Allenic acids, synthesis

Scheme 4.48 Asymmetric synthesis of/i-allenic acids 184,186 and (-)-malyngolide 187 via /Mactones.

Stereocontrolled conjugate addition of lithium dimethylcuprate to the electron deficient 2,3-double bond of allenes 851 leads to 5,6-dihydropyranM-oncs 852 in moderate yield (Equation 343) <2000J(P1)3188>. Similarly, the Ag(l)-catalyzed intramolecular cyclization of the allenic acid 853 is accelerated upon addition of diisopropylethyl-amine to afford the 3,6-dihydropyran-2-one 854, an intermediate during the total synthesis of (—)-malyngolide (Equation 344) <2000JA10470>. 

Janzen, D.J., Allen, L.J., MacGregor, K.B. and Bown, A.W. (2001) Cytosolic acidification and 7 -aminobutyric acid synthesis during the oxidative burst in isolated Asparagus sprengeri mesophyll cells. Can.. Bot., 79, 438-43. 

The reactions thus afford a method for synthesis of allenic acids and jS-keto esters. 

Allene epoxides. Synthesis of allene epoxides is difficult because of the tendency to undergo further epoxidation and to isomerize to the corresponding cyclopropanone (2, 308-309). The first known one was obtained by Camp and Green (2, 309, ref. 3g) by oxidation of 1,3-di-f-butylallene with m-chloroper-benzoic acid. Crandall and Machlcdcr 1 have now reported successful mono-epoxidation of 1,1,3-tri-t-butvlallene (1), also using m-chloroperbenzoic acid. The epoxide (2) is the main product but is accompanied by an oxetanone (3), undoubtedly formed via an intermediate diepoxide. The epoxide (2) is extraordinarily stable and shows no tendency to isomerize to a cyclopropanone. 

As part of a synthesis of santalene sesquiterpenoids, Barrett and McKenna (1971) treated cyclopentadiene (PI5.1) with the allenic acid (P15.2). This gave a mixture of two isomeric acids, (PI 5.3) and (P15.4). One of these, (PI 5.3) rearranged to the lactone (PI 5.5) on treatment with formic acid. The other remained unchanged. What are the structures of (PI5.3) and (PI5.4) and what are the mechanisms of the reactions (Figure PI 5). 

BoranelmethyllithiumIacetic acid Synthesis of terminal allenes from ethylene derivs. 

More than 30 years ago it was reported that flaxseed homogenates convert 13-HpOTrE into a- and -y-ketols, and the enzyme responsible for this reaction was called hydroperoxide isomerase [54]. Later studies indicated that this reaction was actually a two-step process, consisting of an enzyme-catalysed dehydration of the hydroperoxy fatty acid to a rather unstable allene oxide followed by a non-enzymic hydrolysis [55,56]. The enzyme responsible for allene oxide synthesis has been purified and shown to be a cyt E-450 isoform [57]. As an alternative to hydrolysis, the allene oxide may undergo enzymic cyclization forming 12-oxo-phytodienoic acid. This compound is subsequently converted into jasmonic acid, a phytohormone implicated in the reaction of higher plants to a number of stimuli, such as wounding, fungal elicitation, mechanical forces and osmotic stress [54]. 

Another cycloaddition, in which this time the silyl enol ether functions as a dienophile, is the SnCl4-catalysed addition of butadiene to (180 R = Me) giving (181). If R = H in the starting material a 4 + 3 reaction takes place, producing the seven-membered ring (182). Flash-vacuum thermolysis of P-keto-trimethylsilyl enol ethers has been used in a substituted furan synthesis, and the same process has been used to prepare a-allenic acids (183) from siloxy-dienes. ... 

A general route to 6-substituted valerolactones (112) is by condensation between aldehydes and the dianion derived from butynoic acid followed by hydrogenation using Lindlar s catalyst.During the synthesis of some steroid derivatives, use has been made of an intramolecular Wadsworth-Emmonds procedure to construct an unsaturated valerolactone group (114) from phos-phonate (113) (c/. 3, 87). A new preparation of ( )-pestalotin (115) has as its pivotal step a Lewis acid-catalysed condensation between 2-benzyloxyhexanol and diketen. /3-Ethylenic valerolactones (116) can be obtained from the corresponding /3-allenic acids by treatment with methanolic boron trifluoride (c/. 3, 89). 

Extracts from Clavularia viridis and also many other coral species convert arachidonic acid to the prostanoidpreclavulone-A via 8-( f )-hydroperoxy-5,ll,14( Z), QfEj-eicosatetraenoic acid. The carbocyclization is considered to occur from allene oxide and oxidopentadienyl cation intermediates. An enantioselective total synthesis of preclavulone-A was developed to assist the biosynthetic research. 

Allen et al mainly on the evaluation of data reported by previous workers, advanced structure (5) for 2-methylpyrrole dimer. These data were (a) the monobasic nature of the dimer and (b) the conversion by aqueous acid into an indole which they showed by elimination (i.e., by the synthesis of 2,5-, 2,6-, and 2,7-dimethylindoIes) to be 2,4-dimethyIindole (this compound has since been synthesized by Marion and Oldfield ). Structure (5) for the dimer was confirmed by Edwards and Smith by conversion, by way of the methiodide (6), into the pyrrolidinopyrrole (7), the structure of which was proved by synthesis l,5-dimethylpyrrolid-2-one was condensed with 2-methyI-pyrrole by means of POCI3 to give the cation (8), isomeric with the... 

Rearrangement of acetylenic sulphenates to the allenic sulphoxides 151 was discovered when the synthesis of propargylic ester of trichloromethanesulphenic acid 152 was attempted (equation 86). This reaction is of general scope and gives very good yields of allenic sulphoxides (Table 14) from structurally diverse cohols and various sulphenyl chlorides Reaction of alkynols 153 with benzenesulphenyl chloride in the presence... 

The first synthesis of derivatives (77) of pentatetraene-carboxylic acid has been reported using a Wittig reaction of 1-H-allene-l,3-dicarboxylate monoester chlorides (76) in the presence of triethylamine.60 In one case an intermediate was obtained and was converted to (77) by further treatment with base. The reaction of carbon suboxide with phosphonium ylides has also... 

Wang, X. C., C. Allen et al. (2007). Retinoic acid enhances the production of IL-10 while reducing the synthesis of IL-12 and TNF-alpha from LPS-stimulated monocytes/macrophages. J. Clin. Immunol. 27(2) 193-200. 

If the alkenes and acetylenes that are subjected to the reaction mediated by 1 have a leaving group at an appropriate position, as already described in Eq. 9.16, the resulting titanacycles undergo an elimination (path A) as shown in Eq. 9.58 [36], As the resulting vinyltitaniums can be trapped by electrophiles such as aldehydes, this reaction can be viewed as an alternative to stoichiometric metallo-ene reactions via allylic lithium, magnesium, or zinc complexes (path B). Preparations of optically active N-heterocycles [103], which enabled the synthesis of (—)-a-kainic acid (Eq. 9.59) [104,105], of cross-conjugated trienes useful for the diene-transmissive Diels—Alder reaction [106], and of exocyclic bis(allene)s and cyclobutene derivatives [107] have all been reported based on this method. 

The discovery of carbene and carbenoid additions to olefins was the major breakthrough that initiated the tapping of this structural resource for synthetic purposes. Even so, designed applications of cyclopropane chemistry in total syntheses remain limited. Most revolve around electrophilic type reactions such as acid induced ring opening or solvolysis of cyclopropyl carbinyl alcohol derivatives. One notable application apart from these electrophilic reactions is the excellent synthesis of allenes from dibromocyclopropanes 2). 

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