The halogen bond occurs when there is evidence of a net attractive interaction between an electrophilic region associated with a halogen atom in a molecular entity and a nucleophilic region in another, or the same, molecular entity. In this fairly extensive review, after a brief history of the interaction, we will provide the reader with a snapshot of where the research on the halogen bond is now, and, perhaps, where it is going. The specific advantages brought up by a design based on the use of the halogen bond will be demonstrated in quite different fields spanning from material sciences to biomolecular recognition and drug design.

The Halogen Bond

Asymmetric enamine catalysis.

4.2.8. Reductive Coupling 3109 5. Reaction of Aromatic Compounds 3110 5.1. Electrophilic Substitutions 3110 5.2. Radical Substitution 3111 5.3. Oxidative Coupling 3111 5.4. Photochemical Reactions 3111 6. Reaction of Carbonyl Compounds 3111 6.1. Nucleophilic Additions 3111 6.1.1. Allylation 3111 6.1.2. Propargylation 3120 6.1.3. Benzylation 3121 6.1.4. Arylation/Vinylation 3121 6.1.5. Alkynylation 3121 6.1.6. Alkylation 3121 6.1.7. Reformatsky-Type Reaction 3122 6.1.8. Direct Aldol Reaction 3122 6.1.9. Mukaiyama Aldol Reaction 3124 6.1.10. Hydrogen Cyanide Addition 3125 6.2. Pinacol Coupling 3126 6.3. Wittig Reactions 3126 7. Reaction of R,â-Unsaturated Carbonyl Compounds 3127

Organic Reactions in Aqueous Media with a Focus on Carbon−Carbon Bond Formations: A Decade Update

Asymmetric multicomponent reactions involve the preparation of chiral compounds by the reaction of three or more reagents added simultaneously. This kind of addition and reaction has some advantages over classic divergent reaction strategies, such as lower costs, time, and energy, as well as environmentally friendlier aspects. All these advantages, together with the high level of stereoselectivity attained in some of these reactions, will force chemists in industry as in academia to adopt this new strategy of synthesis, or at least to consider it as a viable option. The positive aspects as well as the drawbacks of this strategy are discussed in this Review.

Asymmetric multicomponent reactions (amcrs): the new frontier

Stereoselective organic reactions in water.

β-Lactams: Versatile Building Blocks for the Stereoselective Synthesis of Non-β-Lactam Products

The allene moiety represents an excellent partner for the [2+2] cycloaddition with alkenes and alkynes, affording the cyclobutane and cyclobutene skeletons in a single step. This strategy has been widely studied under thermal, photochemical and microwave induced conditions. More recently, the use of transition metal catalysis has been introduced as an alternative relying on the activation of the allenic component. On the other hand, the intramolecular version has attracted much attention as a strategy for the synthesis of polycyclic compounds in a regio- and stereoselective fashion. This critical review focuses on the most recently developed [2+2] cycloadditions on allenes along with remarkable early works accounting for the mechanism, the regio- and diastereoselectivity of the cycloadducts formed (103 references).

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Exploiting [2+2] cycloaddition chemistry: achievements with allenes

ed via -hydride elimination, collapsing into the 1,3diene derivative 419. Alternatively, the formation of this product might be interpreted as a result of the direct thermal ene-type reaction of allenenes 418. To understand the latter process, compound 418b was refluxed in CH2Cl2 without the catalyst Ru-2 for a prolonged time, but no reaction took place. In addition, when heated at higher temperature (refluxing in toluene or xylene), the thermal [2 + 2]-cycloaddition between the terminal olefin and the distal double bond of the allenyl moiety furnished the corresponding cyclobutane derivative. When trienyne 421 was subjected to ring-closing metathesis reaction conditions using the second-generation Grubbs’ catalyst Ru-2, an unusual nonmetathetic activity was observed, with the cycloisomerization product being obtained as the major product. The main fraction of the reaction of trienyne 421 was found to be a mixture of the metathesis product 422 and the cycloisomerization adduct 423 (1:2 ratio) in 45% combined yield. Besides 422 and 423, a minor product 424 was isolated (11%) along with starting material 421 (6.5%). When the Hoveyda-Grubbs’ catalyst Ru-3 was used, further cycloisomerization occurred and all that was isolated was a mixture of 422 and 423 in a 1:4 ratio (45% yield) and 421 (6.5%) (Scheme 132).109 This result suggested that the alkyne was more reactive toward the ruthenium-carbene complex than the terminal alkene for trienyne 421. Therefore, initial coordination preferentially occurred at the alkyne to give the metallacyclopentene 425 (path a). Scheme 138. Vinylcyclopropane Epimerization Catalyzed by Carbene Ru-1 Scheme 139. Tandem RCM-Dehydration Catalyzed by Ru-1a 3854 Chemical Reviews, 2009, Vol. 109, No. 8 Alcaide et al.

Grubbs' ruthenium-carbenes beyond the metathesis reaction: less conventional non-metathetic utility.

Since the advent of penicillin, the beta-lactam antibiotics have been the subject of much discussion and investigation, within both the scientific and public sectors. The primary biological targets of the beta-lactam antibacterial drugs are the penicillin binding proteins, a group of transpeptidases anchored within the bacterial cellular membrane, which mediate the final step of cell wall biosynthesis. The extensive use of common beta-lactam antibiotics such as penicillins and cephalosporins in medicine has resulted in an increasing number of resistant strains of bacteria through mutation and beta-lactamase gene transfer. Thus, a handful of nonconventional fused polycyclic beta-lactams have been described in the literature in order to overcome the defence mechanisms of the bacteria. In fact, tricyclic beta-lactam antibiotics, generally referred to as trinems, are a new class of synthetic antibacterial agents featuring good resistance to beta-lactamases and dehydropeptidases. In addition, recent discoveries have shown other biological properties of these compounds apart from their antibacterial action. In this sense, beta-lactams can serve as inhibitors of serine proteases, such as human leukocyte elastase (HLE) or thrombin, acyl-CoA cholesterol acyltransferase inhibitors and inhibitors of human cytomegalovirus. Additional impetus for research efforts on beta-lactam chemistry has been provided by the introduction of the beta-lactam synthon method, a term coined by Ojima 20 years ago, according to which 2-azetidinones can be employed as useful intermediates in organic synthesis. The usefulness of beta-lactams in the stereocontrolled synthesis of heterocycles of biological significance is based on the impressive variety of transformations, which can be derived from this system, due inter alia to a high chirality content that can be transferred into a variety of products. The cyclic 2-azetidinone skeleton has been extensively used as a template on which to build the heterocyclic structure fused to the four-membered ring, using the chirality and functionalisation of the beta-lactam nucleus as a stereocontrolling element. Alternatively, the direct one-pot generation of fused nitrogen heterocyclic systems from the nitrogen framework of 2-azetidinone derivatives has been achieved by selective bond breakage and rearrangement. It is our aim in this Review to highlight the state of the art in this endeavour, consisting either of the stereocontrolled synthesis of fused polycyclic beta-lactams of antibacterial interest, or stereoselective synthesis of different sized heterocycles of biological significance. Representative examples of the latter include indolizidines, pyrrolizidines, pirrolidines, pyrroles, taxoids and macrolide natural products.

Benito Alcaide

Papers

β-Lactams: Versatile Building Blocks for the Stereoselective Synthesis of Non-β-Lactam Products

Exploiting [2+2] cycloaddition chemistry: achievements with allenes

Grubbs' ruthenium-carbenes beyond the metathesis reaction: less conventional non-metathetic utility.

Beta-lactams as versatile synthetic intermediates for the preparation of heterocycles of biological interest.

The Direct Catalytic Asymmetric Aldol Reaction