Contents
`
`4219 Contributors to this issue
`
`M. Sletzinger, T. Liu,
`. A. Reamer and I. Shinkai
`
`4221 A facile transformation of bicyclic keto esters to bisprotected (±)-8-
`epithienamycin via enol activation
`
`4225 A simple and efficient method of thioacetal- and ketalization
`
`4229 Further studies on stereospecific epoxidation of allylic alcohols
`
`D. A. Evans and J. M. Takacs
`
`4233 Enantioselective alkylation of chiral enolates
`
`.W. M. Schubert and D. C. Green
`
`4237 Solvolytic behavior of p-dimethylamino-a-bromostyrene
`solutions
`
`in water
`
`4241 Behavior of p-dimethylamino-a-bromostyrene and its dimer in dioxane(cid:173)
`water
`
`E. J. Corey, H. Park, A. Barton
`andY.Nii
`
`4243 Synthesis of three potential inhibitors of the biosynthesis of leuko(cid:173)
`trienes A-E
`
`E. Schau mann, A. Rohr and
`G. Adiwidjaja
`
`4247 4-Thioxo-2-azetidinones by cycloaddition of thioketenes with isocyan(cid:173)
`ates
`
`E. Schaumann and F.-F. Grabley
`
`4251 Stable selenoketenes via Selena-Cope rearrangement
`
`W. S. Woo, S. S. Kang, 0. Seligmann,
`V. M. Chari and H. Wagner
`
`H.-U. Rei~ig and B. Scherer
`
`A. N. Sasaki and E. Bricas
`
`4255 The structure of new lignans from the seeds of Phytolacca americana
`
`4259 A simple synthesis of thiol esters from copper-1-mercaptides and acyl
`chlorides
`
`4263 Synthesis of mono- and di-acylated L-2,6-diamino-4-hexynoic acid
`potential derivatives for preparation of 3 H-I abel led lysine containing
`peptides
`
`[continued on back cover]
`Pergamon Press: Oxford New York Paris Frankfurt
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`2
`
`

`

`Tetrahedron Letters Vol, 21, pp 4275 - 4278
`©Pergamon Press Ltd, 1980, Printed in Great Britain
`
`0040-40~9/BO/ 1029-4275$02. no/o
`
`iiiCROBIOLOGICAL SYNTHESIS AND CIRCULAR DICHROISM OF OPTICALLY ACTJVE 2-DEUTERJO-CYCLOALKANOI\FS
`
`By G. Dauphin, J.C. Gramain, A. Kergomard , ti.F. Renard and H. Veschambre
`
`Dcpartement de Chimie (ERA CNRS 392)
`UER Sciences, Universite de Clermont II, RP. 45
`63170 AUBIERE (France)
`
`summary : Optically active 2-deuterio-cyclopentanone and 2-deuterio-cyclohexanone have fJeen prc(cid:173)
`pal·ed by microbiological reduction of 2-deuterio a,B-unsaturatecl cyclic ketones by fieauvevio
`
`sulfurescens.
`
`We recently described (1) the synthesis of optically active 3-cleuterio cycloalkanones hi'
`microbiological reduction of the corresponding 3-cleuterio- 2-cycloalkenones with Beauveria .s u l fc~­
`rescens (ATCC 7159). The same method is now used to prepare the optically active 2-deuterio-cycjo<~'­
`',(anones ~@ and ~~· Hitherto, the only reported 2-deuterio-cyclohexanones had been substituted ~n
`position 4, giving them a blocked confonnation
`(2,3).
`The study of the optical properties or
`2-cleuterio -cyclohexanone
`can give us the confirmation of the contribution of the deuterilml <JtOJII
`as determined by C. Djerassi (2) and S.G. Levine (3).
`
`No 2-deuterio-cyclopentanones had hitherto been described. The optical properties of
`2-deuterio-cyclopentanone enable the contribution of the cleuterilUn atom in a five memsel·ed ring
`
`to be evaluated.
`
`The 2-deuterio-cycloalkenones 1~ and 1~ (4) were prepared by the method of~!.!\. C:uacial'Cl
`and al. (5) from the corresponding cycloalkenones in four steps.
`
`&D Dcam:c;;:o oulJ""'""""'
`
`+
`
`1~
`Reduction of 2-deuterio-2-cyclohexenone lg by Beauveria sulfurescens (ATCC 71591 under
`previously described conditions (6) took 48 hours (yield 8S ~,), giving <I mixture oC (i{j- (+)-!-clcLL(cid:173)
`terio-cyclohexanone ~g (80 ~,) (4) and the two diastereoisomers of (2R)-(+)-2-cleuterio-cyclohexa(cid:173)
`nol ~ (20 %) , ~g and ~were separated by chromatography on silicagel.
`
`4275
`
`3
`
`

`

`4276
`
`2a
`
`Eb = 155°
`
`.)
`
`; {cd_~ 578 = + 2°.5 (c = O.OS, Cl!CL);c.ct.1ul
`= + CJSo at ~88 Jlill.
`lc = 9.cl g/1, I tUI!)
`max
`:r
`( 13c- 1II) = 2ll II::,
`Si) 211.9 (C-1), 42.0 (C-b), 41.7 (t. 1J
`l:)C N.M.R.
`,s (p.p.m. fromMe
`4
`7
`C-2), 27.1 (C-3 c.mu C-5), 25.1 (C-4); ~H N.M.R. 38.39/,lliz i\ (p.p.m. frondlc
`
`Si) 2.1.
`
`4
`
`Results obtained previously for the microbiological rcuuction of 2-methyl- 2-cyclohexcnunc'
`shmvcd that the asynunetric carbon atom fanned· al1vays ll<tcl absolute configuration 1'. 1.\c·
`(G, 7),
`thus assume that the a-carbon in ~g also has absolute configuration E.
`
`C. Djerassi (2) and S.G. Levine (3) were able to sh01v from the stucly of the circuLJr di(cid:173)
`chroism of (ZS) and (ZR)-ueuterio- ( 4R)- isopropylcyclohex:mone ~ and ~ that the contribution or the
`a-,txial ancl a-eCJU:O.toJ·i,~J deuteriwn is anti-octant (dissignate).
`
`0
`
`0
`
`D 0~
`0~
`
`D
`
`H
`
`The circular dichroism curve of ~~ and octant diagrmns of its t1-:o confonncrs arc sho1m
`in figure 1. We asswne that no confonmational preference is int,rocluced by the presence or the clcu(cid:173)
`teriwn atom (8). The positive sign of the circular dichroism is consistent with the presence or an
`axial deuterium in a negative octant. The contribution of equatorial clcuteritml is lvcak. '!he value
`of the circular dichroism observed for ~g is consistent with the value calculated fron1 the c i rcu(cid:173)
`lar dichroismsof ~ and ~ (2) in which the deuterituu is blocked in the axial and cquaturi~il pus t(cid:173)
`tion respectively.
`{8
`
`+
`
`100
`
`50
`
`I ~0
`
`D
`
`D
`
`+
`
`+
`
`300
`
`!-nm.
`
`+
`
`Figure 1 : Circular dichroism curve of ~g and octant diagrams of its tlvo confonncrs.
`
`4
`
`

`

`The unresolvable mixture of ::tlcohols ~ consists of a 50/50 mixture of e-is and tr•ans isomers
`(2H N.M.R. analysis).
`
`4277
`
`TI1e analogous reduction o£ l~ took 48 hours (80 ~yield) and gave only (R)-(+)-2-deutcricl
`cyclopentanone ~~ (4), purified by chromatography on silicagel and distilled.
`~~ Eb = 130°
`{a}
`= + 0°.6 (c = 0.05, CHC1
`); c.d. {G} =- 55° at 299 run.
`(c = 5,65 g/1, Etlllll
`3
`8
`l1laX
`13c N.M.R. o (p.p.m. from Me
`Si) 220.5 (C-1), 38.3 (C-5), 38.0 (t. 1J(13c- 1H) =20Hz C-~),
`23.2 (C-3 and C-4).
`
`57
`52
`
`4
`
`The absolute configuration of the a-carbon is asswned to be R for the follow in_o;tHo reaso;i~;
`(i) reduction of 2-methyl-2-cyclopentenones and 2-methyl-2-cyclohexenones always produced an R
`configuration, (6) and (7).
`(ii) the stereochemistry of the reduction of 2-deuterio-cyclohexenones is the same as that of
`2-methyl-2-cyclohexenone (as indicated previously).
`
`The circular dichroism curve of ~~ and octant diagrams of its two confonners are shown
`in figure 2.
`
`{G}
`
`250
`
`300
`
`350 Anm.
`
`D
`
`~so
`
`0
`A,,,,o
`LJ'~
`
`+
`
`+
`
`+
`
`+
`
`F2o
`
`D
`
`~0
`
`D
`
`Figure 2 Circular dichroism of 2b and octant diagrams of its two conformers.
`
`5
`
`

`

`The sign of the circular dichroism implies (asswning the deuteriLun has no prefered confor(cid:173)
`mation and does not modify u'le conformations of figure 2) that in a cyclopentanone, a pseudo-equa(cid:173)
`torial or pseudo-axial deuteriwn makes a consignate contribution, unlike that in analogous cyclo(cid:173)
`hexanones (2) and (3).
`
`Ho1vever, such an interpretation assum~s that the atom of deuterium does not modify the
`relative populations of the two conformers to the extent that the sign of the circular dichroism
`is detennined by the contribution of carbon atoms 3 and 4 of the ring. Further study of other
`homologous 2-deuterio-cyclopentanones is required to ascertain whether this assumption is a valid
`one.
`
`The use of a microbiological reducing age~~ enables optically active 2-deuterio-cyclo(cid:173)
`alkanones to be easily prepared. TI1e optical activity of these derivatives is solely due to the
`presence of the deuteriwn atom. Previous results (6) and (7) with substituted cyclic ketones jus(cid:173)
`tify the assumption that ~~ and ~g are optically pure.
`
`AKNOWLEDGEMENTS
`
`. We thank Mrs F. Picot (Insitut de Chimie des Substances Naturelles, CNRS, Gif(cid:173)
`sur-Yvette) for c .d. curves and Dr. C. Brevard (Bruker Spectrospin, \Vissembour~.J
`2
`for H N.M.R. spectra.
`
`REFERENCES AND NOTE
`
`(1) G. Dauphin, J.C. Gramain, A. Kergomard, M.F. Renard and H. Vescharnbre, Chern. Com., 318 (1980).
`
`(2) P. Sundararaman and C. Djerassi, Tetrahedron Letters, 2457 (1978).
`
`(3) S.G. Levine and B. Gopalakrishnan, Tetrahedron Letters, 699 (1979).
`(4) The isotopic purity of the deuterio compounds is > 95 % (mass and 1H N.M.R. spectroscopy).
`
`(5) M.A. Guaciaro, P.M. Wovkulich and A.B. Smith, Tetrahedron Letters, 41;61
`
`(1978)
`
`(6) A. Kergomard, H.F. Renard and H. Veschambre, Tetrahedron Letters, 5197 (1978).
`
`(7) A. Kergomard, M.F. Renard and H. Veschambre, to be published.
`(8) S.F. Lee, G. Barth, K. Kieslich and C. Djerassi, J. Am. Chern. Soc., IQQ, 3965 (1978).
`
`(Received in France 31 July 1980)
`
`6
`
`