The Diels-Alder reaction has both enabled and shaped the art and science of total synthesis over the last few decades to an extent which, arguably, has yet to be eclipsed by any other transformation in the current synthetic repertoire. With myriad applications of this magnificent pericyclic reaction, often as a crucial element in elegant and programmed cascade sequences facilitating complex molecule construction, the Diels-Alder cycloaddition has afforded numerous and unparalleled solutions to a diverse range of synthetic puzzles provided by nature in the form of natural products. In celebration of the 100th anniversary of Alder's birth, selected examples of the awesome power of the reaction he helped to discover are discussed in this review in the context of total synthesis to illustrate its overall versatility and underscore its vast potential which has yet to be fully realized.

https://www.ch.ic.ac.uk/local/organic/pericyclic/DA.pdf

The Diels--Alder reaction in total synthesis.

The past decade of organic chemistry may be charcterized as a period of violent development of new synthetic methods. This was accompained by a systematization of the analysis of synthetic problems (synthetic strategy). The planning of the synthesis of an organic target molecule is greatly facilitated by distinguishing between reagents X(C)n … with normal reactivity (acceptor properties at C1,3,5…, donor properties at X, C2,4…) and with reactivity umpolung (acceptor properties at X, C2,4…, donor properties at C1,3,5…). In this context, reactivity umpolung turned out to be useful as a heuristic principle, as a classification scheme, and as an aid for locating so-called strategic bonds (synthon, transform, and antithesis according to E. J. Corey). There are six principal methods of umpolung: 1 2n-oxidation, heteroatom exchange and modification, homologation and its reversal, the cyclopropane “trick”, use of acetylenes, and redox reactions; under certain circumstances none of these techniques is necessary in cases where direct umpolung is possible. Throughout the article, normal reactivity is indicated by green print; reactivity umpolung by red print.

Methods of Reactivity Umpolung

The invention relates to a liquid-crystalline medium based on a mixture of polar compounds having negative dielectric anisotropy (Δe), which contains at least one compound selected from the group of compounds of the formula I, II A and II B and at least one compound of the formula I* in which R0, R1, R2, R1*, X1, X2, A1, A1*, A2*, Z1, Z1*, Z2*, L1*, L2*, p, q, v, m and m* are as defined in Claim 1, and to the use thereof for an active-matrix display based on the ECB, VA, PS-VA, FFS, PALC or IPS effect.

Liquid Crystalline Medium

Ferroelectric liquid crystal mixture containing at least one compound of the general formula … … where n is 0 or 1, X is a single covalent bond, -COO- or -OOC-, X is a single covalent bond, -COO-, -OOC-, -CH2CH2-, -OCH2- or -CH2O-, the rings A , A and A are each independently of the others unsubstituted or cyano-, halogen- or lower alkyl-substituted 1,4-phenylene or one of the rings may also be pyrimidine-2,5-diyl or pyrazine-2,5-diyl and/or when n is 1 one of the rings may also be trans-1,4-cyclohexylene or trans-m-dioxane-2,5-diyl, with the proviso that one of the rings present is pyrimidine-2,5-diyl or pyrazine-2,5-diyl if a further ring is trans-1,4-cyclohexylene or, if n is 0 and X is a single covalent bond, R and R are each as defined in Claim 1, at least R having a C-C double bond,… and novel compounds of the formula I.

Ferroelectric liquid crystals

α-Methylene-γ-butyrolactones [dihydro-3-methylene-2(3H)furanones] constitute an important group of natural products and possess wide-ranging biological activities. Progress in the synthesis of the heterocycle and the classification of the synthetic methods are not only of practical interest, but also fundamentally important as a current example for the construction of an unusual 1,4-functionality distance and an α-substituted acrylic ester moiety which is susceptible to nucleophilic attack.

Synthesis and Biological Activity of α‐Methylene‐γ‐butyrolactones

There is described a liquid crystalline mixture for electro-optical devices which are operated according to the two-frequency matrix addressing procedure. The mixture consists of three components A, B and C, each of which contains one or more compounds. Component A has a viscosity of at most about 40 cp, a clearing point of at least about 40° C. and a dielectric anisotropy between about -2 and about +1. Component B has a dielectric anisotropy below about -2 both above and below the cross-over frequency of the total mixture and component C has a dielectric anisotropy above about +10, a clearing point of at least about 100° C. and there is a cross-over frequency in the total mixture of at most about 15 kHz at 20° C. Novel compounds for such mixtures and their manufacture and use are also described. The novel mixtures make possible especially high multiplex rates and short response times.

Liquid crystal mixture

Liquid crystalline mixtures containing compounds of the formula ##STR1## wherein n stands for the number 0 or 1; X1 and X2 denote single covalent bonds or one of the symbols X1 and X2 also denotes --COO--, --OOC-- or --CH2 CH2 --; the rings A1, A2, and A3 represent 1,4-phenylene, 2-fluoro-1,4-phenylene or trans-1,4-cyclohexylene or one of these rings also represents a 2,5-disubstituted pyrimidine ring or a trans-2,5-disubstituted m-dioxane ring; R1 signifies 4-alkenyl or on a cyclohexyl ring also 2Z-alkenyl; and R2 denotes alkyl, alkoxy, --CN or --NCS, as well as the manufacture of these compounds and the use for electro-optical purposes are described.

Novel liquid crystal mixtures

The Ag+-induced reaction between N-cyclohexyl-α-chloro-propionaldonitrone and the two diastereomeric 2-butenes in liquid SO2 is a stereospecific cis-addition. The use of N-cyclo-hexyl-α,β-dichloro-propionaldonitrone in this type of reaction provides a preparative route from olefines to α-methylidene-butyrolactones.

α‐Chlor‐nitrone IV: Zur Stereochemie der λ‐Lacton‐Synthese und eine Methode zum Aufbau von α‐Methyliden‐λ‐lactonen aus Olefinen. Über synthetische Methoden, 8. (vorläufige) Mitteilung

Starting from ethyl 2-cyclohexen-1-carboxylate (3) the total synthesis of the perhydrohistrionicotoxin intermediate 23 was achieved in 25% overall-yield. The two key steps involve a positionally specific addition of HOBr to the oxime-olefin 7 and the alkylation of bromooxime 17 with 1-lithio-1-butyne. The latter represents a novel method for stereospecific and position-specific introduction of a nucleophilic butyl equivalent in α-position to a ketonic carbonyl group.

Martin Dr. Petrzilka

Papers

Liquid crystal mixture

Novel liquid crystal mixtures

α‐Chlor‐nitrone IV: Zur Stereochemie der λ‐Lacton‐Synthese und eine Methode zum Aufbau von α‐Methyliden‐λ‐lactonen aus Olefinen. Über synthetische Methoden, 8. (vorläufige) Mitteilung

A New Synthetic Route to (±)-Perhydrohistrionicotoxin

A short and efficient synthesis of (−)-Ambrox® from (−)-sclareol using a ruthenium oxide catalyzed key step.