Midland s reagent

Conversion ofpropargyl esters to dihydrofurans1 (11,469-470). The reaction can be used for an enantioselective synthesis of dihydrofurans. Thus reduction of 3-hydroxy-l-alkynyl ketones (2) with Midland s reagent, (+)-l, provides (4S)-2-bu-tyne-l,4-diols (3) in 84-91% ee. Monoacylation (4) followed by treatment with... 

Two other purely chemical routes to chiral acetic acid have been pursued in our laboratory. In one of these, outlined in Scheme 4, stereospecifically o-deuterated or -tritiated 3,5-dimethoxybenzyl alcohol is prepared by reduction of the aldehyde with Midland s reagent (B-3-pinanyl-9-borabicyclo [3.3.1 ] -nonane, cr-pinanyl-9-BBN) (35), followed by conversion to the tosylate and reductive displacement with lithium aluminum hydride or superhydride (lithium... 

Diisopinocampheylchloroborane has been demonstrated to reduce aromatic prochiral ketones, even those which prove to be less reactive towards Midland s reagent (Vol.2, p.115), in enantiomeric... 

The, B-3-pinanyl-9-borabicyclo[3.3.1]nonane or Midland s reagent or Alpine-Borane is commercially available [9]. 

An early success4 was Midland s Alpine-Borane , derived from 9-BBN 28 and a-pinene 22. Hydroboration takes place from the less hindered side of the double bond, away from the gem dimethyl groups, to give alpine borane 29. The reagent works well for acetylenic alcohols and the transition state 30 puts the acetylene in the outside position. 

Alpine borane (the Midland reagent, 3) has found broad use in the synthesis of complex natural products. As early as 1980, only one year after Midland s seminal publication, Johnson and co-workers used 3 for the reduction of ketone 18 to afford alcohol 19 in 75% yield and 97% ee.12 This material was used to complete the synthesis of 20, a cyclization precursor in Johnson s total synthesis of hydrocortisone acetate. 

Midland and coworkers [Ic] have reported that reduction of alkynyl ketones affords excellent chemical and optical yields that approached 100% in many cases. In general, under Midland s reaction condition, for example, 4-phenyl-3-butyn-2-one takes 48 h for complete reduction at 25 °C with 100% excess of Alpine-Borane. On the other hand Brown has reported [3] the reduction of ketones in 8-12 h, using a 40% excess of the neat reagent (Scheme 26.2 Table 26.12), and products show a substantially higher optical rotation as compared to reported by Midland [Ic]. 

Reviews on stoichiometric asymmetric syntheses M. M. Midland, Reductions with Chiral Boron Reagents, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 2, Chap. 2, Academic Press, New York, 1983 E. R. Grandbois, S. I. Howard, and J. D. Morrison, Reductions with Chiral Modifications of Lithium Aluminum Hydride, in J. D. Morrison, ed.. Asymmetric Synthesis, Vol. 2, Chap. 3, Academic Press, New York, 1983 Y. Inouye, J. Oda, and N. Baba, Reductions with Chiral Dihydropyridine Reagents, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 2, Chap. 4, Academic Press, New York, 1983 T. Oishi and T. Nakata, Acc. Chem. Res., 17, 338 (1984) G. Solladie, Addition of Chiral Nucleophiles to Aldehydes and Ketones, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 2, Chap. 6, Academic Press, New York, 1983 D. A. Evans, Stereoselective Alkylation Reactions of Chiral Metal Enolates, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 3, Chap. 1, Academic Press, New York, 1984. C. H. Heathcock, The Aldol Addition Reaction, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 3, Chap. 2, Academic Press, New York, 1984 K. A. Lutomski and A. I. Meyers, Asymmetric Synthesis via Chiral Oxazolines, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 3, Chap. 

Midland MM (1983) Reductions with chiral boron reagents. In Morrison JD (ed) Asymmetric synthesis. Academic, New York, vol 2, chap 2, p 45 Itsuno S (1996) The Alembic, Morton Performance Chemicals 53 1 Fiaud JC, Kagan HB (1969) Bull Soc Chim Fr 2742 Borch RF, Levitan SR (1972) J Org Chem 37 2347 Grundon MF, McCleery DG, WUson JW (1976) Tetrahedron Lett 295 Grundon MF, McCleery DG, WUson JW (1981) J Chem Soc Perkin Trans 1 231 Johnson CR, Stark CJ (1979) Tetrahedron Lett 4713... 

Midland and coworkers [13,14] achieved the reduction of sterically less congested propargyl ketones with AIpine-Borane. The reduction is accomplished using 2 equiv of 0.5-M solutions of AIpine-Borane (Table 26.11) [14]. Terminal acetylenic ketones and acetylenic ketoesters are completely reduced after 8 h at room temperature. Internal acetylenic ketones require 1-4 days at room temperature for complete reductions. The optically active chromanyl substrates (entries 7, 8) yield diastereomeric alcohols with (R,R) R,S) ratios of 85 15 for internal and 91 9 for the terminal acetylenes with the AIpine-Borane derived from (-i-)-a-pinene of 100% ee. The reagent obtained from pure (-)-a-pinene affords 18 82 ratio of the two diastereomeric internal propargylic alcohols. 

Reagent A, B-Ipc-9-BBN, THF. This reagent is available from Aldrich Chemical Co. as Al-pine-Borane (a) Midland MM, Greer, S, Tramontane A, Zderic SA (1979) J Am Chem Soc 101 2352 (b) Midland MM, Tramontane A, Kazubski A, Graham RS, Tsai DJS, Cardin DB (1984) Tetrahedron 40 1371 (c) Tramontane A (1980) Ph.D. Thesis, University of California, Riverside... 

---