Inverse addition protocol

Lithiation of compound 560 with s-BuLi-TMEDA in THF at —78 °C following an inverse addition protocol provided the anion 561. It reacts with primary alkyl iodides and triflates, silyl chlorides, diphenyl disulfide, epoxides, aldehydes, ketones, imines, acyl chlorides, isocyanates and sulfonyl fluorides to yield the expected compounds 562 (Scheme 152). The transmetallation of compound 561 with ZnBr2 allowed the palladium-catalyzed cross-coupling reaction with aryl and vinyl bromides837. When the reaction was quenched with 1,2-dibromotetrafluoroethane, the corresponding bromide 562 (X = Br) is obtained838. 

Among all these new NHC platinum(O) catalysts, (ICy)Pt(dvtms) 15c displays a fest reaction rate while still retaining high selectivity (see Figure 5.4, curve C). Accordingly, it was elected for further optimization. Whereas modifications of several reaction conditions proved fruitless, a simple inverse addition protocol, that is, a slow addition of the silane to the reaction mixture, led to the desired... 

The in situ quench (ISQ) technique [47] involves premixing of a hthium amide base (usually LDA or LTMP) and the electrophile at low temperature before addition of the arene. As soon as the orf/io-lithio anion forms, it can immediately react with the electrophile. The inverse addition protocol is equally productive, that is, a mixture of the arene and the electrophile is treated with a lithium amide base. The electrophile must be either unreactive to or react nondestructively with the lithium amide base, which therefore drastically limits useful base-electrophUe combinations. This concept was introduced by Martin for cyanobenzene deprotonation-sUylation sequences [47]. Low concentrations of aryllithiums lead to increased functional group tolerance. The ISQ technique was extended to a number of electrophiles that are compatible with lithium amide bases, including TMSCl, MejSnCl, B(OiPr)j [125, 126], benzaldehyde, Mel, EtI, and Me S. ... 

When the protocol is applied to allylcarbamates 170, the deprotonation in the presence of (—)-sparteine does not occur with kinetic preference. Indeed, a dynamic resolntion by crystallization takes place. The epimeric allylfithinm componnds 171 and 172 are eqni-librating, whereby one of them crystallizes predominantly. Under optimized conditions, when n-butyllithium is used for the deprotonation and cyclohexane serves as a cosolvent, the preference of the diastereomer 172 leads to snbstimtion products in 90-94% gg393-395 enantioselective homoaldol reaction has been developed based on this protocol Transmetalation of the organolithium into the titaninm compound occnrring nnder inversion of the configuration (172 173) and subseqnent addition to aldehydes leads to... 

Related complexes of group 10 metals are accessible by an oxidative addition/reductive cyclization protocol, exploiting the inverse electron demand (Scheme 27) (Pt <2005JA13494>, Ni <20030M3604>). The nickel complex is thermally unstable, proceeding to perylene via a bimolecular reductive elimination or, in the presence of alkynes, delivering acenaphthylene derivatives by an insertion/reductive elimination pathway. 

In addition, the efficiency of inverse electron demand Diels-Alder reactions with 1,2,4-triazines has been improved to include microwave-activated procedures <07T8286>. The approach allows access to higher reaction temperatures, which results in shorter reaction times. Several highly substituted dihydrofuro- and dihydro-2//-pyranopyridines 25 are produced from alkylnol-substituted triazines 26 in excellent yields via a one-pot cycloaddition/ aromatization protocol. 

The detection of OP compounds by biosensors modified with ChE-ChOx or ChE enzymes relies on an inhibition of catalytic activity of ChE enzymes by OPs. Therefore, it is a drawback of the sensors that the magnitude of the output signal correlates inversely with the concentration of OP compounds in the sample. The protocol in measurements is somewhat complicated because the substrate of ChE has to be added in the sample solution before measurements, resulting in multiple steps needed for OP detection. In addition, inhibition of ChE by OP compounds is usually irreversible and thus reactivation of ChE activity is required for repeated use of the sensors, although this problem can be circumvented by using disposable sensor tips. 

Water, alcohols, hydroperoxides or carboxylates can be added regioselectively to a,/ -unsaturat-ed carbonyl compounds by the oxymercuration demercuration protocol. In this sequence, the oxymercuration step yields the -addition product. Depending on whether the demercura-tion is performed with retention or inversion of configuration, two sets of diastereomeric pairs of enantiomers (racemic mixtures) are obtained. 

Two additional developments that impacted the elaboration of synthesis protocols of proanthocyanidins via catechin (2) and epicatechin (3) derivatives and/or analogues, involved the transformation of readily available and inexpensive catechin (2) into the considerably more expensive epicatechin (3), and the design of experimental conditions permitting 0-benzylation of the phenolic hydroxy groups of flavan-3-ols in high yield. The transformation of catechin (2) into tetra-0-benzylepicatechin (52) (Scheme 7) involved the per-0-benzylation of the phenolic hydroxy groups of catechin (2) to afford tetra-0-benzylcatechin (50) in approximately 20% yield. Inversion of the configuration at C-3 was accomplished by oxidation to the... 

Under these conditions, the levels of ingestion are high when the diets are palatable and only the AMEn is determined. Unlike force-feeding methods, this protocol is not suitable when the feed material is fed alone and poorly or not consumed. Therefore, it is necessary to replace part of the reference diet by an equivalent amount of the feed material to be tested and its ME is calculated by difference, assuming that the values are additive. The levels of incorporation of the feed materials depend on their nature and on their practical conditions of use. For instance, maize can represent 96% of the diet while fats only represent a few %. For this latter type of ingredient, several levels of incorporation are generally used to assess whether there is a synergy between feed materials and to improve the precision, which is inversely proportional to the level of incorporation. 

Fig. 3 Allylstannane addition to a p-alkoxy-aldehyde reported following two protocols, normal" and "inverse. ...

Azide additions to a,P-unsatnrated systems are another method for the preparation of 1,2,3-triazoles. Cydoaddition of aryl azides to a,P-unsaturated aldehydes 88 in the presence of catalytic diethylamine and DBU afforded 1,4-disubstituted-l,2,3-triazoles 89 via an inverse electron-demand process (13CC10187). Michael addition of sodium azide with ethyhdene bisphospho-nates 90 in cydoaddition reactions via sonication afforded bisphosphono-1,2,3-triazoles 91 (13T4047).A one-pot protocol for the synthesis of 1,2,3-triazoles was prepared from unactivated alkenes with azidosulfenylation of the carbon-carbon double bond followed by the copper-catalyzed azide—alkyne cycloaddition (13JOC5031). 1,5-Disubstituted-l,2,3-triazoles 93 were synthesized from enamides 92 with tosyl azide (13AG(E)13265). Reaction of ethyl 3-(alkylamino)-4,4,4,-trifluoro-but-2-enoates 94 with mesyl azide in the presence of DBU afforded l,2,3-triazole-4-carboxylates 95 (13EJ02891). 

This expression is referred to as Boltzmann inversion, and it is the starting point to build several CG potentials. The main issue related to this approach is that the statistical distributions of different CG parameters are not uncorrelated. Therefore, it is not possible to use additive potential of mean forces derived tout-court from the Boltzmann inversion for the different variables of interest to build a CG potential without introducing significant bias. Separation oigenuine contributions from spurious one can be rigorously obtained by the iterative Boltzmann inversion procedure as introduced by Reith et al In this protocol, one starts from an initial potential of mean function Ui, which will generate a probability distribution for the parameter equal to i(9- The potential is then iteratively corrected according to the formula ... 

This method has also been extended to the synthesis of mono(benzaimulated) spiroacetals [139, 140] (Scheme 66). For both the threo and erythro glycal-deiived epoxides, the retention spiroacetals 265a and 266b could be obtained selectively using the Ti(Oi-Pr)4 protocol. The inversion spiroacetals 265b and 266a could be accessed upon addition of MeOH or AcOH to the reaction mixture however, the selectivity was much lower. 

---