Transition metal catalyzed total synthesis

These reactions are covered in other chapters of Volume 11 (Chapters 11.06 and 11.07). This part deals only with examples which are in connection with other sections of this chapter. Additions of metallocarbenoids to unsaturated partners have been extensively studied. Most of the initial studies have involved the transition metal-catalyzed decomposition of cr-carbonyl diazo compounds.163,164 Three main reaction modes of metallocarbenoids derived from a-carbonyl diazo precursor are (i) addition to an unsaturated C-C bond (olefin or alkyne), (ii) C-H insertion, and (iii) formation of an ylid (carbonyl or onium).1 5 These reactions have been applied to the total synthesis of natural... 

This chapter has been organized into three sections. The first section deals with transition metal-catalyzed hydroboration in organic synthesis and this is divided into three subsections - mechanism, chemoselectivity, and stereoselectivity. The second section deals with the application of transition metal-catalyzed hydroalumination reactions in organic synthesis, and this is also divided into three subsections - mechanism, chemoselectivity, and stereoselectivity. The third section examines the application of both hydroborations and hydroaluminations in total synthesis. 

While transition metal-catalyzed hydroboration is a well-established reaction, the same cannot be said for the transition metal-catalyzed hydroalumination. The synthetic utility of this reaction is only just beginning to emerge. Lautens has led the way in the use of hydroaluminations as the key step in the total synthesis of complex natural products. The synthesis of the anti-depressant sertraline130 involved the formation of the tetrahydronaphthalene core, and this is best achieved using the nickel-catalyzed hydroalumination of oxabicyclic alkenes (Table 16). 

In many cases, transition-metal catalyzed reactions fulfill the criteria cited. For this reason Uovedct took considerable advantage of such chemistry in his total synthesis of fluvirucin-Bi-aglycone (IV2... 

In one additional example, the transition-metal-catalyzed coupling reaction of a glycal is used for creating a C-glycosidic bond in the total synthesis of vineomycinone B2 methyl ester by Tins [33]... 

Krohn, K., Zimmermann, G. Transition-Metal-Catalyzed Oxidations. 11. Total Synthesis of ( )-Lacinilene C Methyl Ether by P-Naphthol to a-... 

Applications of asymmetric transition metal-catalyzed allylic alkylations in total synthesis 03CRV2921. 

Photochemical decomposition of diazo(trimethylsilyl)methane (1) in the presence of alkenes has not been thoroughly investigated (see Houben-Weyl Vol. E19b, p 1415). The available experimental data [trimethylsilylcyclopropane (17% yield) and la,2a,3j8-2,3-dimethyl-l-trimethylsilylcyclopropane (23% yield)] indicate that cyclopropanation occurs only in low yield with ethene and ( )-but-2-ene. In both cases the formal carbene dimer is the main product. In reactions with other alkenes, such as 2,3-dimethylbut-2-ene, tetrafluoroethene or hexafluoro-propene, no cyclopropanes could be detected.The transition-metal-catalyzed decomposition of diazo(trimethylsilyl)methane (1) has been applied to the synthesis of many different silicon-substituted cyclopropanes (see Table 3 and Houben-Weyl Vol.E19b, p 1415) 3.20a,b,2i.25 ( iQp. per(I) chloride has been most commonly used for carbene transfer to ethyl-substituted alkenes, cycloalkenes, styrene, and related arylalkenes. For the cyclopropanation of acyl-substituted alkenes, palladium(II) chloride is the catalyst of choice, while palladium(II) acetate was less efficient, and copper(I) chloride, copper(II) sulfate and rhodium(II) acetate dimer were totally unproductive. The cyclopropanation of ( )-but-2-ene represents a unique... 

The transition-metal catalyzed cross-coupling reaction of (hetero)aryl hahdes and triflates with primary and secondary amines or (hetero)aryl amines is know as the Buchwald-Hartwig reaction [144]. Mechanistically, this reaction is related to the crosscoupling reactions outlined thus far (Fig. 4.6). The modification arises at the point of transmetalation. This step in the process is substituted with the coordination of the amine reactant. Deprotonation of the amine nitrogen now precedes the reductive elimination step to generate the aryl amine product. This reaction has foimd utility in the academic setting, for use in natural product total synthesis, and in industry, for the preparation of materials up to the multi-hundred kilogram scale. 

Asymmetric Transition Metal Catalyzed Allylic Alkylations Applications in Total Synthesis ... 

B. M. Trost, M. L. Crawley, Asymmetric transition-metal-catalyzed aUylic alkylations applications in total synthesis, Chem. Rev., 2003, 103, 2921-2944. 

Transition-metal catalysts play an ever-increasing and important role in modem chemistry [3]. Numerous transition-metal-catalyzed coupling reactions have been developed and applied in the total synthesis of natural products, such as the Suzuki reaction, the Negishi reaction, the Heck reaction, and many others [4]. Interestingly, the power of transition-metal catalysts is even more visible in the area of domino reactions, where terms such as palladium walking show the value of transition metals in bond formations. 

Transition-metal-catalyzed reactions have become very popular in the total synthesis of natural products since they usually allow a late-stage assembly of functionalized structural fragments and, especially when used in a domino process, a rapid increase of complexity. 

There is an impressive number of publications on the application of transition metal-catalyzed carbonylation reactions in total synthesis. In 1980 Tsuji and colleagues applied palladium-catalyzed alkoxycarbonylation in the synthesis of Zearalenone [22] and Curvularin [23]. Starting from the corresponding aryl iodides or benzyl chlorides and alcohols, the parent molecules for Zearalenone and Curvularin were prepared in good yields and finally transferred to the target products by a few more steps (Scheme 10.1). 

In this chapter we have summarized and discussed the applications of transition metal catalyzed carbonylation reactions in total synthesis. A number of biologically active molecules have been synthesized by using carbonylation as one of the key steps. These examples of total synthesis greatly increased the values of carbonylation reactions and encouraged the basic methodology development in this area. 

As demonstrated throughout this review, rapid progress has been made in the field of the total synthesis of polycyclic ether natural products. Particularly, most of these accompUshments were concentrated over the last five years. Convergent assembly of the polycycUc ether fragments is, of course, the key to successful construction of the large ladder-shaped polycycUc ether system. In this context, the completed total syntheses have benefited enormously from the transition-metal catalyzed carbon-carbon bond forming reactions, such as olefin metathesis and cross-coupUng reactions. These powerful tools will imdoubtedly enable even more impressive accompUshments in this field. 

In 2012, Maes and co-workers reported a new transition-metal-catalyzed methodology for the direct C2-H functionalization of piperidines [67], via pyridine-directed Ru-catalyzed C(sp )-H alkylation with alkenes [68]. Based on previous work [69-73], they discovered that a combination of a bulky alcohol (2,4-dimethyl-3-pentanol) and a catalytic amount of a carboxylic acid [74] is necessary to avoid side reactions such as isomerization and/or reduction of the alkene reactant (Scheme 11). They successfully applied this method to the total synthesis of ( )-... 

This reaction was developed by Oppolzer and he succeeded in the total synthesis of ( )-pentalenolactone E (57). He also succeeded in the first total synthesis (+)-3-isoraunitidne (51) using sultam-directed asymmetric alkylation and a transition-metal-catalyzed carbometalation/carbonylation reaction. An AcOH solution of carbonate 52, Pd(dba>2, and BujP was stirred at 80 "C for 3 h under carbon monoxide (1 atm), giving a 67 22 11 mixture of cyclized compound 53 (45-53%) and two stereoisomers. Hydrogenation of compound 53 followed by treatment with MCPBA and then with p-nitrobenzyl lithium afforded 54, which was converted into (+)-isorauniticine (51). 

Abstract Transition metal-catalyzed cycloadditions of cyclopropanes have been well developed over the past several decades, leading to numerous new types of cycloadditions which are complementary to the traditional cycloadditions for the synthesis of carbocycles. Cycloadditions of vinylcyclopropanes (VCPs) and methylenecyclopropanes (MCPs) constitute two main aspects of this field. VCPs can act either as five-carbon synthons or three-carbon synthons, depending on whether the vinyl substituent is acting as an additional two-carbon synthon or not. As five-carbon synthons, VCPs are involved in [5-1-1], [5-1-2], [5-I-2-1-1], and [5+1+2-I-1] cycloadditions. As three-carbon synthons, VCPs are mainly involved in [3-1-2] and [3-1-2-t-l] cycloadditions. MCPs mostly act as three-carbon synthons and can have [3-1-2] cycloadditions with different jt systems. Other types of cycloadditions involving MCPs are also reviewed, such as [3-rl], [3+2+2], and [4+3+2] cycloadditions. CycloadditirMis of some other unusual cyclopropane derivatives are also introduced briefly. The cycloadditions of VCPs and MCPs have found applications in total synthesis and some representative molecules are tabulated as selected examples. 

Chem. Rev. 95,395,1995 B.M. Trost, M.L. Crawley - Asymmetric Transition-Metal Catalyzed Allylic Alkylations Applications in Total Synthesis,... 

The goal of this chapter is to highlight and discuss a selection of MBTFs employed in the total synthesis of natural products during the past 10 years. As MBTFs usually involve many distinct steps, which make it hard to classify them, this chapter is divided into five parts anionic-initiated MBFTs, cationic-initiated MBFTs, radical-mediated MBFTs, pericyclic MBFTs, and transition-metal-catalyzed MBFTs, hoping that the division can help show the MBFTs employed in the synthesis of natural products clearly and concisely. 

Before this total synthesis project began, we had just completed a diversity-oriented synthesis project that made use of the allylboration reaction to access simple substituted a-methylene y-lactones, which were further functionalized using a variety of transition metal-catalyzed reactions. We were now interested in applying this allylboration methodology to pursue a target-oriented synthetic problem that would demonstrate its suitability toward a complex natural product. Chinensiolide B presented this sort of challenge. 

A similar design principle that benefited from the use of tethered alkyne nitriles in transition-metal-catalyzed [2 + 2 + 2] cycloadditions, giving rise to pyridines annu-lated in the 2,3-position, led to the total synthesis of (-l-)-complanadine A (155) (Scheme 7.32) [45]. 

Transition metal-catalyzed domino reactions are of special interest in the preparation of natnral products and analogs as important lead structures in the development of bioactive componnds. Moreover, they can be used for the synthesis of any other types of compound as well as being used in combinatorial chemistry. Recently, a nnmber of excellent transition metal-catalyzed cascades were developed and reported which have attracted significant attention for synthetic chemists, dne to their high efficiency and diversity. Using well-designed strategies, transition metal-catalyzed cascades have been used successfully in the total synthesis of some natural products. 

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