Multistep procedures

In the presence of a large excess of PH, primary phosphines, RPH2, are formed predominantiy. Secondary phosphines, R2PH, must be either isolated from mixtures with primary and tertiary products or made in special multistep procedures. Certain secondary phosphines can be produced if steric factors preclude conversion to a tertiary product. Both primary and secondary phosphines can be substituted with olefins. After the proper selection of substituents, mixed phosphines of the type RRTH or RR R T can be made. 

In spite of the good yields of L-foUc acid obtained in this reaction, all of the pubHshed methods for the synthesis of 6-bromomethylpterin (20) are multistep procedures with low overall yields (33—36). For example, the route starting from 2,4,5,6-tetraanainopyrimidine [5392-28-9] (21) gave 6-bromomethylpterin (20) in three steps with an overall yield of only 18% (33,35,36). This synthesis is not economical because the intermediate 6-bromomethyl-2,4-diamino-4-pterin (22) has to be deaminatedin an additional step to form 6-bromomethylpterin (20). 

A third approach for the synthesis of 6-formylpterin (23) starts from iminodipropionitrile [2869-25-2] (27). The intermediate pyra2ine (28) is also prepared starting from chloropymvaldehyde oxime (41,42). The required formylpterin (23) is obtained in three steps in 71% yield, starting from the intermediate pyra2ine (28). A few other routes for the synthesis of 6-formylpterin (23) are described in the Hterature. AH are multistep procedures with only moderate overall yields (43—45). 

Dendrimers have structures similar to that of hyperbranched polymer and can be taken as the perfectly branched polymer with monodispersity. However, they need to be prepared by a multistep procedure. Therefore, very little work has been done on dendritic polyfarylcnc ether)s. Morikawa et al. prepared a series of monomers with a various number of phenylene units.164,165 These monomer were used to prepare poly(ether ketone) dendrons with graded structures (Scheme 6.24). 

Previously published methods for electrophilic bromination of isoquinoline"" lead to mixtures of isomers only separable with difficulty, use expensive additives or large excesses of reactants, or involve multistep procedures. 

Recently a novel chiral ferrocene-based amidinato ligand and its rhodium complexes have been described. The chiral N,N -bis(ferrocenyl)-substituted formamidine (N,N -bis[(S)-2- (lR)-l-(diphenylphosphino)ethyl ferrocen-l-yl]for-mamidine was prepared from commercially available (IR)-l-(dimethylamino) ethyl ferrocene by a multistep procedure in an overall yield of 29%. Deprotonation of the ligand with -butyllithium followed by addition of [RhCl2(COD)2] as illustrated in Scheme 167 yielded the corresponding (formamidinato)rhodium(l)... 

The much more stable MIL-lOO(Cr) lattice can also be impregnated with Pd(acac)2 via incipient wetness impregnation the loaded catalyst is active for the hydrogenation of styrene and the hydrogenation of acetylene and acetylene-ethene mixtures to ethane [58]. MIL-lOl(Cr) has been loaded with Pd using a complex multistep procedure involving an addition of ethylene diamine on the open Cr sites of the framework. The Pd-loaded MIL-lOl(Cr) is an active heterogeneous Heck catalyst for the reaction of acrylic acid with iodobenzene [73]. 

Enantiomerically pure cyclam-type ligands derived from L-proline have been prepared via multistep procedures and shown to form complexes of Ni11, e.g., (593).1508 The Ni11 ion in (594) is encapsulated by a face-to-face bis(macrocyclic) ligand that forms upon treatment of [Ni(tren)2]2+ with formaldehyde.1509... 

A multistep procedure that defines how a phenome is constructed, not what a phenome is to look like. 

The synthesis of a bridgehead sulfonium salt analogue 59, of the naturally occurring glycosidase inhibitor castanospermine, proceeded by a multistep procedure starting from 5-thio-d-glucopyranose pentaacetate <2000JA10769>. The desired bicyclic sulfonium salt 57 could not be obtained from the key bromide precursor... 

A complex naturally occurring amino acid 5-hydroxypiperazic acid (5HyPip) 100 was prepared by a multistep procedure that included Diels-Alder addition of 2,4-pentadienoic acid to phthalazinedione 83a as a first step (Scheme 24). Adduct 97 was esterified and oxidized with mercuric acetate to 98, which on hydrogenation over rhodium on alumina and subsequent hydrolysis provided a mixture of enantiomers from which the required enantiomer 99 was obtained by resolution with quinine. Its hydrazinolysis provided 100 [71JCS(C)514 77H119],... 

However, this multistep procedure is experimentally complex. A simpler variation described in 199127 consists of the reaction of an aldehyde and a nitro compound in the presence of triethylamine, TBAF and tert-butyl-dimethylsilyl chloride. Under these conditions, nitro sugars are obtained in good yieds and higher diastereoselectivities than those afforded by the standard conditions. This procedure was used in several synthesis of 2-nitro-2-deoxyaldoses, as for the condensation of l,l-diethoxy-2-nitroethane and l,2 3,4-di-0-isopropylidene-a-D-galacto-hexodialdo-l,5-piranose.28 More recently, it was applied to the addition of ethyl nitroacetate to the D-glucose derived aldehyde 18, to give nitro sugar derivatives 26, key precursors of polysubstituted cyclohexane a-amino acids (Scheme 10).29... 

Addition of l,3-bis(methylthio)allyllithium to aldehydes, ketones, and epoxides followed by mercuric ion-promoted hydrolysis furnishes hydroxyalkyl derivatives of acrolein5 that are otherwise available in lower yield by multistep procedures. For example, addition of 1,3-bis-(methylthio)allyllithium to acetone proceeds in 97% yield to give a tertiary alcohol that is hydrolyzed with mercuric chloride and calcium carbonate to saturated aldehyde.8 Similarly, addition of l,3-bis(methylthio)allyl-lithium to an epoxide, acetylation of the hydroxyl group, and hydrolysis with mercuric chloride and calcium carbonate provides a 5-acetoxy-a,/ -unsaturatcd aldehyde,6 as indicated in Table I. Cyclic cis-epoxides give aldehydes in which the acetoxy group is trans to the 3-oxopropenyl group. 

Although convection, axial diffusion, and radial diffusion actually occur simultaneously, a multistep procedure was adopted in the finite-difference calculation. For each 5-cm increment in tidal volume and for each time increment At, the differential mass-balance equations were solved for convection, axial difihision, and radial diffusion in that order. This method may slightly underestimate the dosage for weakly soluble gases, because the concentration gradient in the airway may be decreased. 

The extracellular matrix of mammalian tissue is composed of a complex mix of constitutive proteins. This matrix must be broken down to recover single cells effectively for culture and/or staining (1). Tissue dissociation and its affiliated problems were described and defined over 80 yr ago by Rous and Jones (2). More recent reviews (3,4) have revealed newer methods for creating single-cell suspensions. Numerous procedures exist for dissociating solid tumors. They are usually multistep procedures involving one or a combination of mechanical, enzymatic, or chemical manipulations. Ideally, the dissociation protocol is individualized for the tissue of interest and evaluated relative to both optimal and representative cell yield. 

The key step employed a rhodium(l)-catalysed allenic Pauson-Khand reaction to generate the tricyclic ring system 276 from the allenyne 275. However, all attempts to introduced the missing methyl group by a 1,4-addition protocol failed to provide the completed neodolastane framework. Allenyne 275 was synthesized from the enone 274 by a multistep procedure. The quaternary atom was constructed by sequential enolate alkylations. 

Hoping to improve or to shorten our total synthesis of L-daunosamine, we explored the following reactions with 112 and 113, the adducts of the racemic 7-oxanorbomene derivative 47 + 48 to PhSeCl and PhSCl, respectively. Saponification of 112 and 113, followed by treatment with formalin, afforded ketones 114 and 115, respectively. Treatment of with tributyltin hydride in toluene/benzene (AIBN 1 - 2%, 80 °C) gave the key intermediate ( )-I03 in 69 % yield. Under the same conditions, 115 was reduced to ( )-I03 in 40 - 45 % yield. Raney nickel reduction of 115 afforded ( )-103 in 50 % yield together with 40 % of ( )-7-oxabicyclo[2.2.1]heptan-2-one. However, we found the multistep procedure 32 100 101 102 103 easier to scale up. Several intermediates in our synthesis do not have to be isolated. For instance, transfomation of 32 into 102 can be carried out in the same pot in 94 % yield. 

Cosford et al. [60] have used a commercial Syiris Africa system [14] to S3mthe-size a library of 1,2,4-oxadiazoles (Scheme 27). By a multistep procedure using connected microreactors in a single sequence, the procedure was performed in an efficient way the intermediate product purification was avoided and the reaction time was considerably reduced from several days to 30 min. 

Similar to the furobenzazepine derivatives (Scheme 17, Section 2.1.2), thieno benzazepines 96 and 97 (X = S) were synthesized in good yields by a multistep procedure involving in situ generation of azomethine imines from thiene-3-carbaldehyde and A/ ,N -disubstituted hydrazines followed by cycloaddition to... 

The procedure for synthesizing sulfanilamide (a sulfa drug) is a multistep procedure as illustrated in Figure 13-50. The first step also works if you substitute an acyl chloride for the acid anhydride. The conversion of the amine to an amide converts the strong activator into a medium activator, limiting multiple attacks. The last step converts the amide back into an... 

Biologists and life scientists have developed a tradition of fitting and extracting the rate constants of the M-M equation with a multistep procedure, as follows... 

Lobanov et al. electroplated curium (ultimately converted to Cm02) in a series of electrodeposition steps from solutions of curium nitrate in isobutanol [158]. The electrochemical setup consisted of a Ti foil cathode, Ti or At foil anode, potential difference of 600 V, and a plating time of 10-15 min for each plating step. Between each deposition step the deposited curium was converted to Cm02. The multistep procedure allowed targets of curium with the desired thickness (300-400 pg cm ) to be obtained with a deposition yield of no less than 90%. Ramaswami and coauthors electroplated curium from isopropanol solution [159]. A 100 pL aliquot... 

Technology for bonding to dentin is currently going through significant changes and critical controversy. The current systems rely on a multistep procedure. Generalization of these procedures follow. 

By following this multistep procedure, the kinetics were evaluated on a wide range of data (both conditions and feedstock) not used in the parameter estimation. The start-of-cycle kinetics were extended to other catalysts and catalyst states by defining an appropriate catalyst state vector (a = aD, al5 a , ac), which is different from 1 at the start of cycle. A catalyst characterization test was developed to estimate parameters for new catalysts. 

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