Diene-Aldehyde Reductive Cyclizations

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). 

It should be noted that the Grob fragmentation reaction and the reductive cyclization (homoallylation) discussed in this section involve the same oxanickellacyclopentane 66 as a common intermediate (Scheme 17). The reversibility of these C - C bond cleavage reaction and C - C bond formation reaction is also supported by the isolation and characterization (by X-ray analysis) of an oxanickellacyclopentane-like 66 (without a tether), which is prepared from a stoichiometric amount of Ni(cod)2, a diene, an aldehyde, and a monodentate phosphine ligand [41]. 

Studies by Mori demonstrate that triethylsilane and dienals undergo reductive cyclization in the presence of bis(T] -cycloocta-l,5-diene)nickel(0) (2) and triphenylphosphine (1 2) to produce the silyl ether of cycloalkanols P l in this instance, y.b-misaturated products are obtained. However, if the reaction is carried out in the presence of cyclohexa-l,3-di-ene, an analogous reaction proceeds to give 8,e-unsaturated products. This effect is reported to be derived from selective diene hydrometalation followed by addition of the or-ganonickel intermediate to the tethered aldehyde. The reaction proceeds with five-, six-, and seven-membered ring formation and with heterocyclic substrates. Several synthetic applications of this cyclization methodology are reported (Scheme 8). Intermolecular processes with simple dienes and aldehydes to afford y.S-unsaturated silyl ethers are also possible. 

Pd-cataly2ed reactions of butadiene are different from those catalyzed by other transition metal complexes. Unlike Ni(0) catalysts, neither the well known cyclodimerization nor cyclotrimerization to form COD or CDT[1,2] takes place with Pd(0) catalysts. Pd(0) complexes catalyze two important reactions of conjugated dienes[3,4]. The first type is linear dimerization. The most characteristic and useful reaction of butadiene catalyzed by Pd(0) is dimerization with incorporation of nucleophiles. The bis-rr-allylpalladium complex 3 is believed to be an intermediate of 1,3,7-octatriene (7j and telomers 5 and 6[5,6]. The complex 3 is the resonance form of 2,5-divinylpalladacyclopentane (1) and pallada-3,7-cyclononadiene (2) formed by the oxidative cyclization of butadiene. The second reaction characteristic of Pd is the co-cyclization of butadiene with C = 0 bonds of aldehydes[7-9] and CO jlO] and C = N bonds of Schiff bases[ll] and isocyanate[12] to form the six-membered heterocyclic compounds 9 with two vinyl groups. The cyclization is explained by the insertion of these unsaturated bonds into the complex 1 to generate 8 and its reductive elimination to give 9. 

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. 

Hydride abstraction from dienyl tricarbonyl iron complexes furnishes cationic dienyl tricarbonyl iron complexes. For example, reaction of the diene-iron tricarbonyl complex (115) with triphenyhnethyl hexafluorophosphate followed by trimethylsilyl cyanide furnished with excellent regio- and stereoselectivity a new diene iron tricarbonyl complex (116) (Scheme 170). Excellent regio- and stereoselectivity is seen upon reaction of the cationic complex (116) with trimethylsilyl cyanide (TMS-CN) (Scheme 170). Reduction of the nitrile affords a spirocyclic lactam complex. Intramolecular cyclization of in situ formed enols furnishes spirocyclic compounds again with excellent stereoconfrol (Scheme 171). An interesting example of hydride transfer from a cyclohexadiene ring to a pendant aldehyde followed by nucleophilic addition is seen in Scheme 172. 

Both disubstituted alkynes (Chapter 3.3, this volume) and isolated terminal double bonds may be reduced by alkali metals in NH3, but isolated double bonds are usually stable to these conditions. However, 16,17-secopregnanes (10 equation 8) afford mixtures of cyclization products (11) and (12) in 61% to 80% yield with Na naphthalenide-THF, Na-NHs-THF, Na-THF or Li-NHs-THF. With Na-NHa-THF-r-butyl alcohol, a 91% yield of a 72 28 mixture of (11) (12) (R = Me) is obtained. This type of radical cyclization of alkenes and alkynes under dissolving metal reduction conditions to form cyclopentanols in the absence of added proton donors is a general reaction, and in other cases it competes with reduction of the carbonyl group. Under the conditions of these reactions which involve brief reaction times, neither competitive reduction of a terminal double bond nor an alkyne was observed. However, al-lenic aldehydes and ketones (13) with Li-NHs-r-butyl alcohol afford no reduction products in which the diene system survives. ... 

Scheme 12.59. A representation of a pathway to an amino acid using the hydantoin (glycolyl urea, imidazolidme-2,4-diene) synthetic route. Glycine (Gly, G) is allowed to react with potassium cyanate in the presence of an acid catalyst. Addtion occurs at nitrogen and cyclization with loss of water produces the hydantoin (glycolyl urea, imidazolidine-2,4-diene). The hydantoin is then available to react with a choice of aldehydes (in the presence of acetate anion— to serve as a proton sink). Dehydration, reduction, and hydrolysis then generate the amino acid.

In our earlier publication (15) the synthesis of the southern part was described. This is shown in Scheme 2, including some improvements. The diene ester prepared from methacrolein and trimethyl-phosphonoacetate >3 underwent a Diels Alder cyclization with methyl vinyl ketone to give only one regio isomer, which after equilibration with base gave the all trans keto ester 9, in an overall yield of 75%. Linder Wadsworth Emmons conditions, 9 reacted smoothly with the t-butyl dimethylphosphonoacetate 10 to give the a, p unsaturated ester 11. Hydrolysis, followed by acid chloride formation and reduction with n-tributyltin hydride gave the aldehyde 12 the yield over 4 steps was 70%. 

The Woodward synthetic route was initiated with a Diels-Alder reaction between 1,4-benzoquinone (14) and diene 15. The cycloadduct 16 formed in this way underwent Meerwein-Pondorff-Verley reduction to afford tricyclic lactone 17 which was converted to bromoether 18. Treatment of this substance with methoxide gave the methyl ether 19. Conversion of 19 to its halohydrin followed by chromium oxidation provided the a-bromo ketone 20 which upon treatment with zinc in glacial acetic acid afforded the bicyclic enone 21. This substance was transformed to the aldehyde-acid 23 by an osmylation-periodate cleavage sequence. The acid function in 23 was es-terified and the aldehyde moiety was condensed with 6-methoxytryptamine. The Schiff base intermediate obtained in this fashion was reduced to give an amine which provided the lactam 24 upon intramolecular acylation. Bischler-Napieralski cyclization of 24 gave the pentacyclic intermediate 25 in which... 

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