Highly Stereoselective Ring Expansion Reactions Mediated by Attractive Cation–n Interactions

Abstract

Electrostatic control of leaving group stereochemistry leads to superior diastereoselectivity in an asymmetric ring expansion reaction.Keywords ring expansion; non-bonded interactions; azides; Schmidt reaction; stereoselectivity † Supporting information for this article is available on the WWW under http://www.angewandte.org or from the author. CDCD Correspondence to: Jennifer L. Poutsma; Jeffrey Aubé. NIH Public Access Author ManuscriptAngew Chem Int Ed Engl. Author manuscript; available in PMC 2012 November 29. Most stereoselective reactions are ruled by steric effects. In particular, kinetically controlled asymmetric transformations utilizing chiral reagent, auxiliaries, or catalysts succeed due to energy differences in transition states that most often arise by the minimization of repulsive, non-bonded interactions. Stereoelectronic considerations, which arise when the alignment of particular orbitals are necessary for a successful reaction, can also play a role. [1] An iconic stereoelectronic effect in organic chemistry is the anomeric effect. [2] Reactions controlled by the anomeric effect, such as glycosidations, largely depend on the relative orientation of the non-bonding or n electrons of a nearby alkoxy group. In recent years, alkoxy group control of stereoselective reactions via electrostatic interactions has received renewed scrutiny, led by the Woerpel group. [3] In this communication, we report an alternative and highly effective approach to stereocontrol through the maximization of attractive non-bonded interactions between an alkoxy or alkylthio group and a positively charged leaving group.The Lewis acid-promoted reaction of a symmetrically substituted cyclic ketone with a chiral hydroxyalkyl azide provides a stereoselective route to lactams (Scheme 1). [4] In this reaction, initial formation of a spirocyclic intermediate sets up the selective migration of one of the alkyl groups originally adjacent to the ketone carbonyl. Migration of a C-C bond antiperiplanar to the N 2 + leaving group (only possible when the latter is in an axial position as shown) affords an iminium ether that is converted into lactam by workup with aqueous base. For 1-or 3-substituted azidopropanols (not shown), 10:1 selectivities are obtained, corresponding to preferential reaction through the most stable chairlike heterocyclic ring (A or B) resulting from equatorial addition of azide relative to the tert-butyl group.Intermediates A and B can interconvert through conformational reorganization or by reversion to the initially formed oxonium ion followed by reclosure. In this scenario, selectivity is attained by stabilization of A over B due to traditional minimization of 1,3-diaxial interactions by placement of the R 1 or R 3 into equatorial positions in the former.2-Substituted 1,3-azidopropanols present a special case that is unusually susceptible to stereoelectronic control due to three factors: (1) the methylene groups near the spiro linkage are locally isoelectronic, so the reaction cannot be controlled by "m...

A metal-free approach for the synthesis of amides/esters with pyridinium salts of phenacyl bromides via oxidative C–C bond cleavage

“…The conventional synthesis of amides involves the reaction of carboxylic acids or their derivatives such as acyl halides [6–7], anhydrides [8], esters [9], and acyl azides [10] with amines by employing coupling reagents [11]. Alternative protocols include the Staudinger–Vilarrasa reaction [12], Schmidt reaction [13–14], Beckmann rearrangement [15], aminocarbonylation of aryl halides [16], Staudinger ligation [17], rearrangement of aldoximes [18], hydration of nitriles [19], dehydrogenative coupling of primary alcohols with amines [20–21] and hydration of organonitriles to amides [22–24]. However, these traditional methods have certain disadvantages such as generation of toxic chemical waste, involvement of tedious work-up procedures and the requirement of stoichiometric amounts of coupling reagents.…”

Polymer‐anchored Ru(II) complex as an efficient catalyst for the synthesis of primary amides from nitriles and of secondary amides from alcohols and amines

“…The substituted benzonitriles bearing electron-withdrawing groups ( Table 2, entries 2-10) exhibit slightly more efficient conversions to amides than those with electron-donating groups (entries [11][12][13][14][15][16]. Presumably, the presence of an electronwithdrawing group makes the nitrile carbon more susceptible to nucleophilic attack by an activated water molecule.…”

“…[1][2][3][4][5][6][7] The classical method for amide synthesis is the acylation of amines with carboxylic acid derivatives (acid chlorides, anhydrides, active esters, etc.). [8,9] Several alternative strategies such as the Staudinger reaction, [10][11][12] the Schmidt reaction, [13,14] the Beckmann rearrangement, [15,16] direct amide formation from unactivated carboxylic acids with amines [17,18] and the oxidative amidation of aldehydes [19][20][21][22][23][24][25][26] have been developed. Many of these methods have innate drawbacks of producing a stoichiometric amount of waste product and of using highly hazardous reagents.…”

“…. Several alternative strategies such as the Staudinger reaction, the Schmidt reaction, the Beckmann rearrangement, direct amide formation from unactivated carboxylic acids with amines and the oxidative amidation of aldehydes have been developed. Many of these methods have innate drawbacks of producing a stoichiometric amount of waste product and of using highly hazardous reagents.…”

Schmidt Rearrangement Reactions with Alkyl Azides

“…38 When ( R ) -3 -azido -2 -methoxypropan -1 -ol was reacted with 4 -tert -butylcyclohexanone under Lewis acid promoted ring expansion conditions, a highly stereoselective reaction occurred to provide a 7 : 93 mixture of lactams 24a and 24b , respectively (Scheme 7.19 ). In this case, the intermediate containing the methoxy group in a cis -1,3 -diaxial orientation vis -à -vis the positively charged leaving group correlated with the major product of the reaction.…”