2,3-Butanediol1

[513-85-9]  · C4H10O2  · 2,3-Butanediol  · (MW 90.12) (2R,3R)

[24347-58-8] (2S,3S)

[19132-06-0]

(resolution of enantiomers;2 determination of enantiomeric purity by 13C NMR;3 asymmetric aldol reactions;4 asymmetric cleavage of chiral acetals;5 asymmetric b-elimination of chiral alkynic acetals;6 asymmetric allylations;7 cyclization of chiral dienic acetals;8 enantioselective epoxidation;9 diastereoselective cyclopropanation;10 boronic ester homologation11)

Physical Data: bp 179-182 °C; d 0.99 g cm-3.

Solubility: sol H2O, alcohol, ether, acetone.

Form Supplied in: colorless liquid.

Handling, Storage, and Precautions: avoid breathing vapor. Avoid contact with eyes, skin, and clothing. Hygroscopic. Air sensitive. Store under nitrogen in a cool dry place.

Resolution of Enantiomers.

The availability of optically pure tartrate-derived diols has led to their widespread use in asymmetric synthesis. Mixtures of diastereomeric acetals prepared from (2R,3R)-(-)-2,3-butanediol are usually easily separated. Resolution of DL-camphor12 was one of its earliest uses, but many nonracemic mixtures have been separated more recently.2,13-15 Acetals prepared from this reagent also give distinct 13C NMR spectra which can be interpreted to determine the enantiomeric purity of the starting ketones.3,16-23

Enantiomeric Monoacetalization of Diones.24

The acid-catalyzed monoacetalization of diones with (2R,3R)-(-)-2,3-butanediol forms a separable mixture of diastereomeric acetals. Retro-Claisen fragmentation of the b-keto acetals with TsOH in benzene under reflux, followed by transesterification with methanol, provides a route to optically active 2,3-disubstituted cycloalkanones (eq 1).24b

Asymmetric Aldol Reactions.4

Acetals prepared from (2R,3R)-(-)-2,3-butanediol react cleanly with a-silyl carbonyl compounds in the presence of Tin(IV) Chloride to give the crossed aldol products with high ee (eq 2).4b The product can be converted into an optically active b-hydroxy ketone by Swern or Pyridinium Chlorochromate oxidation, Baeyer-Villager oxidation, and methanolysis in an overall yield of 70%. The asymmetric aldol reaction is also catalyzed by Boron Trifluoride.

Diastereoselective Nucleophilic Addition.

(2R,3R)-(-)-2,3-Butanediol a-keto acetals react with Grignard reagents25 with poor stereoselectivity, but reduction of b-keto acetals with Lithium Aluminum Hydride occurs with good de (eq 3).26

Asymmetric cleavage of chiral acetals by R2CuLi/BF3 gives the corresponding ring-opened products with high de (eq 4).5 The diastereoselectivity of this ring opening is due to an unfavorable 1,3-diaxial interaction. A similar interaction in the b-elimination reaction of chiral alkynic acetals with Grignard reagents gives alkoxyallenes with very high de (eq 5).6

Asymmetric allylations of protected cyclopentenonecarbaldehydes proceed with high de. Subsequent anionic oxy-Cope rearrangement provides a convenient route to the prostaglandins (eq 6).7

Asymmetric Diels-Alder Reaction.27,28

The chiral aluminum diolates prepared from Ethylaluminum Dichloride and 2,3-butanediol catalyze the Diels-Alder reaction of methacrolein and cyclopentadiene in good yield, but the ee is very low. The catalyst prepared from (S)-1,1-diphenyl-1,2-dihydroxypropane gives superior results, with 74% ee.27

Intramolecular Cyclization.

The SnCl4-catalyzed cyclization of dienic acetals derived from (2R,3R)-(-)-2,3-butanediol occurs with a high degree of asymmetric induction (eq 7).8

Enantioselective Epoxidation.

Asymmetric epoxidation of aliphatic alkenes with molybdenum(VI) (oxo-diperoxo) reagents in the presence of either (2S,3S)- or (2R,3R)-2,3-butanediol in nitromethane gives high ee, probably because of an efficient kinetic resolution of the oxiranes formed (eq 8).9 This method makes possible asymmetric syntheses of epoxides not available by other routes (e.g. Sharpless epoxidation).

Diastereoselective Cyclopropanation.10

Diastereoselective Simmons-Smith cyclopropanation of 2-cyclohexen-1-one acetals of 2,3-butanediol occurs with good de (eq 9).10a

Boronic Ester Homologation.11,29

Dichloromethaneboronic esters of (2R,3R)-2,3-butanediol react with alkyllithium reagents to give a borate complex which rearranges diastereoselectively in the presence of Zinc Chloride with the introduction of a chiral center adjacent to boron (eq 10).11a

Substitution Reactions.

Both (2R,3R)- and (2S,3S)-2,3-butanediol have been used as starting materials for the preparation of optically pure compounds, such as (2R,3R)-2,3-Bis(diphenylphosphino)butane,30 (2S,3R)-3-bromo-2-butanol,31 and (R)-acetoin.32


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W. Christopher Hoffman

Union Carbide, South Charleston, WV, USA



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