Catalyst-controlled transformation

Site-selective molecular transformations can be performed in either a substrate-controlled or a catalyst-controlled manner, at least in principle. More arbitrary and diverse molecular transformation is expected, especially by such catalyst-controlled transformations. The molecular recognition process with its dynamic nature seems to be responsible for the performance of catalyst-controlled site-selective molecular transformation. Various examples of catalyst-controUed site-selective functionalization and its application to biological active natural products with complex structures are described. We know, however, that we are still at the preliminary stage in this emerging scientific field of site-selective catalysis. 1 believe that publication of this book can stimulate extensive development of methods for these future-oriented molecular transformations. 

Porco s synthesis of ( )-kinamycin C (3) constituted the first reported route to any of the diazofluorene antitumor antibiotics. This synthesis invokes several powerful transformations, including a modified Baylis-Hillman reaction, a catalyst-controlled asymmetric nucleophilic epoxidation, and a regioselective epoxide opening to establish the D-ring of the kinamycins. The tetracyclic skeleton was constructed by an... 

Compared to carbohydrate feedstocks, fewer studies have addressed the controlled transformation of lignin into potential fuel compounds. Zakzeski et al. published a comprehensive review summarizing the literature outlining the utilization of catalysts in the production of value-added products from lignin [110]. 

The reduction of multiple C—C bonds with excess in a suitable solvent in the presence of a metal catalyst can achieve controlled transformations with little experimentation. This addition proceeds easily and is widely used in organic synthesis. 

One interesting aspect of asymmetric catalysis is that sequential reactions with a chiral catalyst can often lead to an enhancement in the enantioselectivity over a single transformation with the same catalyst in a process called kinetic amplification. Doyle was able to exploit this phenomenon in the synthesis of novel tricyclic products from the bis-diazoacetate of irans-1,4-cyclohexanediol (56, Scheme 12) [71]. Although formation of C2-symmetric product 58 was expected, resulting from the typically preferred five-membered insertion event, it was found that 57 could be produced preferentially with appropriate choice of catalyst, and with very high ee (95-99%). Bis- )-lactone 59 was never the major product, but could be formed as up to 34% of the product mixture. Notably, similar catalyst-controlled mixtures of [1- and y-lactone products were also obtained with diazoacetates derived from cholesterol derivatives [72],... 

Starting material and the product (Scheme 1.58, middle). Furthermore, the catalyst control of site selectivity was achieved by changing the catalyst to the CFa-modified complex C22. Artemisinin 151 was transformed to ClO-oxi-dized hydroxyl artemisinin 152 under the catalysis of C21. However, when C22 was used, C9-oxidized 9-oxo-artemisinin 153 was obtained as the main product. Furthermore, the development of quantitative structure-based catalyst reactivity models could predict the ratio of the site selectivity (Scheme 1.58, bottom). This discovery should inspire and guide future catalyst design. 

The above studies established (1) that broad peptide sequence space can furnish catalysts that are effective across both a wide array of substrates and for several chemical transformations and (2) that nucleophilic peptide catalysis was effective at modulating barriers to reaction in the context of enantioselective reactions and site-selective reactions such that inherent preferences could be enhanced, e.g., inositols (Fig. 2c), or inverted (Fig. 2c) in a catalyst-controlled manner. At this time it became clear that the stage was set to explore beyond model systems and to begin treating large, complex natural products as substrates themselves. 

Abstract Development and scope of conventionally difficult molecular transformation on site-selective acylation of carbohydrates and polyol compounds are described. A salient feature is that the site-selectivity can be controlled independently from the intrinsic reactivity of the substrate, i.e., catalyst-controlled selectivity. Therefore, some substrates undergo acylation with reversal of their intrinsic reactivity. The mechanistic aspects of catalyst-controlled site-selective acylation are discussed with the emphasis on the strategy relying on the accelerative reaction rather than the decelerative one. An unconventional retrosynthetic route based on catalyst-controlled site-selective acylation is proposed toward extremely short-step total synthesis of natural glycosides of an ellagitannin family. Application to the late-stage functionalization of the complex natural products of biological interest is also described. 

Examples for catalyst-controlled site-selective acylation of carbohydrates and polyol compounds were described. The salient feature of these molecular transformations is that the site-selectivity can be controlled independently from the intrinsic reactivity of the substrate. Some substrates undergo acylation with reversal... 

To prepare the anti-compounds, bromide 276 was transformed via chain elongation into aldehyde 278, which on treatment with dialkyl-zinc reagents and a homochiral catalyst yielded 279-anti as the major product in a catalyst-controlled reaction. 

Promoters are sometimes added to the vanadium phosphoms oxide (VPO) catalyst during synthesis (129,130) to increase its overall activity and/or selectivity. Promoters may be added during formation of the catalyst precursor (VOHPO O.5H2O), or impregnated onto the surface of the precursor before transformation into its activated phase. They ate thought to play a twofold stmctural role in the catalyst (130). First, promoters facilitate transformation of the catalyst precursor into the desired vanadium phosphoms oxide active phase, while decreasing the amount of nonselective VPO phases in the catalyst. The second role of promoters is to participate in formation of a soHd solution which controls the activity of the catalyst. 

Enantioselective processes involving chiral catalysts or reagents can provide sufficient spatial bias and transition state organization to obviate the need for control by substrate stereochemistry. Since such reactions do not require substrate spatial control, the corresponding transforms are easier to apply antithetically. The stereochemical information in the retron is used to determine which of the enantiomeric catalysts or reagents are appropriate and the transform is finally evaluated for chemical feasibility. Of course, such transforms are powerful because of their predictability and effectiveness in removing stereocenters from a target. 

Contrary to the expectation that a sulfur-containing substituent will be a catalyst poison, a phenylthio group serves as an effective selectivity control element in TMM cycloadditions. A single regioisomer (30) was obtained from the carbonate precursor (31) in good yield. The thermodynamically more stable sulfide (32) is readily accessible from (30) via a 1,3-sulfide shift catalyzed by PhSSPh. A wide array of synthetically useful intermediates could be prepared from the sulfides (30) and (32) with simple transformations (Scheme 2.10) [20]. 

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