Sequential coupling process

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-... 

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. 

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 above examples demonstrate that mirror symmetry breaking by self-assembly of non-chiral molecules into chiral architectures is indeed a feasible process. However, in order to preserve the handedness and amplify the stochastically-generated chirality, it is imperative to couple such chance events with efficient sequential autocatalytic processes. We refer now to several experimental systems that illustrate the occurrence of such scenarios. We shall allude in particular to systems undergoing amplification via non-linear asymmetric catalysis processes, via the formation of 2-D and 3-D crystalline systems and amplification of homochiral bio-like polymers in general and oligopeptides in particular. 

Corsico, E.F. and Rossi, R.A. (2002) Sequential photostimulated reactions of trimethylstannyl anions with aromatic compounds followed by palladium-catalyzed cross-coupling processes. Journal of Organic Chemistry, 67, 3311-3316. 

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. 

DNA Synthesis for Nanoconstruction Single strands of DNA, otherwise known as oligomers, are most commonly produced using a solid-support synthesis process [161, 162], This is a cyclic process where each nucleotide is sequentially coupled to form a nucleotide chain (working from the 3 end to the 5 end). The 3 end is initially covalently linked to a solid support and the nucleotide monomers are added sequentially. This is a well-established process and its key parameters and critical process steps are well documented in the literature [163,164],The DNA strands can be tailored according to the desired nanoconstruction scheme and target structure [165]. 

The catalytic generation of alkynones and chalcones by palladium catalyzed reactions is an entry to sequential, consecutive, and domino transformations and opens new routes to heterocycles by consecutive coupling-cyclocondensation or Cl-cyclocon-densation sequences. The advantages are not only the compatibility of similar reaction conditions but also the tunable reaction design that allows the combination of several organic and organometallic elementary reactions to new diversity oriented syntheses. Future developments will address also sequentially catalyzed processes... 

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... 

Anionic Methods. Of the various methods used for nonpolar block polymer synthesis, the anionic approach is by far the most useful and most precise in producing a given segmented chain design [A-B-A, (A-B)j, A-B-C, etc.]. The linear A-B-A block polymer may be synthesized by two basic routes, sequential polymerization of all three blocks or sequential polymerization of two blocks, followed by coupling. The "sequential" method is illustrated in Reaction la for the preparation of S-B-S the "coupling" process is depicted in Reaction lb. 

Triblock polymers are generally made in sequential addition processes with the aid of sodium naphthalene or alkyl lithium. They can also be produced in a "coupling" process wherein a dlblock is prepared first and is coupled with the aid of phosgene or alkyl dlhalides to form the ABA triblock. Tapered blocks can be made by starting with a polystyrene block and then copolymerizing a mixture of styrene and diene. 

Ketyls generated by the reaction of SmE with aldehydes and ketones have been incorporated into numerous sequential processes in which a radical reaction is involved. Sequential radical processes, radical cyclization/carbonyl additions, radical cyclization/substitution reactions, nucleophilic acyl substitution/radical cyclizations, cyclization/elimination processes, and others have all been realized. Because these types of reactions have been extensively reviewed [2b, 25], further details will not be given here. Needless to say, new sequential processes based on SmE-promoted ketyl/olefin coupling reactions are still being developed (Eq. 75) [88]. 

Crews HM, Clarke PA, Lewis DJ, Owen LM, Srutt PR and Izquierdo A (1996) Gastrointestinal extracts of cooked cod by High performance liquid chromatography-inductivdy coupled plasma mass spectrometry and electrospray mass spectrometry. J Anal At Spectrom 11 1177-1182. Dernovics M, Stefanka ZS and Fodor P (2002) Improving selenium extraction by sequential enzymatic processes for Se-speciation of selenium enriched Agaricus bisporus. Anal Bioanal Chem 372 473-480. 

As an extension of the Heck reaction, Pd-catalyzed hydroarylation of alkynes and alkenes continues to attract high level of research interest in simple coupling processes and in cyclization reactions. The use of this type of transformation as part of a domino reaction will be of increasing interest. The research in the field of domino reactions is attracting considerable attention in synthetic organic chemistry since it enables the rapid assembly of complex molecules in one-pot processes. Very elegant examples of palladium-catalyzed cascade processes where a single catalytic cycle entails several sequential bond transformations have been recently reported [la, b, 2a, b, c]. 

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