The design and implementation of cascade reactions is a challenging facet of organic chemistry, yet one that can impart striking novelty, elegance, and efficiency to synthetic strategies. The application of cascade reactions to natural products synthesis represents a particularly demanding task, but the results can be both stunning and instructive. This Review highlights selected examples of cascade reactions in total synthesis, with particular emphasis on recent applications therein. The examples discussed herein illustrate the power of these processes in the construction of complex molecules and underscore their future potential in chemical synthesis.

Cascade reactions in total synthesis.

I. Introduction 1485II. Scope of This Review 1485III. Transformations of Cyclobutane Derivatives inOrganic Syntheses1486A. Ring-Opening Reactions 1486B. Ring-Contraction Reactions 1493C. Ring-Expansion Reactions 14951. Five-Membered Rings 14952. Six-Membered Rings 15093. Seven-Membered Rings 15174. Eight-Membered Rings 15215. Nine-Membered Rings 1523IV. Transformations of Cyclobutane Derivatives inNatural Product Syntheses1524A. Ring-Opening Reactions 1524B. Ring-Expansion Reactions 15261. Five-Membered Rings 15262. Six-Membered Rings 15293. Seven-Membered Rings 15324. Eight-Membered Rings 1533V. Conclusion 1534VI. Acknowledgments 1534VII. References 1534

The application of cyclobutane derivatives in organic synthesis.

Die Entwicklung und Umsetzung von Kaskadenreaktionen hat zu beachtlichen neuartigen, eleganten und effizienten Synthesestrategien gefuhrt. Als besonders anspruchsvoll erwies sich die Anwendung von Kaskadenreaktionen in der Naturstoffsynthese, doch gerade hier winken verbluffende und zugleich aufschlussreiche Ergebnisse als Belohnung. In diesem Aufsatz werden ausgewahlte Kaskadenreaktionen in der Totalsynthese erlautert, wobei neuere Anwendungen besonders hervorgehoben werden. Die erorterten Beispiele sollen die Leistungsfahigkeit dieser Prozesse beim Aufbau von komplexen Molekulstrukturen veranschaulichen und ihr Potenzial fur zukunftige chemische Synthesen verdeutlichen.

Kaskadenreaktionen in der Totalsynthese

o-Quinone methides: intermediates underdeveloped and underutilized in organic synthesis

Cascade Radical Cyclizations via Biradicals Generated from Enediynes, Enyne-Allenes, and Enyne-Ketenes.

Rearrangement of 4-alkynylcyclobutenones: a new synthesis of 1,4-benzoquinones

Les alcynyl-4 dimethoxy-2,3 trimethylsiloxy-4 cyclobutenones sont pyrolysees dans le p-xylene a reflux pour donner des produits cycliques a 5 et 6 chainons

(2-Alkynylethenyl)ketenes: A New Benzoquinone Synthesis.

Abstract To balance trade-offs between livestock’s negative environmental impacts and their positive contributions (e.g. maintaining semi-natural grasslands, varied agricultural landscapes and crop rotations), a better understanding is needed of how the supply of ecosystem services differs across farms. We analysed a suite of indicators for non-provisioning ecosystem services on a large subset of Swedish farms (71% of farms, covering 82% of agricultural land) and related these to farm type, farm size and livestock density. The analysed indicators exhibited clear geographical patterns with hotspots especially in less productive regions. Controlling for this spatial variation we still found that small-scale and ruminant farms were associated with more varied landscapes, small-scale habitats, semi-natural grasslands and better crop sequences compared to nearby farms specialised in crop production, while farms specialising in monogastric livestock were associated with less varied landscapes and inferior crop sequences. Results for cultural ecosystem services indicated that farms with more semi-natural grassland were associated with more visitors and more likely located within designated recreation or nature conservation areas. 

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Smaller farm size and ruminant animals are associated with increased supply of non-provisioning ecosystem services

Bioreductive alkylation is the term used to describe the effect of those compounds which express their mode of biological action as alkylating agents, but do so subsequent to their reduction in vivo.1 That is, they are pro-drugs which are activated by a bioreduction. Quinones are a class of compounds ideally suited to function as the reducible moiety of bioreductive alkylating agents since their facile reduction in vivo and in vitro to the corresponding hydro-quinones is a well known and extensively studied reaction.2 If the quinone is further substituted with a side-chain bearing a leaving group X at the 1-position of the substituent, then quinonemethide formation can result by an elimination of HX from the hydroquinone.2,3 The reactive quinonemethide is suggested as the discrete alkylating agent and functions as such by a Michael addition of a biologically important nucleophile (Nu-:DNA, protein, carbohydrate, etc.) to the enone of the methide. This postulate is represented by the sequence of reactions outlined in Scheme . i.e., 1 → 2 → 3 → 4.

J. Olle Karlsson

Papers

Rearrangement of 4-alkynylcyclobutenones: a new synthesis of 1,4-benzoquinones

(2-Alkynylethenyl)ketenes: A New Benzoquinone Synthesis.

Smaller farm size and ruminant animals are associated with increased supply of non-provisioning ecosystem services

Naturally Occurring Quinones as Bioreductive Alkylating Agents