[133683-82-6] · C12H24Si2 · (1E,3E,5E)-1,6-Bis(trimethylsilyl)-1,3,5-hexatriene · (MW 224.49)
(building block for the stereodefined construction of conjugated polyenyl chains1-6)
Physical Data: bp 71-73 °C/0.75 mmHg.
Analysis of Reagent Purity: GC/MS, IR, 1H and 13C NMR.
Preparative Methods: conveniently prepared by means of the cross-coupling reactions of 2 equiv of the Grignard reagent derived from (E)-2-(trimethylsilyl)-1-bromoethylene with (E)-1,2-dichloroethylene (75% yield) or with (E)-2-phenylthio-1-chloroethylene (55% yield),7 in the presence of NiCl2(dppe) in THF at rt. [2-(Trimethylsilyl)-1-bromoethylene is commercially available in an (E)/(Z) 87/13 ratio. The mixture is distilled two or three times on a Fisher column MMS 202 at 50-52 °C/42 mmHg and fractions enriched in (Z)-isomer are collected. The (E)-isomer is recovered and purified by simple distillation (bp 54-55 °C/42 mmHg, stereoisomeric purity 98-99%)].
Handling, Storage, and Precautions: can be stored at -15 °C for several months, without isomerization.
The reaction of the trienylsilane with equimolar amounts of acyl chloride and Aluminum Chloride at 0 °C in CH2Cl2 affords unsaturated keto silanes with high retention of configuration (>98%). Subsequent substitution of the second silyl group with another acyl chloride in the same reaction flask at rt leads to the diketone derivative (eq 1).1
The highly efficient synthetic potential of the bis-silylated triene is illustrated by the synthesis of the (6E)-isomer of leukotriene B32 and of SM-9064, a potential LTB4 antagonist (eq 2).3 The key step of the synthesis of both compounds is represented by the double acylation of the bis-silylated triene with the appropriate acyl chlorides [(6E)-LTB3: nonanoyl chloride and methylglutaryl chloride; SM-9064: 3-(p-methoxyphenyl)propanoyl chloride and methylsuccinyl chloride]. Other steps require reduction with Sodium Borohydride of the diketo ester intermediates and, in the case of SM-9064, the amide formation reaction with Pyrrolidine in methanol.
Unsaturated keto silanes and diketones prepared according to eq 1 can be further transformed into saturated keto silanes or 1,8-diketones by means of Pd-catalyzed selective hydrogenation reactions.4
Polyunsaturated secondary alcohols, obtained by reduction of keto silanes, can be kinetically resolved with a high (>97%) enantioselectivity by lipase-catalyzed transesterification with Vinyl Acetate.5 A representative example is reported in eq 3.
Reaction of the bis-silylated triene with Benzenesulfenyl Chloride in THF at rt leads to the trienyl sulfide with inversion of configuration at the terminal double bond (Z,E,E/E,E,E = 90/10).6 The substitution reaction with the commercially available S-phenyl carbonochloridothioate leads to the corresponding monosilylated thioester with high retention of configuration. A straightforward decarbonylation reaction with Ni0 in DMF8 affords the corresponding sulfide (E,E,E/Z,E,E = 85/15) (eq 4).6
Francesco Naso, Vito A. Fiandanese, & Francesco Babudri
CNR Centre MISO, University of Bari, Italy