Alcohols are versatile compounds with many uses. We'll look at how to make them from alkenes using different methods. Each method has its own quirks, giving us different types of alcohols depending on the starting material.

We'll compare these methods, focusing on which carbon the OH group ends up on and how the 3D structure of the molecule is affected. Understanding these differences helps us choose the right method for making specific alcohols.

Preparation of Alcohols from Alkenes

Methods of alcohol preparation

• Hydroboration-oxidation
  • Involves syn addition of borane ($BH_3$) to an alkene followed by oxidation with hydrogen peroxide ($H_2O_2$) under basic conditions
  • Results in anti-Markovnikov regiochemistry producing primary or secondary alcohols (1-butanol, 2-pentanol) depending on the alkene substrate
  • Applicable to terminal, internal, or cyclic alkenes (1-hexene, 2-methyl-2-pentene, cyclopentene)
• Oxymercuration-demercuration
  • Involves addition of mercury(II) acetate (Hg(OAc)$_2$) to an alkene in the presence of water followed by reduction with sodium borohydride (NaBH$_4$)
  • Proceeds via Markovnikov regiochemistry yielding secondary or tertiary alcohols (2-butanol, 2-methyl-2-propanol) through a mercurinium ion intermediate attacked by water
  • Suitable for terminal, internal, or cyclic alkenes (1-pentene, 3-hexene, cyclohexene)

Synthesis of 1,2-diols

• Alkene hydroxylation (syn dihydroxylation)
  • Involves syn addition of two hydroxyl groups to an alkene using osmium tetroxide (OsO$_4$) and a stoichiometric oxidant (N-methylmorpholine N-oxide)
  • Produces a vicinal diol with specific stereochemistry determined by the geometry of the starting alkene
    1. Cis alkene → erythro diol ((2R,3S)-butane-2,3-diol from cis-2-butene)
    2. Trans alkene → threo diol ((2R,3R)-butane-2,3-diol from trans-2-butene)
• Epoxide hydrolysis
  • Involves ring-opening of an epoxide with water under acidic or basic conditions producing a vicinal diol with anti stereochemistry
  • Under acidic conditions, proceeds via an SN1 mechanism with a planar carbocation intermediate resulting in a mixture of enantiomers ((R,S)-1,2-cyclohexanediol and (S,R)-1,2-cyclohexanediol from cyclohexene oxide)
  • Under basic conditions, follows an SN2 mechanism leading to inversion of stereochemistry at the site of attack ((R,R)-1,2-cyclohexanediol from (S,S)-cyclohexene oxide)

Comparison of Alcohol Preparation Methods

Regioselectivity and stereochemistry in alcohol products

• Regioselectivity
  • Hydroboration-oxidation anti-Markovnikov producing primary or secondary alcohols (1-butanol from 1-butene, 2-pentanol from 2-pentene)
  • Oxymercuration-demercuration Markovnikov yielding secondary or tertiary alcohols (2-butanol from 1-butene, 2-methyl-2-propanol from 2-methyl-1-propene)
  • Alkene hydroxylation no regioselectivity as both carbons of the alkene are hydroxylated ((2R,3S)-butane-2,3-diol from cis-2-butene)
  • Epoxide hydrolysis regioselectivity depends on the epoxide structure and reaction conditions ((R,R)-1,2-cyclohexanediol from (S,S)-cyclohexene oxide under basic conditions)
• Stereochemistry
  • Hydroboration-oxidation syn addition retaining the stereochemistry of the starting alkene ((R)-2-butanol from (Z)-2-butene)
  • Oxymercuration-demercuration proceeds through a planar carbocation intermediate resulting in a racemic mixture of alcohols ((R)-2-butanol and (S)-2-butanol from 1-butene)
  • Alkene hydroxylation syn addition producing erythro diols from cis alkenes and threo diols from trans alkenes ((2R,3S)-butane-2,3-diol from cis-2-butene, (2R,3R)-butane-2,3-diol from trans-2-butene)
  • Epoxide hydrolysis anti addition inverting the stereochemistry at the site of attack under basic conditions or producing a mixture of enantiomers under acidic conditions ((R,R)-1,2-cyclohexanediol from (S,S)-cyclohexene oxide under basic conditions, (R,S)-1,2-cyclohexanediol and (S,R)-1,2-cyclohexanediol from cyclohexene oxide under acidic conditions)

Redox Reactions and Stereochemistry in Alcohol Synthesis

• Oxidation and reduction processes
  • Hydroboration-oxidation involves the oxidation of an organoborane intermediate to form the alcohol product
  • Oxymercuration-demercuration includes a reduction step using sodium borohydride to form the final alcohol
• Addition reactions
  • Both hydroboration-oxidation and oxymercuration-demercuration are examples of addition reactions to alkenes
• Stereoisomers
  • The stereochemistry of the starting alkene influences the stereochemistry of the alcohol product in methods like hydroboration-oxidation and alkene hydroxylation
• Regiochemistry
  • The regiochemistry of alcohol formation is determined by the method used, with hydroboration-oxidation favoring anti-Markovnikov products and oxymercuration-demercuration favoring Markovnikov products