Hydroxymethyl complex, synthesis

Ai,A/-bis(hydroxymethyl) formamide [6921-98-8] (21), which in solution is in equiUbrium with the monomethylol derivative [13052-19-2] and formaldehyde. With ben2aldehyde in the presence of pyridine, formamide condenses to yield ben2yhdene bisformamide [14328-12-2]. Similar reactions occur with ketones, which, however, requite more drastic reaction conditions. Formamide is a valuable reagent in the synthesis of heterocycHc compounds. Synthetic routes to various types of compounds like imida2oles, oxa2oles, pyrimidines, tria2ines, xanthines, and even complex purine alkaloids, eg, theophylline [58-55-9] theobromine [83-67-0], and caffeine [58-08-2], have been devised (22). 

Seven procedures descnbe preparation of important synthesis intermediates A two-step procedure gives 2-(HYDROXYMETHYL)ALLYLTRIMETH-YLSILANE, a versatile bifunctional reagent As the acetate, it can be converted to a tnmethylenemethane-palladium complex (in situ) which undergoes [3 -(- 2] annulation reactions with electron-deficient alkenes A preparation of halide-free METHYLLITHIUM is included because the presence of lithium halide in the reagent sometimes complicates the analysis and use of methyllithium Commercial samples invariably contain a full molar equivalent of bromide or iodide AZLLENE IS a fundamental compound in organic chemistry, the preparation... 

Unsymmetric compartmental ligands that allow for the controlled synthesis of unsymmetric Ni2 or heterobimetallic NiM complexes have received particular attention.1876,1892 A wide range of such ligands derived particularly from 2-hydroxy-3-hydroxymethyl-5-methylbenzaldehyde and 2-hydroxy-3-hydroxymethyl-bromo-benzaldehyde has now been prepared and used for Ni com-plexation. These ligands have monopodal iminic pendent arms and either mono- or dipodal aminic pendent arms and the terminal donors of the pendent arms can be provided by pyridine, imidazole, and tertiary amino groups.1893-1897 Complexes are usually prepared by reaction of the requisite Ni11 salts with the preformed ligand. 

Chloromethyl-l,2,4-triazoles can be valuable intermediates in the synthesis of more complex compounds containing a 1,2,4-triazole moiety, and they can be accessed using a number of established methods for the synthesis of the triazole ring system. However, these processes often give variable yields and require much work to construct the starting material. A more convenient procedure has been developed, by which a hydroxymethyl-1,2,4-triazole is converted to the chloromethyl derivative by reaction with thionyl chloride (Equation 20 and Table 6) <2006S156>. 

In connection with the enantioselective alkylation of Pro or 4-hydroxy-proline, the azabicyclo[3.3.0]octane system 81 was obtained after reaction with pivaldehyde (81HCA2704 85HCA155). In a more complex transformation A-protected L-Pro was transformed into the same bicyclic system (Scheme 49) (81JA1851 84JA4192). The product was prepared as a model substance in the total synthesis of pumiliotoxin. A related compound 82 was prepared from 5-(hydroxymethyl)-2-pyrrolidinone (prepared from L-pyroglutamic acid) by an acid-catalyzed condensation with benzaldehyde (86JOC3140). 

Several variants of this useful and novel MCR thiazole synthesis have since been reported, including complexity-oriented syntheses of thiazolo-/> -lactams [18], in which two ring systems and five heavy atom bonds are newly formed (2 C-N, 2 C-S, 1 C-C), solid phase synthesis [19], and a Passerini variant of this reaction leading to 2-hydroxymethyl thiazoles [20], Scheme 3.13 illustrates some of the possibilities [21]. 

Chiral bis(phosphinites) derived from (2/J,51 )-2,5-di(hydroxymethyl)tetrahydrothiophene have been prepared (Equation 73). These ligands have been used in the synthesis of rhodium complexes from Rh(COD)2X (COD = cyclooctadiene X = OTf, SbF6) and tested in the asymmetric hydrogenation of methyl a-acetamidocinna-mate. A maximum of 55% enantioselectivity was observed <19980M4976>. 

Synthetic Applications. (5 )-Dihydro-5-(hydroxymethyl)-2(3H)-furanone (2) was first described in 1971 as an intermediate in the synthesis of o-ribose from r-glutamic acid. Since then, this lactone and its (f )-enantiomer have found widespread use as chirons for constructing a rich variety of natural products ranging from simple pheromones to complex macrocycles and ionophore antibiotics. The chemical manipulation of these chirons often involves lactone cleavage at an early stage, - - as illustrated by the preparation of suitable intermediates for the synthesis of the Vespa orientalis pheromone (R)-S-n-hexadecanolactone (14) (eq 4), the antiviral fungal metabolite brefeldin A (15) (eq 5), and (7aa)-cp/-hemibrevetoxin B (16) (eq 6). ... 

Other water-soluble tertiary phosphines can be used as ligands for the synthesis of hydrogenation catalysts. An example of such a phosphine is l,3>5-triaza-7-phosphaadamantane, which has been prepared by reacting tris(hydroxymethyl) phosphine, formaldehyde, and hexamethylenetetramine (Eq. 35) (111,112). The ruthenium(ll) complex of 1,3,5-triaza-7 phos-... 

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