Question

Starting with cis-3-hexene, show how to prepare the following diols. (a) Meso 3,4-hexanediol (b) Racemic 3,4 -hexanediol

Short answer

Answer: (a) To synthesize meso 3,4-hexanediol, perform the following steps: 1) Epoxidation of cis-3-hexene with mCPBA, and 2) Epoxide ring-opening with an achiral nucleophile (water) in the presence of an acid catalyst. (b) To synthesize a racemic mixture of 3,4-hexanediol, perform the following steps: 1) Epoxidation of cis-3-hexene with a Sharpless asymmetric epoxidation, 2) Epoxide ring-opening with an achiral nucleophile (water) in the presence of an acid catalyst, and 3) Mixing of both enantiomers obtained from using both enantiomers of the chiral catalyst in step 1.

Step-by-step solution

Part (a): Synthesis of meso 3,4-Hexanediol

For preparing meso 3,4-hexanediol, follow these steps: 1. Epoxidation of cis-3-hexene with mCPBA Add meta-chloroperoxybenzoic acid (mCPBA) to the cis-3-hexene. The reaction will create an epoxide at the double bond, leaving the stereochemistry intact. 2. Ring-opening with an achiral nucleophile Treat the epoxide obtained from step 1 with water in the presence of an acid catalyst. The ring-opening reaction will occur under thermodynamic control, resulting in an anti addition of water across the epoxide ring. The resulting product is meso-3,4-hexanediol. Overall reaction: cis-3-hexene + mCPBA -> epoxide + water + acid -> meso 3,4-hexanediol

Part (b): Synthesis of racemic 3,4-Hexanediol

To prepare a racemic mixture of 3,4-hexanediol, follow these steps: 1. Epoxidation of cis-3-hexene with a Sharpless asymmetric epoxidation Treat the cis-3-hexene with a chiral catalyst such as a titanium(IV) isopropoxide complex and a chiral ligand in the presence of tert-butyl hydroperoxide. This approach gives Enantiomerically enriched epoxide. 2. Epoxide ring-opening with an achiral nucleophile Treat the epoxide obtained from step 1 with water in the presence of an acid catalyst in a similar fashion as in part (a). The ring-opening reaction will occur under thermodynamic control, resulting in an anti addition of water across the epoxide ring. 3. Mixing of both enantiomers Since step 1 yields an enantiomerically enriched product, to prepare a racemic mixture, intentionally perform the reaction with both possible enantiomers of the chiral catalyst in step 1. In other words, perform the shapless asymmetric epoxidation with both enantiomers of chiral ligand in two separate reactions. Mix the products of these separate reactions to obtain the racemic mixture of 3,4-hexanediol. Overall reaction: cis-3-hexene + chiral catalyst + tert-butyl hydroperoxide -> enantiomeric epoxide + water + acid -> enantiomer of 3,4-hexanediol mixture