Allylic derivatives heterocyclic synthesis

The synthesis of the allyl ethers in nitrogen heterocyclic systems presents an element of complication in that the allylation could occur on the oxygen atom or the basic nitrogen atom. This is a feature of alkylation of ambident anions.3 However, this applies only when the allylation is effected by reacting the oxo or hydroxy derivative of the compound with an allyl halide in the presence of a base.3 The alternative method is to react the appropriate halo derivative with sodium allyloxide in allyl alcohol. The latter approach provides not only better yields of the allyl ethers but also certainty of the constitution of the ethers obtained. A diagnostic tool in deciding between the 1-allyl derivative and the O-allyl compound that has commonly been employed is the infrared absorption of the amide carbonyl in the case of the former which is clearly absent in the latter. 

Allyl derivatives of B- and B,0-heterocycles in asymmetric synthesis 90MI48. 

Allylic boron and zinc derivatives in synthesis of nitrogen heterocycles 00PAC1641. 

The conventional methods for the synthesis of N-vinyl nitrogen-containing heterocycles have been covered in monographs [96,107-109] and reviews [93,95] and involve either dehydration of p-oxyethyl compounds [92,94,458-461], dehydrohalo-genation of haloethyl derivatives [462,463], or the vinylation of NH heterocycles with acetylene [93,95,96,109], vinyl chloride [95,464,465], vinyl bromide [466], dihaloal-kanes [467-469], and vinyl ethers [470]. All these processes have been used mainly for carbazole. Sirotkina et al. have successfully elaborated efficient methods for the preparation of N-vinylcarbazoles via isomerization of N-allyl derivatives [471] and catalytic decomposition of available N-(l-alkoxyalkyl)carbazoles [472]. The credit for the systematic development of direct methods for vinylation of various NH heterocycles, including indole, with acetylene is given to Skvortsova et al. [93,473,474]. 

The development of Ir-chiral N,P ligand system opens another promising way for the hydrogenation of allylic alcohol and its derivatives. For example, a cationic Phox-Ir complex catalyzes the hydrogenation of ( )-2-methyl-3-phenyl-9-propen-l-ol in a highly enantioselective fashion.178 With 1 mol.% (5)-92-Ir catalyst, the hydrogenation proceeds completely to provide the chiral alcohol product in 96% ee. Under the same conditions, a para- Bu-substituted chiral alcohol derivative is obtained with 94% ee for the synthesis of lilial (Equation (59)). Heterocyclic N, P-ligand, HetPHOX 113, is also efficient for this reaction.191... 

If the alkenes and acetylenes that are subjected to the reaction mediated by 1 have a leaving group at an appropriate position, as already described in Eq. 9.16, the resulting titanacycles undergo an elimination (path A) as shown in Eq. 9.58 [36], As the resulting vinyltitaniums can be trapped by electrophiles such as aldehydes, this reaction can be viewed as an alternative to stoichiometric metallo-ene reactions via allylic lithium, magnesium, or zinc complexes (path B). Preparations of optically active N-heterocycles [103], which enabled the synthesis of (—)-a-kainic acid (Eq. 9.59) [104,105], of cross-conjugated trienes useful for the diene-transmissive Diels—Alder reaction [106], and of exocyclic bis(allene)s and cyclobutene derivatives [107] have all been reported based on this method. 

Yttrium-catalyzed diene cyclization/hydrosilylation was applied to the synthesis of aliphatic nitrogen heterocycles such as the indolizidine alkaloid ( )-epilupinine. l-Allyl-2-vinylpiperidine 30 was synthesized in four steps in 59% overall yield from commercially available ( )-2-piperidinemethanol (Scheme 10). Treatment of 30 with phenylsilane and a catalytic amount of Gp 2YGH3(THF) gave silylated quinolizidine derivative 31 in 84% yield, resulting from selective hydrometallation of the A-allyl G=G bond in preference to the exocyclic vinylic G=G bond. Oxidation of the crude reaction mixture with tert-huVf hydrogen peroxide and potassium hydride gave (i)-epilupinine in 51-62% yield from 30 (Scheme 10). 

Related intramolecular aminomercurations of cyclic guanidine derivatives have been studied in some detail,2 0 but are primarily useful for the synthesis of bicyclic heterocycles (equations 127 and 128). Cy-clizations of allylic isothiouronium salts have also been reported (equation 129).260b,260e... 

In 1997, the first truly catalytic enantioselective Mannich reactions of imines with silicon enolates using a novel zirconium catalyst was reported [9, 10]. To solve the above problems, various metal salts were first screened in achiral reactions of imines with silylated nucleophiles, and then, a chiral Lewis acid based on Zr(IV) was designed. On the other hand, as for the problem of the conformation of the imine-Lewis acid complex, utilization of a bidentate chelation was planned imines prepared from 2-aminophenol were used [(Eq. (1)]. This moiety was readily removed after reactions under oxidative conditions. Imines derived from heterocyclic aldehydes worked well in this reaction, and good to high yields and enantiomeric excesses were attained. As for aliphatic aldehydes, similarly high levels of enantiomeric excesses were also obtained by using the imines prepared from the aldehydes and 2-amino-3-methylphenol. The present Mannich reactions were applied to the synthesis of chiral (3-amino alcohols from a-alkoxy enolates and imines [11], and anti-cc-methyl-p-amino acid derivatives from propionate enolates and imines [12] via diastereo- and enantioselective processes [(Eq. (2)]. Moreover, this catalyst system can be utilized in Mannich reactions using hydrazone derivatives [13] [(Eq. (3)] as well as the aza-Diels-Alder reaction [14-16], Strecker reaction [17-19], allylation of imines [20], etc. 

The reactions of arylation of heterocyclic /3-ketoesters were employed in the synthesis of a number of isoflavanones and isoflavones.27,28 cr-Methylene cr-arylketones can be easily and selectively obtained by arylation of allyl /3-ketoesters which are eventually deprotected by the Tsuji s procedures. a Deallyloxycarbonylation was performed by treatment of the allyl cr-aryl-/3-ketoesters with catalytic amounts of palladium(n) acetate, triethylammo-nium formate and triphenylphosphane in THF at room temperature and afforded the a-arylketones in 75-97% yield.27 Deallyloxycarbonylation-dehydrogenation can be realized with the same allyl esters by treatment with catalytic amounts of palladium(n) acetate and l,2-bis(diphenylphosphino)ethane (DPPE) in acetonitrile under reflux and affords the ct-aryl cr,/3-unsaturated ketones in 60-90% yield (Scheme 4).28 In particular, this reaction was used in a direct convergent synthesis of 2 -hydroxyisoflavones involving arylation of an appropriate allyl /3-ketoester with the MOM-protected (2-methoxymethoxyphenyl)lead triacetate derivative (Scheme 4). The reaction of the isomeric... 

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