\

si-t', I0-2J FUSED RINGS AND BRIDGI!D RINGS 279

;hl' l'll11Jucti~1ity of boric acid_2a (~f. Fig. 6-19) and must thus be able to form
,iexes of the type shown m Fig. 10-20· actually the · ct· h h ·
l'l1111r' ' ffi t · h . ' c1s 101 as t e some-
,,,11:1 t greater e ec , s~1ggestmg t at i_t forms the stronger borate com lex.
Among the fused SlX.-mem~ered-nng systems of which the 6-3 6-f
and 6-5
systems have alrea~y tee~- discussed, by far the most important 'com.'pound is
1he 6-6 com~oun . eca m .. It_ was probably the demonstration by W
rri·ckel24 that decalin may exist m cis and trans fonns of h. h th t •·
ril bl h" h fir . , w 1c e rans 1s
the more sta e, w IC st convinced chemists that cyclohexane rings in
decalin and els~where are puckered, as postulated by Sachse and Mohr (cf.
sec. 8-1~, and n<?t pla_nar, as post1:I1ated by _Baeyer.t The counting of butane-
gauche mter~c~ions 111 th e d~cahns ( cf. Sec: 8-3) reveals three such interac-
tions in the ~is isome~t (cf. Fig. 10-21) and none in the trans.§ Therefore the
calculated difference m he~ts of for1:1-ation between the decalins is 3 X 0.9, or
2_7, kcal./n~ole, t~e trans isomer bemg the more stable.25 The experimental
value, obta_med ~i~h~: from te~perature dependence of the cis-decalin ~
trans-decalm eqt1ihb~ium ( estabhshed_at eleva~ed temperature over a plati-
num catalyst) 26a or directly from the difference m heats of combustion 26 b,c is
2.7 kcal./mole for the liquid phase 26a or 3.1 kcal./mole for the vapo'r,26b in
good agreeme~t wi~h the calculated value.
trans-Decahn (Fig. 10-21) has a center of symmetry (midway between Cg
and C10) and is theref9re an optically inactive molecule. It also has a two-
fold axis of symmetry (passing horizontally between C 2 and C 3 , C 9 and C 10,
and C 7 and CB); thus its symm~try number is 2. ci~-Decalin (Fig. 10-21) is

t Actually, J. Boeseken [Rec. trav. chim., 40, 553 (1921)] had somewhat earlier concluded that
cis-cyclohexane- l ,2-diol could not be either planar or boat-shaped, since it does not enhance the
conductivity of boric acid and forms a cyclic isopropylidene ketal with less readiness than other
1,2-diols in which the hydroxyl groups may become coplanar. He reasoned that .the cyclohexane
ring was therefore chair-shaped.
t In the earlier literature, cis-decalin is often depicted as a double boat. However, electron-
diffraction studies [O. Bastiansen and 0 . Hassel, Nature, 157, 765 (1946)] indicate that it exists in
the double-chair form (Fig. 10-21). In view of the unfavorable interactions in the boat (Sec. 8-1),
this is what one would expect.
§ The reader should convince himself of the correctness of this statement by contemplating
appropriate ball-and-stick models. By analogy with 1,2-dimethylcyclohexane (Sec. 8-3), one
might have expected two butane~gauche interactions in the t:ans isomer, considering ea~h ri~g
as a 1,2-disubstituted cyclohexane. However, these int~ract10n.s (5-10-~-8 and 4-10-9-_l m Fig.
l0-21) would then be all within the other ring, and such mte~actions, which al~o occu! m ~yclo-
h.ex_ane itself, are not counted. By a similar argument, _the six butane-_gauche .mter_a ctl?ns m t~1e
c1s isomer are reduced to four. Furthermore, in countmg these four mteract10ns m czs-decalm,
it will be noted that one (5-10-9-1 in Fig. 10-21) has been counted twice over, so that there are
actually only three, viz., 5-10-4-3, 5-10-9-1, and 1-9-8-7 in Fig. 10-21.

3
~ H. G. Derx, Rec. trav. chim., 41, 329 ( 1922).
21
W. H iickel, R. Mentzel, w. Brinkman, and E. Goth, Ann., 441, 1 ( 1925); see also Ref. IS.
25
R. B. Tu rner, J . A m. Ch em. soc., ,74 , 2118 (1952). Turner uses 0.8 kcal. / mole for
b the
· butane-
f h
gauche interaction and refers to an older value for the difference in heats of com uStion
decal ins.
°t e

26(a) N. L. Allinger and J. L. Coke, J. Am. Chem. Soc., 81, 4080 (1959)°; (b) D. M . Speros and
P. D. Rossini, J. Ph s. Chem., 64, 1723 ( I 960). (c) See also W. A. Roth and R. Lasse, A_nn., 441,
48 (1925) (d) S ~I J p M C II h H L F1· nke J F Messerly S. S. Todd, T. C. Kmcheloe,
anu G. W•add mgton,ee a so c t1 ou g • · · · · · · K s p· J A
' J. . .
Phys. Ch em., 61 , 1105 (1957) and T. Miy azawa and . . itzer, . m.
0
i en1, Soc., 80, 60 ( 1958). ,
 ON CoMPOUNDS [CBA}), lQ
F CARB . h . . ·ct
HEtdISTRY o decalin-w hic is ngi because th
280 STEREOC er unlike trans-t through a,a, bonds-the cis isoTh e
. , Howev , h e e no . ·1 t . 1 2 d. h ."1er
dissymmetnc . 1 be throug ' ~ations, sum ar o czs- ' - unet Ylcyclo.
••
0
fusion can on Y.bl chair confo . the case of the latter, the "fiippin ,,
t ';s°two interconve8rt12) e Also, just as iuln to its mirror image.
h cis-Decalin~
f Table - · molec e al h as a two10 1s
.- 1d axis of
fiexane (~ . . n converts the . cis-Decalin so
or chair invers10 olvable di pair, C bond at right angles to the bond in a
therefore a no;:e~hroug h the Cg- b~~ween the 9- and 10-hydrogens. Its
symmet~, p~s tie dihedral angle
plane bisec~ber is thus also 2. . have a symmetry numbe: o_f 2, their dif.
sYffi:IDetry ~h cis- and trans-decah ~ from the fact that the c1s isomer is a di
O
Smee _bo tropy should result Yd should favor the cis isomer. by R 1n 2
fer_ence m ~~ough non-resolvable) fn The experiment al value26a is 0.55 cal./
8 that at least in the liquid
pairl .3(e8vealn /deg. mole (cf. Table - )_. 1 suggestino h · ·
or c · h theoretica , 0
deg.· mole' i.e., less than t e . f the molecules oft e c1s isomer than of
phase there 1s . slightly more ordermg o
the trans. 26d

10

cis-Decalin trans-Decaiin
Fig. 10-21. cis-Decalin and trans-decalin.

From the enthalpy and entropy differences between cis- and trans-decalin
their free-energy difference at 250° C. may be calculated to amount to a_b0~}
2.4 kcal./mole. This is in semiquantit ative agreement with the obs_erv~twn
that the equilibrium between cis- and trans-1-dec alone favors the trans isomer
by between 10: I and 20: l.t .
That trans-decalin is a rigid molecule whereas the cis isomer has two mter-
conver~ible conformations is dramaticall y demonstra ted by the nu~le~:
magnetic resonance spectra of these compounds .27a cis-Decalin shows a sing!
narrow resonance 1me, . ·
smce, . ale
b ecause of the rapid flipping of t he molecu
from one chair form into the other, all methylene hydrogens become idenuc d
and are seen man average position as far as the NMR spectrum is concern)
(cf. Sec. 6-2d). trans-Decalin, on the other hand, shows a broad and part1a y

t Strictly quantitative comparisons are n . si tion of the

1-decalone equilibrium is not know b ~t possible, not only because the exact po he _and
3-ketone effects; cf. Sec. 8-7. n. ut a so because there are complications due to t 2

21 H ·
270 E. Zimmerman and A. Mais, J. A m. Chem
·
J. Musher and R. E. Richards Pr Ch · Soc., 81, 3644 (1959).
' oc. em. Soc. , 230 ( 1958).
 /

.;i:1·. 1()-21 Fusm) RiNos ANO 810001m RINos 281

;0 ,,,1vcd b,_ind caused by t(ie n~n-equiv~Jent equatorial and axial hydrogen,
,nd co mplicated ~y the spu:i-spm couphng between them.
1
· rhc difference ~ potentia! energy bet~een the cis- and trans-9-methyl-
dccalin system (which oc~urs In t~e A/B ru~gs ~f the steroids) is considerably
ll;ss than that between_ cz~- ,an~ t, ans-d.ecaln~.20 The angular methyl group
.. trans-9-methyldecahn ~s axial and gives nse to four butane-gauche inter-
::~iions (two with _respect to either ring; cf. methylcyclohOxane, Sec. 8-2). In
·. · _9_111 ethyldecalm, however,
C/S • 1 . h the methyl group
. is axial with respect to one
ring only and e9uat?nadwdiit_ respehct toh the other, giving rise to two butane-
0 uche interactions m a hon to t e t ree already present in the cis-decalin
"~stem. The total number of butane-gauche interactions in the cis compound
~) therefore five, i.e., only one more than in the trans isomer, and the differ-
is ce in enthalpy should thus be 0.9 kcal./mole. With such a small Mi,
~:lferences in entropy (LiS} betw_e en the isomers may cause
28
to be either /iF
sitive or negative. a Accordingly, m some 9-methyldecalm systems the _
~i~ isomer is found to be more stable, thermodynamically, whereas in others

H 2 C ~ /CH3
~c
H:

HO HO
H 3C CH3

,S-Amyrin ·Lupeol
Fig. 10-22. The triterpenes ,B-amyrin and lupeol.

. 'b . m 28 For the parent compound,

the trans form predominates at eqmh .r~u · er has the lower enthalpy,_ ~H
9-methyldecalin (liquid state), the trans iso;ature dependence of eguihb-
being 0.55 + 0.28 kcal./mole from temp erence in heats of combustion. 289
th
rium2sr or 1.39 + 0.64 kcal./mole froI? et~~ entropy favors the cis isomer
Here, as in the case of the decalms, Id b expected on the basis that the
s!ightly, although again by less th an ~ou e . · .
CIS isomer is a (non-resolvable) di pa~. S system occurs m the C/ D rmg or
I 6
b, Polycyclic Systems. Although e ;r natural products, such as lu_Pe~
the steroid skeleton29 and in a few otl} yclic systems are made up of fuse
(Fig. 10-22), by far the most common po ye
S· Smith, and A.
A Ross · P· AJ ·cgcr · S.
21 9 J 5 ( I 956); (b ) · 0 and L. Ru z.1cka,
~~_(r'.) N. L. Allinger, J. Org. Chem.,. 'ni, J . Kalvoda, H. H_~ussci~. Shopp~c. and G. 1-1~ R.
~>1c1u1ng, Ibid., 20,905 ( 1955); (c) D. AngoN. Jones, J . R. Lewis, f~scnthnl, J, Am. ('!,em. .~oc.,
,:. ,"·Iv. Chim. Acta, 38, 1857 (1955); (c'.)(~ · F Sondheimer and D., I ·20, 2096 ( 196 1): (.i:) W. G.
u,ntncrs, J. Chem. Soc., 2876 ( l 95 5 ), t .L Coke, J. Org. Chun.,'., 283 ( I960).
~!J, 3995 (10 58). (}') N L Allinger and J. · . . / p!,vs. Chem .. <, , ·
I). 0 ~ , · · D Rossin i, · · '/
~~ .cn, 0. Rohr, A. Labbauf, and F. ·
Sec Ref. 84, pp. 212- 2 16.,
 . STRY Of CARDON
COMPOUNDS [C
liAp, I
282 STEREOCHEMI .. t' n will be devoted exclusively to s h O
d this sec I l (F'1g. 8 Uc sYs-
.
s1x-mc n,bered rings, an 'd 10
h stero1 s,84 such as cho estano d -17)· nul'h
. ' •11er
amples are t e . b' (Fig 8-22); an many d1- and t .0Us
tems. Ex him ine · . . ·d (F. 8 18 rtte
·tlkaloids,9o, 91 e.g., yo d b dehydroabietic aci ig. - ) and f3-arn ~-
' enes,86, 88, 89 exemphfie . Y _22 ), respecti~ely. . Yrin
10
rFig. 10-22) and lu_peol (~•:~en a relatively simple polycyclic system such
The stereochem1stry O . 10_23 ) has not been easy. to unravel. Perhyd as
perhydrophen~nthrene (Fl of the ABBA type (cf. Fig. 3-18) an~ may
phenanthrene 1s a molec forms. The nomenclature of these 1s indic tlSt
e?·
as four di pairs and twofimeso ·s· and trans refer to the stereochemistry ofatehd
. I0-23 The pre xes ct t nngs,
. h
in Fig.
. h . · d'vidua1 term1•nal ri·ngs to the cen er • 1 . w ereas . syn ande
fus10n oft e m 1 th orientation of the tenmna nngs with respect t
anti are used to denot~ t ~1 dicates a hydrogen in front of the plane of tho

paper whereas the a

6
each other. A heav se~ce ~f a dot denotes a hydrogen behind the plane ~
hemistry of a number of perhydrophenanthren0
the paper. The stereoc e

Qy.
(IV) cis-syn- (II) cis-syn- (III) cis-anti-
cis (meso) trans (di) cis (di)

~
~
(II) cis-an ti- (V) trans-syn- (I) trans-anti-
trans (di) trans (meso) trans (di)
Fig. 10-23. The ten stereoisomeric perhydrophen~nt~rene s. (In the ca_s~ of di pairs,
only one enantiomer is shown. Roman numerals md1cate order of stability.)

derivatives, including several of the ketones and all the perhydrodiphenic

acids (Fig. 10-25), has been elucidated by the elegant work of Linstead and
coworkers 30 whose arguments will be given here in detail.t ·.
The correlation of several perhydrophenanthro nes with the perhydrodi-
phenic acids is schematized in Fig. 10-24 and requires no comment bey?nd
~he observatio~ that epimerization during oxidation must be guarded aga1?51
•~ th_e assu~phon of equal configuration of a ketone and the correspo~dmg
d1ac1d obtamed from it by oxidation is to be valid. The configurat10~al
assignment of the perhydrodiphenic acids themselves is summarized in Fig.
I0-25.

t F~r th e elucidation of the stereochemistry of even more complicated steroid terpenoid, and
alkaloid systems. the reader is referred to the monographs in these areas.84-91, 9;

:io R P Linstcad W E D · Chem.

64· ·1985 1991' 2 · · oenng, S. B. Davis P Levine and R R Whetstone J. Am.
Soc., , , , 003, 2006, 2009, 2014 (1942); J. Che~. Soc., . 1425, 1428 (1950).
 l.
~,·, ·. I 0-2
'
Fusnn. RI N o s
AND B1
(':i tnlyt1c hydrogenation of diphetl' , . . lIDGilD RINGS 283
. ' ,'d ti f ' lC clCtd g1v
di phclllC ,1c 1 . , uee o the six possibl ' ' '
es, 111 addition to ah ,
,roduct mclt1!1g at 2890 and minor e perhydrodiphenic 'd exahyd~o-

qy
turther stere01somer is obtained by ep1menzm
pr?du~t~ meltinl!
HNo~
th '?. . at 198 oac1
an ds, 2a001!1aJor
Q - Dter of the 289' acid
. A

0 H02C CO 2 H
Fig. 10-24. Correlation of perhydrophenanthrones · h perhydrodiphenic acids.
wit
with base, f~llowed by saponification. Simi
oives a fifth isomer melting at 247° Th . lar !reatment of the 198° acid
o . d b . . . . e six th isom 1.
obtatne y ep1menzat1on of the half- t er, me tmg at 206° is
saponification. es er of the 1980 acid, followed 'by

Ho,c--p
C02 H
ds-Hexahydro-
phthalic acid

NaOCH a on hair-ester

H02C
~
C02H
+ q-p ex=>
H02C C02H
+
H02C C02H
(meso) m.p. 289° m.p. 198° m.p. 200°
( ~50%) (2%) (2%)

l NaOCH 3
on diester 1 NaOCH 3~
on halr-este; ~
NaOCH 3
n diester

m.p. 223° (meso) m.p. 206° m.p. 247°

rig. 10-25. ~ynthesis and configurational assignment of the perhydrodiphenic acids.

t Since epimerization can affect only the asymmetric carbon atoms adjacent
t~ a~ ester group and not the "backbone" atoms involved in the linkage of
e nngs, it follows that the 198°, 206°, and 247° acids all have one and the
i~~e backbone configuration and that the 289', 223.' , and 200' acids h~ve
opposite backbone configuration. Now 1t follows from stereochenucal
 · 'THY (}I '
. (' 'AIUION COMPOUNDS IC11Ap I()
,~., s n •ttH H ·1t1 •MIS kb e:> series is the one that has Lhc two '
, , , -bac on · h ·b k rne~
. I ·r•11ions that thL: syn_ inetry) whereas t e anti- ac bone scric,· 1 o
"•11ns1l L , •
t' )n\\s (pnsscssing p anL:,.
I ·s of sym ' 11 l t ti 289 223 20 ,) ias:_
1 ex erimenta y t rn 1e - - 0 0 series
,:l) n;cso forms. I~ was sl10w_10 fo~ns and therefore has the syn backbone· .'~
the one 11.1 I . t con t·1
• ms the mes ' as
follows : 0 'd were both resolved; therefore the 198-206-2470
l, The l 980 and 247 act s . . .
. two meso fot ms.
series cannot con tam . . of the 2890 acid was resolved but, upon trcatmen
2 The monomethyl este1 . acti've diester Hence the diester and its p l
.· • ti . e gave
with diazome mi1 .' ' an 111. forms (cf. page ·
184). re.
ti 289 0 acid are meso . , 'd l . F'
curs_or, 1e . . ~f the hexahydrodiphemc ac1 s 1own m ig. 10-25 gave
. Smee oz01.11zf ttlo~. cid the phenyl substituent and carboxyl group in the
f 1
c1s-hex~1Y~~ 0 t ~a ~cc:d n;ust be cis. Further hydrogenation of this acid
hexahy rlo _1p 1lent1lc1e 2890 acid and therefore this acid also has the carboxyl
oave exc us1ve Y ' . 1 d b h
groups an d adJ·acent ring 3·uncture c1s.
ti
. It bhas-area
h . y een . . s own that the
289° acid is syn and meso, and hence 1t must et _e c1s-syn-c~s isomer, as ~hown
O
in Fig. 10-25. The configuration o~ the 200 _acid _as t_he cis-syn-trans isomer
follows from its method of format10n by epimenzat10n of the half-ester of
the 289° acid.t The 223 ° acid must, therefore, be the trans-syn-trans isomer,
which is in agreement with the observation that (being a meso form) it could
not be resolved.
Assignments in the anti series do not rest on as firm a basis as those in the
syn series. It should be noted that, in the syn series, conversion of the half-
ester of the 289° acid to the 200° acid and of the diester of the 289° acid to
the 223 ° acid involves, in all cases, a change from a cis acid to a trans acid.
By analogy, it may then be tentatively assumed that the (most stable) 247°
acid. in the anti series is the trans-anti-trans; its (least stable) precursor,
melti!1g at _198°, the cis-anti-cis; and the intermediate isomer, melting at 206°,
the c1s-ant1-trans.
w Al th0 ugh t~e con~gurational_assi_gnment of these compounds was originally
ork~d out with a view to elucidatmg the stereochemistry of catalytic hydro-
gen~ti~n (~- Chap. 12), the assignment of configuration of derivatives of the
6
per rap_ enanthrenes shown in Fig. 10-23 which was deduced30 from the
~~gn_ 1fi-~~t)whn of thke perhydrodiphenic acids to which they are related (cf.
, as ta en on new mea · · h . · I on·
siderations adduced b W J n;~g m t e 11ght of some the~ret1ca c ,
the relative stability th. ?hnson. lr Johnson was able to predict correct!)
following premises: e isomers shown in Fig.\ 10-23 on the basis of the
I. If the ring-fusion bo d . t
to the central ring the n s are ~on sidered equatorial or axial with respel
will be the more stable.;~stem having the larger number of equatorial bon s
i' It rnight be noted th· th
<.:; 1rhoxyl , · at c 289 ° acid c· f · •hich
l A _gr~iup is csterified. an orm only one half-ester (di pair), regardless ol "
. pnu11, there arc Iw
c1>1h 1dercd to he eith o ways of labelin a
number or equat ) .
_ __
t~ .
equatorial or axial g T;ystem, since the first bond might be
c na 0nd s. ·
. i1 r:1ril~·
"'°i,
r••t•SI
e proper labeling is that which gives illc '1 :::
·11 w· ·s· John son /" .
. ' \Xfit'rll'llfi(I 7 ] Is
' ' · ( 195 I)· 1
' · Am. Chem. Soc., 75, 1498 ( I 953 ).
SI;( ',I0-2] FUS ED RIN GS AND B
. RIDGED RIN GS 285
2. Whe n ther e are two axia l bon d
s at the rmg -fusth
l bon ds 1,2 or. I ,4 with resp ion poin ts the sys tem
having the axia
l. l h I ect to eacl ,
more stab l
l bon ds I 3 . I 1 o er will be
thnn tlmt w 11c 1 as t le axia resp ect to each othe r In the
latter system ther e will be a seve re int' . w1~ 1 of the l ,3-diaxial m~thylen e
oroups (cf. Fig. 8-46). e1 acti on
. . e
3. Regardless of pr~ mis e I or 2, if a rin .u
0
gJ nc.h on Involves two axial bonds
either way the syst1em IS labe led ' the system can not e · ·
· · d xist ~n that form but the
central rm~ m sue 1 a syst em mus t be boa t-sh ape (or flexible) and the system
will be qmt e \ms tabl e.
In Fig. I0-23 the bon ds are labe led e (e t •
to the cent ral ring , and the Rom an
num e (~a a
ona l) or (axial) with respect
te its rela tive ord er of stab ility (I ~a st mt P:re n theses below each isomer
deno
e; V, leas t stable).
Figure 10-26 sho ws the five ster eo/s o os _s a
e for the read er to con ~en ctre r;yd roan thra cen es.32 It is
left as an exe rcis
e l dor mes o natu re of these
compounds, labe l the ring fusi on bon ds rm a or e, an con firm the indi cate d
urder of stability.

cco
trans-syn-trans
cco C O ) cis-an ti-trans cis-anti-cis
(I) meso (II) di (III) meso

CO) cco
cis-syn-cis trans-anti-trans
(V) di
(IV) meso
Fig. 10-26. The perhydroanthracenes.

phe nan thre nes (Fig. 10-23)

The pred icte d ord er of stab ility of the perh ydro
in at leas t thre e cases: 3 0 The
h_as been_ con firm ed by equ ilib rati on of keto nes
s-syn-cis (II), the cis-anti-trans
cis-syn-c1s syst em (IV ) is con vert ed to the tran
the cis- syn- tran s (II) could
(II) 1s con vert ed to the tran s-an ti-tr ans (I), and
The last inst ance, shown in ~ig.
not be .converted to the tran s-sy n-tr ans (V).
y to the primitive (but not
10-27, 1s the mos t rem arka ble bec ause it is con trar
the max imu m num ber of tran~
alw_ays corr ect) noti on that a syst em with
fusions shou ld be the mos t stab le.
s_ on perh y?ro phe nan thre n~
A?_ imp orta nt app lica tion of the ab~ ve idea 33
A prec urso r
stability has bee n in w. Joh nso n's clas sica l ster01d synthesis.
rse of t~s synthesis by cata~ytic
of the alicyclic D ring was form ed in the cou
8. _Smee th_e ster~och~IDistry
hydrogenation of a phe nol, as sho wn in Fig. 10-2
iof the ~/ D ring fusi on ( espe<;:ially as rega rds
<;
14) 1s esta blis hed m t~s step,

t Was imp orta nt to dete rmi ne the con

figurat10n of the two steremsomers

s there cited .
J A
Cf. R . L Cla rk Ch Soc 83 965 ( J961) and earli er refer ence6278 6322 (1956) .
:il
e. ·R m. em. ·, ' n, J. Am. Chem. Soc., 18, '
·13 •
E R . and J. A cker ma
. W. S. John son , . . og1er,
 . ( 'AIUlON
( ' MPOUNDS
o ' I( ·'11 AI•. I()
1 . '11
' x(,
1 s 11 ,u,<u ,11 11MI ·SIHYOI J A was stereoc 1em1ca y homogcncou
ctl Since compoun.t r . asymmetric carbon atoms pro,, \
•
ll y 1,,rn1 • 1 n at 1 s •'001 . h d ' uuc;..
·" '' un' the con Ii gum tion s 10~ ,· toms in the catalyt1c y rogenation could
ha, 11\gf I ·c new. asymmetric a o1·someric alcohols (each new asymmetnc .
tnm <' tin.: 2 ., r 8 stere . h
. 1 • • in JJrinc1plc, . ' o ' ber of isomers m t e precursor molecule)
l, r l iu\lCl.:. iplics hy 2 the num bta1·ned presuma bly b ecause the hydrogen·
, tom lly nlult
only two isomer
. .s
'
were o 11 c1·s approach, · d'd · h h
as it I wit· t e perhydro·
·
. · . . tly an a - C) d'"'
Ac tua
,1,·on
1 involves predomman Tl1 two isomers (Band tuer m configuration
• · f '
1 IO 25) e h d I ·
diphenic ac1~s ( ~· ·.1th~r than just of the y . roxy group, smce, upon
f the ring Junct10n r~ . . t ketones D and E. Because of the expected
o , two d1stmc • ·t
oxidation, they .gave . the hydrogenation step, 1 .was assumed that
h 10
predominant c1s approac C/ D cis fusion and that (if the B-C-D ring
both ketones ·would have ah drophenanthrene system) one would be trans-
system was regarded as a per Y -cis Upon treatment with base, one of the
anti-cis and the ot~er t~an~i!I's) w~s epimerized to a new ketone F but the
10
ketones (labeled E ~igd changed Since the cis-syn-trans system is not
otl~er k~tone (D) ~emtt{7) ~:t the cis.-anti-trans system would be expected
cp1menzed (cf. Fig.

Base
>< •

0 0
cis-syn-trans trans-syn-trans
Fig. 10-27. Evidence of instability of the trans-syn-trans perhydrophenanthrene
system.

to be epimerized to trans-anti-trans (Fig. I 0-23), it may be concluded that

ketone D is cis-syn-trans, Eis cis-anti-trans, and F is trans-anti-trans .
Although it is not pertinent to the present discussion, it may be added .that
the configurations of the alcohols B and C were also assigned on the basis of
the fact that B, the precursor of D, was less rapidly oxidized to the ketone
than .was <:=, .the precursor of E. Since equatorial alcohols are gen.erally less
readily oxidized than axial alcohols (see below), it may be tentatively con·
eluded that the hydroxyl group in B is equatorial and in C axial. The com·
plete_ configurations of these alcohols are, therefore, as shown at the botto~1
of Fig ..10· 2~- (Note that, since the C / D ring fusion is cis, a bond th at 15
equatonal w.1th respect to ring C is axial with respect to ring D, and vice versa,.)
If t~~se assignments are correct, B and C are indeed products of al1-c1s
add1t1on of hydrogen t0 th . . . ' '
e aromatic nng m the precursor A . .
. A_s/he ab?ve e~ample indicates, stereochemical , and especially confornl' .1•
~\~~~t~;~~:~~~~~ 1 : .ons) afre of great importance
1
a ion °
in the synthesis (as
natural products · Unfortunately , it is not possi
we\;~!
even to attempt to h' f , text·
hook We h 11 . covert .1s ~rea at all adequately within the scope O '~ ' 01
.1iome. of th~li ~ o; i~s~ead, 1.1m1t ourselves in this chapter to a considerat1~.':me
e m erestmg conformational aspects of the chemiSt ry 0
 11 1 'I 1:wrnn l~IN W, AN1, ll1t11H11!1, R1 N<1 '1 7.WI
"1'
,, 111 11 :11111 nlL'lHll)l~Hlllds , nanwl~, lht· NtcroldH. 111 ( ' '111p. I 1 we sh11II re 111, n
, 1, ·lh " 1 stcrt'llChc1111c11I aspects ol n11111rnl-prod11cl 11y111hcsi,.,,
11
t· ~ 111111s1 :di slt·roids _cnnlnm the rin g system shown 111 I :1g. I0-2'J. 'Jhe A / H
, l\ i:-hlll ll\llY he c1tl~cr t_rnns (nlso called ) ,v or 11110) or cis (al"" c1tllc<l ~fl
11111
• 11 nud): nil nthcr nng Jllncturcs nrc lrn11s. The llf)proprialc confonna -
' I 1 1II •
, c shnwn Ill ·1g.
I " I() -207 , '"'-' Ilie
' I1 correctly rc1wcscnts th e ah1mlutc confl,,-
11,111, . 11 • I . . o
tlllll of the stero1l s m question . Clro11ps pointing upward (i11 the direction
.
. ar I~•lr.nn .
'Iy assigned . . I ,.,,c rco-
,,r the ( · 10 an~. 1 '-r 1:1 me ti1y I groups ) arc
111,1 the tnvrn
,·hrnti (:tl prchx # whereas the groups po1nt111 g downward arc c.:a lle<l ,r. r,

011 OJI 0
j

,'l½'6
A
11 2 , l'l

AcOH c6D two isomers

(B, C)
Ox
---+
'

two isomcn.
)

(D, E)

0 0

D E
o56 F

OH OH

B C
Fig. 10-28. Esta blishment of stereochemistry of D ring in Johnson's steroid synthesis.

~h~)uld be noted that the designations a and /3 have nothing to do with the
ax ial or equatorial nature of the substituent; as Fig. I0-29 shows, an ex (or
fi~!-,Ubstituent may be either axial or equatorial. In the tr.ans series. /3 sub-
'l tlluents at C 2 , C 1 , C 6 , C 8 , C 10 , C 11 , a nd C1a and ,x subst1tue nts at C 1 , C 3 •
\'i, C1, Co, C 1 2 , and C 11 are a xial. Contrariwise, c\' subs tituents at C.!, C 4 •
< r., and C 11 a nd f3 substituents at C 1 , C:1, C1, and Ci:.! a re equatorial. In the
c,., , cries, /3 substituents at C 1 , C:1, C 0 , CH, C 11, and Cm and l\' substituents
t ~-~. _C1, C 1, C 9 , C 12 ,. and C 1.1 are axial, wh er~as l\' substitu~nts at C 1, C:h
'•· .i nd C 11 andµ subst1tuents at Ci, C,., C1, and C 1z are cquatonal. T hl! µ sub-
"11tu~nts a t c~ a nd C 10 in th e c is series are eq uatorial with rl!spect to one of
111 1: rings a nd axial with respect to the other.