Strategy slow-addition

This reductive Heck reaction has become a useful tool in cyclization reactions for complex molecule synthesis. In his protecting group free synthesis of ambiguine H (119), Baran successfully applied this strategy. Slow addition of Herrmann s catalyst 91 to substrate 117 provided intermediate 118 in a reliable 65% yield. This chemistry proved both robust and scalable, providing gram quantities of 118. 

An allylic halide has been used to give a better result than the corresponding allylic acetate (Scheme 8E.21) [134]. Notably, only 0.05 mol% of catalyst was sufficient to produce the enantiopure product in 96% yield. To achieve high enantioselectivity, the reactivity of the substrate had to be modulated by slow addition of the nucleophile, This deracemization strategy offers an efficient alternative method for the preparation of hydroxylactone, which has served as a synthetically useful building block for various natural product syntheses [135,136]. 

An analogous strategy was applied for annelation of ring D in Kuehne s syntheses of 20-epi- ((/-vincadifformine (96) and yz-vincadifformine (97). Upon slow addition of n-BujSnH and AIBN via syringe pump to the phenylselenyl ether 94,20-epi- vincadifformine (96) and vincadifformine (97) were formed in a 1 2 ratio. The separated products did not epimerize under the reaction conditions, indicating a facial preference in the hydrogen transfer to the pentacyclic radical intermediate 95. The ethyl substituent blocked 5-exo-trig cyclization. 

Another strategy for positioning a catalytic center across the entrance of a conical cavity is to employ a cavitand functionalized at one entrance by a pendent chelate arm (Scheme 13.16). Enantioselective epoxidations of aromatic alkenes was realized with catalysts 62, 63, and 64, 65, although the enantioselectivity remained modest [46]. (For experimental details see Chapter 14.13.11). The reaction requires the slow addition (over 1 h) of a solution of alkene 66 and Oxone to a solution of the catalyst. Both the size of the cavity and the structure of the bridged ketone influenced the reactivity. Hence, whilst the formation of the diol 68 was observed when 62 and 63 were used, the presence of 64 and 65 resulted only in the formation of epoxide 67. 

This strategy has also been applied to the one-pot double deoxygenation of simple alkyl- and polyether-tethered aromatic dialdehydes to give macrocyclic allenes in high yield without the need for slow-addition techniques. ... 

Different synthetic strategies have been employed for the preparation of the pure organic hyperbranched polymers [23-25]. The most commonly adopted approach is self-condensation of AB -type monomers with n > 2 [26-29]. This type of polymerization can be carried out in a concurrent mode or by slow addition of the monomer or even in the presence of a core molecule of By (/ > 3), which allows various structural control over the growing polymer [30-32]. Another approach is copolymerizations of A monomers with B comonomers (n > 3) [33-35]. However, the stoichiometric requirements between the pairs of the functional comonomers... 

The strategy for the asymmetric reductive acylation of ketones was extended to ketoximes (Scheme 9). The asymmetric reactions of ketoximes were performed with CALB and Pd/C in the presence of hydrogen, diisopropylethylamine, and ethyl acetate in toluene at 60° C for 5 days (Table 20) In comparison to the direct DKR of amines, the yields of chiral amides increased significantly. Diisopropylethylamine was responsible for the increase in yields. However, the major factor would be the slow generation of amines, which maintains the amine concentration low enough to suppress side reactions including the reductive aminafion. Disappointingly, this process is limited to benzylic amines. Additionally, low turnover frequencies also need to be overcome. 

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