Synthesis of unusually strained spiroheterocyclic ring systems and their exploits in synthesis (original) (raw)

phosphonium ylides. However, an appropriate directing group (i.e. ether) was required because of the modest diastereoselectivity observed. After this initial report, several other methods were devised for the synthesis of oxaspiro[2.2]pentanes, which include addition of lithiated bromocyclopropanes 5 or diazocompounds to ketones,6 reaction of singlet oxygen with bicyclopropylidene,7 , 8 selenone additions to ketones, 9 and the addition of cyclopropyl sulfur ylides to carbonyl compounds. By far the most widely used and arguably the most diastereoselective synthesis of oxaspiro[2.2]pentanes remains the addition of cyclopropyl sulfoxonium ylides to carbonyl compounds. 12, 13 A series of elegant studies revealed that ylide addition proceeds via equatorial attack at the carbonyl carbon in cyclic compounds. While this process is highly diastereoselective, an enantioselective process has not been developed. Although Johnson reported chiral sulfoximine ylide additions to α,β-unsaturated carbonyl compounds, the racemic counterpart performed poorly with simple carbonyl compounds as in the reaction of cyclohexanone 3 with sulfoximine ylide 4, thus the chiral series was not attempted (Scheme 2). 14 Oxaspiro[2.2]pentanes display two primary modes of reactivity. One mode, leading to a cyclobutanone, appears to be driven by the release of the strain energy of the ring system (Scheme 3).12 However, as cyclobutanes possesses essentially the same amount of strain energy as cyclopropanes (26 kcal/mol and 27 kcal/mol, respectively) due to the eclipsing interactions of the substituents on a cyclobutane, the rearrangement is driven not only by the release of ring strain of both the starting epoxide and the cyclopropane but also by the formation of a C=O bond. The ring expansion of a cyclopropane to a cyclobutane proceeds with oxaspiro[2.2]pentane 6 when appropriate stabilizing groups are present. Ionization of the epoxide, either by addition of a Lewis acid or thermal induction, yields a highly stabilized intermediate cyclopropyl carbinyl cation 7. This type of cation is uniquely stabilized due to the enhanced π-character of the σ-bonds in cyclopropanes, which consequently permits a pinacol like rearrangement to cyclobutanone 8. This process is favorable due to the release of ring strain of the starting epoxide and cyclopropane in addition to the formation of a C=O bond.