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                           Isosafrole from piperonal
                              typed by psychokitty
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Firstly, here is the isosafrole synthesis as detailed in Vogel's Textbook of
Practical Organic Chemistry, Fifth Edition:

Found on page 500-502; Experiment 5.19 (Z)- and (E)-ISOSAFROLES

(Z)-Isosafrole.
(1RS,2SR)-2-Diphenylphosphinoyl-1-(3,4-methylenedioxy-phenyl)-propan-1-ol.

n-Butyllithium (1.5 M in hexane; 5.8 ml) is added dropwise from a syringe (1) to
a stirred solution of ethyldiphenylphosphine oxide (2.0 g, 8.69 mmol) (2) in dry
tetrahydrofuran (30 ml) at 0 deg C (3).  After 30 minutes the red reaction
solution is cooled to -78 deg C (acetone-solid carbon dioxide) and a solution of
3,4-methylenedioxybenzaldehyde (1.3 g, 8.69 mmol) in dry tetrahydrofuran (10 ml)
is added dropwise from a syringe.  The rate of addition is such that the
internal temperature is maintained at -78 deg C.  The orange solution is allowed
to warm to room temperature over 2 hours and then water (25 ml) is added.  The
tetrahydrofuran is removed under reduced pressure and the aqueous residue is
diluted with brine (15 ml) before extraction with dichloromethane (3 tms 50 ml).
The combined organic extracts are dried (magnesium sulphate) and evaporated to
dryness to give the product as a crystalline mixture of diasterioisomers which
are separated by flash column chromotography (elution with ethyl acetate) (4).
The first diastereoisomer to be eluted from the column is the (1RS,2SR)-adduct
(erythro-isomer), microcrystals (2.5 g, 75.8%) m.p. 137-140 deg C
[recrystallized from ethyl acetate-light petroleum (b.p. 60-80 deg C... The
second diastereoisomer to be eluted from the column is the (1RS, 2RS)-adduct
(threo-isomer) (277 mg, 8.4%), m.p. 197-199 deg C [from ethyl acetate-light
petroleum (b.p. 40-60 deg C].

(Z)-Isosafrole.  Sodium hydride (80% dispersion in oil; 24 mg, 0.79 mmol) is
added in one portion to a stirred solution of the (1RS, 2SR)-phosphine oxide
(erythro-isomer) (300 mg, 0.79 mmol) in dry dimethylformamide (30 ml) (3). The
clear reaction solution is warmed to 50 deg C for 30 minutes by which time a
white solid precipitates from solution.  The raction mixture is coooled and the
precipitate dissolved by the addition of water (25 ml).  The mixture is diluted
with brine (15 ml) and extracted with ether (3 tms 40 ml).  The combined organic
extracts are washed with water (3 tms 40 ml), dried (magnesium sulphate), and
the solvent removed under reduced pressure.  Bulb-to-bulb distillation
(Kugelrohr apparatus) gives (Z)-isosafrole (108 mg, 84.4%) as a colourless
liquid. . . . Gas-liquid chromotography analysis . . . shows that the product
contains c.4 per cent of the (E)-isomer.

Notes.
(1) All reactions in non-aqueous solutions are carried out under a nitrogen
    atmosphere.
(2) Preparation of alkyldiphenylphosphine oxides.  General proceedure from
    phosphonium salts.  Triphenyl phosphine is heated under reflux with an
    excess of alkyl halide.  The precipitated phosphonium salt is filtered off,
    washed well with ether, and then heated with 30 per cent w/w aqueous sodium
    hydroxide (c.4 ml/g) until the benzene has distilled out.  The mixture is
    cooled and extracted with dichloromethane, and the extracts are dried
    (magnesium sulphate) and evaporated to dryness.  In this way
    ethyldiphenylphosphine oxide is obtained from triphenyl phosphine (65.6g,
    0.25 mol) and iodoethane (42.9 g, 0.275 mol) in dry toluene (250 ml) to
    give first the phosphonium salt (103.4 g, 97.9%)after 3.5 hours, from which
    the phosphine oxide is obtained as needles (53.2 g, 92.5%), m.p. 123-124øC
    (from ethyl acetate)...
(3) Dry tetrahydrofuran is freshly distilled from sodium wire using benzophenone
    radical as an indicator.  Toluene and ether are dried by distillation from
    sodium wire and are stored over sodium.  Dimethylformamide is dried by
    distillation from 4A molecular sieves and stored over 4A molecular sieves.
(4) (In my opinion, worthless).

Information for the above experiment was taken from JCS Perkin I, 2307 (1984).

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