Evaluation of Chelation Effects Operative during Diastereoselective Addition of the Allylindium Reagent to 2- and 3-Hydroxycyclohexanones in Aqueous, Organic, and Mixed Solvent Systems

• Published in: Journal of organic chemistry Vol. 63; no. 16; pp. 5604 - 5616
• Main Authors: Paquette, Leo A, Lobben, Paul C
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 07.08.1998; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; KETONES; ASYMMETRIC-SYNTHESIS; ALPHA-OXY ALDEHYDES; STEREOCHEMISTRY; TWO-DIMENSIONAL NMR; CARBONYL-COMPOUNDS; 1,4-ASYMMETRIC INDUCTION; INDIUM-MEDIATED ALLYLATION; PI-FACIAL DIASTEREOSELECTION; COUPLING-CONSTANTS
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo980974y

The unprotected 2- and 3-hydroxycyclohexanones 1−8 were prepared by methods that skirted as much as possible their proclivity for α-ketol rearrangement (where the possibility for such isomerization exists). The diastereofacial selectivity of their reaction with the allylindium reagent in water, 50% aqueous THF, and anhydrous THF is described. The neighboring α-hydroxyl substituent is construed to be capable of engaging in chelation, thereby controlling the stereochemical outcome of the coupling process. When the hydroxyl substituent is oriented in the equatorial plane, kinetic acceleration accompanies exclusive entry of the allyl group from the equatorial direction. Steric congestion in the vicinity of the binding hydroxyl and ketonic centers is well tolerated. Alternative projection of the OH group into the more crowded axial region may not curtail chelation. For coordination to occur, however, a twist-boat conformation must initially be adopted. While the evidence suggests that this may indeed occur in water, the necessity of crossing the added energy barrier precludes the attainment of rates that are competitive with those exhibited by the equatorial epimers (competition experiments). Placement of the hydroxyl group at C-3 provides no evident opportunity for chelation control. However, excellent stereoselectivity is seen upon axial orientation of the 3-OH group. This phenomenon is attributed to steric and/or electronic effects alone or in combination.