Bicyclic rings, synthesis

This chapter provides an update of Chapter 8.33 in CHEC-II(1996) <1996CHEC-II(8)863>. The work carried out on the bicyclic ring systems with ring junction P, As, Sb, or Bi has focused primarily on phosphorus. Very little work has been done on the other heteroatoms and as such the synthesis and reactivity of these compounds have been reviewed as one section, Section 12.12.7. Most of the compounds in this class contain more than one heteroatom, the additional atoms usually being oxygen and nitrogen. 

Intramolecular cycloadditions are among the most efficient methods for the synthesis of fused bicyclic ring systems [30]. From this perspective, the hetisine skeleton encompasses two key retro-cycloaddition key elements. (1) a bridging pyrrolidine ring accessible via a [3+2] azomethine dipolar cycloaddition and (2) a [2.2.2] bicyclo-octane accessible via a [4+2] Diels-Alder carbocyclic cycloaddition (Chart 1.4). While intramolecular [4+2] Diels—Alder cycloadditions to form [2.2.2] bicycle-octane systems have extensive precedence [3+2], azomethine dipolar cycloadditions to form highly fused aza systems are rare [31-33]. The staging of these two operations in sequence is critical to a unified synthetic plan. As the proposed [3+2] dipolar cycloaddition is expected to be the more challenging of the two transformations, it should be conducted in an early phase in the forward synthetic direction. As a result, a retrosynthetic analysis would entail initial consideration of the [4+2] cycloaddition to arrive at the optimal retrosynthetic C-C bond disconnections for this transformation. 

Both natural and non-natural compounds with a 2ff,5ff-pyrano[4,3-fc]pyran-5-one skeleton are of interest in medicinal chemistry. Several natural products, such as the pyripyropenes, incorporate this bicyclic ring system. The group of Beifuss has described an efficient microwave-promoted domino synthesis of the 2ff,5H-pyr-ano[4,3-fo]pyran-5-one skeleton by condensation of a,/3-unsaturated aldehydes with 4-hydroxy-6-methyl-2]-f-pyran-2-one (Scheme 6.244) [428]. It is assumed that in the presence of an amino acid catalyst a Knoevenagel condensation occurs first, which is then followed by a 6jr-electron electrocyclization to the pyran ring. While the conventional thermal protocol required a reaction time of up to 25 h (refluxing ethyl... 

Synthesis of 5-5 Bicyclic Ring Systems 11.08.7.1 Photochemical Synthesis... 

Synthetic chemists can now work with three-dimensional pictures of the conjugate addition available on a website [80]. In the absence of steric hindrance (5-methylcyclohexenone, for example), an axial attack through a half-chair conformation is favored, while in the cortisone synthesis an equatorial attack through a half-boat conformation is favored because of the constraint imposed by the bicyclic rings [83]. 

Until recently, these unusual classes of bicyclic nucleosides had eluded the grasp of synthetic chemists. It is clear that the main challenge in the synthesis of these unusual nucleosides resides in the method of bicyclic ring formation. If one also considers the type of functionality that adorns these molecules, then the whole exercise becomes one of judicious choice of reactions and protective... 

Synthesis by Transformation of Another Bicyclic Ring System... 

When a high-yield synthesis of the enantio- and diastereomerically pure mono-cyclic 2,3-dihydrofurans 44 from the vinyl sulfoximines 39 had been developed, the synthesis ofbicyclic 2,3-dihydrofurans of type 50 (Scheme 1.3.19) was investigated. Since a number of tetrahydrofuranoid natural products contain a fused bicyclic ring skeleton, the attainment ofbicyclic 2,3-dihydrofurans of the 50 type would also be desirable. 

Synthesis of Bicyclic Ring Systems without Ring Junction Heteroatoms 605... 

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