Type II IMDA reactions

The diene precursor 78 is readily accessed in a few steps from the Wieland-Miescher ketone 79, which also provides the A- and B-rings of the steroid skeleton. Furthermore, the presence of an axial methyl group at C(19) (steroid numbering) allows the possibility of controlling the absolute stereochemical outcome of the key cycloaddition used to 

In Shea s approach to the polyhalogenated cyclohexane 87, derived from a red marine alga, Plocamium sp., a Type II IMDA reaction utilizing a disposable (allyl)silyl tether was used as a key step [29nj. The triene cyclization precursor 88 was readily prepared and underwent Diels-Alder reaction in 74% yield with the expected, complete regiocon-trol affording exclusively bicycle 89. The rigid, bicyclic framework of the cycloadduct 

The work, by the Shea group in particular, exemplifies the power of the temporary connection in Type II IMDA reactions not only for controlling the regiochemical outcome of the cyclization but also for exerting absolute stereocontrol. 

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Scheme 7 ImidazoUdinone catalysed Type I and Type II IMDA reactions...

Another important application of the iminium catalysis concept has been the development of enantioselective Type I [15, 30] and Type II [15] intramolecular Diels-Alder reactions (IMDA). (For experimental details see Chapter 14.18.3). For these transformations, both catalysts 1 and 3 proved to be highly efficient, as demonstrated by both the short and effective preparation of the marine methabo-lite solanapyrone D via Type I IMDA (Scheme 3.4, top) and the development of an early example of an enantioselective, catalytic Type II IMDA reaction (Scheme 3.4, bottom) [35]. Importantly, cycloadducts incorporating ether and quaternary carbon functionalities could be efficiently produced. 

Simple diastereoselection is also a potential concern for type II IMDA reactions. However, type II substrates with bridging chains of three or four members cyclize exclusively to the syn cycloadduct, since the transition state leading to the anti diastereomer is more strained than that leading to the syn dia-stereomer. It should be noted as well that type II cycloadditions are restricted to substrates with bridging chains of at least three members owing to the strain that develops in the transition state. 

Scheme 10-26 Shea s retrosynthesis of adrenosterone incorporating a Type II IMDA reaction.

Two variants of the IMDA reaction may be recognized. In the first, the so-called Type I IMDA, the dienophile is joined to a terminal position of the diene, producing relatively strain-free bicyclic products. In the Type II IMDA [5], the dienophile is linked to an internal position of the diene. Cyclization in this case results in the formation of a more strained system containing a bridgehead double bond (Figure 10-2). 

There are two types of IMDA reactions Type-I and Type-II. Type-I reactions are those in which the diene is attached to the dienophile by a tether from its terminus while in Type-II reactions, the tether is attached to an internal diene position (Figure 4.18). In general, both Type-1 and Type-11 IMDA reactions only occur if the tether contains three or more atoms. This is due to the high level of strain involved in the transition states of reactions of precursors with one or two atoms in the connecting chains. 

Two major classes of intramolecular Diels-Alder (IMDA) reactions may be identified based on the point of connection of the diene to the dienophile (Figure 1). Type I reactions involve trienes with the connecting chain attached to the diene terminus, while type II substrates have the dienophile tethered via one of the internal diene positions. 

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