Soft moiety

This is not to say that there are no SHAB problems of donor-acceptor incompatibility. Several groups have adopted the strategy of synthesizing ligands that have hard and soft moieties, such as (8). For example, Fryzuk and coworkers use ligands with a hard center to anchor to the hard metal, in this case Zr or Hf enabling the phosphorus chelating moieties to form a stable complex (9). 

The thermal silicon-Pummerer rearrangement (41,42) leads to a more compatible partnership among the various hard and soft moieties of the molecules. 

Ferrocen-l,l -diylbismetallacycles are conceptually attractive for the development of bimetal-catalyzed processes for one particular reason the distance between the reactive centers in a coordinated electrophile and a coordinated nucleophile is self-adjustable for specific tasks, because the activation energy for Cp ligand rotation is very low. In 2008, Peters and Jautze reported the application of the bis-palladacycle complex 56a to the enantioselective conjugate addition of a-cyanoacetates to enones (Fig. 31) [74—76] based on the idea that a soft bimetallic complex capable of simultaneously activating both Michael donor and acceptor would not only lead to superior catalytic activity, but also to an enhanced level of stereocontrol due to a highly organized transition state [77]. An a-cyanoacetate should be activated by enolization promoted by coordination of the nitrile moiety to one Pd(II)-center, while the enone should be activated as an electrophile by coordination of the olefinic double bond to the carbophilic Lewis acid [78],... 

ABA-type triblock copolymerization of MMA/BuA/MMA should give rubberlike elastic polymers. The resulting copolymers should have two vitreous outer blocks, where the poly(MMA) moiety (hard segment) associates with the nodules, and the central soft poly(BuA) elastomeric block provides rubber elasticity. Ihara et al. [35] were the first to synthesize an AB-type block copolymer, with MMA (190 equivalents of initiator) first polymerized by... 

A polymeric structure is also observed in the adduct LE 2I2 (LE = 4,5-6z s(bromomethyl)l,3-dithiole-2-thione). LE-I2- I2 bent-shaped units, which are typical in discrete extended spoke adducts with 1 2 (LE/I2) stoichiometry, are joined head-to-tail by soft-soft I- -I interactions involving the terminal iodide atom of the LE-I2 moiety and the terminal iodide atom of the second coordinated di-iodine molecule.37... 

In general, Pd-catalyzed allylic substitutions with soft nucleophiles involve nudeophilic attack directly on the allyl unit, on the opposite face to that occupied by the metal. This is contrasted with the situation for hard nucleophiles where the initial attack occurs at the metal, with subsequent migration of the nudeo-phile to the allyl moiety - the addition to the allyl unit therefore occurring from the same face as the metal. Obviously, this has profound implications on the stereochemical outcome. 

Soft fi-blockers have a particular therapeutic role to play, accounting for the amount of attention they have received. For example, a comprehensive study of ca. 80 analogues of general structure 7.64 has established the in vitro and in vivo activity of many of these compounds and confirmed that their enzymatic hydrolysis is highly sensitive to structural effects [137]. Here, the labile moiety is incorporated into the side chain, with the consequence that hydrolysis destroys the pharmacophore. 

It seems logical that these reactions are mechanistically related. In every case reported to date, the relative stereochemistry between the nucleophile and alcohol moiety is trans, indicating anti addition in the ring-opening event. Lautens and coworkers suggest a syn insertion of the rhodium to form the allyl rhodium alkoxide. Anti addition of the soft nucleophile, with possible initial protonation of the... 

Enamine nucleophiles react readily with soft conjugated electrophiles, such as a, 3-unsaturated carbonyl, nitro, and sulfonyl compounds [20-22], Both aldehydes and ketones can be used as donors (Schemes 27 and 28). These Michael-type reactions are highly useful for the construction of carbon skeletons and often the yields are very high. The problem, however, is the enantioselectivity of the process. Unlike the aldol and Mannich reactions, where even simple proline catalyst can effectively direct the addition to the C = O or C = N bond by its carboxylic acid moiety, in conjugate additions the charge develops further away from the catalyst (Scheme 26) ... 

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