Question

Borohydride anion, the active reducing agent, is sufficiently mild that it can be used in polar protic solvents such as alcohols. As depicted below, these alcohol solvents typically activate the carbonyl substrate to reaction with a nucleophile by forming a hydrogen bond to the carbonyl oxygen atom. In other reduction reactions, the activation occurs via a metal ion Lewis acid, however, sodium is a weak Lewis acid and not able to provide this activation. Conveniently, due to the H-bond activation of the alcohol solvent, it is able to provide a proton to the oxygen atom. Simultaneously, the borohydride provides a hydride to the carbon atom. The nucleophilic addition reaction is irreversible because the ?c-li bond formed is relatively strong and hydride is a very poor leaving group. Overall, the reduction of a carbonyl to an alcohol is a one-step process, in which the Tc-o bond is replaced by ?c_? and ?0-11 bonds. : O ?? BH ???" still an active reducing agent Newman projection of carbonyl reduction CH In this laboratory experiment, the carbonyl group of benzoin (pronounced benzo-in, 2-hydroxy-2- phenylacetophenone) is reduced using an excess of NaBH4 in ethanol to generate hydrobenzoin (1,2-diphenyl-1,2-ethanediol) : ?? NaBH4 EtOH OH : OH hydrobenzoin (1.2-diphenyl-1,2-ethanedio) benzoin

5) Rationalizing the stereochemical outc ome of this reaction requires an understanding of the f borohydride borohydride lcohol. An three-dimensional structure of benzoin and the general reaction mechanism o reductions. As shown previously (10-1), the usual mode of activation tor reduction occurs via an intermolecular H-bond between the carbonyl group and an a intramolecular H-bond can stabilize the lowest-energy conformation of benzoin (pre and serve to activate the carbonyl for reduction, thus generating the lowest-energyt state. a) Draw the lowest-energy, H-bonded conformation of both (R)- and (S)-benzoin. Clearly mar the location of the intramolecular H-bond. b) Convert each of those benzoin enantiomer depictions into Newman projections citing along C-atom behind. It the central ?csp2-Cp3 bond. Place the carbonyl C-atom in front and the sp3 will be very helpful to construct a physical model and/or use a B3LYP/6-31G(d) optimized to structure to visualize the Newman projection. For both visualization methods, be sure construct the conformational isomer to include the H-bond. To construct this conformational isomer in WebMO, construct benzoin and use either of the cleanup tools. Set the O-Cspa-Csp3-O dihedral angle to 0° and then set the H-O-Csp3 C sp2 dihedral angle to approximately 10°. A correctly built benzoin conformer should have Ci symmetry and will take approximately two hours to optimize c) For each enantiomer, use the benzoin models (computational or hand-held) and Newman projections to determine which face of the planar sp2 hybridized carbon of benzoin is most sterically available to the borohydride (H attachment) during the reaction. Draw the resulting product of attaching a hydride on that face of the molecule as both a Newman projection and as a wedge-dash structure for each enantiomer. Label the configuration of each stereocenter in the resulting hydrobenzoin as either (R) or (S) d) Identify the stereochemical relationship (enantiomeric, diastereomeric, or identical) of the products generated in step 5c above. 6) Briefly explain whether the spectroscopic data for the reduction of benzoin and subsequent formation of the acetal are consistent with a mode of activation via an intramolecular H-bond as proposed in Q5

Answer 1

(4) Rationalizing the stereochemical outcome of this reaction requirs an understanding of the three dimensional structure of bercoin and the general reaction mechanism of borohydride reactions. PH OH (Benzoin) ph Pt 0 PH & ㅂ PH (R)-benzon (S.) - benzin А ете те the order of priority of the functional group [-on - CopH > pH > H2 To determine Rands momentom one should go from 1 2-3 and look the path from opposite side of the 4th Prior group. if it is clockwise thon (R) Compone if it is Anticlock wise thin (s)- Conforme

The structure of (R)- benzoine in Hi bond A Intramoleculer H-bonding region (lowest energy conformer) Ph Mbond The structure of (S)-benzoine- H- Intramolecules Hobonding region. 'ph Conformer] H o t philha (Lowest energy (b.) Newmano projection of the TR)-benzoin. (S.)-benzoin Hy ph ph ph

(C) For (R)-benzoin HI o HO H-BH₃ 'n ph ph ph on Ho oh H H om ph H ph () р, for (s)- benzoin. H H 애 BH .ph H .ph Roth ph ph OH OM 애 H phu 4 ph Ph (2) h H ph