The new methodology referred to in this section was made possible by two new cycloaddition reactions developed in our laboratories at Central Queensland University (Warrener and Butler) and Deakin University (Russell).

These are part of a suite of reactions which we have developed as part of a building BLOCK approach to synthesis. The concept has been to form two classes of molecular BLOCKs corresponding to LEGO blocks. This analogy requires that the BLOCKs are available in a range of shapes and sizes, that they are able to be stored (stable at ambient), and that they form rigid structures when joined. In the LEGO block, the linking is between specific faces of the block where recognition depends on a geometric alignment of male, female subcomponents; the molecular equivalent uses two complementary functional groups which react specifically with one another. Like the LEGO blocks, similar face do not react with themselves only with partners with appropriate parity. We have designated such blocks as A-BLOCKs (alkenes, a-diamines etc) and B-BLOCKs (1,3-dienes, 1,3-dipoles, a-diones).

2.1 The ACE Reaction

This reaction was the first to be discovered and involves the cycloaddition between an Alkene and a Cyclobutene Epoxide (ACE is an acronym for these reagents). These two reagents react together in what is considered to be a 1,3-dipolar reaction, although we have only indirect evidence for this. We believe that the thermal conditions (ca 140 ^oC, sealed tube, DCM) generates the transient 1,3-dipole (Step 1, Scheme 1) which reacts with the alkene to form cycloaddition products characterised by the presence of a 7­oxanorbornane ring (Step 2, Scheme 1). The key feature of this reaction is that it occurs stereoselectively when norbornenes act as the alkene and affords a product where the norbornene methylene bridge has syn­geometry in relation to the oxygen bridge of the newly formed 7­oxanorbornane. Further, when the cyclobutene epoxide is itself part of an alicyclic frame, then products containing several syn­facial bridges can be produced.

The required cyclobutene epoxides are prepared in a two-step sequence from the corresponding norbornene. The first step is well precedented in the original report of the ruthenium catalysed addition of DMAD to norbornanes by Mitsudo and co-workers and has been applied in much of our own work on molrac synthesis and functionalisation. The epoxidation step had to be suitable for application to an electron-deficient p-bond, and we have found that low temperature treatment with tertiary butyl peroxide anion achieves this goal.

A feature of the ACE reaction in BLOCK assembly protocols is that most alkene A-BLOCKs of the norbornene type can be converted to their B-BLOCK counterpart, in the simple two-step protocol outlined in Scheme 2. This has special synthetic value when the A-BLOCK is itself difficult to make, yet with little more effort can be converted to its complementary BLOCK type.

2.2 The aza-ACE reaction

The aza-ACE reaction is the aza-analogue of the ACE reaction where the epoxide ring has been replaced with an aziridine. Accordingly, the products contain a 7-azanorbornane ring and the same cycloaddition stereoselectivity is observed on heating the aziridinocyclobutane with norbornenes as that observed in the ACE protocol (Scheme 3). Furthermore, introduction of heteroatoms (O or N) at the 7-position of the norbornene maintains the same stereoselectivity and provides polynorbornane products containing one or more 7-azabridges with syn-facial geometry (see Section 3.2).

The preparation of the aziridine can be achieved in 3 steps from the appropriate norbornene, and this is illustrated in Scheme 4 using the 7-oxa-benzonorbornene 11 as the starting product. The initial step is common to both ACE and aza-ACE protocols and involves formation of the exo-fused cyclobutene 12 by ruthenium catalysed addition of DMAD. Addition of benzylazide occurs slowly under thermal conditions (RT, 1 week). Conversion of the triazoline 13 to the aziridine 14 occurs smoothly by irradiation (Rayonet reactor, l 300 nm) in benzene solution.