P carbons, a, P-Unsaturated carboxylic acids, carboxylic acid esters, nitriles, acids, ketones, sulfones, aldehydes, ethers, olefins and heterocyclic alkene can all react with nitroalkane via addition reactions to form the corresponding nitro-derivatives. 

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