Dienyl aldehydes

The intramolecular version, achieved by using both dienyl amine and dienyl-aldehydes, has also been investigated and applied to the synthesis of dihydro-cannivonine [23] (Scheme 6.11). 

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

The synthetic utility and generality of the reaction is demonstrated by an intramolecular/intermolecular double allylation using an oo-dienyl aldehyde 38 as a probe. The internal diene terminus selectively undergoes nucleophilic allylation intramolecularly to form a cyclopentanol structure. The terminal... 

A rationale for the cz s-selective cyclization for the intramolecular homoal-lylation of oo-dienyl aldehyde 64 is illustrated in Scheme 16. The scenario is essentially the same as the one proposed for the intermolecular reaction, and a Ni(0) species undergoes oxidative addition upon the diene and the aldehyde moieties through a conformation placing the aldehyde substituent and the diene anti to each other. An intermediate 66 undergoes (>-II elimination and czs-reductive elimination of the thus-formed Ni - H complex to produce 65. 

Scheme 16 Intramolecular reductive homoallylation of a>dienyl aldehydes...

The reaction proceeds at room temperature and is rationalized invoking oxidative addition of a Pd(0) species upon the allylic C - O bond of 67, followed by decarboxylation to form an oxapalladacyclopentane intermediate 66 (Pd in place of Ni), which undergoes a facile b-C elimination to finally give an co-dienyl aldehyde 68 (Scheme 17). Recently, it has been revealed that a combination of Ni(cod)2 and a phosphine ligand also catalyzes the same... 

For example, a dienyl aldehyde reductively cyclizes in the presence of an Ni(0)/PPh3 complex and triethylsilane to give homoallylic cyclopropentanol with high regio- and stereoselectivities, while bishomoallylic cyclopropentanol is obtained as major product under the conditions using stoichiometric Ni(0)-diene complexes (Scheme 85). 

Enantioselective catalysts have been developed for cyclization of dienyl aldehydes and coupling of aldehydes with alkynes (Equations (74) and (75)). For reactions with dienes see Refs 433 and 433a, and for reactions with alkynes see Refs 433b I33e. Chiral monodentate phosphines have proved to be effective. 

Attempts at enantioselective cyclization have met with only limited success, but provide further insight into the catalytic mechanism. a Silane-mediated reductive cyclization of dienyl aldehyde 74a in the presence of... 

Another interesting reaction is the Pd-catalysed /i-dccarbopalladation of 4-vinyl cyclic carbonates 382 to afford dienyl aldehydes or ketones 384. The 2-oxa-l-... 

Kocienski and coworkers [134] at a certain stage of the Rapamacin synthesis used dienyl aldehyde 300 and saturated sulfone 301, as indicated in Scheme 97. Triene 302 was obtained, 68% yield, E/Z 95/5. 

The participation of an aldehyde intermediate was suggested by the detection of a CHO proton in the nmr spectrum of a crude distillate in a related experiment. This observation suggests that dienyl aldehyde XIII may be on the way to compound III. This should not be surprising since every reaction pathway of those just postulated, converge towards this aldehyde. 

Another intramolecular version of the aza-Diels-Alder reaction was realized with the condensation of a dienyl aldehyde and benzylamine hydrochloride at 70 °C in 50% aqueous ethanol (Scheme 10) [59]. This methodology was used in the synthesis of racemic dihydrocannivonine [60] and substituted octahydro-quinolines related to pumiliotoxin C [61]. 

Table 10 Ni-catalyzed reductive cyclization of o>dienyl aldehydes 64 at room temperature...

Scheme 18.38 l.S-Sulfinyl transposition via sequential Mislow-Evans rearrangement provides an a-p-y-fi-dienyl aldehyde anion equivalent.—... 

Reactions of reagents 1 and 2 with metal-complexed aromatic, propargylic and dienylic aldehydes provides homoallylic alcohol products with improved selectivity compared to their uncomplexed counterparts. The reaction of benzaldehyde chromium tricarbonyl complex 14 with (R,R)-1 followed by oxidative decomplexation provided ( -15 in 90% yield and 83% ee. The (JE)-crotylboration of 14 with (R,R)-2 provided 16 in 90% yield and 92% ee. Reaction of aldehyde 14 with (. -crotylboronate 3, however, provided adduct 17 in only 41% ee. 

Finally, the reaction of dienylic aldehyde 23 with provides the... 

A representative octahydroquinoline backbone can be constructed via cyclocondensation of dienyl aldehyde 6 with benzylamine hydrochloride. Slow addition of 6 over 20 h to a 1.0 M solution of the amine hydrochloride (S.Oequiv) in 50% aqueous ethanol at 70°C affords a 63% yield of adducts 7 and 8 in a 2.5/1 ratio ... 

Grieco et al. have also probed an intramolecular variant of the iminium reaction with cyclohexadiene [19]. The intramolecular cyclization of cyclo-hexadienyl aldehyde 45 provides the precursor to dihydrocannivonine 46. Initial attempts to execute the intramolecular iminium-ion Diels-Alder reaction under standard conditions gave rise to poor yields (<10%), probably due to the inherent instability of dienyl aldehyde 45. Yields are dramatically improved by slow addition of a solution of 45 in ethanol over 20-30 h to monomethylamine hydrochloride in aqueous ethanol at 70°C. This modified protocol results in a 66% yield of tricyclic amine 46. Subsequent hydrogenation of 46 affords racemic dihydrocannivonine 47 ... 

Accordingly, a dilute ethanol solution of chiral dienyl aldehyde 49 is treated with an equal volume of a saturated aqueous ammonium chloride solution at 75°C for 48 h. Workup provides a 55% yield of two octahydroquinolines, 50 and 51, in a 2.2/1 ratio (Scheme 2.6) no other stereoisomers were detected. 

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