P(CH(3)NCH(2)CH(2))(3)N as a dehydrobromination reagent: synthesis of vitamin A derivatives revisited.
Although P(CH(3)NCH(2)CH(2))(3)N (1) was found to be less effective than 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in the removal of hydrogen bromide from vitamin A intermediates 13-cis-10-bromo-9,10-dihydroretinyl acetates (6) and 14-bromo-9,14-dihydroretinyl acetate (11) when the reaction was carried out in refluxing benzene, in acetonitrile at room temperature it was superior to DBN and DBU. A (31)P NMR study of this reaction suggests that the carbanion generated from acetonitrile-d(3) in the presence of 1 is the basic species that initiates the elimination step. Diastereoselectivity of the nucleophilic addition of (Z)-HC triple bond C(CH(3))=CHCH(2)OH to the carbonyl group of (E)-2-methyl-4-(2',6',6'-trimethyl-1'-cyclohexen-1'-yl)-3-butenal (2) was only moderate (20%), and (9R,10S)-13-cis-11,12-didehydro-9,10-dihydro-10-hydroxyretinol (3b) predominated. The LiAlH(4) reduction of the C triple bond C bond in the diastereoisomeric diols 3 afforded 13-cis-9,10-dihydro-10-hydroxyretinols 4a and 4b as major products together with 11-cis-13-cis-isomers and the deoxygenated compound (3EZ,5EZ,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1,3,5,8-nonatetraene (9). Reaction of 15-acetates of the pure diastereoisomeric allylic alcohols 4a and 4b with PBr(3) occurred with significant but not identical retention of configuration, and with concomitant formation of the rearranged bromide 11.
Wróblewski
Andrzej E
AE
Department of Chemistry, Iowa State University, Ames, Iowa 50011-3111, USA.
Verkade
John G
JG
D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry; D001965:Bromides / Q000138:chemical synthesis* / Q000737:chemistry*; D002384:Catalysis; D002855:Chromatography, Thin Layer; D004224:Diterpenes; D018054:Hydrobromic Acid / Q000737:chemistry; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D014801:Vitamin A / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry
C449944:(9R,10S)-13-cis-11,12-didehydro-9,10-dihydro-10-hydroxyretinol; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001965:Bromides; D004224:Diterpenes; D007659:Ketones; D009943:Organophosphorus Compounds; D014801:Vitamin A; D018054:Hydrobromic Acid; C013554:1,5-diazabicyclo(4.3.0)non-5-ene; C031033:1,8-diazabicyclo(5.4.0)undec-7-ene; C449943:P(CH(3)NCH(2)CH(2))(3)N