Mukaiyama reagent, and

Figure 1 Rates of Guanidinylation of Benzylamine with iV -Bis(tert-butoxycarbonyl)-S-methylisothiourea ( ), iV,iV -Bis(te/r-butoxycarbonyl)pyrazole-l-carboximidamide ( ), Ai,Ai -Bis(tert-butoxycarbonyl)thiourea in the Presence of the Mukaiyama Reagent ( ), and l,3-Bis(tert-butoxycarbonyl)-2-triflylguanidine ( )...

Reagents such as 1 are coined Mukaiyama reagents and have demonstrated a great deal of synthetic versatility by converting carboxylic acids and alcohols into esters, amides, lactones, lactams, thiol esters, acid fluorides, olefins, allenes, carbodiimides, isocyanates, isothiocyanates, and nitriles.1... 

The racemic bicyclic -lactone 246 is obtained in 68 % yield on treatment of the acid chloride 245 with three equivalents of A -methyl-2-chloropyridine (Mukaiyama reagent) and four equivalents of triethylamine at room temperature. ... 

Scheme 15 Parallel synthesis of 2-oxazolines from carboxylic acids and aminoalcohols using PS-Mukaiyama reagent...

Entries 5 to 9 illustrate some of the modified reagents and catalytic procedures. Entry 5 uses a phosphine-stabilized reagent, whereas Entry 6 includes BF3. Entry 7 involves use of TMS-C1. Entries 8 and 9 involve cyanocuprates. In Entry 9, the furan ring is closed by a Mukaiyama-aldol reaction subsequent to the conjugate addition (Section 2.1.4). 

Mukaiyama, Shiina and co-workers used a reagent generated by L1AIH4 reduction of a low-valent titanium derived... 

Hirashita, T. Kamei, T. Horie, T. Yamamura, H. Kawai, M. Araki, S. Preparation of y-het-erosubstituted allylindium and diindium reagents and their reactions with carbonyl compounds./. Org. Chem. 1999, 64,172-177. Yamaguchi, M. Mukaiyama, T. The stereoselective synthesis of d- and L-ribose. Chem. Lett. 1981, 1005-1008. 

In 1973 Mukaiyama, Tyrlik, and McMurry discovered a remarkably simple reaction that couples aldehydes or keto compounds reductively to olefins [1, 2]. This methodology following eq. (1) differs from that of Section 3.2.10 in that no extra methylene or alkylidene transfer reagent is required. The stereochemistry of the product depends on the nature of the substituents R and whether an open-chain or a cyclic olefin results. 

To a solution of the acid (300 mg, 1.1 mmol) in CH2CI2 (5 mL) was added 2-chloro-1-methyl-pyridinium iodide (the Mukaiyama reagent, 330 mg, 1.3 mmol) and the aniline (1.29 g, 5.89 mmol). The mixture was heated at reflux for 1 h and then allowed to cool. EtsN (0.30 mL, 2.2 mmol) was added, and the mixture was heated at reflux for an additional 20 h, allowed to cool, poured into water (40 mL), and extracted with CH2CI2 (3 x 20 mL). The combined organic extracts were dried, filtered, and concentrated. The crude material was purified by column chromatography (25% EtOAc in hexanes) to furnish the amide (387 mg, 75%). 

Polymer supported pyridinium salts, such as Mukaiyama reagent, have proven very useful synthetic tools in the preparation of 2-oxazoline libraries 05JC0688> and in automatable esterification reactions <05TL2817>. Yamamoto et al. have examined the use of polymer supported boronopyridinium salts for the preparation of amides and esters in good to excellent yield <050L5043,05TL5047>. 

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],... 

Although Mukaiyama reagent is commonly referred to as 1, 2-halo-benzoxazolium and benzothiazolium (7 and 8, respectively) species are also referred to as Mukaiyama... 

A variety of specialized reagents have been developed for macrolactonization reactions. Two of the more important are the Corey-Nicolaou reagent, 2,2 -dipyridyl disulfide (232)10 jjjg Mukaiyama reagent, which is 2-chloro-l-methylpyridinium iodide (233). A number of related reagents have been developed, including imidazole disulfide 234 [2,2 -dithio-(4-ferf-butyl-l-isopropylimidazole)]l 2 and imidazole 235 [N-(trimethylsilyl)imidazole].l 3 All of these reagents are effective for the cyclization of co-hydroxy acids, as shown in Table 6.1. For comparison, available cyclization results with DEAD and 234 are included. In this table, a hydroxy acid is converted to a lactone (219). 

The activation of the carboxylic acids can be achieved also with the Mukaiyama reagent (2-chloro-l-methylpyridinium iodide, see p 308). Carboxylic acids react with this reagent, tri- -propylamine and imines in dichloromethane to give azetidin-2-ones [9]. 

The first use of a polymer-supported Mukaiyama reagent for microwave-mediated synthesis of amides was presented in 2004 [125]. To prove its effectiveness, even in difficult coupling reactions, it was used in the microwave-accelerated synthesis of an amide from sterically hindered pivalic acid (Scheme 16.83). The mixture was subjected to microwave irradiation at 100 °C for 10 min and the desired product was obtained in 80% yield. 

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