Face Selection in Additions to the Trigonal C2 Site in Quaternized 5-Azaadamantane Derivatives

Abstract

The quaternary TV-allyl bromide salt 5 of allyl a-[2-(5-azaadamantylidene)]benzyl ether upon warming gave the Claisen rearrangement products 6 is the ratio E/Z = 93:7. The epoxidation of the V-oxide 8 of 2-methylene-5-azaadamantane 7 with m-CPBA gives rise to the two diastereomeric epoxides 9 in the ratio E/Z = 19:81. Reaction of the methyl iodide salt of this olefin with bromine in water produces the Eand Z-dibromides 10 in the ratio 74:26 as well as the corresponding glycols 12 in the ratio 86:14. The same reaction in methanol gives the Eand Z-isomers of 10 alone, in the ratio of 35:65. The interpretation is that, in all of these reactions, the trigonal carbon preferably undergoes addition at that face which is antiperiplanar to the more electron-rich vicinal bonds, and does so by margins substantially in excess of those observed with the corresponding 5-fluoroadamantanes. This fact lends further strength to our previously drawn conclusion that hyperconjugative transition state stabilization is the principal factor in the electronic component of face selection.

Nature of the Electronic Factor Governing Diastereofacial Selectivity in Some Reactions of Rigid Saturated Model Substrates

“…It is important to note that the distinct unambiguous facial preferences for 37 (X = Sn(CH 3 ) 3 ; see Table ) confirm that an earlier result of iodine atom abstraction for this radical, which suggested capture with essentially random stereochemistry, is clearly spurious . Doubts had initially been expressed regarding the latter result on the grounds that the radical was generated in a complex free radical chain reaction and that the iodo-tin compounds were minor components (14−26%) of the product mixtures 14 Product Distribution in the Atom Capture of 5-Substituted (X) Adamant-2-yl Radicals ( 37 ) a Xatom source% E % Z F n -Bu 3 SnD 36 64 F CCl 4 30 70 F CF 3 CHClBr 25 75 F CF 3 CH 2 I 29 71 Sn(CH 3 ) 3 n -Bu 3 SnD 59 41 Sn(CH 3 ) 3 CCl 4 66 34 a Taken from ref . …”

“…The fact that preference for syn delivery of hydride does indeed become more pronounced and, as well, that changing the solvent from methanol to water or even saturated sodium chloride did not influence stereoselection as might have been expected for dominant Coulombic interactions, strongly suggested the operation of the Cieplak model. 95 An extension of this idea has confirmed an augmented syn approach by the reagent in electrophilic and sigmatropic reactions as well 96 for the same structural change of the substrate. However, high-level ab initio molecular orbital calculations indicate that incorporating nitrogen into the skeletal framework induces structural distortions which introduces steric bias into the model substrate.…”

Inductive and Resonance Effects of Substituents on π-Face Selection

“…The CH 3 Li alkylation and NaBH 4 reduction of this ketone occur with a small anti preference, in spite of a subtle distortion which makes the syn face slightly more accessible . This preference is dramatically reversed in the corresponding N -oxide and ammonium iodide . The results of NaBH 4 reductions in different alcohols show a large dependence of π-face selection on solvent properties; this is not observed in reductions of other adamantan-2-ones, Scheme …”

Orbital-Controlled Stereoselections in Sterically Unbiased Cyclic Systems

“…Adamantan-2-one ( 5a ) can be regarded as a cyclohexanone derivative which is sterically and electronically symmetrized in both the axial and equatorial directions by means of additional bridging of the cyclohexanones ( A1 ) and is also conformationally rigid. Facial selectivity of 5-substituted adamantan-2-ones ( A2 ) was initially studied by Giddings and Hudec, followed by intensive studies by le Noble's group ,− on the adamantan-2-ones themselves and related analogues. Electron-withdrawing groups such as phenyl ( 5b ), fluoro ( 5c ), hydroxyl, and trifluoromethyl groups at the 5-position favored syn addition of the reducing agent (NaBH 4 ) (with respect to the substituent at the 5-position). , For example, in the hydride reduction with NaBH 4 of 5-phenyladamantan-2-one 5b , syn addition was favored over anti addition (syn:anti = 58:42).…”