Bicyclic phosphoranes, synthesis

Introduction - The year has again seen a consolidation of knowledge in the area of hypervalent phosphorus chemistry with emphasis on the synthesis and properties of monocyclic and bicyclic phosphoranes. A considerable effort has been made to resolve the mechanism of the Mitsunobu Reaction (see Section 3) and the principles established by studies of pentaco-ordinate phosphorus compounds have again been extended to hypervalent compounds of other elements (e.g. As, Sb, and Si). A comprehensive review of the reactions of phosphorus acids with chlorine includes a number of examples of acyclic, monocyclic and bicyclic phosphoranes prepared by this route together with a useful catalogue of their 31p 5-values. 

Despite the overall decline in output, the year has produced ftirther interesting developments in the fteld of hypervalent phosphorus chemistry. These include phosphoranes containing acetylenic links, the synthesis and enantiomeric separation of a bicyclic phosphorane with chirality only at phosphorus, and a wide range of phosphoranes incorporated within macrocyclic ring systems (Houlla et al). In addition Lattman has reported on phosphoranes bound to transition metals or enclosed within calixarene skeletons and Holmes and his co-workers have made further substantial contributions on the X-ray crystal structures of phosphoranes containing eight-membered rings. 

Cyclization by way of the aldehyde (22, R = CHO) provides the appropriate ester of the bicyclic nucleus (23), which on deprotection gives an unstable sodium salt. Formation of the [2,3] double bond by this intramolecular Wittig procedure has been widely used for both analogue and natural product synthesis (35). Cyclization is achievable even using a thiol ester such as (24) which leads to the protected olivanic acid MM 22383 [74819-56-0] (25), C28H26N4OiiS (36). Addition of thiols to the double bond of phosphorane-derived derivatives lacking a C-2 substituent (26) has been used for the... 

The synthesis of novel perfectly anti-apicophilic phosphoranes (6a-d) was achieved by reacting 1-hydro-5-carbaphosphatrane (4) with an appropriate alkyl- or aryllithium reagent in THF, followed by the hydrolysis and further oxidation of the bicyclic intermediate (5a-d) with iodine (4a and 4b) or by pyrolysis (4c and 4d) (Scheme 2). 

Prior to the discovery of the naturally occurring 1-carbapenem nucleus (94), a synthesis of the racemic material had been described (J06). The 4-acetoxyethyl substituted p-lactam (124) derived from (113) was converted by standard procedures to the phosphorane (125). Hydrolysis to the alcohol (126) followed by oxidation resulted in cyclisation to the bicyclic ester (127). 

---