Retro-allylation

Base removes bepzylic H, retro- allyl anion+alkene, all-s gives trans-cyclooctene retro [2+2], s on both a-bonds makes trani-double bond. This is an exercise in drawing believable transition structures like 6.42. 

A homoallyl alcohol has been used to generate an allylrhodium species via retro-allylation.173 Subsequent reaction with an aldehyde (RCHO) yields the corresponding secondary alcohol, R-CH(OH)CH2-C(Me)=CH2, in situ. This can be isomerized in the same pot to yield saturated ketone, R-C(=0)CH2-CHMe2. 

A procedure has been developed for the palladium-catalysed a-arylation of amides by aryl bromides using the zinc enolates of the amides. The reaction works well with bromoarenes carrying a variety of ring substituents and with bromopyridine. In addition, the reaction has been shown to be effective with morpholine amides to give products which are precursors for aldehydes and ketones.39 A new method has been reported for the allylation of aryl halides using homoallyl alcohols as the allyl source the palladium-catalysed reaction, which may be both stereo- and regio-sepecific, uses a retro-allylation reaction to form a a-allyl(aryl)palladium intermediate.40... 

In a gallium-mediated allyl transfer process, bulky gallium homoallylic alkoxides have been retro-allylated to generate (Z)- and ( )-crotylgallium reagents stereo- (g) specifically.195 Immediate reaction with aromatic aldehydes gives erythro- and threo-homoallylic alcohols. 

Scheme 12.62 Regio- and stereospecific allyl-aryl coupling via retro-allylation [6].

In an interesting example described by the Oshima group [182a], the electrophilic Ni-allyl species is formed by a retro-allylation of malonates 167. Subsequent coupling with an arylzinc reagent as an hNu affords the aUylation products 168 in good yields (Scheme 12.80). 

Scheme 12.80 Retro-allylation for the formation of electrophilic Ni- it-allyl species [182a].

The same group has reported an efficient method for the synthesis of 1,5-hexadienes 171 by Ni-catalyzed reactions of Boc-protected allyl alcohols 169 with homoallyl alcohols 170. Ni-mediated retro-allylation allows for the use of homoallyl alcohols as allylmetal equivalents (Scheme 12.81) [182bj. 

The metal-catalyzed allylation of carbonyl groups is a classical reaction in organic chemistry. However, the reverse reaction pathway, the retro-allylation, is... 

Scheme 16 Metal-promoted C-C bond cleavage by retro-allylations...

In general, metal-catalyzed retro-allylation of homoallylic fcrf-alcohols 67 proceed by a six-membered transition state 68, and have become a relatively unorthodox method to generate allylmetal species 70 and ketones 69 [52]. 

Intriguingly, rhodium catalysts display with the same substrates a complementary reactivity profile (Scheme 19) [55]. Moreover, the pathway after the retro-allylation step is heavily dependent on the conditions employed and substrate substitution. For instance, enantioselective retro-allylative C-C bond cleavage... 

Scheme 19 Desymmetrization pathways of meso-tert-norbomenols induced by rhodium(I)-catalyzed retro-allylation...

Hayashi S, Hirano K, YOTunitsu H, Oshrma K (2006) Palladiiun-catalyzed stereo- and regiospecific allylation of aryl halides with hrunoallyl alcohols via retro-allylation selective generation and use of o-allylpalladiurtt. J Am Chem Soc 128(7) 2210-2211. doi 10.1021/... 

Waibel M, Cramer N (2011) Desymmetrizations of meso-tert-norbomenols by rhodium(I)-catalyzed enantioselective retro-allylations. Chem Commun 47(l) 346-348. doi 10.1039/ c0cc01950j... 

In 1996, when transition-metal-catalyzed carbon-carbon bond cleavage was just emerging as a current topic in organic chemistry, Kondo and Mitsudo reported the first transition-metal-catalyzed retro-allylation of homoallylic alcohol to simply cleave off the allylic moiety with a ruthenium complex [7]. After 10 years of silence, transition-metal-catalyzed retro-allylation has been rapidly developing since 2006. Nowadays, catalytic retro-allylation can be regio- and stereoselective, hence being a useful tool for modern organic synthesis [8]. 

It is necessary to suppress this isomerization for selective reactions. The allylic transition metal complexes generated in situ can undergo protonation, fi-hydride elimination, nucleophilic addition, or reductive elimination. The fate of the initially formed o-allylic metal species depends on the reaction conditions, mainly on the character of the transition metal used. With proper conditions, retro-allylation is a useful tool in organic synthesis. This section categorizes the chemistry of retro-allylation according to the transition metals used. 

Kondo and Mitsudo are the pioneers of transition-metal-catalyzed retro-allylation [7]. They described this phenomenon as deallylation and fi-allyl elimination . Ruthenium-catalyzed reaction of tertiary homoallylic alcohols proceeds in the presence of allyl acetate under an atmosphere of carbon monoxide in tetrahydro-furan (THF) at a relatively high temperature of 180 C to afford the corresponding ketones (Scheme 5.3). Although the exact roles of allyl acetate and carbon monoxide are not clear, they propose a mechanism involving oxidative addition of the... 

Advantage of Palladium-Catalyzed Allylation via Retro-allylation... 

The retro-allylation is applicable to arylative ring-opening of cyclic homoallylic alcohols such as 5 (Scheme 5.13). 

The stereospecificity of the allylation in Scheme 5.12 is rationalized by identifying the most favorable transition state of the retro-allylation (Scheme 5.14). Oxidative addition of Np-Br followed by bromide-alkoxide exchange with 4 generates intermediate 6 or 7. In the case of threo-4,6a should be the more favorable conformation than 6b according to the routine conformational analysis of chairlike transition states. The retro-allylation thus predominantly proceeds from 6a to yield ( )-8. Thanks to bulky tricyclohexylphosphine, the following reductive elimination should take place rapidly prior to o-jt interconversion to retain the E-stereochemistry. A similar picture is applicable to the reaction of erythro-4, where 7a is more favorable than 7b to afford the corresponding Z-product selectively. 

The retro-allylation/arylation cascade expands the utility of homoallylic alcohols that are the products of particular reactions. 

Homoallylic alcohol 9 is readily prepared by palladium-catalyzed directed cyanoboration followed by Suzuki-Miyaura cross-coupling (Scheme 5.15) [15]. Palladium-catalyzed allyl transfer from 9 to aryl bromide results in removal of the hydroxymethyl directing group and concomitant formation of 3,4-diaryl-2-butenenitrile albeit the lack of regio- and stereospecificity. The overall transformation proposes a concept of intramolecular reaction with a carbon tether removable through retro-allylation. 

The allyl transfer chemistry is applicable to the synthesis of aryl-substituted vinylic and allylic sUanes of synthetic importance [17]. Homoallyhc alcohol bearing a ferf-butyldimethylsUyl group at the allylic position participates in the allyl transfer to yield ( )-3-aryH-alkenylsilanes (Scheme 5.17). The transition state of the retro-allylation should have the bulky silyl group at the equatorial position, accounting for the -stereoselectivity. 

The reactions of optically active homoallylic alcohol with aryl bromides culminate in excellent chirality transfer to the corresponding crotylsilanes (Scheme 5.19). The chirality transfer is explained by the preference of transition state 12 due to sterics, which leads to fe-face selective retro-allylation, finally giving ( ,S)-products. 

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