Olefins acceptor-substituted

TABLE 1. Sulfones from sulfinic acids RS02H and acceptor-substituted olefins, acetylenes or quinones ... 

Stimulated by extensive research activities on donor/acceptor substituted stilbenes, Mullen and Klarner have reported a donor/acceptor substituted poly(4,4 -biphenyl-diylvinylene) derivative (85) in which the NR2 donor and CN acceptor substituents are located on the vinylene unit [111]. The synthesis is based on a C-C-coupling reaction of in situ generated carbanion functions with a (pseudo)cation function, followed by a subsequent elimination of MeSH with formation of the olefinic double bond. 

Some particular features should be mentioned. Instead of Michael additions, a-nitroolefins are reported to yield allyl sulfones under Pd catalysis (equation 21). Halogenated acceptor-olefins can substitute halogen P to the acceptor by ipso-substitution with sulfinate (equation 22 , equation 23 ) or can lose halogen a to the acceptor in the course of a secondary elimination occurring P to the introduced sulfonyl groups (equation 24). On the other hand, the use of hydrated sodium sulfinates can lead to cleavage at the C=C double bond (equation 25). 

Rhodium(n) carboxamidates are clearly superior to all other types of catalysts in effecting highly chemo-, regio-, diastereo-, and enantioselective intramolecular C-H activation reactions of carbenoids derived from diazoacetates. Specifically, Rh2(4Y-MPPIM)4 is the catalyst of choice for C-H activation reactions of simple primary and secondary alkyl diazoacetates. Likewise, Rh2(4Y-MACIM)4 thus far has been the most successful catalyst with tertiary alkyl diazoacetates, whereas for primary acceptor-substituted diazoacetates with a pendant olefin side chain, Rh2(4A-MEOX)4 has proved to be highly selective. 

The nucleophilic attack on an acceptor-substituted allene can also take place at the acceptor itself, especially in the case of carbonyl groups of aldehydes, ketones or esters. Allenic esters are reduced to the corresponding primary alcohols by means of diisobutylaluminum hydride [18] and the synthesis of a vinylallene (allenene) by Peterson olefination of an allenyl ketone has also been reported [172]. The nucleophilic attack of allenylboranes 189 on butadienals 188 was investigated intensively by Wang and co-workers (Scheme 7.31) [184, 203, 248, 249]. The stereochemistry of the obtained secondary alcohol 190 depends on the substitution pattern. Fortunately, the synthesis of the desired Z-configured hepta-l,2,4-trien-6-ynes 191 is possible both by syn-elimination with the help of potassium hydride and by anti-elimination induced by sulfuric acid. Analogous allylboranes instead of the allenes 189 can be reacted also with the aldehydes 188 [250]. 

Knoke and de Meijere [60] recently developed a highly flexible domino Heck-Diels-Alder reaction of a symmetrically substituted cumulene 125, which also involves cross-couplings of an allene at the central position. Both aryl and hetaryl halides react efficiently with l,3-dicyclopropyl-l,2-propadiene (125) and furnish 1,3,5-hexatriene derivatives 126 as intermediates, which are usually trapped by acceptor-substituted olefins in a subsequent cycloaddition, providing adducts 127a/b in moderate to good overall yields (Scheme 14.30). 

Several other observations suggest that nucleophilic carbene complexes, similarly to, e.g., sulfur ylides, can cyclopropanate acceptor-substituted olefins by an addition-elimination mechanism. If, e.g., acceptor-substituted olefins are added to a mixture of a simple alkene and the metathesis catalyst PhWCl3/AlCl3, the metathesis reaction is quenched and small amounts of acceptor-substituted cyclopropanes can be isolated [34]. 

Isonitrile complexes, having a similar electronic structure to carbonyl complexes, can also react with nucleophiles. Amino-substituted carbene complexes can be prepared in this way (Figure 2.6) [109-112]. Complexes of acceptor-substituted isonitriles can undergo 1,3-dipolar cycloaddition reactions with aldehydes, electron-poor olefins [113], isocyanates [114,115], carbon disulfide [115], etc., to yield heterocycloalkylidene complexes (Figure 2.6). 

The transition metal-catalyzed reaction of diazoalkanes with acceptor-substituted alkenes is far more intricate than reaction with simple alkenes. With acceptor-substituted alkenes the diazoalkane can undergo (transition metal-catalyzed) 1,3-dipolar cycloaddition to the olefin [651-654]. The resulting 3//-pyrazolines can either be stable or can isomerize to l//-pyrazolines. 3//-Pyrazolines can also eliminate nitrogen and collapse to cyclopropanes, even at low temperatures. Despite these potential side-reactions, several examples of catalyzed cyclopropanations of acceptor-substituted alkenes with diazoalkanes have been reported [648,655]. Substituted 2-cyclohexenones or cinnamates [642,656] have been cyclopropanated in excellent yields by treatment with diazomethane/palladium(II) acetate. Maleates, fumarates, or acrylates [642,657], on the other hand, cannot, however, be cyclopropanated under these conditions. 

As mentioned in Sections 3.1.6 and 4.1.3, cyclopropenes can also be suitable starting materials for the generation of carbene complexes. Cyclopropenone di-methylacetal [678] and 3-alkyl- or 3-aryl-disubstituted cyclopropenes [679] have been shown to react, upon catalysis by Ni(COD)2, with acceptor-substituted olefins to yield the products of formal, non-concerted vinylcarbene [2-1-1] cycloaddition (Table 3.6). It has been proposed that nucleophilic nickel carbene complexes are formed as intermediates. Similarly, bicyclo[1.1.0]butane also reacts with Ni(COD)2 to yield a nucleophilic homoallylcarbene nickel complex [680]. This intermediate is capable of cyclopropanating electron-poor alkenes (Table 3.6). 

Particularly interesting is the reaction of enynes with catalytic amounts of carbene complexes (Figure 3.50). If the chain-length between olefin and alkyne enables the formation of a five-membered or larger ring, then RCM can lead to the formation of vinyl-substituted cycloalkenes [866] or heterocycles. Examples of such reactions are given in Tables 3.18-3.20. It should, though, be taken into account that this reaction can also proceed by non-carbene-mediated pathways. Also Fischer-type carbene complexes and other complexes [867] can catalyze enyne cyclizations [267]. Trost [868] proposed that palladium-catalyzed enyne cyclizations proceed via metallacyclopentenes, which upon reductive elimination yield an intermediate cyclobutene. Also a Lewis acid-catalyzed, intramolecular [2 + 2] cycloaddition of, e.g., acceptor-substituted alkynes to an alkene to yield a cyclobutene can be considered as a possible mechanism of enyne cyclization. 

The order of reactivity of these three catalysts towards alkenes (but also towards oxygen) is 1 > 3 > 2. As illustrated by the examples in Table 3.18, these catalysts tolerate a broad spectrum of functional groups. Highly substituted and donor- or acceptor-substituted olefins can also be suitable substrates for RCM. It is indeed surprising that acceptor-substituted alkenes can be metathesized. As discussed in Section 3.2.2.3 such electron-poor alkenes can also be cyclopropanated by nucleophilic carbene complexes [34,678] or even quench metathesis reactions [34]. This seems, however, not to be true for catalysts 1 or 2. 

Ylides other than acceptor-substituted diazomethanes have only occasionally been used as carbene-complex precursors. lodonium ylides (PhI=CZ Z ) [1017,1050-1056], sulfonium ylides [673], sulfoxonium ylides [1057] and thiophenium ylides [1058,1059] react with electrophilic transition metal complexes to yield intermediates capable of undergoing C-H or N-H insertions and olefin cyclopropanations. 

In acceptor-substituted carbene complexes with hydrogen at Cp fast hydride migration to the carbene will usually occur [1094,1095]. The resulting olefins are often formed with high stereoselectivity. 1,2-Hydride migration will also occur in P-hydroxy carbene complexes, ketones being formed in high yields (Table 4.2). Intramolecular 1,5-C-H insertion can sometimes compete efficiently with 1,2-insertion [1096]. 

A wide range of olefins can be cyclopropanated with acceptor-substituted carbene complexes. These include acyclic or cyclic alkenes, styrenes [1015], 1,3-dienes [1002], vinyl iodides [1347,1348], arenes [1349], fullerenes [1350], heteroare-nes, enol ethers or esters [1351-1354], ketene acetals, and A-alkoxycarbonyl-[1355,1356] or A-silyl enamines [1357], Electron-rich alkenes are usually cyclopropanated faster than electron-poor alkenes [626,1015],... 

Polystyrene-bound benzaldehydes can be smoothly olefinated with benzyl- or cin-namylphosphonium salts in DMF or THF using sodium methoxide as a base (Entry 1, Table 5.5 [64-67]). Alkylphosphonium salts, however, only react with resin-bound aldehydes upon deprotonation with stronger bases, such as butyllithium [30,68-70]. The more acidic acceptor-substituted phosphonium salts, on the other hand, even react with resin-bound aldehydes and ketones upon treatment with tertiary amines, DBU, sodium ethoxide, or lithium hydroxide [71-75], but stronger bases are also used occasionally [76]. 

Figure 5.9. Wittig olefination with acceptor-substituted, polystyrene-bound phosphonates and phosphonium salts [87,94], Ar 2-nitrophenyl.

Intramolecular coordination is apparently responsible for most examples of regioselective Wacker oxidations of internal olefins, but electronic effects are also operating [28], specifically in acceptor-substituted olefins. Steric effects are currently not well explored [8], Recent theoretical studies on the mechanism of the Wacker and related reactions are available elsewhere [29, 30],... 

The formation of trans-products is observed to a lesser extent in the reaction of 3-alkoxycarbonyl-substituted cyclohexenones, in the reaction with electron-deficient alkenes and in the reaction with olefinic reaction partners, such as alkynes and allenes, in which the four-membered ring is highly strained (Scheme 6.11). The ester 26 reacted with cyclopentene upon irradiation in toluene to only two diastereomeric products 27 [36]. The exo-product 27a (cis-anti-cis) prevailed over the endo-product 27b (cis-syn-cis) the formation of trans-products was not observed. The well-known [2 + 2]-photocycloaddition of cyclohexenone (24) to acrylonitrile was recently reinvestigated in connection with a comprehensive study [37]. The product distribution, with the two major products 28a and 28b being isolated in 90% purity, nicely illustrates the preferential formation of HH (head-to-head) cyclobutanes with electron-acceptor substituted olefins. The low simple diastereoselectivity can be interpreted by the fact that the cyano group is relatively small and does not exhibit a significant preference for being positioned in an exo-fashion. 

Thiocoumarin (127) underwent [2 + 2]-photocycloaddition reactions in better yields than 126. In contrast to coumarin, cis- and trans-fused products are being found, however, for example, in the reaction with 2,3-dimethyl-2-butene, possibly because the thiopyran ring is more flexible than the pyran ring due to the longer C—S bonds. HTproduct is favored with electron donor-substituted olefins [121]. Electron acceptor substitution in 3-position, as in 3-cyano-l-thiocoumarin (128), leads to an improved performance in [2 + 2]-photocycloaddition reactions [122]. 

Freidlina et al. used 10 mol% of FeCl3 and 40 mol% of /V,/V-dimethylaniline to promote Kharasch additions of methyl dibromoacetate, methyl 2,2-dibromopropionate, methyl tribromoacetate, or dibromomalonate to acceptor-substituted olefins (cf. Fig. 6) [89]. Either linear addition products 32 or lactones were obtained in 23-60% and 43 -8% yield, respectively. 

From the three direct [2 + l]-cycIoaddition routes, path a employing electronrich olefins and acceptor-substituted carbenes is the most efficient one, since the alkenes can be synthesized from carbonyl compounds or other precursors and the carbenes are produced from easily available diazo alkanes. Therefore this very flexible mode to construct donor-acceptor substituted cyclopropanes is by far the most frequently used route. 

The initial reports 39) only contain a few examples with unsaturated esters used as the olefinic component in large excess (entries 1-3, Table 1). Recent investigations 40), however, underline that this complementary approach to donor-acceptor-substituted cyclopropanes is rather general. Since equimolar amounts of olefins and carbene complexes are sufficient to give good results (entries 4-8), this method might be of preparative value. 

Vicinally donor-acceptor-substituted olefins usually are rather unreactive species. Nevertheless cyclopropanation of 2,2-dimethyl-3(2 H)-furanone 70 could be executed with dimethyl oxosulfonium methylide as a methylene source. The bicyclic compound 71 is formed in modest yield accompanied by the spiro epoxide as a second product in almost equal amounts. Carbinols 72 derived from 71 by alkyl lithium addition can be nitrosated and photolyzed to suffer a Barton fragmentation. The resulting y-oxoaldehydes are directly cyclized to afford the 2-substituted cyclopentenones 73 in good yield 41. ... 

According to Scheme 1 methyl 2-siloxycyclopropanecarboxylates should also be available from donor-acceptor-substituted olefins like 100, which are easily synthesized by silylation of the corresponding 1,3-dicarbonyl compounds. Cyclopropanation of 100 with methyl diazoacetate or diazomethane could be realized in the presence of Cu(II)-catalysts, but due to the relatively low reactivity of the olefins a large excess of diazoalkanes had to be employed. This makes the isolation of 101 troublesome and therefore direct hydrolysis with acid to give 1,4-dicarbonyl compounds 102 is advantageous (Eq. 32) 66). 

Fig. 1.13. NaBH4-mediated addition of (/3-hydroxyalkyl )mercury (II) acetates to an acceptor-substituted olefin.

Nucleophiles can be added to acceptor-substituted olefins. In that case, enolates and other stabilized carbanions occur as intermediates. Reactions of this type are discussed in this book only in connection with 1,4-additions of ylids (Section 9.2.2), organometallics (Section 8.6), or enolates (Section 10.6) to a,/3-unsaturated carbonyl and carboxyl compounds. 

Fig. 8.36. Nucleophilic substitution I on an acceptor-substituted olefin with a leaving group in the /3 position.

Fig. 8.38. Nucleophilic substitution III on acceptor-substituted olefins with a leaving group in the ft position.

On the other hand, stabilized ylides react with aldehydes almost exclusively via trans-oxaphosphetanes. Initially, a small portion of the cw-isomer may still be produced. However, all the heterocyclic material isomerizes very rapidly to the fnms-configured, four-membered ring through an especially pronounced stereochemical drift. Only after this point does the [2+2]-cycloreversion start. It leads to triphenylphosphine oxide and an acceptor-substituted fnms-configured olefin. This frara-selectivity can be used, for example, in the C2 extension of aldehydes to /ran.v-con figured aj8-unsaturated esters (Figure 9.11) or in the fnms-selective synthesis of polyenes such as /1-carotene (Figure 9.12). 

A simple example of photopolymerization based on PET is realized, if the monomers polymerized are the electron donor (D) and electron acceptor (A) themselves [12]. Therefore, the electron densities of both compounds must be very different. With vinyl monomers, combinations of donor and acceptor substituted olefins are especially suitable systems. 

Nucleophiles will open acceptor-substituted vinylcyclopropanes either by attacking the three-membered ring resulting in a 1,5-addition or by a 1,7-addition to the olefin moiety . In most cases two acceptor groups are a prerequisite for sufficient activation (see Chapter 9). An interesting nucleophile-dependent dichotomy is demonstrated by equation 143. Organoaluminium compounds add in a 1,5-fashion whereas the corresponding ate-complexes prefer the 1,7-mode . 

The magnitude of the LCAO MO coefficients of the interacting orbitals permits a prediction of the expected oxetane regiochemistry. Both in the HOMO of a donor-substituted olefin and in the LUMO of an acceptor-substituted olefin, the coefficient of the unsubstituted carbon atom is the larger one in absolute value. Therefore, electron-poor olefins regioselectively afford the oxetane with the substituted carbon next to the oxygen. (Cf. Barl-trop and Carless, 1972.) In contrast, an electron-rich olefin predominantly yields the oxetane with the unsubstituted carbon next to the oxygen. (Cf. Scheme 22.)... 

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