Mukaiyama cyclization

Mukaiyama cyclization promoted with 2-chloro-l-pyridinium iodide in boiling methylene dichloride <87JOC5296,92JOM(43i)335> was used for the formation of seven-membered alkynic lactones with the triple bond stabilized by complex formation from respective alkynic hydroxy acids (Equation (8)). 

A series of chiral binaphthyl ligands in combination with AlMe3 has been used for the cycloaddition reaction of enamide aldehydes with Danishefsky s diene for the enantioselective synthesis of a chiral amino dihydroxy molecule [15]. The cycloaddition reaction, which was found to proceed via a Mukaiyama aldol condensation followed by a cyclization, gives the cycloaddition product in up to 60% yield and 78% ee. 

The dihydropyrones are not produced directly in the initial BINOL-titanium(IV)-cat-alyzed reaction. The major product at this stage is the Mukaiyama aldol product which is subsequently cyclized by treatment with TFA [19fj. The formal cycloaddition product 3d (97% ee) obtained from a-(benzyloxy)acetaldehyde is an important intermediate for compactin and mevinolin. Scheme 4.13 outlines how the structural subunit 13 is available in three steps via this cycloaddition approach [19 fj. 

A tandem combination initiated by a Mukaiyama reaction generates an oxonium ion that cyclizes to give a tetrahydropyran rings.48... 

As described above, our synthetic strategy involves the convergent construction of the central cyclopentanone ring with a carbonylative cross-coupling reaction and a photo-Nazarov cyclization reaction (Chart 2.2). The electrophilic coupling component 51 was synthesized by an intramolecular Diels-Alder reaction [34] and the nucleophilic coupling component 52 by a vinyiogous Mukaiyama aldol reaction [35]. 

The zinc chloride-mediated tandem Mukaiyama aldol-lactonization reaction of aldehydes 21 and thiopyridylketene acetals 22 gave mainly the trans isomer 23. However, if the catalyst is stannic chloride and the reaction is carried out at -78 °C, then the cyclization is highly diastereoselective and yields the cis-isomer 24 <990L1197>. 

This method can also be applied to silyl enol ethers of homologous unsaturated ketones as well as of unsaturated aldehydes or esters [85-87]. While unmodified unsaturated esters give only the corresponding aldehydes without cyclization under tandem hydroformylation/aldol reaction conditions, the corresponding silylated ester enolates smoothly cyclize in a tandem hy-droformylation/ Mukaiyama aldol reaction (Scheme 32) [85-87]. 

Owing to the high Lewis acidity the group 14 organometallic cations are polymerization catalysts par excellence. so Silanorbonyl cations and triethylsilyl arenium have been shown to be efficient catalysts for metal-free hydrosilylation reactions. Chiral silyl cation complexes with acetonitrile have been applied as cata -lysts in Diels Alder-type cyclization reactions °792 intramolecularly stabilized tetracoordinated silyl cations have been successfully used as efficient catalysts in Mukaiyama-type aldol reactions. 

The synthesis of Taxol completed by a group led by the Japanese chemist Teruaki Mukaiyama and shown in Scheme 13.46 takes a rather different approach. Much of the stereochemistry is built into the B ring by a series of acyclic aldol condensations in steps A-D. The ring is closed by a samarium-mediated cyclization at step E-3. 

Auto-tandem hydroformylation-cyclization, catalyzed by [RhCl(cod)]2, enables expansion of the organic skeleton of unsaturated silyl enol ethers (Scheme 10). Linear aldehydes generated in the hydroformylation step subsequently undergo Rh-catalyzed, intramolecular Mukaiyama aldol addition. Bicyclic ketones are also accessible from cyclic silyl enol ethers. 

A novel method for the synthesis of /1-lactams (35), starting from / -amino acids (34) by means of a PT system, has been recently proposed by Watanabe and Mukaiyama.61 The reaction involves initial esterification of the carboxylic acid, which can later undergo the cyclization. 

Keck [63] and Carreira [64] have independently reported catalytic asymmetric Mukaiyama aldol reactions. Keck et al. also reported the aldol reaction of an a-benzyloxy aldehyde with a Danishefsky s diene. The aldol product was transformed to the corresponding HDA-type product through acid-catalyzed cyclization. In these reactions, the catalyst that is claimed to... 

Paulsen, H., Antons, S., Brandes, A., et al. (1999) Stereoselective Mukaiyama-Michael/Michael/Aldol domino cyclization as the key step in the synthesis of penta-substituted arenes an efficient access to highly active inhibitors of cholesteryl ester transfer protein (CETP). Angew. Chem. Int. Ed. 38, 3373-3375. 

Aldehydes undergo a Mukaiyama-aldol reaction followed by a Prins cyclization with the highly reactive allylsilane 329 to afford jy -2,6-tetrahydropyrans 330 that feature an oeo-methylene group at C-4 (Equation 140, Table 12). This Mukaiyama-aldol-Prins (MAP) cascade cyclization has been used to form a key bis-tetrahydropyran intermediate during the total synthesis of leucascandrolide A <2001JA8420>. Similarly, titanium tetrabromide mediated MAP reactions afford 4-bromo tetrahydropyrans <20030L3163>. 

Mukaiyama et al. transformed the Co(II)-catalyzed hydrofunctionalizations (see Sect. 5.7) to intramolecular oxidative alkoxyl radical cyclizations by omission of the silane (Fig. 98). 4-Penten-l-ols 417 (R2=H) cyclized in the presence of 20 mol%... 

Immunosuppressant (-)-FK-S06 (2). This 23-membered lactone-lactam resembles cyclosporin A, a macrocyclic polypeptide, in that they both inhibit immune responses to transplantation, but FK-506 seems to be more active. The total synthesis of (- )-FK-506 has been achieved by a process research group at Merck.1 The cyclization to a carboxamide was carried out with Mukaiyama s reagent (1) under high dilution in 81% yield. The most unusual feature of 2 is the presence of a three-keto sequence at C8, C9, and C,(l (hemiketal). 

Intramolecular Mukaiyama aldol condensation.5 The silyl ketene acetal 1 cyclizes to the tetrahydrofuran 2 in 32% yield on exposure to TiCl4 (1 equiv.) in CH2C12 at 0°. The product is convertible into 3, an analog of cycloleucine. 

A short asymmetric synthesis of the 2-ketocarbacepham (27) involving as the initial step for the preparation of the starting piperidone, a hetero Diels-Alder reaction of the benzylimine derived from the enantiomer of Gamer s aldehyde with Danishesky s diene, has been described <02JOC598>. The key cyclization step to form the bicyclic P-lactam system was achieved from a P-amino acid precursor using the Mukaiyama reagent, 2-chloro-A-methylpyridinium iodide. 

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