Mukaiyama’s salt

Scheme 22 Stereoselective synthesis of P-lactams using Mukaiyama s salt...

Delpiccolo CML, Fraga MA, Mata EG. An efficient, stereoselective solid-phase synthesis of lactams using Mukaiyama s salt for the Staudinger reaction. J. Comb. Chem. 2003 5 208-210. 

A closely related method, which often gives higher yields, involves treatment of the hydroxy acids with 1-methyl- or l-phenyl-2-halopyridinium salts, especially l-methyl-2-chloropyri-dinium iodide (Mukaiyama s reagent).6 3 Another method uses organotin oxides.644... 

Colombo et al. tested the hydroxypyrroHdine 8 as well as its 0-methylated derivative with -BuLi and PhCHO in a ratio of 3 2 1 [39]. In analogy to Mukaiyama s results, protic 8 gave in dimethoxymethane a higher optical purity [36% of (k)-l-phenyl-1-pentanol] than its aprotic dimethyl ether derivative in hexane [15% of (S)-l-phenyl-l-pentanol]. Salt impurities (e.g.,Lil, LiC104) were foimd to decrease the enantioselectivities. 

This reaction was first reported by Breckpot in 1923. It is the synthesis of )0-lactam via the cyclization of esters of /3-amino acids with Grignard reagent and is known as the Breckpot -lactam synthesis. This reaction has been modified to form )0-lactam by the treatment of )0-amino acid with Mukaiyama s reagent, or the /3-amino ester with /V-methyl pyridinium salt." ... 

This reaction has been modified by using Mukaiyama s reagent or A/ -methyl pyridinium salt" to convert the jS-amino acids into )0-lactams. 

Stereoselectivities of 99% are also obtained by Mukaiyama type aldol reactions (cf. p. 58) of the titanium enolate of Masamune s chired a-silyloxy ketone with aldehydes. An excess of titanium reagent (s 2 mol) must be used to prevent interference by the lithium salt formed, when the titanium enolate is generated via the lithium enolate (C. Siegel, 1989). The mechanism and the stereochemistry are the same as with the boron enolate. 

Aldol and Related Condensations As an elegant extension of the PTC-alkylation reaction, quaternary ammonium catalysts have been efficiently utilized in asymmetric aldol (Scheme 11.17a)" and nitroaldol reactions (Scheme ll.lTb) for the constmction of optically active p-hydroxy-a-amino acids. In most cases, Mukaiyama-aldol-type reactions were performed, in which the coupling of sUyl enol ethers with aldehydes was catalyzed by chiral ammonium fluoride salts, thus avoiding the need of additional bases, and allowing the reaction to be performed under homogeneous conditions. " It is important to note that salts derived from cinchona alkaloids provided preferentially iyw-diastereomers, while Maruoka s catalysts afforded awh-diastereomers. 

Kobayashi et al. studied the catalytic activity of many metal salts in Mukaiyama-aldol reactions in aqueous THE They came to the conclusion that the catalytic activity of a metal in aqueous media should be related both to the hydrolysis constant, /Ch, and water exchange rate constant (WERC) of the metal [8]. All metals with good catalytic activity had p/Ch values ranging between 4.3 and 10.08 and WERC > 3.2 X 10 s This was because when for a metal is < 4.3, the metal cation is readily hydrolyzed to generate oxonium ion, which then helps the decomposition of the silyl enol ethers. When pMh > 10.08 the Lewis acidity of the metal is too low to promote the reaction. When the WERC is < 3.2 x 10 m s, exchange of water molecules seldom occurred and aldehydes had a very little chance to coordinate to the metal to be activated. The metals which fulfill these criteria are Sc(III), Fe(II), Cu(II), Zn(ll), Y(IIl), Cd(Il), Ln(Ill) and Pb(ll). 

Mukaiyama proposed an oxotitanium reagent 191 (Figure 4.6) in the presence of triflic anhydride [423] and diphenyltin sulfide with trifiic anhydride [424] for the synthesis of (3-ribofuranosides. The addition of LiC104 to the latter promoter system resulted in the formation of a-ribofuranosides [424]. Mukaiyama and coworkers [344] also reported the use of diphenyltin sulfide with silver salts such as AgC104, or Lawesson s reagent 150 in combination with silver salts. 

Mukaiyama, T, Suda, S, Diphosphonium salts as effective reagents for stereoselective synthesis of 1, 2-cA-ribofuranosides, Chem. Lett., 1143-1146, 1990. 

Mukaiyama and co-workers have pioneered many routes to the total s)uitheses of rare carbohydrates such as the 2-amino-2-deoxypentoses. In 1982 they reported that the potassium enolate derived from the magnesium salt of a (R)-atrolactic acid derivative adds to... 

A differently anchored Mukaiyama reagent is the N-methylpyridinium iodide salt 57 [71], which has been obtained by reaction of the Merrifield resin with N-Boc-aminocaproic acid in the presence of cesium carbonate to give the supported ester 55 (Scheme 7.19). Further Boc-deprotection and reaction with 6-chloronicoti-noyl chloride in the presence of Hxinig s base furnished the anchored 2-chloro-pyridine 56, which was transformed into the final N-methylpyridinium salt 57 after N-methylation in neat methyl iodide. This supported reagent has been used in the rapid microwave-assisted esterification of carboxylic acids and alcohols in the presence of triethylamine as base, with dichloromethane as solvent at 80 °C, the products being obtained in high purity after simple resin filtration [72],... 

A soln. of the startg. sulfonium salt in abs. ethanol added dropwise with icecooling to a stirred mixture of ethyl acetoacetate and Na-ethoxide in abs. ethanol, and the product isolated after 5 hrs. -> 9-ethoxycarbonyl-8-methyl-7-oxabicyclo-[4.3.0]-8-nonen-5-one. Y 91-98%. F. e. s. T. Mukaiyama, T. Adadii, and T. Kumamoto, Bull. Chem. Soc. Japan 44, 3155 (1971) furans from 2-acetylenesulfo-nium salts cf. J. W. Batty, P. D. Howes, and C. J. M. Stirling, Soc. Perkin I 1973, 65. 

Mukaiyama-Michael Reactions. 1,4-Addition of ketene alkyl silyl acetals to a./S-unsaturated carbonyl compounds (eq 10) is promoted by a variety of Lewis acids (for example, TiCU, Ti(OR)4, SnCU, trityl perchlorate, lanthanide salts, Al-montmo-rillonite clay), or Lewis bases such as fluoride ion (eq 11), or quaternary ammonium carboxylates. Lanthanide salts are particularly effective catalysts, and in the case of ytterbium(III) tri-fluoromethanesulfonate, the catalyst can be recovered (eq 10). ... 

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