1.4- Diene-3-ones, 1,5-disubstituted

The reactivity of different alkenes toward mercuration spans a considerable range and is governed by a combination of steric and electronic factors.24 Terminal double bonds are more reactive than internal ones. Disubstituted terminal alkenes, however, are more reactive than monosubstituted cases, as would be expected for electrophilic attack. (See Part A, Table 5.6 for comparative rate data.) The differences in relative reactivities are large enough that selectivity can be achieved with certain dienes. 

The reaction is E-selective, which means that a simple synthesis of an E.Z-diene z is possible from the symmetrical acetate with two Z-allylic alkenes. The one that rearranges goes Eand the one that stays behind remains Z. It does not matter which way the acetate goes. The driving force for this rearrangement, from one disubstituted alkene to another, is establishment of conjugation. 

These two dienes (33 and 34) are in equilibrium, and the equilibrium favors the more thermodynamically stable compound. In this case, the more stable diene is 34, where each C=C unit is disubstituted (see Chapter 12, Section 12.1). This rearrangement is called the Cope rearrangement, after Arthur C. Cope (United States 1909-1966). The temperatures required for a Cope rearrangement are sometimes quite high, and the fact that an equilibrium is established between the two dienes is a problem. If the substitution pattern of the dienes is identical, the mixture of products may be difficult to separate. An example is the Cope rearrangement of 1,5-diene 35, which, upon heating, gives 36. There is one disubstituted C=C unit in 35 and one disubstituted C=C unit in 36, so the equilibrium will not favor one over the other and close to a 1 1 mixture of these two dienes is expected. In other words, this reaction will produce a mixture and it is probably difficult to separate one from the other. 

Part structure A is recognised to be a 2,5-disubstituted cyclohexa-1,3-diene on the basis of its chemical shift values. The ethyl group is one substituent, the other is a carboxy function judging by the chemical shift value of 8c = 174.1. The CH multiplicities which follow from the DEPT subspectra, 2C, 4CH, 5CH2 and CHj, lead to the CH part formula C2 + C4H4 + CsHw + CH3 = C12///7. Comparison with the given molecular formula, Ci2/7j 03, indicates an OH group. Since... 

Complete diastereoselection is observed in the HDA reaction of Danishefsky s diene with o-substituted benzaldehyde chromium tricarbonyl complexes. Decomplexation is facile and good yields of 2-aryl-2,3-dihydropyran-4-ones result <96SL258>. Cis-2,3-disubstituted pyranones are accessible from the Lewis-acid catalysed HDA reaction between (triisopropylsilyloxy) dienes and aldehydes and dehydrogenation of the resulting dihydropyrans <96JOC7600>. 

Trost et alJ2 also explored the compatibility of di-, tri-, and tetrasubstituted allenes with their intermolecular Alder-ene protocol. Multiple substituents present the opportunity for a mixture of products to arise from differing regio- and chemoselectivity. 1,1-Disubstituted allenes were coupled to methyl vinyl ketone with excellent chemo-selectivity only when one set of /3-hydrogens was activated by an cy-ester or amide (Equation (69)). If the /3-hydrogens were of similar acidity, a mixture of products was obtained, as in the coupling of allenol 103 with methyl vinyl ketone dienes 104 and 105 are produced in a 1.3 1 mixture (Equation (70)). 

With the C12,C13 disconnection producing an effective solution to the synthesis of epothilone A (4), it would seem likely that the metathesis approach could be extended readily to the preparation of epothilone B (5). However, installation of the desired C12 methyl group requires ring-closure of a diene precursor in which one of the olefins is disubstituted. Recently, such reactions have been shown to be problematic for Grubbs initiator 3 but more successful with Schrock s molybdenum initiator 1 [19]. Consistent with these reports, Danishefsky demonstrated that triene 38 would not undergo RCM with 3, whereas 1 was effective in promoting the transformation of 38 into a 1 1 mixture of 39a and 39b in good yield [14b] (Scheme 8). 

The second example is an intermolecular crystal-state reaction. Cross-conjugated 1,5-disubstituted 1,4-dien-3-ones in solution undergo both cis-trans photoisomerization and photodimerization, yielding complex mixtures of products, including die all-trans-substituted cyclobutane 2 in the case of 1,5-diphenyl-1,4-pentadien-3-one. In contrast, dienones such as 3a in whose crystals adjacent molecules lie parallel and strongly overlapped react in the solid to give 3b as the sole photoproduct. This isomerically pure tricyclic diketone results, formally, from an eight-center dimerization. It is not formed in the reaction in solution, and could be prepared by other methods only with considerable difficulty (4). 

A structural requirement for the asymmetric Birch reduction-alkylation is that a substituent must be present at C(2) of the benzoyl moiety to desymmetrize the developing cyclohexa-1,4-diene ring (Scheme 4). However, for certain synthetic applications, it would be desirable to utilize benzoic acid itself. The chemistry of chiral benzamide 12 (X = SiMes) was investigated to provide access to non-racemic 4,4-disubstituted cyclohex-2-en-l-ones 33 (Scheme 8). 9 Alkylation of the enolate obtained from the Birch reduction of 12 (X = SiMes) gave cyclohexa-1,4-dienes 32a-d with diastereoselectivities greater than 100 1 These dienes were efficiently converted in three steps to the chiral cyclohexenones 33a-d. 

The catalyzed reaction of acetylenic esters and alkenes can lead to ene products and/or cis [2 + 2]cycloaddition. The relative reactivity of alkenes established by reactions with dienes is 1,1-disubstituted > trisubstituted > monosubstituted and 1,2-disubstituted. Ene reactions predominate with alkenes containing two substi tuents on one carbon.1... 

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