Stereospecific transformations

In a Kumada-Corriu reaction, an aryl halide is oxidatively coupled with a homogeneous nickel(ll)-phosphine catalyst [2], This species reacts with a Grignard reagent to give biaryl or alkylaryl compounds. Later, palladium-phosphine complexes were also successfully applied. By this means, stereospecific transformations were achieved. 

It may be of interest to note that the stereospecific transformation shown in equation 15 has been cited as the first reported observation of an 1 - 3 chirality transfer. It is evident that on rearrangement of optically active 6d to 7d, the chiral center at C-a is eliminated and a new one created at C-y. The term self-immolative asymmetric synthesis has also been used to describe syntheses of this kind. As pointed out by Hoffmann , quantitative 1 - 3 chirality transfer will follow from the suprafacial - course of rearrangement, provided the reactant has a uniform configuration at the j8, y-double bond. This stereochemical prediction has also been confirmed by the results obtained in several other [2,3]sigmatropic rearrangements, subsequently reported " . 

It is important to select stoichiometric co-reductants or co-oxidants for the reversible cycle of a catalyst. A metallic co-reductant is ultimately converted to the corresponding metal salt in a higher oxidation state, which may work as a Lewis acid. Taking these interactions into account, the requisite catalytic system can be attained through multi-component interactions. Stereoselectivity should also be controlled, from synthetic points of view. The stereoselective and/or stereospecific transformations depend on the intermediary structure. The potential interaction and structural control permit efficient and selective methods in synthetic radical reactions. This chapter describes the construction of the catalytic system for one-electron reduction reactions represented by the pinacol coupling reaction. 

The thiophene endoperoxide (18) is a powerful episulfidation reagent. The stereospecific transformation of cis- or trani-cyclooctene suggests a concerted process. First-order consumption kinetics have now shown that (18) is not itself the active -transfer reagent two such intermediates are proposed, possibly oxathiiranes such as (19) or (20), based on similarities in the trends for epoxidations of the same substrate by DMDO. ... 

Selectivity and Stereochemistry. An important property of transition-metal complexes is that they coordinate groups in a specific manner permitting high regio-and stereoselectivity in the catalytic reaction. The migratory insertion step is a highly stereospecific transformation. The four-center transition state 16 illustrated for the Wilkinson catalyst requires a coplanar arrangement of metal, hydride, and alkene n bond ... 

Select reaction conditions that would allow you to carry out each of the following stereospecific transformations ... 

The classical tin-lithium exchange reaction was first applied to cyclopropanes in the stereospecific transformation of 7-ewrfo-bromo-7-ex o-trimethyltinnorcarane to the corresponding 7-exo-lithio compound with BuLi in THF, at -95 °C (vide supra)10. The retention of configuration in cyclopropyl tin-lithium exchange reactions has also been confirmed in monocyclic 2-metallacyclopropane carboxamides60. More recently, this metal exchange reaction was used for the preparation of sensitive methylenecyclopropanes (equation 21)61. 

The bromonium ion concept was quickly used by other investigators to account for stereospecific transformation of alkenes, notably by Winstein and Lucas, but... 

A wide variety of enzyme controlled stereospecific transformations are known. These transformations include oxidations, reductions, reductive animations, addition of ammonia, transaminations and hydrations. In each case the configuration of the new asymmetric centre will depend on the structure of the substrate. However, substrates whose reactive centres have similar structures will often produce asymmetric centres with the same configuration. Enzyme based methods are economical in their use of chiral material but suffer from the disadvantage that they can require large quantities of the enzyme to produce significant quantities of the drug. 

One example of a cyclobutyllithium (36) appears to indicate configurational stability. However, the stereospecific transformation of 35 to 37 could equally be explained by thermodynamic stabilisation of one epimer of an otherwise configurationally unstable organolithium.24... 

We have said little in this chapter about the stereospecific transformation of one ring into another but we now have an opportunity to remedy that defect. Iodolactonization of a terminal alkene with a stereogenic centre next to it is as stereoselective as (if not more than) the example we have just seen. The two side chains on the ring end up trans to one another as we should expect. This is a purely stereoselective process as the alkene has no geometry. 

It is important that you note the link between the OSO4 reaction and the stereospecific transformations that we highlighted at the beginning of Chapter 34. in particular, you now know ways to add two hydroxyl groups both syn... 

The stereospecific transformation of oxiranes on exposure to organoaluminium amides under mild conditions has been described." " Isomerization of tram-epoxycyclododecane has been investigated with dialkylaluminium 7V,A -dialkyl-amides of various compositions (Eq. 116)." ... 

Alkenyl, Alkynyl, Aryl and Heteroaryl Acids. Treatment of readily accessible (E)- and (Z)-alkyl and aryl substituted vinyl boronates (196) with triethyl phosphite in the presence of lead diacetate results in their stereospecific transformation into (E)- and (Z)-vinylphosphonates (197) (Scheme 53). ° Palladium acetate catalysed Mizoroki-Heck reaction of arylboronic acids (198) with diethyl vinylphosphonates (199) is an effective synthetic approach to... 

BINAP is a new type of fully aryl-substituted dlphosphine with only an axial element of chirality. Optically pure BINAP was first synthesized by the optical resolution of (l)-BINAP using optically active d1-iJ-chlorob1s[(S)-N,N-dimethyl-a-phenylethylam1ne-2C,N]d1pallad1um. The phosphine Is also obtained by stereospecific transformation of optically active 2,2 -d1bromo-l,l -binaphthyl The procedure outlined here, however, is the best preparative-... 

The Shaipless asymmetric epoxidation reaction is often used as a key step in synthetic protocols involving the synthesis of natural products such as terpenes, carbohydrates, insect pheromones, and pharmaceutical products. The SAE reaction is characterized by its simplicity and reliability. The epoxides are obtained with predictable absolute configuration and in high enantiomeric excess (ee). Moreover, 2,3-epoxy alcohols serve as versatile intermediates for a host of stereospecific transformations. 

Furthermore, the stereospecific transformation of (R)-3-(p-ZerZ-butylphenylthio)-cyclohexan-l-one, obtained in optically pure form by recrystallization, into cyclohexanol derivatives was achieved by employing several common reducing reagents. The results are summarized in Table 20... 

The use of substrate control in rhodium catalyzed C H aminations is covered in detail in Espino and Du Bois recent review of rhodium catalyzed oxidative amina tion [51]. A brief summary of relevant material is provided here, leading to a discussion of recent advances in the synthesis of chiral amines from achiral substrates. Rhodium catalyzed C H amination proceeds via a concerted insertion process rendering it a stereospecific transformation. Thus, the appropriate choice of an enantioenriched starting material can facilitate the synthesis of enantioenriched amines, which would often be particularly difficult to access in any other manner. As exemplified in Scheme 12.9, the C H insertion reaction of enantiomerically pure carbamate 9 was accomplished with complete retention of configuration providing the chiral oxazolidinone 10 in greater than 98% ee [13]. 

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