Versatile enantioselective synthesis of four diastereomers of serricornin, a sex pheromone of the cigarette beetle, using the SAMP/RAMP-hydrazone method

Article abstract of DOI:10.1135/cccc20000524

Serricornin is a female-produced sex pheromone of the cigarette beetle (Lasioderma serricorne), which is a pest of dried foodstuffs and tobacco. We report a versatile and short synthesis of all possible 6,7-syn-isomers of serricornin, including the natura

Full text of DOI:10.1135/cccc20000524

524
Job, Nagelsdiek, Enders:
VERSATILE ENANTIOSELECTIVE SYNTHESIS OF FOUR
DIASTEREOMERS OF SERRICORNIN, A SEX PHEROMONE OF THE
CIGARETTE BEETLE, USING THE SAMP/ RAMP-HYDRAZONE METHOD
1
2,+
3,
Andreas JOB , René NAGELSDIEK and Dieter ENDERS *
Institut für Organische Chemie, Rheinisch-Westfälische Technische Hochschule,
Professor-Pirlet-Strasse 1, D-52074 Aachen, Germany; e-mail: 1 andreas.job@post.rwth-aachen.de,
2
3
rene.nagelsdiek@post.rwth-aachen.de, enders@rwth-aachen.de
Received February 2, 2000
Accepted March 16, 2000
Dedicated to Professor Otakar Červinka on the occasion of his 75th birthday in recognition of his
outstanding contributions to the area of organic stereochemistry.
Serricorn in is
a fem ale-produced sex ph erom on e of th e cigarette beetle (Lasioderma
serricorne), wh ich is a pest of dried foodstuffs an d tobacco. We report a versatile an d sh ort
syn th esis of all possible 6,7-syn-isom ers of serricorn in , in cludin g th e n atural isom er. Startin g
from th e SAMP an d RAMP derivatives of dieth yl keton e we obtain ed four differen t
en an tiopure an d diastereom erically pure serricorn in s. Th e m ain advan tage of th is m eth od is
th at on ly a sin gle kin d of ch iral startin g m aterial is n eeded for th e con struction of th ree
stereogen ic cen ters. Durin g th e syn th esis furth er useful in term ediates in cludin g (R)- an d
(S)-1-ben zyloxy-2-m eth ylpen tan -3-on e (4) an d (2S,3R)- an d (2R,3S)-1-iodo-3-(m eth oxy-
m eth oxy)-2-m eth ylpen tan e (9) were obtain ed.
Key w ord s: Asym m etric syn th esis; Hydrazon es; Natural products; Ph erom on es; Reduction s;
Total syn th esis.
Th e title com poun d (4S,6S,7S)-7-h ydroxy-4,6-dim eth yln on an -3-on e (1,
serricorn in ) is th e fem ale-produced sex ph erom on e of th e cigarette beetle
(Lasioderma serricorne). Th is species is a pest of dried foodstuffs an d tobacco.
It was first isolated an d ch aracterized by Ch um an 1 in 1979. Its absolute
con figuration was assign ed by com parin g differen t syn th etic diastereom ers
an d en an tiom ers of its acetate derivative with th e acetate obtain ed from th e
n atural serricorn in 2. Th e absolute con figuration of th e n atural isom er was
assign ed to be 4S,6S,7S.
+ Un dergraduate research participan t.
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Four Diastereomers of Serricornin
525
The natural isom er of serricornin (1) exists as an equilibrium m ixture of the
cyclic hem iacetal 1b and an open-chain form 1a (1b : 1a = 3 : 1, Schem e 1),
wh ereas th e (4R,6S,7S) isom er exists on ly in th e open -ch ain form . Th is dif-
OH
O
OH
O
1a
1b
SCHEME 1
feren t beh aviour en ables th e separation of both isom ers by sim ple colum n
ch rom atograph y3. Sin ce 1979 m an y syn th etic an d biological in vestigation s
h ave been m ade4. Even a large scale syn th esis h as been developed for th e
use of serricorn in in com m ercial in sect lures4f,5. Despite of all syn th etic
work carried out on serricorn in , it is still a ch allen ge for syn th etic con cepts
an d m eth ods.
RESULTS AND DISCUSSION
Th e retrosyn th etic an alysis depicted in Sch em e 2 sh ows th at it is possible to
gen erate th e th ree stereogen ic cen ters of 1 based on a sin gle ch iral startin g
m aterial. First a ch iral equivalen t of th e dieth yl keton e en olate A can be
used to gen erate th e stereogen ic cen ter of th e substituted keton e C by an
asym m etric α-alkylation . Th e carbon yl group of C can be reduced selec-
tively to yield th e syn-isom er of th e in term ediate B′. A secon d asym m etric
α-alkylation of A with th e h alide B′ gen erates th e th ird stereogen ic cen ter
in th e target m olecule. If both en an tiom ers of a ch iral equivalen t of A are
available th e com bin ation of both syn th etic path ways (Sch em e 4) results in
four diastereom ers of serricorn in (1).
O
OH
O
OH
OPG
+
X
1
B'
A
B
O
O
+
X
X
Y
X
D'
D
A
C
PG = protective group
X, Y = halides or equivalent groups
SCHEME 2
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526
Job, Nagelsdiek, Enders:
Th e SAMP/RAMP-h ydrazon e m eth odology developed in th is group6 pro-
vides excellen t con dition s for th is purpose. Th e n atural diastereom er of
serricorn in can be obtain ed by usin g on ly (S)-1-am in o-2-(m eth oxym eth yl)-
pyrrolidin e (SAMP) as ch iral auxiliary (vide infra).
Th e startin g h ydrazon e (S)-2 can be obtain ed in quan titative yield from
SAMP an d dieth yl keton e7. Th e reaction of th e h ydrazon e (S)-2 with lith -
ium diisopropylam ide an d ben zyloxym eth yl ch loride (BOMCl) provided
th e substituted h ydrazon e (S,R)-3 in 94% de (Sch em e 3). Th e con figuration
of th e n ew stereogen ic cen ter was con firm ed by NOE experim en ts an d by
th e rotation value of th e resultin g keton e (S)-4 (ref.8). Th is in dicated th at
th e reaction follows th e m ech an ism for electroph ilic substitution reaction s
of SAMP-h ydrazon es9. Ozon olytic cleavage of 3 provided th e kn own keton e
(S)-4 in 94% ee an d good yield. (S)-2-(Meth oxym eth yl)-1-n itrosopyrrolidin e
produced in th e reaction with ozon e can easily be separated from th e prod-
uct by colum n ch rom atograph y. Th e by-product can be recycled to SAMP
by m ean s of lith ium alum in ium h ydride.
O
1) LDA,
2) BOMCl
O3
N
N
BnO
85% (2 steps)
ee = 94%
N
N
OCH3
(S,R)-3
OCH3
(S)-2
(S)-4
BnO
L-selectride®
93%
syn : anti = 6.5 : 1
OH
OMOM
MOMCl, lutidine,
OMOM
[DMAP]
Pd/C, H2
BnO
BnO
HO
95%
ee = 94%
de > 96%
(after HPLC)
(S,S)-5
(S,S)-6
(S,S)-7
TsCl, pyridine
OMOM
OMOM
NaI, acetone
83% (3 steps)
overall yield: 62%
ee = 94%
de > 96%
TsO
I
(S,S)-8
(R,S)-9
OMOM
8 steps
analogously:
(R)-2
I
overall yield: 53%
ee = 93%
(S,R)-9
de > 96%
SCHEME 3
Th e secon d stereogen ic cen ter was gen erated by a syn-selective reduction
of th e carbon yl fun ction ality of keton e 4. Various kn own m eth ods10 were
in vestigated usin g differen t solven t system s (Table I). Th e solven t given in
th e table correspon ds to th at in wh ich th e best selectivity was observed for
th e given reagen t. Sin ce th e reaction with L-Selectride® in dich lorom eth an e
gave th e best syn/anti ratio in our experim en ts an d sin ce th e reagen t is com -
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Four Diastereomers of Serricornin
527
m ercially available, we h ave ch osen th is reagen t for our syn th esis. Al-
th ough th e syn/anti ratio was on ly 6.5 : 1, it was possible to separate th e
diastereom ers of th e m eth oxym eth yl (MOM)-protected alcoh ol 6 by HPLC
in th e n ext step. Con version of th e diastereom eric m ixture 5 to th e MOM
derivatives was ach ieved usin g m eth oxym eth yl ch loride an d lutidin e in th e
presen ce of a catalytic am oun t of 4-(dim eth ylam in o)pyridin e (DMAP) to
obtain diastereom erically pure (S,S)-6 in 94% ee after HPLC purification .
Th e diastereom eric purity was determ in ed by NMR an alysis, wh ile th e
en an tiom eric excess was taken from th e keton e 4 on th e assum ption th at
th e reduction with L-Selectride® occurs with out an y racem ization . Th e very
low selectivities of th e reduction (Table I, en tries 3–9) can be explain ed by
th e absen ce of an un protected h ydroxy group for ch elation an d by a system
with few steric dem an ds.
A sim ple th ree-step sequen ce gave (R,S)-9 from dieth er 6. First th e
ben zylic protective group was reduced with h ydrogen an d palladium on
ch arcoal. Th e resultin g alcoh ol 7 was th en con verted in to th e correspon d-
in g tosylate 8 by th e reaction with tosyl ch loride an d pyridin e. Th e crude
product was subsequen tly refluxed with sodium iodide in aceton e to pro-
vide th e iodide (R,S)-9 (ref.11) as in term ediate for th e syn th esis of th e (S,S,S)
an d (R,S,S) diastereom ers of serricorn in . Th e com plete eigh t-step procedure
was also accom plish ed startin g from h ydrazon e (R)-2 resultin g in th e
en an tiom eric iodide (S,R)-9 (ee 93%) for th e syn th esis of th e (R,R,R) an d
(S,R,R) diastereom ers of serricorn in .
TABLE I
Results of th e diastereoselective reduction of keton e 4
En try
Reagen t
Solven t
Tem perature, °C
syn/anti-ratioi
1
2
3
4
5
6
7
8
9
L-Selectride
LiBHBu3
CH2Cl2
CH2Cl2
eth er
–90
6.5:1
6.5:1
1.7:1
1.7:1
1.5>1
1.4:1
1.4:1
1.2:1
1:1.3
–90
Zn (BH4)2
–78
NaBH4/AcOH
LiAlH4
CH2Cl2
CH2Cl2
THF
0
0
NaBH4/Bu3B
Sm I2/MeOH
NaBH4
–78
THF
0
0
EtOH
THF
Catech olboran e
–20→0
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Job, Nagelsdiek, Enders:
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Four Diastereomers of Serricornin
529
Th e h ydrazon es (S)-2 an d (R)-2 were deproton ated with LDA an d each
subsequen tly treated with eith er of th e iodides (R,S)-9 an d (S,R)-9 (Sch em e 4).
Th e asym m etric α-alkylation was carried out for th e four possible com bin a-
tion s, resultin g in th e four correspon din g isom ers of 10. Ozon olytic cleav-
age yielded th e correspon din g MOM-protected serricorn in s 11 in good
yields an d with good diastereom eric excesses. Th e h ydrazon es 11 were also
cleaved usin g oxalic acid12 with th e sam e selectivities but in on ly 60% yield
over 2 steps.
Th e loss of diastereom eric purity in th e case of th e (S,S,S) an d (R,R,R) iso-
m ers of 6 an d 7%, respectively, com pared to th e loss of 2 an d 3% for th e
(R,S,S) an d (S,R,R) isom ers m ay be a result of a m atch in g an d m ism atch in g
of th e reaction partn ers13. Th ese results in dicated a preservation of th e
en an tiom eric purity of th e products. Th e cleavage of th e MOM protective
group was ach ieved by applyin g brom odim eth ylboran e14 to obtain th e cor-
respon din g serricorn in s in good yields. No epim erisation was observed in
th is reaction . Sin ce it is possible to separate th e differen t diastereom ers by
colum n ch rom atograph y as m en tion ed before, th e products could be ob-
tain ed in diastereom erically pure form . Th e cleavage of th e MOM group
with brom odim eth ylboran e proceeds un der very m ild con dition s at low
tem perature. Th is proved to be a very suitable cleavage m eth od, givin g
good yields with out th e form ation of by-products. Th e stron g acidic con di-
tion s usually em ployed can n ot be used on serricorn in , as it is kn own th at
deh ydration takes place in th e presen ce of on ly trace am oun ts of acid3,15
.
In con clusion , we h ave developed a sh ort an d versatile approach for th e
asym m etric syn th esis of all possible 6,7-syn-isom ers of serricorn in in excel-
len t diastereom eric an d en an tiom eric excess.
EXPERIMENTAL
All reaction s were carried out un der argon atm osph ere. Th e solven ts were purified an d dried
before use. Petroleum eth er (40–60 °C) an d pen tan e were distilled from CaH2, THF an d di-
eth yl eth er (eth er) were distilled from Na/Pb alloy an d ben zoph en on e un der Ar an d CH2Cl2
was distilled from CaH2 un der Ar. SAMP (ref.6), BOMCl (ref.16) an d Me2BBr (ref.14) were syn -
th esized accordin g to literature procedures. All oth er ch em icals were purch ased from
Aldrich , Acros, Merck an d Fluka. Ozon e was gen erated by a Fisch er Ozon e apparatus (M502).
Optical rotation s were m easured at 25 °C on a Perkin –Elm er P 241 polarim eter usin g sol-
ven ts of UVASOL quality an d are given in 10–1 deg cm 2 g–1. In frared spectra were recorded
on a Perkin –Elm er FT 1750 spectrom eter (waven um bers in cm –1). Mass spectra were recorded
on a Varian MAT 212 (EI 70 eV an d CI 100 eV, isobutan e), h igh resolution m ass spectra on
a Fin igan MAT 95 spectrom eter. Microan alyses were perform ed on a Heraeus CHN-O-Rapid.
NMR spectra were m easured on Varian Gem in i 300 (1H: 300 MHz, 13C: 75 MHz), Varian
In ova 400 (1H: 400 MHz, 13C: 100 MHz), Varian Un ity 500 (1H: 500 MHz, 13C: 125 MHz) at
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

530
Job, Nagelsdiek, Enders:
22 °C in CDCl3 or C6D6 usin g tetram eth ylsilan e as in tern al stan dard. Ch em ical sh ifts are
given in ppm (δ-scale), couplin g con stan ts J in Hz. Gas ch rom atograph y on ch iral station ary
ph ases was perform ed on a Siem en s Sich rom at (colum n : Lipodex E®, 25 m , Ch rom pack).
Preparative HPLC was carried out on Gilson Abim ed (colum n : Hibar®, 250 m m × 25 m m ,
LiCh rosorb Si 60, 7 µm , Merck). Th in layer ch rom atograph y was perform ed on silica gel F254
plates (Merck), with detection by UV (254 n m ) or a solution of am m on ium m olybdate (5 g)
an d ceric sulfate (30 m g) in 10% sulfuric acid (100 m l). Preparative ch rom atograph y was
don e on silica gel 60 (40–63 µm , Merck).
Preparation of LDA Solution s. Gen eral Procedure
A solution of 1.2 equivalen ts (based on am oun t of th e h ydrazon e) diisopropylam in e in eth er
(5 m l/m m ol h ydrazon e) or THF (3 m l/m m ol h ydrazon e) was cooled un der an in ert atm o-
sph ere to 0 °C. At th is tem perature a solution of BuLi (1.6 M in h exan e) was added an d
stirred for an oth er 5 m in .
Ozon olytic Cleavage of Hydrazon es. Gen eral Procedure
A crude h ydrazon e was dissolved in CH2Cl2 (25–70 m l) an d th e m ixture was cooled to –78 °C
un der an in ert atm osph ere. Ozon e was passed th rough th e solution un til it ch an ged th e
color from yellowish to a blue or grey sh ade. After th e reaction was com pleted, Ar was
passed th rough th e solution un til th e color disappeared. Th is procedure is n ecessary to ex-
pun ge surplus ozon e. Th e m ixture was warm ed to room tem perature an d con cen trated in
vacuo. Th e resultin g yellow oil was purified by flash ch rom atograph y to afford th e products
as a colorless oil.
(S)-1-{[(R)-1-Ben zyloxy-2-m eth ylpen tan -3-yliden e]am in o}-
2-(m eth oxym eth yl)pyrrolidin e [(S,R)-3]
To a solution of LDA (6.00 m m ol, procedure described above) in eth er (25 m l) was added
h ydrazon e (S)-2 (992 m g, 5.00 m m ol) at 0 °C. Th e resultin g solution was stirred for 4 h at
th is tem perature, th en cooled to –115 °C an d ben zyloxym eth yl ch loride (BOMCl; 936 m g,
6.00 m m ol) was added. Th e solution was allowed to warm to room tem perature overn igh t
an d quen ch ed with 20 m l of a buffer (pH 7)/15 m l THF. After stirrin g for 10 m in , th e aque-
ous layer was extracted with eth er. Th e com bin ed organ ic ph ases were wash ed with brin e
an d dried over Na2SO4. Th e solution was filtered th rough a silica gel pad (5 m m ) an d con -
cen trated in vacuo. Th e crude product (2.000 g) was em ployed in th e n ext step with out fur-
th er purification .
A sm all am oun t of th e crude product was purified by ch rom atograph y on a sh ort colum n
(4 cm silica gel, petroleum eth er–eth er 10 : 1) for ch aracterization . RF 0.23 (petroleum
eth er–eth er 2 : 1). [α]D +113.7 (c 0.97, CHCl3), de = 94% (13C NMR). 1H NMR (500 MHz,
C6D6): 0.88 (d, 3 H, J = 7.1, CH3); 1.23 (t, 3 H, J = 7.3, CH3); 1.58–2.02 (m , 4 H,
NCH2CH2CH2); 2.13 (dq, 2 H, J = 13.5, 7.3, CH3CH2); 2.53 (m , 1 H, NCHH); 2.94 (m , 1 H,
NCHH); 3.13 (s, 3 H, OCH3); 3.18–3.57 (m , 5 H, NCHCH2O, CH2O); 3.98 (m , 1 H, CH3CH);
4.32 (m , 2 H, CPh CH2O); 7.05–7.33 (m , 5 H, CPh H). NOE (500 MHz, C6D6): CH3CH →
pro-S-NCHH: 3%; CH3CHCH2 → CH3CH2: 6%; pro-S-NCHH → CH3CH: 8%; pro-R-NCHH →
NCH: 6%. 13C NMR (125 MHz, C6D6): 11.35 (CH3); 14.60 (CH3); 22.35 (NCH2CH2CH2);
24.53 (CH3CH2); 27.59 (NCHCH2); 34.96 (CH3CH); 55.90 (NCH2); 58.81 (OCH3); 66.76
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Four Diastereomers of Serricornin
531
(NCH); 72.70 (OCH2Ph ); 72.79 (CH2O); 76.26 (NCHCH2O); 127.62, 128.04, 128.52 (CPh );
139.20 (CPh , ipso); 173.08 (N=C). MS (EI): 318 (7, M+); 274 (18, MH+ – CH2OCH3); 273 (96,
M+ – CH2OCH3); 91 (100, Ph CH+2); 70 (11); 56 (9). IR (n eat): 1 950, 1 872, 1 808 (Ph ); 1 631
(C=N); 1 100, 1 049 (s, C–O); 737, 698 (Ph ). For C19H30N2O2 (318.5) calculated: 71.66% C,
9.50% H, 8.80% N; foun d: 71.89% C, 9.40% H, 8.34% N.
(R)-1-{[(S)-1-Ben zyloxy-2-m eth ylpen tan -3-yliden e]am in o}-
2-(m eth oxym eth yl)pyrrolidin e [(R,S)-3]
To a solution of LDA (2.40 m m ol, procedure described above) in eth er (10 m l) was added
h ydrazon e (R)-2 (397 m g, 2.00 m m ol) at 0 °C. Treatm en t with BOMCl (375 m g, 2.40 m m ol)
as described for (S,R)-3 an d subsequen t workup provided 715 m g crude product, wh ich was
em ployed in th e n ext step with out furth er purification . A sm all am oun t of th e crude product
was purified by ch rom atograph y on a sh ort colum n (4 cm silica gel, petroleum eth er–eth er
10 : 1) for ch aracterization . [α]D –112.7 (c 0.22, CHCl3), de = 93% (13C NMR). All spectro-
scopic data are iden tical with th ose given for (S,R)-3.
(S)-1-Ben zyloxy-2-m eth ylpen tan -3-on e [(S)-4]
A solution of crude h ydrazon e (S,R)-3 (2.000 g) in CH2Cl2 (70 m l) was cleaved with ozon e
(as in th e gen eral procedure). Purification by ch rom atograph y (elution with petroleum
eth er–eth er 10 : 1) provided 878 m g (4.26 m m ol; 85%) colorless product. RF 0.53 (petroleum
eth er–eth er 2 : 1). [α]D +24.7 (c 1.25, CHCl3), ee = 94% (GC, Lipodex E). All oth er data are
iden tical with th ose reported in literature8.
(R)-1-Ben zyloxy-2-m eth ylpen tan -3-on e [(R)-4]
A solution of crude h ydrazon e (R,S)-3 (655 m g) in CH2Cl2 (25 m l) was cleaved with ozon e
(as in th e gen eral procedure). Purification by ch rom atograph y (elution with petroleum
eth er–eth er 10 : 1) provided 318 m g (1.54 m m ol; 84%) colorless product. [α]D –24.5 (c 1.50,
CHCl3), ee = 93% (GC, Lipodex E). All oth er data were iden tical with th ose given for (S)-4.
(2S,3S)-1-Ben zyloxy-2-m eth ylpen tan -3-ol [(S,S)-5]
To a cold (–90 °C) solution of keton e (S)-4 (1.204 g, 5.84 m m ol) in CH2Cl2 (25 m l) were
slowly added L-Selectride® (8.00 m l, 1.0 M solution in THF). Th e m ixture was stirred for
an oth er 2 h an d allowed to warm to –78 °C. Th e reaction was quen ch ed with m eth an ol (15 m l)
an d stirred for an oth er 1 h wh ile warm in g to room tem perature. Th e volatile com poun ds
were rem oved in vacuo an d th e residue was diluted with THF (10 m l). After addin g 10%
NaOH (5 m l) an d 30% H2O2 (5 m l) th e m ixture was stirred overn igh t at room tem perature.
Th e aqueous ph ase was extracted with eth er an d th e com bin ed organ ic ph ases were wash ed
with a buffer (pH 7) an d brin e. After dryin g with Na2SO4 an d con cen tratin g in vacuo, th e
crude oil was purified by ch rom atograph y on silica gel (elution with petroleum eth er–eth er
5 : 1) to give 1.126 g (5.41 m m ol; 93%) colorless product. RF 0.26 (petroleum eth er–eth er
2 : 1). Syn/anti = 6.5 : 1 (determ in ed by 13C NMR). 1H NMR (300 MHz, CDCl3, syn-isom er):
0.92 (d, 3 H, J = 7.1, CH3); 0.94 (t, 3 H, J = 7.4, CH3); 1.43 (m , 2 H, CH2CH3); 1.87 (m , 1 H,
CHCH3); 2.62 (s, 1 H, OH); 3.51 (m , 2 H, OCH2CH); 3.65 (m , 1 H, CHOH); 4.49 (m , 2 H,
CH2Ph ); 7.24–7.37 (m , 5 H, CPh H). 13C NMR (75 MHz, CDCl3, syn-isom er): 10.61 (CH3);
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

532
Job, Nagelsdiek, Enders:
10.71 (CH3); 26.88 (CH2CH3); 37.49 (CHCH3); 73.38, 74.80 (CH2OCH2Ph ); 75.42 (CHOH);
127.57, 127.66, 128.41 (Cph ); 138.12 (Cph , ipso). MS (CI): 210 (15); 209 (100, MH+). IR (n eat):
3 449 (OH); 1 949, 1 872, 1 808 (Ph ); 1 096, 1 029 (C–O); 736, 698 (Ph ). For C13H20O2
(208.3) calculated: 74.96% C, 9.68% H; foun d: 74.47% C, 9.47% H.
(2R,3R)-1-Ben zyloxy-2-m eth ylpen tan -3-ol [(R,R)-5]
A solution of keton e (R)-4 (541 m g, 2.62 m m ol) in CH2Cl2 (12 m l) was con verted to 5 usin g
L-Selectride® (4.00 m l) in th e sam e m an n er as described for (S,S)-5. Purification by ch rom a-
tograph y provided 499 m g (2.40 m m ol; 91%) product. Syn/anti = 6.3 : 1 (determ in ed by
13C NMR). All oth er spectroscopic data were iden tical with th ose given for (S,S)-5.
(2S,3S)-1-Ben zyloxy-3-(m eth oxym eth oxy)-2-m eth ylpen tan e [(S,S)-6]
Alcoh ol (S,S)-5 (1.126 g, 5.41 m m ol; syn/anti m ixture) was dissolved in 2,6-lutidin e (2.80 m l)
an d stirred at room tem perature for 2.5 h . Th is solution was added to a solution of
m eth oxym eth yl ch loride (MOMCl; 3.00 m l, 39.50 m m ol) in CH2Cl2 (6 m l) con tain in g cata-
lytic am oun ts of 4-(dim eth ylam in o)pyridin e (DMAP). After stirrin g at room tem perature for
6 h , th e reaction was quen ch ed with a buffer (15 m l, pH 7) an d th e organ ic m aterial was ex-
tracted with CH2Cl2. Th e organ ic layer was wash ed with 1 M HCl solution un til th e aqueous
layer becam e acidic, th en on ce with a buffer (pH 7) an d brin e. After dryin g over Na2SO4 an d
evaporation un der reduced pressure, th e crude product was purified by colum n ch rom atog-
raph y (elution with petroleum eth er–eth er 10 : 1). Th e product was obtain ed as colorless oil
(1.300 g, 5.15 m m ol; 95%). On ly th e desired syn product was ch aracterized after HPLC puri-
fication . RF 0.62 (petroleum eth er–eth er 2 : 1). [α]D –8.0 (c 0.95, CHCl3), de > 96% (deter-
m in ed by 13C NMR), ee 94% (based on th e keton e (S)-4). 1H NMR (500 MHz, CDCl3): 0.90
(t, 3 H, J = 7.5, CH3); 0.93 (d, 3 H, J = 7.0, CH3); 1.54 (m , 2 H, CH2CH3); 2.00 (m , 1 H,
CHCH3); 3.32 (dd, 1 H, J = 9.1, 6.5, OCHHCH); 3.34 (s, 3 H, OCH3); 3.48 (dd, 1 H, J = 9.1,
6.8, OCHHCH); 3.56 (td, 1 H, J = 6.6, 3.4, CHOH); 4.48 (m , 2 H, CH2Ph ); 4.62 (s, 2 H,
OCH2O); 7.22–7.34 (m , 5 H, CPh H). 13C NMR (125 MHz, CDCl3): 10.26 (CH3); 11.44 (CH3);
24.68 (CH2CH3); 36.22 (CHCH3); 55.51 (OCH3); 72.83, 73.05 (CH2OCH2); 80.13 (CHOH);
96.49 (OCH2O); 127.44, 127.59, 128.29 (Cph ); 138.62 (Cph , ipso). MS (EI): decom position . IR
(n eat): 1 950, 1870, 1 808 (Ph ); 1 098, 1 039 (C–O); 737, 699 (Ph ). For C15H24O3 (252.4) cal-
culated: 71.39% C, 9.59% H; foun d: 71.02% C, 9.61% H.
(2R,3R)-1-Ben zyloxy-3-(m eth oxym eth oxy)-2-m eth ylpen tan e [(R,R)-6]
Alcoh ol (R,R)-5 (258 m g, 1.24 m m ol; syn/anti m ixture) was con verted to 6 with 2,6-lutidin e
(0.70 m l), MOMCl (1.00 m l, 13.17 m m ol), catalytic am oun ts of DMAP an d CH2Cl2 (0.5 m l)
in th e sam e m an n er as described for (S,S)-6. Purification by ch rom atograph y provided 287
m g (1.14 m m ol; 92%) product. On ly th e desired syn product was ch aracterized after HPLC
purification . [α]D +8.0 (c 1.03, CHCl3), de > 96% (determ in ed by 13C NMR), ee = 93% (based
on th e keton e (R)-4). All oth er data were iden tical with (S,S)-6.
(2S,3S)-3-(Meth oxym eth oxy)-2-m eth ylpen tan -1-ol [(S,S)-7]
To a solution of (S,S)-6 (1.103 g, 4.37 m m ol) in eth er (80 m l) was added Pd/C (30 m g; 10%)
an d th e flask was equipped with a balloon con tain in g H2. Th e m ixture was stirred overn igh t
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Four Diastereomers of Serricornin
533
at room tem perature an d was th en filtered th rough a celite® pad. Evaporation of th e solven t
provided 709 m g (4.37 m m ol, quan t.) colorless oil, wh ich was em ployed in th e n ext step
with out furth er purification . RF 0.16 (petroleum eth er–eth er 2 : 1). [α]D +66.2 (c 1.63,
CHCl3), de > 96% (13C NMR), ee = 94% (based on th e keton e (S)-4). 1H NMR (500 MHz,
CDCl3): 0.84 (d, 3 H, J = 7.0, CH3); 0.93 (t, 3 H, J = 7.3, CH3); 1.51–1.62 (m , 2 H, CH2CH3);
1.93 (m , 1 H, CHCH3); 2.68 (s, 1 H, OH); 3.42 (s, 3 H, OCH3); 3.52 (dd, 1 H, J = 11.0, 5.5,
CHHOH); 3.61 (m , 1 H, CHOH); 3.62 (dd, 1 H, J = 11.0, 8.5, CHHOH); 4.68 (m , 2 H,
OCH2O). 13C NMR (125 MHz, CDCl3): 10.51 (CH3); 10.70 (CH3); 24.28 (CH2CH3); 37.71
(CHCH3); 55.86 (OCH3); 65.30 (CH2OH); 81.16 (CHOH); 96.76 (OCH2O). MS (CI): 164 (9);
163 (100, MH+); 145 (8, MH+ – H2O). IR (n eat): 3 425 (OH); 1 098, 1 039 (C–O). For
C8H18O3 (162.2) calculated: 59.23% C, 11.18% H; foun d: 58.80% C, 11.26% H.
(2R,3R)-3-(Meth oxym eth oxy)-2-m eth ylpen tan -1-ol [(R,R)-7]
A solution of (R,R)-6 (187 m g, 0.74 m m ol) in eth er (30 m l) was treated an alogously to
(S,S)-7. Con cen tration in vacuo provided 114 m g (0.73 m m ol; 95%) of th e crude product.
[α]D –66.1 (c 1.12, CHCl3), de > 96% (13C NMR), ee = 93% (based on th e keton e (R)-4). Th e
oth er spectroscopic data are iden tical with th ose given for (S,S)-7.
(2S,3S)-3-(Meth oxym eth oxy)-2-m eth ylpen tyl Tosylate [(S,S)-8]
To a cold (0 °C) solution of alcoh ol (S,S)-7 (675 m g, 4.16 m m ol) in pyridin e (10 m l) was
added tosyl ch loride (1.810 g, 9.50 m m ol). Th e solution was stirred overn igh t at 0 °C, fol-
lowed by th e addition of a buffer (15 m l, pH 7). Th e aqueous layer was extracted with
CH2Cl2 an d th e organ ic ph ase was wash ed with 1 M HCl solution un til th e wash in gs becam e
acidic. Th e organ ic ph ase was wash ed with a buffer (pH 7) an d brin e. Dryin g over Na2SO4,
filtration over a silica gel pad (5 m m ) an d evaporation of th e solven t provides 1.279 g of th e
crude product as a colorless oil. RF 0.42 (petroleum eth er–eth er 2 : 1). Th is product was em -
ployed in th e n ext step with out ch aracterization .
(2R,3R)-3-(Meth oxym eth oxy)-2-m eth ylpen tyl Tosylate [(R,R)-8]
Th e alcoh ol (R,R)-7 (114 m g, 0.73 m m ol) was con verted with pyridin e (4 m l) an d tosyl ch lo-
ride (268 m g, 1.41 m m ol) in th e sam e m an n er as described for (S,S)-8. Th e crude product
(221 m g) was obtain ed as colorless oil. RF 0.42 (petroleum eth er–eth er 2 : 1). Th is product
was em ployed in th e n ext step with out an y ch aracterization .
(2R,3S)-1-Iodo-3-(m eth oxym eth oxy)-2-m eth ylpen tan e [(R,S)-9]
To a solution of crude tosylate (S,S)-8 (1.279 g) in aceton e (50 m l) was added NaI (3.030 g,
20.21 m m ol) an d a catalytic am oun t of EtNiPr2. Th e m ixture was refluxed for 6 h an d evap-
orated after coolin g to room tem perature. Th e residue was taken up in water (15 m l)–eth er
(15 m l) an d th e aqueous layer was extracted twice with eth er. Th e organ ic ph ase was wash ed
with 5% Na2S2O3 solution , brin e an d dried over Na2SO4. Con cen tration in vacuo an d colum n
ch rom atograph y (elution with petroleum eth er–eth er 10 : 1) provided 944 m g (3.47 m m ol;
83%, 2 steps) colorless product. RF 0.72 (petroleum eth er–eth er 2 : 1). [α]D +15.5 (c 1.54,
CHCl3), de > 96% (13C NMR), ee = 94% (based on th e keton e (S)-4). 1H NMR (500 MHz,
CDCl3): 0.91 (t, 3 H, J = 7.5, CH3); 1.03 (d, 3 H, J = 6.7, CH3); 1.50–1.59 (m , 2 H, CH2CH3);
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534
Job, Nagelsdiek, Enders:
1.94 (m , 1 H, CHCH3); 3.09 (dd, 1 H, J = 9.8, 7.3, CHHI); 3.36 (dd, 1 H, J = 9.8, 5.8, CHHI);
3.39 (s, 3 H, OCH3); 3.50 (m , 1 H, CHOH); 4.67 (m , 2 H, OCH2O). 13C NMR (125 MHz,
CDCl3): 9.94 (CH3); 12.18 (CH2I); 15.17 (CH3); 24.09 (CH2CH3); 39.06 (CHCH3); 55.70
(OCH3); 81.78 (CHOH); 96.47 (OCH2O). MS (CI): 273 (25, MH+); 242 (7, MH+ – CH3O); 241
(100, M+ – CH3O). IR (n eat): 1 101, 1 039 (C–O). For C8H17IO2 (272.1) calculated: 35.31% C,
6.30% H; foun d: 35.24% C, 6.07% H.
(2S,3R)-1-Iodo-3-(m eth oxym eth oxy)-2-m eth ylpen tan e [(S,R)-9]
Th e tosylate (R,R)-8 (221 m g) was treated with NaI (524 m g, 3.50 m m ol) in th e sam e m an -
n er as described for (R,S)-9. Purification by ch rom atograph y provided 150 m g (0.55 m m ol;
79%, 2 steps) product. [α]D –15.5 (c 1.17, CHCl3), de > 96% (13C NMR), ee = 93% (based on
th e keton e (R)-4). All spectroscopic data were iden tical with th ose given for (R,S)-9.
(S)-1-{[(4S,6S,7S)-7-(Meth oxym eth oxy)-4,6-dim eth yln on an -3-yliden e]am in o}-
2-(m eth oxym eth yl)pyrrolidin e [(S,S,S,S)-10]
To a solution of LDA (1.20 m m ol, prepared as m en tion ed above) in eth er (8 m l) h ydrazon e
(S)-2 (198 m g, 1.00 m m ol) was added at 0 °C. After stirrin g at th is tem perature for 4 h th e
solution was cooled to –115 °C. Th e iodide (R,S)-9 (100 m g, 0.37 m m ol; ee = 94%) was
added at th is tem perature. Th e m ixture was allowed to warm to room tem perature overn igh t
an d was quen ch ed with a buffer (20 m l, pH 7) an d THF (20 m l). After stirrin g for 10 m in
th e crude product was extracted with eth er an d th e com bin ed organ ic ph ases were wash ed
with brin e an d dried over Na2SO4. Th e organ ic ph ase was filtered over a silica gel pad (5
m m ) an d evaporation of th e solven t afforded 203 m g of th e crude product (con tain in g ex-
cess 2). Th is was em ployed in th e n ext step with out furth er purification . RF 0.22 (petroleum
eth er–eth er 2 : 1). 1H NMR (300 MHz, C6D6): 0.93 (t, 3 H, J = 7.4, CH3); 0.94 (d, 3 H, J = 6.9,
CH3); 0.95 (d, 3 H, J = 6.9, CH3); 1.23 (t, 3 H, J = 7.3, CH3); 1.30–1.76 (m , 9 H, CH3CH2,
CHCH2CH, NCH2CH2CHH); 2.09 (m , 3 H, NCH2CH2CHH, CH3CH2); 2.43 (m , 1 H, NCHH);
3.02 (m , 1 H, NCHH); 3.21 (s, 3 H, OCH3); 3.24 (s, 3 H, OCH3); 3.28–3.65 (m , 4 H, CHOH,
NCHCH2O); 4.63 (m , 2 H, OCH2O). 13C NMR (75 MHz, C6D6): 9.36 (CH3); 10.29 (CH3);
13.51(CH3); 16.78 (CH3); 21.13 (CH3CH2); 22.53 (NCH2CH2); 23.38 (CH3CH2); 26.38
(NCHCH2); 31.34, 32.56 (2 CH3CH); 36.70 (CHCH2CH); 54.02 (OCH3); 54.40 (NCH2); 57.47
(OCH3); 65.55 (NCH); 75.52 (NCHCH2O); 81.11 (CHOH); 95.32 (OCH2O); 171.68 (C=N).
(R)-1-{[(4R,6R,7R)-7-(Meth oxym eth oxy)-4,6-dim eth yln on an -3-yliden e]am in o}-
2-(m eth oxym eth yl)pyrrolidin e [(R,R,R,R)-10]
Accordin g to th e procedure for syn th esis of (S,S,S,S)-10 h ydrazon e (R)-2 (198 m g, 1.00 m m ol)
was treated with LDA (1.20 m m ol) in eth er (8 m l) an d iodide (S,R)-9 (100 m g, 0.37 m m ol; ee =
93%). After workup, 210 m g of crude product (con tain in g excess 2) was obtain ed, wh ich was
em ployed in th e n ext step with out furth er purification . RF 0.22 (petroleum eth er–eth er
2 : 1). Th e NMR data correspon d with isom er (S,S,S,S)-10.
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Four Diastereomers of Serricornin
535
(R)-1-{[(4R,6S,7S)-7-(Meth oxym eth oxy)-4,6-dim eth yln on an -3-yliden e]am in o}-
2-(m eth oxym eth yl)pyrrolidin e [(R,R,S,S)-10]
Accordin g to th e procedure for syn th esis of (S,S,S,S)-10 h ydrazon e (R)-2 (198 m g, 1.00 m m ol)
was treated with LDA (1.20 m m ol) in eth er (8 m l) an d iodide (R,S)-9 (149 m g, 0.55 m m ol; ee =
94%). After workup, 302 m g of crude product (con tain in g excess 2) was obtain ed, wh ich was
em ployed in th e n ext step with out furth er purification . RF 0.22 (petroleum eth er–eth er 2 : 1).
1H NMR (300 MHz, C6D6): 0.93 (t, 3 H, J = 7.4, CH3); 0.94 (d, 3 H, J = 7.1, CH3); 1.03 (d, 3 H,
J = 6.6, CH3); 1.23 (t, 3 H, J = 7.4, CH3); 1.40–1.74 (m , 9 H, CH3CH2, CHCH2CH,
NCH2CH2CHH); 1.98–2.49 (m , 4 H, NCH2CH2CHH, CH3CH2, NCHH); 2.99 (m , 1 H,
NCHH); 3.20 (s, 3 H, OCH3); 3.25 (s, 3 H, OCH3); 3.26–3.63 (m , 4 H, CHOH, NCHCH2O);
4.60 (m , 2 H, OCH2O). 13C NMR (75 MHz, C6D6): 10.86 (CH3); 11.60 (CH3); 15.56 (CH3);
18.95 (CH3); 22.46 (CH3CH2); 23.13 (NCH2CH2); 23.68 (CH3CH2); 27.74 (NCHCH2); 32.52,
33.79 (2 CH3CH); 37.89 (CHCH2CH); 55.36 (OCH3); 55.66 (NCH2); 58.76 (OCH3); 66.86
(NCH); 76.84 (NCHCH2O); 83.45 (CHOH); 95.93 (OCH2O); 172.49 (C=N).
(S)-1-{[(4S,6R,7R)-7-(Meth oxym eth oxy)-4,6-dim eth yln on an -3-yliden e]am in o}-
2-(m eth oxym eth yl)pyrrolidin e [(S,S,R,R)-10]
Accordin g to th e procedure for syn th esis of (S,S,S,S)-10 h ydrazon e (S)-2 (297 m g, 1.50 m m ol)
was treated with LDA (1.80 m m ol) in THF (8 m l) an d iodide (S,R)-9 (200 m g, 0.73 m m ol; ee =
94%). After workup, 383 m g of crude product (con tain in g excess 2) was obtain ed, wh ich was
em ployed in th e n ext step with out furth er purification . RF 0.22 (petroleum eth er–eth er
2 : 1). Th e NMR data are iden tical with th ose given for (R,R,S,S)-10.
(4S,6S,7S)-7-(Meth oxym eth oxy)-4,6-dim eth yln on an -3-on e [(S,S,S)-11]
Th e crude h ydrazon e (S,S,S,S)-10 (203 m g) was dissolved in CH2Cl2 (30 m l) an d treated with
ozon e as described above. Purification by flash ch rom atograph y (elution with pen tan e–eth er
10 : 1) afforded 73 m g (0.32 m m ol; 86%, 2 steps) product as colorless oil. RF 0.48 (petroleum
eth er–eth er 2 : 1). [α]D +2.2 (c 1.10, C6H6), de = 88% (13C NMR), ee > 98%. 1H NMR (500
MHz, C6D6): 0.80 (d, 3 H, J = 7.3, CH3); 0.84 (t, 3 H, J = 7.5, CH3); 0.93 (d, 3 H, J = 6.7,
CH3); 0.99 (t, 3 H, J = 7.3, CH3); 1.35 (qdd, 1 H, J = 7.5, 13.5, 5.5, CH3CHH); 1.45 (m , 2 H,
CH3CHH, CHCHHCH); 1.56 (ddd, 1 H, J = 13.8, 8.5, 6.4, CHCHHCH); 1.67 (m , 1 H,
CH3CH); 2.09 (q, 2 H, J = 7.3, CH3CH2); 2.42 (m , 1 H, CH3CH); 3.20 (s, 3 H, OCH3); 3.25
(m , 1 H, CHOH); 4.49 (d, 1 H, J = 13.4, OCHHO); 4.53 (d, 1 H, J = 13.4, OCHHO). 13C NMR
(125 MHz): 8.06 (CH3); 10.58 (CH3); 14.91 (CH3); 16.56 (CH3); 23.92 (CH3CH2); 33.41
(CH3CH); 33.93, 36.04 (CH3CH2, CHCH2CH); 43.77 (CH3CH); 55.41 (OCH3); 82.95 (CHOH);
96.22 (OCH2O); 212.87 (C=O). MS (EI): 169 (13, MH+ – C2H6O2); 168 (8, M+ – C2H6O2); 139
(16); 130 (69); 111 (10); 89 (25); 86 (10); 83 (16); 69 (10); 57 (47); 55 (12); 45 (100). IR (n eat):
1 714 (C=O); 1 103, 1 039 (C–O). For C13H26O3 (230.3) calculated: 67.79% C, 11.38% H;
foun d: 67.38% C, 11.73% H.
(4R,6R,7R)-7-(Meth oxym eth oxy)-4,6-dim eth yln on an -3-on e [(R,R,R)-11]
Th e crude h ydrazon e (R,R,R,R)-10 (210 m g) was dissolved in CH2Cl2 (30 m l) an d treated
with ozon e as described above. Purification by flash ch rom atograph y (elution with
pen tan e–eth er 10 : 1) afforded 73 m g (0.32 m m ol; 86%, 2 steps) product as colorless oil. [α]D
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536
Job, Nagelsdiek, Enders:
–0.9 (c 1.06, C6H6), de = 86% (13C NMR), ee > 98%. All oth er data were iden tical with th ose
reported for th e (S,S,S)-11.
(4R,6S,7S)-7-(Meth oxym eth oxy)-4,6-dim eth yln on an -3-on e [(R,S,S)-11]
Th e crude h ydrazon e (R,R,S,S)-10 (302 m g) was dissolved in CH2Cl2 (25 m l) an d treated with
ozon e as described above. Purification by flash ch rom atograph y (elution with pen tan e–eth er
10 : 1) afforded 100 m g (0.43 m m ol; 80%, 2 steps) product as colorless oil. RF 0.48 (petro-
leum eth er–eth er 2 : 1). [α]D –28.4 (c 1.14, C6H6), de = 86% (13C NMR), ee > 98%. 1H NMR
(400 MHz, C6D6): 0.83 (d, 3 H, J = 6.9, CH3); 0.86 (t, 3 H, J = 7.4, CH3); 0.91 (d, 3 H, J = 6.9,
CH3); 0.98 (t, 3 H, J = 7.3, CH3); 1.02–1.38 (m , 2 H, CH3CH2); 1.48 (m , 1 H, CHCHHCH);
1.61 (m , 1 H, CH3CH); 1.96 (m , 1 H, CHCHHCH); 2.11 (m , 2 H, CH3CH2); 2.47 (m , 1 H,
CH3CH); 3.22 (s, 3 H, OCH3); 3.25 (m , 1 H, CHOH); 4.55 (s, 2 H, OCH2O). 13C NMR (100
MHz): 7.95 (CH3); 10.48 (CH3); 14.98 (CH3); 17.63 (CH3); 23.95 (CH3CH2); 33.33 (CH3CH);
34.11, 36.51 (CH3CH2, CHCH2CH); 43.68 (CH3CH); 55.33 (OCH3); 82.49 (CHOH); 96.05
(OCH2O); 212.70 (C=O). All oth er data were iden tical with th ose reported for th e (S,S,S)-11.
(4S,6R,7R)-7-(Meth oxym eth oxy)-4,6-dim eth yln on an -3-on e [(S,R,R)-11]
Th e crude h ydrazon e (S,S,R,R)-10 (383 m g) was dissolved in CH2Cl2 (30 m l) an d treated with
ozon e as described above. Purification by flash ch rom atograph y (elution with pen tan e–eth er
10 : 1) afforded 155 m g (0.67 m m ol; 92%, 2 steps) product as colorless oil. [α]D +29.3 (c 1.21,
C6H6), de = 90% (13C NMR), ee > 98%. All oth er data were iden tical with th ose reported for
th e (R,S,S)-11.
(4S,6S,7S)-7-Hydroxy-4,6-dim eth yln on an -3-on e [(S,S,S)-1, Serricorn in ]
MOM-Protected serricorn in (S,S,S)-11 (73 m g, 0.32 m m ol; de = 88%) was dissolved in CH2Cl2
(8 m l) an d cooled to –78 °C. At th is tem perature Me2BBr solution (1.50 m l, 0.75 m m ol, 0.5 M
in CH2Cl2) was added an d th e m ixture was stirred for 1 h m ain tain in g th e tem perature. Th e
solution was tran sfered via a double-en ded n eedle to a vigorously stirred m ixture of satu-
rated NaHCO3 solution (5 m l) an d THF (15 m l). After 10 m in , eth er (20 m l) was added an d
th e organ ic ph ase was isolated. Th e aqueous layer was extracted on ce with eth er an d th e
com bin ed organ ic layers were wash ed with a buffer (pH 7) an d brin e. Dryin g over Na2SO4
an d evaporation of th e solven t afforded th e crude product. Purification by colum n ch rom a-
tograph y (elution with pen tan e–eth er 10 : 1–2 : 1) yielded two fraction s. First 47 m g of de-
sired product (S,S,S)-1 (RF 0.44–0.64, petroleum eth er–eth er 2 : 1) an d secon d 3 m g of
(R,S,S)-1 (RF 0.14, petroleum eth er–eth er 2 : 1). Total yield was 50 m g (0.27 m m ol; 85%, de =
88%). 1H NMR (400 MHz, C6D6): 0.73–2.40 (m , 21 H); 3.15 (m , 0.25 H, CHOH, open ch ain
1a); 3.81 (m , 0.75 H, OCH, h em iacetal 1b). 13C NMR (100 MHz, C6D6, open ch ain 1a): 8.05;
10.79; 13.61; 16.41; 27.44; 33.80; 35.69; 36.72; 43.64; 76.08; 213.21. 13C NMR (100 MHz,
C6D6, h em iacetal 1b): 7.31; 10.70; 11.68; 16.74; 26.14; 30.19; 31.20; 32.99; 36.07; 72.50;
98.33. HR MS (C11H22O2, 186.295): exact m ass calculated for M – H2O: 168.15141; foun d:
168.15152. All oth er spectroscopic data were iden tical with th ose given in th e literature3.
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Four Diastereomers of Serricornin
537
(4R,6R,7R)-7-Hydroxy-4,6-dim eth yln on an -3-on e [(R,R,R)-1]
MOM-Protected (R,R,R)-11 (66 m g, 0.29 m m ol; de = 86%) was reacted with Me2BBr solution
(0.70 m l, 0.49 m m ol; 0.7 M in CH2Cl2) in CH2Cl2 (8 m l) as described for (S,S,S)-1. Ch rom a-
tograph y yielded 41 m g of desired product an d 3 m g of (S,R,R)-1. Total yield was 44 m g
(0.24 m m ol; 83%, de = 86%). All oth er data were iden tical with th ose given for (S,S,S)-1.
(4R,6S,7S)-7-Hydroxy-4,6-dim eth yln on an -3-on e [(R,S,S)-1]
MOM-Protected (R,S,S)-11 (94 m g, 0.41 m m ol; de = 92%) was reacted with Me2BBr solution
(1.50 m l, 0.75 m m ol; 0.5 M in CH2Cl2) in CH2Cl2 (8 m l) as described for (S,S,S)-1. Ch rom a-
tograph y yielded 59 m g of desired product (RF 0.14, petroleum eth er–eth er 2 : 1) an d 3 m g
(S,S,S)-1 (RF 0.44–0.64, petroleum eth er–eth er 2 : 1). Total yield was 62 m g (0.33 m m ol; 82%,
de = 92%). [α]D –14.0 (c 1.01, C6H6), de > 96% (13C NMR), ee > 98%. 1H NMR (400 MHz,
C6D6): 0.83 (d, 3 H, J = 6.9, CH3); 0.88 (d, 3 H, J = 6.9, CH3); 0.92 (t, 3 H, J = 7.4, CH3); 0.96
(t, 3 H, J = 7.1, CH3); 1.01 (m , 1 H, CH3CHH); 1.24–1.46 (m , 3 H, CH3CHH, CHCHHCH,
CH3CH); 1.89–2.20 (m , 4 H, CH3CH2, CHCHHCH, OH); 2.39 (m , 1 H, CH3CH); 3.22 (m , 1 H,
CHOH). 13C NMR (100 MHz, C6D6): 8.00 (CH3); 10.97 (CH3); 13.98 (CH3); 17.79 (CH3);
27.39 (CH2); 34.09 (CH2); 36.27 (CH); 37.10 (CH2); 44.00 (CH); 75.31 (CHOH); 213.92
(C=O). HR MS (C11H22O2, 186.295): exact m ass calculated for M – H2O: 168.15141; foun d:
168.15194. All oth er data were in good correspon den ce with th e data in th e literature3.
(4S,6R,7R)-7-Hydroxy-4,6-dim eth yln on an -3-on e [(S,R,R)-1]
MOM-Protected (S,R,R)-11 (122 m g, 0.53 m m ol; de = 90%) was reacted with Me2BBr solu-
tion (1.20 m l, 0.84 m m ol; 0.7 M in CH2Cl2) in CH2Cl2 (8 m l) as described for (S,S,S)-1. Ch ro-
m atograph y yielded 88 m g of desired product an d 5 m g of (R,R,R)-1. Total yield was 93 m g
(0.50 m m ol; 94%, de = 90%). [α]D +13.7 (c 1.00, C6H6), de > 96% (13C NMR), ee > 98%. All
oth er data were iden tical with th ose given for (R,S,S)-1.
We thank J. Köbberling for helpful discussions concerning the cleavage of MOM-ethers, A. Müller
for measuring the NMR spectra on Inova 400 and Unity 500, Dr J. Runsink for measuring the NOE ef-
fects and helpful discussions concerning the interpretation, K. Glensk and S. Küpper for performing IR
and mass spectra (especially S. Küpper for the high resolution mass spectra), C. Dittrich for measuring
elementary anlayses, D. Gilliam for performing GC spectra and S. Drehsen and S. Rother for separat-
ing diastereomers by preparative HPLC. We thank BASF AG, Degussa–Hüls AG and Bayer AG for do-
nation of chemicals and DFG (SFB 380) for financial support.
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