Science - USA (2020-02-07)

trans-diastereomer ( 24 ). Single-crystal x-ray
diffraction confirmed that pinacol 23 (0.2 g
prepared) thus contained the [3.3.2]-propellane.
To complete the synthesis, we anticipated
from our molecular models that the hydroxyl
groups in 23 would rank from least sterically

hindered at C10 to most hindered at C2.

Therefore, we proceeded from pinacol product

23 with acetylation at both C10 and C9, fol-

lowed by removal of the MOM group with

bromocatechol borane to obtain alcohol 24

alongside triol 25 resulting from deprotection

of the benzylidene acetal. Reprotection of 25

converged the synthetic material to 24. Mono-

deprotection of the acetate at C9 proved fea-

sible and delivered diol 26 in 67% yield.

Selective acetylation of the hydroxyl group

at C2 proceeded with 2.5:1 regioselectivity in

Schneideret al.,Science 367 , 676–681 (2020) 7 February 2020 3of5

Fig. 3. Total synthesis of (–)-canataxpropellane (2) part I: Diels–Alder/
alkene-arene-ortho-photocycloaddition and photooxygenation.Reagents and
conditions: 1. 8 1.0 equivalents (equiv.), THF,–78°C, sodium hexamethyldisilazide
(NaHMDS) (1.14 equiv.), then TBS-Cl (1.14 equiv.), to room temperature (r.t.),
then 7 (2.0 equiv.), 71%. 2. hn(254 nm), r.t., acetonitrile 73%. 3.
Tetrabutylammonium fluoride (1.05 equiv.), THF, 0°C. 4. Ca(BH 4 ) 2 (1.1 equiv.),
0°C, CH 2 Cl 2. 5. MOMCl (5.0 equiv.), diisopropylethylamine (DIPEA) (5.0 equiv.),

CH 2 Cl 2 r.t. 70% (3 steps). 6. LiAlH 4 (3.0 equiv.), THF, 0°C. 7. Oxallylchloride

(4.0 equiv.), dimethylsulfoxide (DMSO) (8.0 equiv.), trimethylamine (NEt 3 )

(12.0 equiv.), CH 2 Cl 2 ,–78°C. 8. Potassium tert-butoxide (KOtBu) (1.2 equiv.),

THF:tBuOH = 5:1, 53% (3 steps). 9. Rose Bengal (5 mol %), CDCl 3 :MeOH-d 4 =

10:1, hn(>530 nm), then THF. 10. BHT (2.0 equiv.), potassium acetate

(KOAc) (4.0 equiv.), 71%. 11. DMSO IBX (1.0 equiv.), r.t. 12. Acetonitrile (CH 3 CN),

AcOH (1 ml), Me 4 NHB(OAc) 3 (3.0 equiv.), r.t.

RESEARCH | REPORT