Tandem reaction, process

The preparation of (S)-ketone cyanohydrins has also been achieved in a one-pot procedure, using the PaHnl, by decomposition of the corresponding racemic cyanohydrins followed by stereoselective addition of the HCN that is liberated to m-bromoaldehydes [97]. This tandem reaction process yielded both (S)-ke-tone cyanohydrins (from the decomposition of the racemic cyanohydrin) and (i )-m-bromocyanohydrins (the HCN addition product), the latter being con-... 

An exciting addition to the armoury of asymmetric phase transfer catalysed reactions has been the oxidative cyclisation of 1,5-dienes (Scheme 13) [21]. This tandem reaction process leads to the formation of tetrahydrofurans such as 35 in a single step from the open chain dienes 34. The step which determines the sense of asymmetry is the initial attack of permanganate anion, and this chiral information is efficiently relayed in the cyclisation to give products with three new stereogenic centres. For example, oxidation of the di-enone 34 with potassium permanganate, catalysed by the salt 36, gave the tetrahydrofuran 35 in 72% ee. 

A series of innovative investigations by Kiyooka and co-workers have introduced the use of tandem reaction processes that commence with a stereoselective aldol addition reaction and are followed by C=0 reduction [13]. A chiral oxazaboroli-dine complex prepared from BH3-THF and A-/ -toluenesulfonyl (L)-valine controls the absolute stereochemical outcome of the aldol reaction. In a subsequent reaction, the /i-alkoxyboronate effects intramolecular reduction of the ester to furnish the corresponding /i-hydroxy aldehyde. 

In addition, a technical use of these base- and acid-supported reagents has also allowed cooperative base-acid reactions and the coexistence of base and acid reactions. Furthermore, the use in one-pot of many kinds of supported reagents is possible and, therefore, it is expected that novel one-pot tandem reaction process will be constructed. 

M. C. Willis has described a tandem reaction process where pyrrolidine is coupled with vinyl bromides (81) to give an enamine.120 In the same reaction vessel, an alkylidene malonate 82 is then added at 80 °C to give the Michael addition product 83. 

Additional aspects of enyne metathesis are depicted in Scheme 28. The conjugated diene products of enyne metathesis can undergo Diels-Alder reactions. Enyne metathesis—Diels-Alder can even be performed as a one-pot tandem reaction process, as exemplified by enyne metathesis of 240 in the presence of maleic anhydride. 

The hypervalent-iodine-mediated tandem reaction process, reported for preparation of benzodiazepinones, when applied to 2-hydroxy-AT-arylben-zamides 92 afforded dibenzo[d,/][l,3]oxazepin-6(7fi)-ones 93 (14AGE6216). 

Starting with -hexane (Cg) metathesis, dehydrogenation should give the corresponding 1-hexene, followed by its homo-metathesis to yield ethylene and decene, which upon hydrogenation, should ideally produce ethane and decane (Cj q products) as the major products (Scheme 2.18, path a). However, this tandem reaction process was not selective since -decane represented <50% of the total primary products of heavy alkanes when the reaction was catalyzed with Ir-2(H2). The authors attributed this unexpected distribution of alkanes to the isomerization of the (x-olefin prior its metathesis, as depicted in pathway b (Scheme 2.18). 

The stability of allylboronates and the high level of diastereoselectivity in their additions to carbonyl compounds and imines represent very attractive attributes in organic synthesis. The examples in this chapter clearly show that recent advances in the preparation of allylboronates will help in furthering their applications. The development of efficient catalytic enantioselective allylboration methods and the invention of more powerful and more elaborate tandem reaction processes constitute two emerging areas for further development. 

Carbonyl ylides continue to be targets of opportunity because of their suitability for trapping by dipolar addition. High enantiocontrol has been achieved in the process described by Eq. 16 [109], but such high enantioselectivity is not general [110] and is dependent on those factors suggested by Scheme 11. Using achiral dirhodium(II) catalysts, Padwa and coworkers have developed a broad selection of tandem reactions of which that in Eq. 17 is illustrative [111] these... 

Neuschuetz K., Velker J., Neier R. Tandem Reactions Combining Diels-Alder Reactions With Sigmatropic Rearrangement Processes and Their Use in Synthesis Synthesis 1998 227-255... 

Experimental studies, combined with thermodynamic analysis, indicate that the CTA hydropurification process is a complex reaction system including both parallel and tandem reactions wherein 4-CBA hydrogenation is exothermic and its paralleled decarbonylation is endothermic. 

For clarification, individual transformations of independent functionalities in one molecule - also forming several bonds under the same reaction conditions -are not classified as domino reactions. The enantioselective total synthesis of (-)-chlorothricolide 0-4, as performed by Roush and coworkers [8], is a good example of tandem and domino processes (Scheme 0.1). I n the reaction of the acyclic substrate 0-1 in the presence of the chiral dienophile 0-2, intra- and intermolecular Diels-Alder reactions take place to give 0-3 as the main product. Unfortunately, the two reaction sites are independent from each other and the transformation cannot therefore be classified as a domino process. Nonetheless, it is a beautiful tandem reaction that allows the establishment of seven asymmetric centers in a single operation. 

Recently, Denmark and coworkers have developed a new strategy for the construction of complex molecules using tandem [4+2]/[3+2]cycloaddition of nitroalkenes.149 In the review by Denmark, the definition of tandem reaction is described and tandem cascade cycloadditions, tandem consecutive cycloadditions, and tandem sequential cycloadditions are also defined. The use of nitroalkenes as heterodienes leads to the development of a general, high-yielding, and stereoselective method for the synthesis of cyclic nitronates (see Section 5.2). These dipoles undergo 1,3-dipolar cycloadditions. However, synthetic applications of this process are rare in contrast to the functionally equivalent cycloadditions of nitrile oxides. This is due to the lack of general methods for the preparation of nitronates and their instability. Thus, as illustrated in Scheme 8.29, the potential for a tandem process is formulated in the combination of [4+2] cycloaddition of a donor dienophile with [3+2]cycload-... 

Another example of the retention of volatile DA reagents is that of cyclopentadiene in a tandem retro-DA/DA prime reaction [15, 16, 38], This reaction type is the thermal decomposition of a DA adduct (A) and the generation of a diene (generally the initial diene) which is trapped in situ by a dienophile leading to a new adduct (B) [39]. Cyclopentadiene (22) (b.p. 42 °C) is generated by thermolysis of its dimer at approximately 160 °C [40]. An equimolar mixture of commercial crude dicyclopenta-diene (21) and dimethyl maleate was irradiated in accordance with the GS/MW process, in an open reactor, under 60 W incident power, for 4 min (8 x 30 s). The expected adduct 23 was isolated in 40% yield (Scheme 7.1). The isomeric composition of 23 (endo-endoIexo-exo = 65/35) was identical with that obtained under classical conditions from 22 and methyl maleate [41]. The overall yield of this tandem reaction can be increased from pure dimer 21 (61%) and the same tandem reaction has also been reported using ethyl maleate as dienophile [31]. 

A direct comparison of the stereochemical efficiency of the fragmentation reaction versus the tandem reaction (Scheme 53) was studied by Porter et al. as a function of the steric effect based on the Taft parameters for different substituents [146]. In general, the tandem reactions perform better and provide higher levels of ee s than the fragmentation reactions. This effect could be due to the tinbromide by-product catalyzing a non-stereoselective process as has been uncovered by the same authors (vide supra) and by Sibi and Ji in their diastereoselective studies [147]. 

Tandem pericyclic processes offer the opportunity to synthesize complex highly substituted cyclic molecules in a completely stereocontrolled fashion in a few consecutive steps. As a consequence, tandem processes have been studied extensively. Some tandem processes involving Diels-Alder reactions have recently been reviewed38,40,107. 

Detailed time-dependent NMR studies were also performed in order to evaluate the kinetic profile of the tandem reaction (Fig. 6.17). Experimental data was coherent with a reversibly-irreversihly-coupled model, suggesting the proposed rearrangement step to he faster compared to the iminolactone cycfizafion. The studies also revealed the forward nitroaldol formation to he of comparable rate to tandem cycfizafion, while the reverse nitroaldol reaction was slower and thereby rate determining for the overall DCR process. 

Many of the recent advances in synthetic applications of allylic boron reagents have focused on the use of these reagents as key components of tandem reactions and one-pot sequential processes, including multicomponent reactions. The following examples briefly illustrate the range of possibilities. Most cases involve masked allylboronates as substrates, and the tandem process is usually terminated by the allylboration step. 

A mild one-pot procedure based on a platinum-catalyzed diborylation of 1,3-butadienes (see Eq. 30) gives doubly allylic boronate 144, which adds to an aldehyde to form a quaternary carbon center in the intermediate 145 (Eq. 105). The use of a tartrate auxiliary in this process leads to good levels of enantiose-lectivity in the final diol product, which is obtained after oxidation of the primary alkylboronate intermediate. Although examples of aliphatic, aromatic, and unsaturated aldehydes have been described, enantioselectivities vary widely (33 to 74% ee), and are good only for aliphatic aldehydes. An intramolecular variant of this interesting tandem reaction is also known. ... 

As a consequence of the complimentary electron demand of the nitroalkene and the product nitronate, there exists the possibility of a one-pot, tandem reaction. In this case, the nitroalkene will react preferentially with the electron-rich alkene to produce an intermediate nitronate. This nitronate can then react with a second alkene bearing an electron-withdrawing substituent. Therefore subjection of the nitroalkene 210 to both ethyl vinyl ether and acrylonitrile provides only the nitroso acetal 211 in moderate yield (Eq. 20) (70). Moreover, this also allows the possibility of intramolecular variants of the process. 

Neuschiitz, K. Velker, J. Neier, R. (1998) Tandem reactions combining Diels-Alder reactions with sigmatropic rearrangement processes and their use in synthesis. Synthesis, 3, 227-55. 

In principle, bifunctional aldehydes should be able to engage in twofold enzymatic aldol additions to both of their acceptor carbonyls in a fashion to be classified as a tandem reaction, that is, without the need for isolation of intermediates. Depending on the specificity of the enzyme used and on the functionalization in the starting material, the isomeric constitution as well as the absolute and relative stereochemistry should be deliberately addressable. Therefore, we engaged in a program to evaluate the scope and the Hmitations of such two-directional chain elongation processes for the construction of extended poly functional molecules [36]. 

The assembly of highly functionalized cydohexene derivatives was achieved by Lee and Shin using a highly stereoselective tandem reaction. In this process, the nucleophilic partidpation of the O-Boc group appeared to intercept a carbocationic (or cyclopropyl carbene) gold intermediate [163]. 

In view of the Zr-catalyzed enantioslective carbomagnesation-elimination tandem reaction of allylic derivatives discussed earlier, a similar process with EtjAl might be expected and has indeed been developed recently [29]. As a representative example, the reaction of 2,5-dihydro-furan with 3 equiv. of Et3Al in the presence of (i )-(EBTHI)Zr[B[NOL-(5)] (8) and (NMTHI)ZrCpCl2 (9) produced, after hydrolysis, (S)-2-ethyl-3-buten-1 -ol in 90 and 67% yields, respectively. The enantioselectivity observed with 8 was >99% ee, whereas that observed with 9 was 85-90% ee. Upon deuterolysis of the organoaluminum products, a mixture of monodeuterated and nondeuterated products was obtained and the extent of D incorporation increased to 94% with neat Et3Al without any solvent. The results indicate that the reaction must produce two organoaluminum products, 10 and 11 (Scheme 4.18). On oxidation with 02 only... 

There has been great interest in recent years in methods for the generation of azomethine ylides and in exploitation of these reactive species in tandem/cascade processes for the rapid assembly of polyaza, polycyclic, multifunctional systems. a-Diazo ketones have featured greatly in such studies, treatment with a catalytic amount of rhodium(II) acetate generating transient rhodium carbenoids. A very common feature of many investigations of this type is the occurrence of quite unexpected reactions. For example, treatment of the diazo ketone 1 with a catalytic amount of... 

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