Efficiency methodology

The hetero Diels-Alder [4+2] cycloaddition (HDA reaction) is a very efficient methodology to perform pyrimidine-to-pyridine transformations. Normal (NHDA) and Inverse (IHDA) cycloaddition reactions, intramolecular as well as intermolecular, are reported, although the IHDA cycloadditions are more frequently observed. The NHDA reactions require an electron-rich heterocycle, which reacts with an electron-poor dienophile, while in the IHDA cycloadditions a n-electron-deficient heterocycle reacts with electron-rich dienophiles, such as 0,0- and 0,S-ketene acetals, S,S-ketene thioacetals, N,N-ketene acetals, enamines, enol ethers, ynamines, etc. 

Tamariz and coworkers [42] have described a versatile, efficient methodology for preparing N-substituted-4,5-dimethylene-2-oxazolidinones 42 (Figure 2.5) from a-diketones and isocyanates and have also studied their reactivity in Diels-Alder reactions. This is a method for synthesizing polycyclic heterocyclic compounds. Some of the reactions of diene 42 are summarized in Scheme 2.18. The nitrogen atom seems to control the regiochemistry of the reaction. 

The discovery that the oxidative coupling of 2-lithiophosphole, obtained from (7a), led to biphosphole (8a) (Scheme 2) was a breakthrough [19], opening the way to oligo(phosphole)s. This very efficient methodology has been... 

The ideas presented in Section III are used to develop a concise and efficient methodology for the compression of process data, which is presented in Section IV. Of particular importance here is the conceptual foundation of the data compression algorithm instead of seeking noninterpretable, numerical compaction of data, it strives for an explicit retention of distinguished features in a signal. It is shown that this approach is both numerically efficient and amenable to explicit interpretations of historical process trends. 

For the delicate transesterification of a p-Lactam intermediate (for carbacephalosphorin skeleton), where originally hydrolysis of methyl ester was done homogeneously and then formation of the benzyl (or substituted benzyl) ester was done separately, Doecke et al. (1991) have devised a mild and efficient methodology using PTC. A dual use of a PT catalyst, Bu4NBr, in one pot was made in a CH2CI2 - H2O system. In the first step 5N NaOH was used, then the pH was adjusted to 7.2 to 7.8 and subsequently benzyl (or substituted benzyl) bromide was added. 

In the same area, a (5)-tryptophan-derived oxazaborolidine including a p-tolylsulfonylamide function has been used by Corey et al. to catalyse the enantioselective Diels-Alder reaction between 2-bromoacrolein and cyclo-pentadiene to form the corresponding chiral product with an unprecedented high (> 99% ee) enantioselectivity (Scheme 5.27)." This highly efficient methodology was extended to various 2-substituted acroleins and dienes such as isoprene and furan. In addition, it was applied to develop a highly efficient total synthesis of the potent antiulcer substance, cassiol, as depicted in Scheme 5.21... 

Johnson, B. G., 1995, Development, Implementation and Applications of Efficient Methodologies for Density Functional Calculations in Modem Density Functional Theory -A Tool for Chemistry, Seminario, J. M., Politzer, P. (eds.), Elsevier, Amsterdam. 

An efficient methodology for the construction of pyrrolizidines and other polycyclic nitrogen heterocycles using a radical domino sequence has been revealed by Bowman and coworkers [46]. These authors employed sulfenamides as substrates, which easily form aminyl radicals by treatment with tributyltin hydride and AIBN. For instance, 3-101 smoothly underwent a twofold 5-exo-trig cyclization to give the tetracyclic pyrrolizidine product 3-105 in 90% yield (Scheme 3.26). As intermediates, the radicals 3-102 to 3-104 can be assumed. 

The enantioselective hydrogenation of a,fj- or / ,y-unsaturated acid derivatives and ester substrates including itaconic acids, acrylic acid derivatives, buteno-lides, and dehydrojasmonates, is a practical and efficient methodology for accessing, amongst others, chiral acids, chiral a-hydroxy acids, chiral lactones and chiral amides. These are of particular importance across the pharmaceutical and the flavors and fragrances industries. 

The application of Heck cyclizations to the synthesis of indoles, indolines, and oxindoles was discovered independently by Mori-Ban s [296-298], and Heck s groups [299]. These investigators found that Pd can effect the cyclization of o-halo-lV-allylanilines to indoles under Heck conditions [300], The cyclization of o-halo-/V-allylanilines to indojes is a general and efficient methodology, especially with the Larock improvements where he cyclized o-halo-W-allylanilines and o-halo-N-acryloylanilides into indoles and oxindoles [301]. For example, the conversion of 279 to 280 can be performed at lower temperature, shorter reaction time, and with less catalyst to give 3-methylindole (280) in 97% yield. Larock s improved conditions, which have been widely adopted, are catalytic (2%) Pd(OAc)2, n-Bu4NCl, DMF, base (usually... 

Mathieu, D., Nony, J., and Phan-Tan-Luu, R. NEMROD (New Efficient Methodology for Research using Optimal Designs) Software, LPRAI, Marseille, France, http //www.nemrodw.com/ (Accessed on January 31, 2008). 

A very efficient methodology for generating carbon radicals utilizes esters of A-hydroxypyridine-2-thione as radical precursors, and these have been used by Blood-... 

Deprotonation at an activated 4-position has been employed extensively in asymmetric synthesis, which is the key step in the Seebach protocol for the preparation of a-alkyl amino acids.The existing alkyl group at the 5-position acts as a directing group for the alkylation and is oriented trans to the new alkyl group (Scheme 8.118). This reaction provides an efficient methodology for normally difficult stereoselective construction of a quaternary chiral center. 

Feringa and co-workers developed an efficient methodology for conjugate addition of dialkylzinc reagents to enones catalyzed by copper(II) and the remarkably versatile chiral monophosphoramidite ligand 27 (Scheme 12.6) [18]. 

In summary, we have described a general, simple and efficient methodology for the synthesis of A r-(/m-butvlsul-finyl)imines by using a heterogeneous polymer-supported catalyst (amberlist-15) under microwave irradiation. This method is useful for the synthesis of A-(fer -butylsulfi-nyl)imines (racemic and chiral) from aromatic as well as aliphatic aldehydes. This method can also be applied for the preparation of A-(ferf-butylsulfinyl)imines on a gram scale. 

Gurjar, M. K. Ravindranadh, S. V. Karmakar, S. Mild and efficient methodology for installation of gem-diallyl functionality on carbohydrate synthons. Chem. Commun. 2001, 241— 242. 

The development of flexible and efficient methodologies to assemble de novo complex molecules endowed with varied substitutions and chiralities, is one of the major concerns of synthetic organic chemistry and this concept is especially pressing when compounds with potential biological activities are involved. 

Several efficient methodologies towards enantiopure carbaaldopyranoses have been reported which exploited diverse natural and synthetic chiral sources [5,25]. 

Driving forces that demand more efficient methodologies for catalyst development include new business opportunities (in all three major application areas of emission control, petroleum conversion, and chemicals), the high cost of empirical developments, and the increasing competitiveness... 

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