Carbenes in Constrained Systems I: 1,3 CH, Insertion Reaction of Adamantylidene within the β‐Cyclodextrin Cavity

Abstract

The chemistry of reactive intermediates (guests) within the confined spaces of another species (host) presents interesting opportunities for the discovery of new reactions."] The reactive behavior of carbenes in constrained systems is expected to be very different from that of free carbenes in solution or in the gas phase. The "tight fit" between the structures of hosts and the guest carbenes should alter both inter-and intramolecular reactions. Furthermore, suitable cavity sizes will restrict the mobility of the entrapped carbenes, which are then anticipated to react more selectively.Carbene chemistry in different media has been studied extensively over the past decades.121 Nearly nothing, however, is known about carbenes generated in constrained systems. Although x-and fi-cyclodextrin (CD) have been the only molecules employed as hosts,[31 the intermediacy of carbenes or the corresponding carbenoids has not been firmly e~t a b l i s h e d .~~]The relatively stabler4] diazirine I derived from adamantaneIsl was chosen as the guest-carbene precursor and fi-CD as the molecular reaction vessel (see Scheme 1). Compound 1 was prepared according to the literature,['] purified by column chromatography (silica gel) under the exclusion of light, and shown to be pure by ' H N M R spectroscopy.The / K D complex of 1 (1 . p-CD) was synthesized (ratio of host: guest ca. 3: 1) and characterized. To avoid the replacement of entrapped guest molecules in the fi-CD cavity by solvent molecules, solid-state NMR spectroscopy was used for the characterization. Cross polarization/magic angle spinning (CP/MAS) 13C N M R spectra provide convincing evidence that an inclusion complex was formed.['] This is further supported by powder X-ray diffraction spectra of 1, P-CD, 1 P-CD, and a physical mixture of 1 and a-CD.Under the conditions of fast atom bombardment (FAB) mass spectrometry, however, the loosely bound complex does not survive, and only the (M -H)-peak of 8-CD is observed.I8]In addition, molecular modeling was used to gain information about the fit and possible position of 1 within the C D cavity.'" According to calculations carried out by using the SYBYL force field with default parameters, 1 is nearly completely submerged into the fl-CD cavity with the diazirine function at the wider rim of the truncated cone.

Carbene Rearrangements, 60.‡ Supramolecular Structure‐Reactivity Relationships: Photolysis of a Series of Aziadamantane@Cyclodextrin Inclusion Complexes in the Solid State

“…[1] We have been studying in particular reactions of carbenes generated by photolysis of diazirine precursors within cyclodextrin and zeolite hosts in the solid state. [2] 2-Aziadamantane {2-azitricyclo[3.3.1.1 3,7 ]decane; (1)} is especially suited for these investigations. [3] A detailed analysis of the complexes of 1 and a-(6-Cy), b-(7-Cy), and g-cyclodextrin (8-Cy) (Scheme 1) by interpretation of induced circular dichroism (ICD) titrations has already been reported.…”

Constrained Carbenes

“…Indeed, carbene 11 undergoes 1,3-CH insertion to 2,4-didehydroadamantane (13) exclusively in the gas phase. [107] In contrast, only traces of 13 are formed by photolysis of diazirine 8 in solution, [99] because bimolecularly derived products predominate, for example, azine 10 and adducts 14d,e (Scheme 5). Likewise, photolysis of diazirine 8 in the solid phase yields no detectable 13.…”

“…Likewise, photolysis of diazirine 8 in the solid phase yields no detectable 13. [99] So, it is not surprising that less than 1 % of 13 was formed during the photolysis of a physical mixture of diazirine 8 and β-CyD. [99] However, the increased yield of 13, that is, 10-30 %, [99,108] when 8@CyD ICs are photolyzed is demonstrative of the powerful influence clathrates can have on reaction outcomes.…”

“…[99] So, it is not surprising that less than 1 % of 13 was formed during the photolysis of a physical mixture of diazirine 8 and β-CyD. [99] However, the increased yield of 13, that is, 10-30 %, [99,108] when 8@CyD ICs are photolyzed is demonstrative of the powerful influence clathrates can have on reaction outcomes. Since there are no solvent molecules with which supramolecular carbene 11 can react and 1,2-H shift by carbene 11 is prohibited, decay by 1,3-CH insertion is greatly enhanced.…”

“…[99][100][101] Its precursor, 2-aziadamantane (8), [102] has been widely studied. [103,104] Believed to have a singlet GS, [105] carbene 11 does not readily undergo a 1,2-H shift to form the strained anti-Bredt compound singlet adamantene (12) (Scheme 5).…”