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Organic Synteses vol 70 - Meyers A.I.

Meyers A.I. , Boecman R.K. Organic Synteses vol 70 - John Wiley & Sons, 1992. - 163 p.
ISBN 0-471-57743
Download (direct link): organicsynthesesvol701992.pdf
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A chemically pure sample of methyloctalone 3, [a]D -190° (ethanol, c 1.00) is
obtained by preparative GLC (3 m x 1/4”, 5% carbowax 20 M on Aeropak 30, 180°C,
retention time 12.4 min) of a distillate sample. The impurity has a 13.2-min retention
time under these conditions. A good approximation of the reaction ee is calculated as
follows, taking into account the optical purity of the starting amine (95.8%) and the 20
[a]D -219° (ethanol, c 1.00) value (Note 8) for optically pure methyloctalone 3: ee = 100 x 190 x 100/95.8 x 219 = 91%.
7. If no crystalline mass is formed but instead an emulsion of the two liquid phases appears, the entire solidification must be repeated (liquid nitrogen cooling).
8. Optically pure methyloctalone 3 is obtained by recrystallizing a sample of
the purified compound several times until a constant [a]D -219° (ethanol, c 1.00 or
methanol, c 1.10) is observed. The [<x]q -219° (methanol, c 1.1) value from the literature3 is confirmed.
9. If a pH lower than 12 is used, recovery of the amine is poor.
Waste Disposal Information
All toxic materials were disposed of in accordance with "Prudent Practices for Disposal of Chemicals from Laboratories"; National Academy Press; Washington, DC, 1983.
3. Discussion
Optically active methyloctalone 3 (or its enantiomer) has been obtained by resolution3'4 and by asymmetric synthesis.5 Both enantiomers are also available commercially. The synthesis described here is by far the most simple and gives the best yield. It is an application of the general method reported for the enantioselective elaboration of quaternary carbon centers through Michael-type alkylation of chiral imines.6
This general method has the following advantages: very simple procedures, very mild conditions involving moderate reaction temperatures and no acids, bases, catalysts, etc., allowing the use of labile reactants, excellent regio- and enantioselectivities as well as high chemical yields, and creation of useful chiral building blocks with quaternary carbon centers involving functionalized chains, allowing one to devise syntheses of natural compounds of various types (terpenes, steroids, alkaloids, etc.). As both optically active amines are commercially available, targets with either desired absolute configuration can be synthesized. Easy recovery of the auxiliary chiral moiety is possible.
Racemic methyloctalone 3 has been used as a starting material for many transformations as well as for syntheses of racemic natural compounds. In the following examples, the absolute configuration of the methyloctalone that would be required to obtain the natural enantiomer is indicated in parentheses: (3-g'orgonene7 (S), widdrol8'9 (R), thujopsene8 10 (R), (R), 7-hydroxycostal11 12 (R), p-selinene13'14
(R), costol, costal and costic acid13 (R), norketoagarofuran15.16 (R), 0-eudesmol13'14-15’17 (R), taxane model18 (S).
The following, chiral, key intermediates have been prepared by a procedure similar to the one described above, generally with excellent chemical and optical yields:
jCb oVO
5 : (R) and (S)1'
6 : (S.S)1 R3
7: R1 = Me; R2 = OMe; R3 = H;
R4 = (CH2)2COOH(S)21 8: R1= Me; R2= R3 = H;
R4 = OMe (S)22 9: R1 = CH2COO-t-Bu; R2= R4= H; R3 = OMe (S)23
R = Me
R = CH2Ph(R)a
10 : R1= Me; R2= (CH2)2COOMe (R f*
R1= OMe, OCHjPh; R2= (CHjJaCOOMe20 R1= COMe; R2= (CH2)2COMe24 R1= COOEt; R2= (CH2)2COOEt, CH(COO-t-Bu)2, (CH2)2COCH3(R)al
R’ = CH2OCH2OMe Rs - (CH2)2coMe (S R1 - Me; R2 = (CH2)2COOMe
A = N-Me; R = CN (+)253 A = N-Me; R - COOMe (-)25a A = S; R = CO-Me (R and S)2!
ROOC o^\
11:A = NCH2Ph;R = Et (R,R) and (S.S)27®
12: A = CH2; R = Me (1 S.2R)28
13: A = NCH2Ph; R = Et (R,R)27a 14: A = CHj; R = Me (1S.2R)28
15 : (6S.7R)29
16: (S)23
Compounds 11-16 arise from an analogous but intramolecular reaction. A special application of the chiral imine procedure, i.e., the use of an oxaziridine rather than an electrophilic olefin, yielding compound 17, has been reported.
Several of these optically active compounds were used for the synthesis of natural products. Thus (R)- and (S)-dimethyloctalones 5 lead, respectively, to natural and ent-geosmin,19 while another natural product was obtained from (S,S)-dimethyloctalone 6, itself a natural compound.19 Compounds 7 and 8 were used to synthesize a ring C aromatic steroid21 and a key [ABC] steroid intermediate,22 respectively.
Tricyclic compound 9 is the starting compound for the preparation of a 14-hydroxyisomorphinan derivative,23 and (R)-keto ester 10 for the preparation of (+)-cassiol31 and (-)-19-noraspidospermidine.32 (R,R)-11 is an intermediate in the total synthesis of (-)-ajmalicine and (-)-tetrahydroalstonine,27a as well as of (+)-y0h i mbine,27t> while its (S.S)-enantiomer can led to (-)-(10R)-hydroxydihydroquinine.273
As in the case of methyloctalone 3, the racemic counterpart of dimethyloctalone
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