One-pot sequential 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. 

The first procedure is a one-pot sequential process in which the acetal is formed from the aldehyde in a Bi(OTf)3-catalyzed reaction with trialkylorthoformate and the corresponding alcohol. After the aldehyde was consumed, the remaining alcohol was removed under reduced pressure. Acetonitrile, allyltrimethylsilane, and additional Bi(OTf)3 were added and the desired homoallyl ethers were obtained in moderate to good yields (Scheme 10). 

Recently, Gabriele and coworkers [140] presented an expedient synthesis of 4-dialkylamino-5H-furan-2-ones 195 by a one-pot sequential process (Scheme 77). 

Scheme 5.6.19 One-pot sequential process interfacing oxypyridinium betaine cycloaddition with cyclization-carbonylation-organostannane capture...

A CuI/DMEDA-catalyzed intramolecular coupling of A-unprotective amidines 181 has been used for assembling 1,2,4-Benzothiadiazine 1,1-dioxides 182, another important class of heterocycles for pharmaceutical design (Scheme 63) [108]. Because the preparation of the amidines 181 could be achieved via a Cul-catalyzed three-component reaction of 1-alkynes, ammonium salts and aryl sulfonyl azides, a more efficient one-pot sequential process has been developed for the synthesis of 182 from these reagents. 

An efficient high yielding synthesis of 3-substituted 2,3-dihydroquinolin-4-ones 90 was developed by using a one-pot sequential multi-catalytic process <06TL4365>. The scheme below shows the one-pot sequential multi-catalytic Stetter reaction of aldehyde 91 and a, (3-unsaturated esters 92, resulting in the formation of the desired dihydroquinolines 90. 

Many synthetic applications of Rh-catalyzed hydrogenation of a-dehydroamino acid derivatives have recently been explored (Scheme 26.2). Takahashi has reported a one-pot sequential enantioseiective hydrogenation utilizing a BINAP-Rh and a BINAP-Ru catalyst to synthesize 4-amino-3-hydroxy-5-phenylpentanoic acids in over 95% ee. The process involves a first step in which the dehydroami-no acid unit is hydrogenated with the BINAP-Rh catalyst, followed by hydrogenation of the / -keto ester unit with the BINAP-Ru catalyst [87]. A hindered pyridine substituted a-dehydroamino acid derivative has been hydrogenated by a... 

A direct method for the respective preparation of the core units of statin analogues (3R,AR)-2, (3S,AS)-2, (3R,AS)-3, and (3S,AR)-3 in enantiomerically pure form is described. These analogues are prepared from the same molecule 1 in a one-pot, sequential asymmetric hydrogenation process utilizing Rh(I)-and Ru(II)-chiral phosphine complexes. Some other examples are depicted in Table 13.1. 

Most recently, Wagaw, Yang, and Buchwald published a full account of the synthesis of indoles using the palladium-catalyzed amination process [185]. From the standpoint of catalysis, new results included improved turnover numbers and rates when Xantphos was used as ligand. Moreover, this ligand allowed diarylation of the hydrazone, including a one-pot sequential diarylation to provide mixed diaryl hydrazones. A procedure for the alkylation of N-aryl hydrazones was also reported. These procedures allow the formation of N-aryl and N-alkyl indoles after subjecting the products to Fischer conditions for indole synthesis. 

S. Y. Tosaki, R. Tsuji, T. Ohshima, M. Shibasaki, Dynamic ligand exchange of the lanthanide complex leading to structural and functional transformation One-pot sequential catalytic asymmetric epoxidation-regioselective epoxide-opening process, J. Am. Chem. Soc. 127 (2005) 2147. 

Since tandem reactions first appeared they have been given many diverse names such as cascade, consecutive, and coupled processes, domino reactions, interrupted polymerisation, one-pot, sequential and serial reactions, and tactical combinations. Some authors have tried to classify... 

An evident acceleration of the reaction time was achieved using ionic liquid as reaction media for the above di- and trimerization processes, simplifying the product isolation and catalyst recycling. For instance, the dimerization of propionalde-hyde can be performed in a 1.5 1 mixture of l-n-butyl-3-methylimidazolium hexafluorophosphate ([bmin][PFg]) and DMF with only 5 mol% of (S)-proline to give the product anti-29 (R =Me and R =Et) in 74% yield with a 60% de and 99% ee. The reaction can be repeated five cycles without changing the achieved yields or enantioselectivities. This media was also used in the one-pot sequential polyketide synthesis of 36 (R =Me and R =Et), affording the expected product in 38 yield% after only 22 h (49% ee)[93]. 

Impregnation is performed by dipping the anodes into the reactant solutions, using either a sequential dipping process in which the oxidant and monomer are deposited separately or a one-pot dipping process in which the monomer and oxidants are deposited from the same solution. Although more uniform, and therefore more conductive, PEDOT films can be deposited, a major obstacle to the one-pot method is the limited pot life. For this reason, most capacitor manufacturers have historically used a sequential dipping process to manufacture polymer capacitors. 

Guirado et al reported a one-pot preparative process involving a benzilic acid rearrangement step followed by a spontaneous epoxidation of the intermediates. Treatment of diketone 32 with sodium hydroxide at room temperature gave 2,5,5-trichloro-l,2-epoxycyclopentane-l-carboxylic acid 35 as a single product in quantitative yield. This transformation has been explained by sequential participation of intermediates 33 and 34. 

A Parham cyclization can be followed in the same pot by a second, remote halogen-lithium exchange and intermolecular reaction. Such a case is 33—>34. ° A related one-pot sequential lithiation process has... 

Zhang et al. reported an efficient synthesis of piperidin-4-ones based on gold-catalyzed cascade process (Scheme 15) [61, 68]. One-pot sequential m-CPBA oxidation and gold-catalysis with Ph3PAuNTf2 led to an excellent yield of piperidin-4-one 39. This chemistry allowed facile preparation of 5-, 6-, and 7-membered ring-fused or spiro-piperidin-4-ones. Initially, Zhang et al. speculated that tertiary... 

The Heck-Mizoroki reaction has also been heavily applied in one-pot sequential reaction sequences. The topic of sequential, domino, consecutive, or tandem catalytic reactions is a very timely subject, as at its core is efficiency, economy, and waste minimization in organic synthesis. In 2010 [59], one of us published a review of this topic which explains the current state of play and includes relevant references on the subject. However, the topic is still rather murky in terms of definitions, and this is something that we feel needs urgent attention. The Heck-Mizoroki is a very suitable transformation for inclusion in a sequential catalytic process, given that it leads to the formation of C=C units, a common functionality for further catalytic transformation. 

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