Retro homoallylic alcohols

The mode of reaction of titanacydobutenes with carbonyl compounds is largely dependent on steric factors (Scheme 14.31) [72]. Ketones and aldehydes tend to insert into the titanium—alkyl bond of 2,3-diphenyltitanacydobutene, and homoallylic alcohols 70 are obtained by hydrolysis of the adducts 71 [65a,73]. On the contrary, when dialkyl-substi-tuted titanacydobutenes are employed, the reaction with aldehydes preferentially proceeds through insertion into the titanium—vinyl bond. Thermal decomposition of the adducts 72 affords conjugated dienes 73 with E-stereoselectivity as a result of a concerted retro [4+2] cycloaddition [72]. 

Not surprisingly, an attempt at direct Mitsunobu inversion of (3-hydroxyketone 14 led only to elimination, yielding the corresponding a,(3-unsaturated ketone. To circumvent this problem, 14 was converted to homoallylic alcohol 15 by Petasis methylenation via the corresponding TES ether. Attempts to methylenate (3-hydroxyketone 14 directly under Petasis conditions led to substantial decomposition via elimination and retro-aldol pathways. Alcohol 15 underwent smooth Mitsunobu inversion to give, following methanolysis and TES ether formation, the desired 1,4-anti compound 16 (Scheme 3). This was then converted in three straightforward steps to aldehyde 17, ready for the proposed aldol union with ketone 10. 

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. 

The other reaction is pyrolytic cleavage (via a retro-ene reaction) of a fatty acid containing a homoallylic alcohol in the chain. This is used to produce two important feedstocks, heptanal and undecylenic acid, from ricinoleic acid, the major fatty acid component of castor oil. The mechanism of this reaction is shown in Scheme 4.61. 

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. 

That Rh-allyl complexes can also act as nucleophiles in addition to aldehydes has been demonstrated by Oshima et al. in 2006 [198]. Retro-aUylation of the homoallyl alcohol 191 under rhodium catalysis generates a nucleophilic aUylrhodium species that reacts with aldehydes 190 to give the corresponding secondary alcohols 192 in situ (Scheme 12.94). Subsequent isomerization of these alcohols proceeds under the reaction conditions to furnish the corresponding saturated ketones 193 in modest to good yields. 

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]. 

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... 

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

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 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. 

Palladium-catalyzed retro-allylation of homoallylic alcohols is extended to retro-propargylation of homopropargylic alcohols [20]. Despite the rigid and linear structure of the triple bond, the reactions of aryl halides with homopropargylic alcohols necessitate slightly modified conditions to afford allenylated arenes (Scheme 5.25). Not only gewi-disubstituted allenes but also tri- and tetrasubstituted ones are accessible. The reactions with diastereomerically pure homopropargylic alcohols threo- and erythro-17 result in stereospecific transfer to afford anti- and syn-18, respectively (Scheme 5.26). 

Palladium-catalyzed reactions of aryl halides with 3,4-alkadien-l-ols were reported by Oh in 2002 (Scheme 5.27) [21]. The finding is an interesting pioneering work on palladium-catalyzed carbon-carbon bond cleavage of homoallylic alcohols. They proposed a mechanism that does not involve retro-allylation but P-carbon elimination. 

A diorganonickel complex generally undergoes reductive elimination more rapidly than the corresponding palladium complex. Nickel can mediate retro-allylation, which is involved in allylation of allylic carbonate with homoallylic alcohols for efficient synthesis of 1,5-hexadienes [25]. A combination of Ni(cod)2 (cod = 1,5-cyclooctadiene) and triethyl phosphite catalyzes the allylation reaction of Boc-protected cinnamyl alcohol (Boc = f-butoxycarbonyl) with homoallylic alcohols (Scheme 5.34). The reactions with alkyl-substituted homoallylic alcohols (R = alkyl) are not regiospecific but are sterically controlled. The highest linear... 

Some mechanistic experiments support the reaction mechanism shown in Scheme 5.35. Oxidative addition of Boc-protected cinnamyl alcohol is accompanied by decarboxylation to yield the (3t-cinnamyl)(tert-butoxy)nickel intermediate 28. Alkoxide exchange between 28 and homoallylic alcohol and subsequent retro-allylation would initially generate (o-allyl)(it-dnnamyl)nickel 29. The configuration of 29 would be fluxional to yield a mixture of several diallylnickel species and to lose regiospecificity. Reductive elimination would take place under steric control by the substituents or under electronic control by the phenyl group. 

Rhodium catalyzes retro-allylation of homoallylic alcohols to generate nucleophilic allylic rhodium species. A combination of [RhCl(cod)]2, PMcj, and cesium carbonate catalyzes crotyl transfer from homoallylic alcohol to benzaldehyde in dioxane at 100 "C to afford the corresponding homoallylic alcohol (Scheme 5.37) [26]. Like allylic nickel, allylic rhodium experiences rapid and E-Z interconversions under the reaction conditions, which prevents stereoselectivity of the crotylation. Interestingly, a similar crotylation is followed by isomerization into saturated ketone with the aid of a bulkier catalyst [RhCl(cod)]2/PtBu3 at a higher temperature. 

Rhodium-catalyzed retro-allylation represents an interesting tool for enan-tioselective carbon-carbon bond cleavage. Shintani and Hayashi developed rhodium-catalyzed kinetic resolution of tertiary homoallylic alcohols via retro-allylation (Scheme 5.40) [28]. The bidentate BINAP series show high selectivity... 

Similar to rhodium, copper mediates retro-allylation when it is complexed with an N-heterocyclic carbene ligand [31]. The allyl transfer takes place not only to aromatic aldehydes but also to aromatic imines (Scheme 5.43). Notably, secondary homoallylic alcohols transfer their allyl groups, retro-allylation dominating over P-hydride elimination from the copper alkoxide intermediates. 

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]. 

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