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Asymmetric synthesis of chiral, nonracemic dialkyl α‐hydroxyarylmethyl‐and α‐, β‐ and γ‐hydroxyalkylphosphonates from keto phosphonates
Author(s) -
Meier Chris,
Laux Wolfgang H. G.,
Bats Jan W.
Publication year - 1995
Publication title -
liebigs annalen
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0947-3440
DOI - 10.1002/jlac.1995199511276
Subject(s) - chemistry , enantioselective synthesis , enantiomer , catalysis , allylic rearrangement , yield (engineering) , reagent , borane , sulfide , enantiomeric excess , substituent , boranes , organic chemistry , medicinal chemistry , derivative (finance) , financial economics , materials science , boron , metallurgy , economics
The enantioselective synthesis of α‐hydroxyarylmethylphosphonates 2a‐p by the oxazaborolidine‐catalyzed reduction of α‐keto phosphonates 1a‐p using different boranes 4a–c was studied in detail. Moderate to good enantioselectivities are found (up to 80% ee) by using the borane‐dimethyl sulfide complex 4a as reducing reagent and the 2‐ n ‐butyl derivative of the ( S )‐5,5‐diphenyl‐3,4‐trimethylene‐1,3,2‐oxazaborolidine catalyst 3b. In contrast, excellent enantiomeric excesses (up to 99% ee) as well as high chemical yields are obtained when catecholborane 4c in combination with low temperature is introduced. Substituent effects on the starting material 1 are discussed with the help of structural information obtained by X‐ray analyses of the benzoylphosphonates 11f γ, 1j γ, and 1n γ. A slight decrease in enantioselectivity was found within the series of α‐, β‐, and γ‐hydroxyalkylphosphonates 6, 8 , and 10 , respectively. Nevertheless, even these compounds are reduced with enantioselectivities ranging from 68% ( 10 ) to 95% ( 6 ) by using catecholborane 4c and catalyst 3b. On the other hand, we synthesized the allylic α‐hydroxyphosphonate 12 in 75% chemical yield and with 56% enantiomeric excess by means of this methodology. The reaction has subsequently been applied to the synthesis of α‐hydroxyalkylphosphonates 14a–c , which were obtained with ee values up to 90%. Compounds 14 are useful precursors for the synthesis of the P‐amino acids 15 .