Sequential coupling

Sequential coupling. Here the link between one model and the other has to be established by the user, e.g., by defining specific input and output files for the airflow and the temperature results respectively and by proceeding in an iterative way toward a solution. 

Another example of a [2s+2sh-1c+1co] cycloaddition reaction was observed by Barluenga et al. in the sequential coupling reaction of a Fischer carbene complex, a ketone enolate and allylmagnesium bromide [120]. This reaction produces cyclopentanol derivatives in a [2S+2SH-1C] cycloaddition process when -substituted lithium enolates are used (see Sect. 3.1). However, the analogous reaction with /J-unsubstituted lithium enolates leads to the diastereoselective synthesis of 1,3,3,5-tetrasubstituted cyclohexane- 1,4-diols. The ring skeleton of these compounds combines the carbene ligand, the enolate framework, two carbons of the allyl unit and a carbonyl ligand. Overall, the process can be considered as a for-... 

Allylsilane additions were used in a formal synthesis of roflamycoin [51] (Eq. 24). A one-pot, three-component sequential coupling of bis-allylsilane 138 with 4-acetoxy-l,3-dioxanes 137 and 139 provided the C11-C22 polyol chain (140) in moderate yield. 

The techniques for automated solid phase synthesis were first highly developed for polypeptides and the method is abbreviated as SPPS. Polypeptide synthesis requires the sequential coupling of the individual amino acids. After each unit is added, it must be deprotected for use in the next coupling step. 

Fused pyrazole compounds have been prepared from A-alkyl substituted pyrazoles. For example, a palladium-catalyzed/norbornene-mediated sequential coupling reaction involving an aromatic sp2 C-H functionalization as the key step has been described, in which an alkyl-aryl bond and an aryl-heteroaryl bond were formed in one pot <060L2043>. A variety of highly substituted six-membered annulated pyrazoles 59 were synthesized in a one-step process in moderate yields from IV-bromoalkyl pyrazoles 57 and aryl iodides 58. 

Furthermore, this protocol can be employed for the highly efficient introduction of two (159) and even three allene entities (161) into an aromatic workbench (Scheme 2.51). Thus, by starting with two different halides, e.g. 162 (or with identical halides in different positions of a heteroaromatic substrate), two diverse allenic groups can be introduced by sequential coupling reactions. Furthermore, a structurally different bisallene 166 was also assembled via a twofold coupling of the bispro-pargyl bromide 165 with the functionalized aryl iodide 164 [85],... 

A variety of substituted seven-membered annulated pyrroles can be synthesized in a one-step process in good yields from readily accessible N-bromoalkyl pyrroles 75 and aryl iodides. The synthesis is based on a palladium-catalyzed/ norbornene-mediated sequential coupling reaction involving an aromatic sp C-H functionalization as the key step. The proposed mechanism suggests that orffzo-alkylation with the formation of intermediate 76 most likely precedes aryl-heteroaryl coupling (Scheme 15 (20060L2043)). 

The techniques for automated solid-phase synthesis were first highly developed for polypeptides. Polypeptide synthesis requires the sequential coupling of the individual amino acids. 

Miktoarm star (or p-star) polymers are star polymers with branches of different polymers. These polymers are also called heteroarm or mixed-arm star polymers. Their synthesis is more difficult but success has been achieved by sequential coupling [Hadjichristidis, et al., 1999]. To obtain a 3-arm star with one polyisoprenyl (PI) and two polystyryl (PS) branches, polyisoprenyllithium is reacted with an excess of CH3SiCl3 to form the one-arm polymer, the unreacted CH3SiCl3 is removed, and then polystyryllithium is added ... 

Instead of quenching with deuterium chloride, the intermediary organomonozinc compound can be used as a new nucleophile. Not only allylic halide but also alkenyl or aryl halide can be used as the first electrophile with bis(iodozincio)methane (3). In Scheme 23, examples for sequential coupling are summarized. In the case of coupling with bromoalkene, a nickel catalyst is more effective than a palladium catalyst. 

As described in the former section, silyl-, boryl- and germyl-substituted gem-dizinc reagents are easily prepared. These dizinc reagents also perform the sequential coupling reaction as shown in Scheme 2622,24,25. 

Finally, the outstanding functional group tolerance of the Stille reaction was exploited to prepare a series of alkylidenebutenolids. y-(Dibromomethylene)butenolide (6.42.) was sequentially coupled with phenyltributylstannane and styryltributylstannane to result in the selective exchange of the two bromine atoms. In the first intermediate it is always the Z-olefin that is formed.62... 

Bromopyrimidine and l-bromo-2-butyne reacted to give the butadienyl-pyrimidine derivative in 92% yield, while the sequential coupling of propargyl bromide and l-bromo-2-butyne with 2,5-dibromopyridine gave the expected product in 65% (7.59.), the first allene moiety being introduced into the more reactive 2-position, and the second allene attached to position... 

Another very important aspect of these transition metal-catalysed cross-coupling reactions stems from the high selectivity observed with stereo-defined vinyl sulfides. Applications to the stereoselective syntheses of pheromones were straightforward (see [321] and references therein), as shown in the two-step synthesis of muscalure from (Z)-l-bromo-2-phenylthioethylene [322] involving its sequential coupling through the bromo and phenylthio substituents with the appropriate derivatives. 

L-amino acids, A, B, and C, in two sequential coupling steps, C — B-C — A-B-C. Suppose that the coupling yield is quantitative, but there is 20% formation of the d isomer in the acylating component in each coupling step. 

As already mentioned, the sequential coupling of functionally terminated chains of different chemical structure can be used to make block copolymers,59,354,355 including those in which one or more of the blocks is a polysiloxane.74,115,356 If the blocks are relatively long, separation into a two-phase system almost invariably occurs. Frequently, one type of block will be in a continuous phase and the other will be dispersed in it in domains having an average size the order of a few hundred angstroms. Such materials can have unique mechanical properties not available from either species when present simply in homopolymeric form. Sometimes similar properties can be obtained by the simple blending of two or more polymers.357... 

Human proto-oncogen ETS1 1993 B Factor 100,000 (IPCR 9.6 x 10 21 mol, ELISA 960 amol) Zhou et al. [24], introduction of the Universal-IPCR method Sequential coupling of biotinylated antibody, STV, and biotinylated DNA (see Fig. 2B and Section 2.1.2... 

Because 2-haloanilines are strongly electronically deactivated with regard to oxidative addition, it may be expected that there is sufficient disparity in reactivity between N-benzyl-2-chloroaniline and 4-chloroanisole for them to undergo the sequential coupling reaction. Very little carbazole product is formed, however, the major product being the intermediate 5a. In this case it seems that the rate of the... 

A flexible and convergent access to 2,3-disubstituted benzo[b]thiophenes has been developed (Scheme 22). The most concise approach involves a sequential coupling of an o-bromoiodobenzene with benzylthiol and zinc acetylides leading to the adduct 78. Treatment with iodine followed by an iodine/magnesium exchange and acylation provides the polyfunctional benzofuran derivatives. a... 

Furthermore, Pd-catalyzed aminations can be sequentially coupled with alkene insertion and amination. Wolfe and Lira [102] have established a transformation involving two different sequential metal-catalyzed reactions that lead to AT-aryl-2-benzylindolines 125 in moderate to excellent yields upon formation of two C - N bonds and one C - C bond in a one-pot process (Scheme 45). Interestingly, the selective installation of two different aryl groups in this sequence can be accomplished by in situ modification of the Pd catalyst system Pd-126 upon addition of the chelating ligand dpephos prior to addition of the second aryl bromide (Scheme 46). The selectively substituted indoline derivatives 127 were isolated in good to excellent yields. 

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