Intramolecular allylations

Diallylsulfonium salts undergo intramolecular allylic rearrangement with strong bases to yield 1,5-dienes after reductive desulfurization. The straight-chain 1,5-dienes may be obtained by double sulfur extrusion with concomitant allylic rearrangements from diallyl disulfides. The first step is achieved with phosphines or phosphites, the second with benzyne. This procedure is especially suitable for the synthesis of acid sensitive olefins and has been used in oligoisoprene synthesis (G.M. Blackburn, 1969). 

The intramolecular allylation of soft carbon nucleophiles with allylic acetates as a good cyclization method has been extensively applied to syntheses of various three, four, five and six-membered rings, and medium and macrocyclic compounds[44]. Only a few typical examples of the cyclizations are treated among numerous applications. 

No 0-allylation is observed in formation of the six-membered ring compound 79 by intramolecular allylation of the /3-keto ester 78(15,57]. Intramolecular allylation is useful for lactone fonnation. On the other hand, exclusive formation of the eight-membered ring lactone 81 from 80 may be in part derived from the preference for the nucleophile to attack the less substituted terminus of the allyl system[58]. 

Intramolecular allylation offers a useful synthetic method for macrocyclic compounds. An application to the synthesis of humulene (83) by the cycliza-... 

The TT-allylpalladium complexes 241 formed from the ally carbonates 240 bearing an anion-stabilizing EWG are converted into the Pd complexes of TMM (trimethylenemethane) as reactive, dipolar intermediates 242 by intramolecular deprotonation with the alkoxide anion, and undergo [3 + 2] cycloaddition to give five-membered ring compounds 244 by Michael addition to an electron-deficient double bond and subsequent intramolecular allylation of the generated carbanion 243. This cycloaddition proceeds under neutral conditions, yielding the functionalized methylenecyclopentanes 244[148], The syn-... 

An interesting and stereoselective synthesis of 1,3-diols has been developed which is based on Lewis acid promoted reactions of /f-(2-propenylsilyloxy (aldehydes. Using titanium(IV) chloride intramolecular allyl transfer takes place to give predominantly Ag/r-l,3-diols, whereas anti-1,3-diols, formed via an / / /-molecular process, are obtained using tin(IV) chloride or boron trifluoride diethyl ether complex71. 

However, the free hydroxyaldehyde and tetra-2-propenylzirconium lead predominantly, in an intramolecular allyl transfer, to the product of formal chelation control87. 

RCM was also used in Yamamoto s total synthesis of the marine neurotoxin gambierol (81) [62], to close the central seven-membered E ring, thereby completing the octacyclic polyether core 80 (Scheme 15). Following previously developed methodology [63], metathesis precursor 79 was produced as the major epimer, by boron trifluoride etherate-mediated intramolecular allylation of a-chloroacetoxy ether 78. Subsequent treatment of 79 with catalyst C produced the octacyclic ether 80 in 88% yield. 

Scheme 15 Formation of the central rings D and E by sequential intramolecular allylation and RCM in Yamamoto s total synthesis of the marine neurotoxin gambierol (81) [62]...

Intramolecular allylation of a-chloroacetoxy ether 185 followed by RCM (Scheme 35) was used by Yamamoto and coworkers to construct the eight-membered cyclic ether in the F-K ring segment 186 of the marine neurotoxin brevetoxin B (184) [91]. 

Scheme 4 Ni(0)-catalyzed intramolecular allylic cydization of a>dienyl aldehydes 11 using hydrosilanes as a reducing agent... 

Hydroxamic acids constitute an important class of siderophores, which play a major role in iron solubilization and transport. Some of them are important as therapeutic agents. The Michael addition of nitroacetyl proline esters to allyl acrylate followed by Pd(0)-catalyzed intramolecular allyl transfer and subsequent reduction of the nitro group yields a novel class of cyclic hydroxamic acids related to pyroglutamic acid (Scheme 5.9).85... 

A few intriguing developments in the area of tetrahydro-P-carboline synthetic methodology include the report of a catalytic asymmetric Pictet-Spengler reaction <06JACS1086> and an enantioselective Pd-catalyzed intramolecular allylic alkylation of indoles <06JACS1424>. A one-step synthesis of 1-substituted-P-carbolines from L-tryptophan has appeared that bypassed the tetrahydro intermediate <06T10900>. 

In rare cases, the Pd-catalyzed intramolecular allylic etherification has been extended to the construction of medium-sized rings. Both an 11-membered bis-ether ring (Equation (34))164 and an eight-membered ether ring (Equations (35) and (36))155 have been prepared in this fashion. In the latter case, the choice of ligand dictated the regiochemical outcome. 

It is proposed that the reaction proceeds through (i) oxidative addition of a silylstannane to Ni(0) generating (silyl)(stannyl)nickel(n) complex 25, (ii) insertion of 1,3-diene into the nickel-tin bond of 25 giving 7r-allylnickel intermediate 26, (iii) inter- or intramolecular allylation of aldehydic carbonyl group forming alkoxy(silyl)nickel intermediate 27, and (iv) reductive elimination releasing the coupling product (Scheme 69). 

A cyclic homoallylic alcohol is efficiently provided by a sequence of Jt-allylpalla-dium complex formation, transmetallation with hexa-n-butyldistannane and intramolecular allylation (Scheme 16.17) [22]. The same transformation can be conducted by means of indium (Scheme 16.18) [23]. 

High levels of asymmetric induction can be achieved intramolecularly if the substrate functionality and the heteroatom ligand are contained in the same molecule. Chiral amido(a]kyl)cuprates derived from allylic carbamates [(RCH= CHCH20C(0)NR )CuR undergo intramolecular allylic rearrangements with excellent enantioselectivities (R = Me, n-Bu, Ph 82-95% ee) [216]. Similarly, chiral alkoxy(alkyl)cuprates (R OCuRLi) derived from enoates prepared from the unsaturated acids and trans-l,2-cyclohexanediol undergo intramolecular conjugate additions with excellent diasteroselectivities (90% ds) [217]. 

Intramolecular Allylic Substitution Catalyzed by Metalacyclic Iridium Pbospboramidite Complexes... 

Several types of intramolecular allylic substitution reactions of carbon, nitrogen, and oxygen nucleophiles catalyzed by metalacyclic iridium phosphoramidite complexes have been reported. Intramolecular allylic substitution is much faster than the competing intermolecular process when conducted in the presence of iridium catalysts. Thus, conditions involving high dilution are not required. Intramolecular... 

Scheme 9.12 Intramolecular allylic alkylations with malonic ester derivatives.

Intramolecular allylic aminations (Scheme 9.20) proceeded with low catalytic efficiency and with ee-values <90% if procedure (a) (cf. Section 9.2.3.2) was used-that is, the catalyst was not activated [18]. The effect of catalyst activation [procedure (c)] was pronounced [18, 22a] for example, activation with TBD increased the rate of formation of N-benzyl-2-vinylpiperidine by a factor of about 1000. Also notable was the fact that substrate concentration as high as 1M was possible, thereby demonstrating the high preference of intramolecular over intermolecular substitutions leading to oligomers. 

Intramolecular allylations can also provide flve-membered rings with ease, and the entropic benefits facilitate additions to ketone substrates. For example, the allylic boronate 121, formed by a Negishi-type coupling between alkenyl... 

A masked allylic boron unit can be revealed through a transition-metal-catalyzed borylation reaction. For example, a one-pot borylation/allylation tandem process based on the borylation of various ketone-containing allylic acetates has been developed. The intramolecular allylboration step is very slow in DMSO, which is the usual solvent for these borylations of allylic acetates (see Eq. 33). The use of a non-coordinating solvent like toluene is more suitable for the overall process provided that an arsine or phosphine ligand is added to stabilize the active Pd(0) species during the borylation reaction. With cyclic ketones such as 136, the intramolecular allylation provides cis-fused bicyclic products in agreement with the involvement of the usual chairlike transition structure, 137 (Eq. 102). 

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