Dienyl side-chain

For the elaboration of the dienyl side-chain of the E-F fragment of (+)-spongistatin 2, A.B. Smith et al. oxidized the sensitive primary allylic alcohol moiety using the Dess-Martin oxidation. The resulting a,p-unsaturated aldehyde was treated with a Wittig reagent to obtain the desired 1,3-dienyl side chain. 

Kiguchi, T., Yuumoto, Y, Ninomiya, I., and Naito, T., Syntheses of proposed structure of pseudodis-tomin A triacetate and its regioisomers on dienyl side-chain. Heterocycles, 42, 509, 1996. 

Aniline that is orf/io-substituted with a hexa-2,5-dienyl side-chain undergoes catalytic, palladium-assisted cyclization to 2-propylquinoline (Scheme 34) this is only one of a series of ring-closure reactions involving palladium-promoted nucleophilic attack on an alkene. A tetrahydroquinoline (55) is produced by the action of trifluoroacetic acid on the hydroxylamine (54). This method has also been used to prepare l,4-benzoxazines. ... 

Conformational details in more mobile systems are harder to derive, as they rely on accurate quantification, and require a number of assumptions to be made. A study was made of the conformation of the dienyl side chain of [IV]. On the basis of the exo-anomeric effect, the diene fragment would be expected to adopt one or both of the conformations [rVA] or [FVB]. Note that there is no direct evidence from NMR for these conformations because NMR... 

While the preparation of 12 was secured, the preparation of the dienyl side chain 21 was undertaken according to a biomimetic strategy using an aldol condensation of enal 19, which was synthesized from p-nitrobenzaldehyde and propanal. Since this transformation worked superbly for accessing -19, it was tempting to produce , -dienal 23 by iteration, a procedure that was actually described by Suzuki with modest efficiency (Scheme 17). Despite numerous attempts from Matthias to enhance the process, dienal 23 could not be obtained in yield higher than 22%. 

Since the vinyl-C//proton at (<5//= 6.33 shows no additional V////couplings apart from the doublet of doublets splitting (cis and trans coupling), the side-chain is a 1-isoprenyl chain E and not a 1-methylbuta-l,3-dienyl residue F. 

The presence of a 4-methoxy substituent on the 2-phenylethyloxyl or 3-phenylpropyl-oxyl side chains radically altered the course of these cyclizations (Scheme 4). 31a and 31b afforded the spiro-fused ring systems 32 and 33 in 26 and 69% yields, respectively, as the only cyclization products. With this substituent, cyclization onto the activated ipso positions was favoured over direct attack, even where the strained transition state for Atj -5 cyclization of 31a to 32 was involved. Demethylation of the intermediate spirocyclohexa-dienyl cation is favoured over rearrangement in these cases. Kikugawa and coworkers effected the formation of 32 (82%) and 33 (39%) with reverse efficiencies using AgaCOs in TFA . 

Monoacyl-type protecting groups are not recommendable for N -protection, since racemi-zation of the related amino acid derivatives during carboxy activation for their coupling represents a serious problem. Consequently, Ai-acyl derivatives such as formyl or tri-fluoroacetyl have been used mainly for side-chain protection. Nevertheless, some new N -derivatives, which address this problem, have been proposed. With the quinone-derived acyl-type protecting group 3-methyl-3-(2,4,4-trimethyl-3,6-dioxocyclohexa-l,4-dienyl)butyryl (74) (Scheme 39) racemization is almost totally suppressed, and it is readily cleaved with sodium dithionite with formation of the chromanone byproduct The Al -(alkyldisulfa-... 

The acid-catalysed intramolecular 1,5-nucleophilic O-heterocyclization of (p -dienyl)tricarbonyliron diols (82) occurs with 1,2-migration of the side chain. This cyclization has been shown to be a key stereoselective step towards racemic and optically active conformationally locked phosphocholins (83) and (84) as potential anticancer agents (Scheme 12). ... 

The introduction of the aminoethyl side chain is accomplished by Suzuki cross-coupling of dienyl triflate 10 with the alkyl borane generated by hydroboration of A -vinyl- er butyl carbamate (11) with 9-BBN. ... 

The vinyltin moiety can form part of a diene system and undergo coupling with a dienyl iodide to form a tetraene [23] (Scheme 4-3). Crisp and Glink [24] have carried out a number of couplings directed towards -amino acid side-chain elaboration steps and observed the occurrence of ipso-substitution as a side reaction. 

In some cases, further modification of the above-described procedure is required. The synthesis of nakienone B [134] and a similar synthesis of nakienone A [135] have provided such examples (Scheme 1-40). Since any attempts to metallate the dienyl iodide corresponding to the side chain lead to the formation of the corresponding enallene via elimination, the cyclic component must be metallated, necessitating temporary reduction of enones to enols. The high sensitivity of the target molecule requires a non-acidic route. 

A number of alkenylcyclopropanes have been prepared by elimination of bromide, either from a side chain or from the cyclopropane ring. The first known example is the synthesis, in 51 % yield, of (buta-l,3-dienyl)cyclopropane (2) by the reaction of(4-bromobut-l-enyl)cyclopropane (1) at 150°C with a solution of the sodium salt of 2-butylcyclohexanol in the alcohol. ... 

When a similar palladium(0)-catalyzed reaction is performed in an acidic medium at room temperature, i.e. in the presence of acetic acid, different products are formed. These result from a reductive ring cleavage of the methylenecyclopropane (see Section 2.2.2.1. for details) and subsequent intramolecular Diels — Alder reaction with the unsaturated side chain in the case of 5-methylenehept-6-enyl propenoate (5) to ultimately yield 3-oxabicyclo[6.3.1]dodec-8-en-2-one (7). ( )-Octa-5,7-dienyl propenoate (6), however, is stable under the reaction conditions. Product 4, obtained from the acid-free reaction, has thus been proven to be different from the potential products of an isomerization/Diels —Alder addition sequence. 

It is known that the reaction of 1,1-dibromo-l-alkenes with organostannanes affords internal alkynes [24]. The (chlorocyclopropyl)dienyne side chain 84 of callipeltoside A was prepared in 95% yield by the coupling of the 1,3-dienyl-stannane 82 with the dibromide 83. The use of DMF is important [38]. 

Figure 3.7 General structures of anticancer chiral ferrocenes functionalized in the cyclopenta-dienyl-derived ligand with (a) a nucleobase (R, =side chain Nb = nucleobase) and (b) an amino acid (R2 = Fmoc-protected amine group) [52,54].

Spirocyclic compounds have been prepared by making use of the regioselectiv-ity of these reactions. Dienyl complexes were constructed which contained latent nucleophiles in the side chain which were released on treatment with a mild base. Similar reactions have also been used to introduce angular substituents into bicyclic systems. 

Reaction of l-chloro-l-(phenylthio)alkanes with sodium dicarbonyl(cyclopenta-dienyl)ferrate provides (a-phenylthio)alkyliron complexes. If these complexes have a double bond in their side chain in an appropriate distance to the iron center, methylation of the thioether results in an intramolecular cyclopropanation via the corresponding sulfonium salt and the (alkylidene)iron complex as intermediates (Scheme 4—63). ... 

One closely related family to resorcinylic macroHdes are the saUcylate enamide macrolides, which are secondary marine metabolites with a 12-membered ring benzolactone and a dienyl enamide side chain. SaHcyhhalamide A (34) is a potent inhibitor of the mammalian vacuolar ATPase and exerts great diSerential cytotoxicity in the National Cancer Institute (NCI) 60 ceU lines [23]. Other members... 

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