A new chiral masked form of glyoxal diimine

Article abstract of DOI:10.1135/cccc20031531

(3R,4R,5R,6R)-3,6-Diphenyl-N,N′-bis[(S)-1-phenylethyl]octa-1, 7-diene-4,5-diamine, by treatment with organolithium reagents RLi in controlled experimental conditions, underwent rearrangement and/or substitution of one or two branched allyl(s) by the R group(s). Hence, this diene behaves as a masked form of the chiral glyoxal diimine from that it is prepared, allowing the preparation of C₁-symmetric 1,2-disubstituted 1,2-diamines, which are generally not available by the direct addition of organometallic reagents to the diimine, and C₂-symmetric 1,2-diamines with good diastereoselectivities.

Full text of DOI:10.1135/cccc20031531

Chiral Masked Form of Glyoxal Diimine
1531
A NEW CHIRAL MASKED FORM OF GLYOXAL DIIMINE
1
2,
Gianluca MARTELLI and Diego SAVOIA *
Dipartimento di Chimica “G. Ciamician”, Universita di Bologna, via Selmi 2, 40126 Bologna,
1
2
Italy; e-mail: martelli@ciam.unibo.it, savoia@ciam.unibo.it
Received April 30, 2003
Accepted Jun e 25, 2003
Dedicated to Professor Sergio Roffia on the occasion of his retirement.
(3R,4R,5R,6R)-3,6-Diph en yl-N,N′-bis[(S)-1-ph en yleth yl]octa-1,7-dien e-4,5-diam in e, by treat-
m en t with organ olith ium reagen ts RLi in con trolled experim en tal con dition s, un derwen t re-
arran gem en t an d/or substitution of on e or two bran ch ed allyl(s) by th e R group(s). Hen ce,
th is dien e beh aves as a m asked form of th e ch iral glyoxal diim in e from th at it is prepared,
allowin g th e preparation of C1-sym m etric 1,2-disubstituted 1,2-diam in es, wh ich are gen er-
ally n ot available by th e direct addition of organ om etallic reagen ts to th e diim in e, an d
C2-sym m etric 1,2-diam in es with good diastereoselectivities.
Keyw ord s: Am in es; Im in es; Addition s; Alkyllith ium reagen ts; Diastereoselective syn th esis;
Lith ium ; Retro reaction s; Rearran gem en ts; Substitution s.
Th e ch iral glyoxal diim in e 1 an d its equally available en an tiom er are ap-
pealin g ch iral syn th on s for th e preparation of en an tiopure C2-sym m etric
secon dary 1,2-diam in es 2 by th e double addition of organ om etallic re-
agen ts; th e correspon din g prim ary 1,2-diam in es 3 are obtain ed by reductive
rem oval of th e auxiliaries (Sch em e 1). However, th e scope of th e reaction is
som ewh at lim ited1–7. Ph en yl-1, m eth yl-1 an d allylm agn esium 2 h alides h ad
to be added very slowly to 1 to ach ieve satisfactory to good diastereo-
selectivities1, wh ereas alkylm agn esium h alides preferably followed th e
N-alkylation path way8. Usin g th e m ore reactive organ olith ium com poun ds,
th e stereocon trol was on ly m oderate; m oreover, particular atten tion h ad to
be taken to quen ch th e reaction m ixtures with degassed water to preven t
form ation of a m on oim in e th rough h om olytic cleavage of th e bis(adduct),
i.e., th e dilith ium bis(am ide), an d oxidation of th e so form ed α-am ido radi-
cal3. Th e addition of allylzin c brom ide4 an d β- or γ-substituted allylic zin c
h alides5,6 led, with excellen t diastereoselectivities to th e correspon din g
octa-1,7-dien e-4,5-diam in e derivatives, wh ich were successively used for
Collect. Czech. Chem. Commun. (Vol. 68) (2003)
doi:10.1135/cccc20031531

1532
Martelli, Savoia:
th e con struction of en an tiopure cycloh exan e-1,2-diam in e9,10 an d cycloh ex-
4-en e-1,2-diam in e11,12 derivatives an d 2,2′-bipyrrolidin e13
.
R
R
Me
Ph
Me
Ph
R
R
2 RM
Me
Ph
Me
Ph
N
N
NH HN
H2N
NH2
1
3
2
R1M
R1
R1
R2
R1
H2N
R2
R2M
Me
Ph
Me
Ph
Me
Ph
Me
Ph
NH
N
NH HN
NH2
5
4
6
H2O
R1
R2
R1
NH
7
R1
H2N
R2
R2M
Me
Ph
Me
Ph
NH OH
O
OH
8
9
SCHEME 1
On th e oth er h an d, th e preparation of th e un sym m etrically 1,2-di-
substituted 1,2-diam in es 5 an d 6 or th e correspon din g m on osubstituted
1,2-diam in es (R2 = H) is h am pered by th e difficult con trol of th e organ o-
m etallic addition , i.e., to avoid th e secon d addition step of th e sam e
organ om etallic reagen t R1M to th e in term ediate am in oim in e 4. Th is is, in
prin ciple, possible, because im in e 4 is less reactive th an th e startin g diim in e
1, but in practice th e successful con trol is ach ieved on ly wh en R1M is
poorly reactive for electron ic an d/or steric reason s. In fact, Rolan d de-
scribed th at tert-butylm agn esium ch loride gave th e m on oadduct even at
room tem perature an d reacted furth er at h igh er tem perature to afford th e
correspon din g 1,2-diam in e 2 as a sin gle diastereom er th rough a “kin etic
resolution ” process7. On th e oth er h an d, th e use of a differen t organ o-
m etallic reagen t or h ydride in th e secon d addition step gave th e un sym m et-
rically di- or m on osubstituted 1,2-diam in es 5 14. An alogously, we h ave
reported th e addition of 3-m eth ylbut-2-en -1-ylzin c brom ide could be
stopped after th e first addition , wh ich occurred by allylic rearran gem en t.
Th e un reacted im in e 4 was isolated an d th en h ydrolysed to aldeh yde 7. We
also described a on e-pot reaction to con vert diim in e 1 to th e 1,2-di-
substituted 1,2-am in o alcoh ol 8, in volvin g a Barbier reaction with
4-brom o-2-m eth ylbut-2-en e an d zin c in th e presen ce of cerium trich loride
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

Chiral Masked Form of Glyoxal Diimine
1533
h eptah ydrate. Th e reactive served also for in situ h ydrolysis of th e secon d
im in e fun ction after th e first organ om etallic step, form in g an aldeh yde
wh ich furth er un derwen t a Barbier-type allylation 15
.
We h ave recen tly described an in direct, two-step approach to eith er C2-
an d C1-sym m etric 1,2-disubstituted 1,2-diam in es startin g from diim in e 1
an d in volvin g th e in term ediate (4R,5R)-N,N′-bis[(S)-1-ph en yleth yl]-3,6-di-
vin ylocta-1,7-dien e-4,5-diam in e16 (10) (Sch em e 2). Th is dien e un derwen t
rearran gem en t an d/or substitution of on e/two pen tadien yl groups on treat-
m en t with 2–4 equivalen ts of an organ olith ium reagen t in tetrah ydrofuran .
By a careful ch oice of th e experim en tal con dition s, C1- or C2-sym m etric
1,2-disubstituted 1,2-diam in es were prepared with good stereocon trol. In
fact, usin g butyl- an d ph en yllith ium with differen t m olar ratios RLi/10 an d
at differen t tem peratures, eith er th e isom eric straigh t-ch ain diam in e 11
with com plete reten tion of con figuration , or th e “m ixed” diam in es 12,
wh ich bear on e pen tadien yl an d on e R substituen t, or th e C2-sym m etric
1,2-diam in es 2a, 2b were predom in an tly form ed in m oderate yields an d
1
diastereoselectivities (ds 71–85%, by GC an d/or H NMR an alysis).
Me
Ph
Me
Ph
NH HN
3 BuLi (−60 °C),
THF, −78 °C,
slow addition
10
4 RLi, THF,
−78 to 20 °C
2 RLi, THF,
−78 °C
R
R
R
Me
Ph
Me
Me
Ph
Me
Me
Ph
Me
NH HN
NH HN
11
NH HN
Ph
Ph
Ph
12
2
11:12a = 70:30;
pure 11: 59%
a: R = Bu, dr 85:5:10 (crude);
pure diastereomer: 60%
a: R = Bu, dr 85:5:10 (crude);
52%, dr 94:6
b: R = Ph, dr 71:4:25 (crude);
pure diastereomer: 55%
b: R = Ph, 44%, dr 85:15
SCHEME 2
We propose th at th e products 11, 12 an d 2 were form ed th rough com pet-
itive path ways wh ich are described in Sch em e 3 for th e m odel lith ium
am ides 13 an d 15 bearin g bran ch ed or straigh t-ch ain Y-substituted allyl
groups. Th e bran ch ed to straigh t-ch ain isom erisation of th e allylic sub-
stituen t sh ould take place at low tem peratures by 1,3-sh ift of th e bran ch ed
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

1534
Martelli, Savoia:
h om oallylic lith ium am ide with reten tion of con figuration of th e in volved
stereocen tre an d com plete E-selectivity, affordin g 14. On th e oth er h an d,
th e substitution of th e group R com in g from th e organ om etallic reagen t for
th e bran ch ed or straigh t-ch ain allylic substituen t sh ould in volve th e
Y
Y
Y
Y
1,3-shift
Me
Ph
Me
Ph
Me
Ph
Me
Ph
N
N
N
N
Li
Li
H
(Li)H
13
14
(H)Y(H)Y
(Y)H
H(Y)
(H)Y
H(Y)
− Y-allylLi
Me
Ph
Me
Ph
Me
Ph
Me
Ph
N
Li
N
N
(Li)H
N
(Li)H
15
16
SCHEME 3
retro-pen tadien yllith iation of 15 to form in term ediate im in e 16. We attrib-
uted th e occurren ce of th ese processes even at low tem perature to th e steric
an d electron ic properties of th e pen tadien yl substituen t an d en vision ed
th at oth er bran ch ed bish om oallylic 1,2-diam in es would beh ave sim ilarly
an d provide even a better selectivity an d/or stereocon trol. In oth er words,
th e n ature of th e substituen t Y in 13 an d 15 would affect th e overall selec-
6
tivity. Hen ce we in vestigated th e beh aviour of th e bran ch ed diam in e 17 ,
also available from th e diim in e 1, towards organ olith ium reagen ts an d also
exten ded our efforts to th e on e-pot preparation of un sym m etrically
1,2-disubstituted 1,2-diam in es 5 by th e previously un explored stepwise ad-
dition of two differen t organ olith ium reagen ts R1Li an d R2Li (Sch em e 4).
We first studied th e reaction with m eth yllith ium an d observed th at treat-
m en t of 17 with 2 equivalen ts of th is reagen t at –78 °C alm ost exclusively
produced th e isom eric straigh t-ch ain diam in e3 18 with a sm all loss of con -
figuration al purity. Sim ilar result was obtain ed wh en 4 equivalen ts of MeLi
was used an d th e tem perature was allowed to reach 0 °C, as n o substitution
process was observed. Con versely, th e reaction s with butyl- an d ph en yl-
lith ium (3 equivalen ts) at –78 to –30 °C afforded th e “m ixed” diam in es 19a
an d 19b, respectively, resultin g from sequen tial isom erisation an d substitu-
tion processes. A m ixture of products, in cludin g sm all am oun ts of th e dou-
ble substitution products, e.g. 2b, an d diastereom ers (dr > 85:15) were
form ed in both cases; colum n ch rom atograph y gave pure 19a with 62%
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

Chiral Masked Form of Glyoxal Diimine
1535
yield, wh ereas th e diastereom ers of 19b were n ot separated in th is way
(69% yield, dr 85:15).
Ph
Ph
2–4 MeLi
Me
Ph
Me
Ph
THF, −78 to −30 °C
NH HN
18,100% (crude), dr > 90:10
Ph
R
NH HN
3 RLi
Ph
Ph
Me
Me
Ph
Me
Ph
Me
THF, −78
NH HN
to −30 °C
Ph
Ph
17
19 (+ 18, 10–15%)
1. 3 R1Li, THF,
a: R = Bu, dr > 90:10 (crude);
pure diastereomer: 62%
b: R = Ph, 69%, dr 85:15
−78 to −30 °C
2. 2 R2Li, THF,
4 RLi, THF,
−78 to 0 °C
−78 to −30 or 0 °C
R1
R2
R
R
Me
Me
Ph
Me
Ph
Me
Ph
NH HN
NH HN
Ph
5
2
a: R1 = Bu, R2 = Me, 41%,
a: R = Bu, dr 89:2:9 (crude),
pure diastereomer: 68%
c: R = Me, dr 88:8:4 (crude);
pure diastereomer: 54%
d: R = t-Bu, dr 80:20 (crude);
pure diastereomer: 62%
e: R = allyl, dr 94:6 (crude);
pure diastereomer: 63%
purity: 92%, dr 90:10
b: R1 = Ph, R2 = Me, 58%, dr 92:8
c: R1 = Ph, R2 = allyl, 65%, dr 90:10
SCHEME 4
Th e preparation of C2-sym m etric 1,2-disubstituted 1,2-diam in es by th e
double substitution process was th en addressed. Th e reaction s with 4 equiv-
alen ts of several RLi reagen ts (R = m eth yl, butyl, tert-butyl, allyl) were car-
ried out at –78 to 0 °C un til com pletion of th e substitution steps, gen erally
with good stereocon trol. Th e best diastereom eric ratio was obtain ed with
allyllith ium (dr 94:6 for 2d , in th is case, th e reaction was com plete even at
–30 °C), wh ereas tert-butyllith ium gave th e worst dr for 2c (80:20). All th e
m ain diastereom ers of 2a–2d were isolated pure with satisfactory yields af-
ter ch rom atograph y on a silica gel colum n . No care was taken to isolate th e
m in or diastereom ers, but th eir C2-sym m etry was eviden t in th e 1H NMR
spectra of th e crude reaction products. Th e stereoisom ers with R,S con figu-
ration of th e NC*C*N carbon s were n ot observed. Th is observation im plies
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

1536
Martelli, Savoia:
th at th e stereocon trol is lost on ly in th e first substitution step, but th e sec-
on d step proceeds with (alm ost) com plete diastereoselectivity.
Fin ally, we devoted som e efforts to th e preparation of 1,2-diam in es 5 by
con trolled, sequen tial addition of two differen t organ olith ium reagen ts,
R1Li an d R2Li. In order to prepare diam in es 5a an d 5b (with on e m eth yl
substituen t), con siderin g th e results of th e previously described reaction s
with m eth yllith ium , by wh ich th e m on osubstitution did n ot take place at
low tem peratures, we perform ed th e first addition with butyl- or ph en yl-
lith ium (R1Li) at –78 °C, an d th en used m eth yllith ium as th e secon d re-
agen t (R2Li). Both com poun ds 5a an d 5b were obtain ed with an overall
good efficien cy an d selectivity, but colum n ch rom atograph y did n ot allow
to separate th e diastereom ers (dr 90:10 for 5a, dr 92:8 for 5b). On th e oth er
h an d, diam in e 5c, with ph en yl an d allyl substituen ts, was obtain ed by th e
stepwise addition of th e correspon din g lith ium reagen ts in a good yield
(65% after colum n ch rom atograph y) an d stereocon trol (dr > 85:15), al-
th ough we did n ot succeed in separation of th e diastereom ers.
It sh ould be un derlin ed th at th e stereoch em istry of th e m in or diastereo-
m ers of th e C1-sym m etric diam in es 19a, 19b an d 5a–5c was n ot deter-
m in ed with certain ty, but th e relative con figuration of th e NC*C*N
stereocen ters in volved in th e rearran gem en t an d substitution steps is prob-
ably syn, in an alogy with th e con figuration of th e m in or diastereom ers of
th e C2-sym m etric diam in es 2a–2d . Min or am oun ts (<2%) of oth er dia-
stereom ers could h ave n ot been detected in th e GC-MS an d/or 1H NMR
an alyses of th e crude reaction m ixtures. Separation of th e diastereom ers of
19b an d 5a–5c was n ot accom plish ed by colum n ch rom atograph y, but th e
ch an ce to purify th e prim ary diam in es or th eir suitable N,N′-derivatives
after rem oval of th e ch iral auxiliaries is left.
Th e results described in th is paper in dicate th at C2-sym m etric 1,2-di-
am in es 2 an d C1-sym m etric 1,2-diam in es 19 an d, in particular, 5 are avail-
able by th e con trolled (stepwise) addition of on e or two differen t
organ olith ium reagen ts to 1,2-diam in e 17. Hen ce, 17, sim ilarly to 10, can
be used as a n ovel “ch iral m asked form of glyoxal diim in e”17 (Sch em e 5),
alth ough th e diim in e is probably n ot an in term ediate in th e reaction path -
way. Th is two-step route (from 1 th rough 17) is obviously plagued by th e
n eed to use an excess of organ om etallic reagen ts in th e two steps; h en ce th e
preparation of sym m etrically 1,2-disubstituted 1,2-diam in es 2 is n ot attrac-
tive, alth ough it gen erally provides a better diastereoselectivity th an th e di-
rect double addition of organ olith ium reagen ts to 1. In stead, th e bran ch ed
diam in e 17 can be m ore advan tageously exploited for th e preparation of
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

Chiral Masked Form of Glyoxal Diimine
1537
C1-sym m etric 1,2-disubstituted 1,2-diam in es 5 from 1, as n o gen eral
m eth od h as been so far described for th is purpose.
R
R
low stereocontrol
2 RM
Me
Ph
Me
Ph
high stereocontrol
4 RLi
NH HN
2
Me
Ph
Me
Ph
Ph
Me
Ph
Me
N
N
NH HN
1
Ph
Ph
17
R1
R2
1. R1Li
2. R2Li
1. R1M
2. R2M
Me
Ph
Me
Ph
NH HN
lack of generality
high stereocontrol
5
SCHEME 5
EXPERIMENTAL
Meltin g poin ts are un corrected. Tetrah ydrofuran an d dieth yl eth er were before use distilled
over sodium ben zoph en on e ketyl an d lith ium alum in ium h ydride. Optical rotation s were
m easured on a digital polarim eter in a 1-dm cell an d [α]D-values are given in 10–1 deg cm 3 g–1
.
1H NMR spectra were recorded on a Varian Gem in i in strum en t at 300 or 200 MHz for sam -
ples in CDCl3 wh ich was stored over m agn esium : 1H ch em ical sh ifts are reported in ppm
(δ-scale) relative to CDCl3 (δH 7.27) an d J values are given in Hz. MS spectra were taken at
an ion izin g voltage of 70 eV on a Hewlett–Packard 5970 or 5890 spectrom eter with GLC in -
jection . Ch rom atograph ic purification s were perform ed on colum n s of silica gel (Merck,
230–400 m esh ) at m edium pressure. Th e followin g organ olith ium reagen ts an d organ ic com -
poun ds were purch ased from Aldrich : butyl-, tert-butyl-, m eth yl- an d ph en yllith ium , glyoxal
11,12
trim eric dih ydrate, (S)-1-ph en yleth ylam in e, allyltributyltin , allylben zen e. Diim in e 1
an d
6
diam in e 17 were prepared accordin g to th e already described procedures. Allyllith ium was
prepared from allyltributyltin an d butylith ium in eth er. All th e organ om etallic reaction s
were perform ed in a flam e-dried apparatus un der a static atm osph ere of dry n itrogen .
GC-MS an d 1H NMR were used to follow th e progress of th e reaction s an d th e com position
of th e crude m ixtures, in cludin g th e diastereom eric ratios. However, products 18 an d 19 de-
com posed durin g GC-MS an alysis. Gen erally, on ly two diastereom ers were observed in th e
3,7
reaction m ixtures. Th e con figuration of th e kn own com poun ds 18 3, 2a 3, 2c 1,3, 2d
an d 2e 4
was assign ed by th eir order of elution (GC) an d spectral properties. For th e n ew com poun ds
19a, 19b an d 5a–5c, m in or am oun ts of oth er diastereom ers (<2%) could h ave n ot been de-
tected.
Syn th esis of (E,E)-(4R,5R)- an d (E,E)-(4S,5S)-1,8-Diph en yl-N,N′-bis[(S)-1-ph en yleth yl]octa-
1,7-dien e-4,5-diam in e (18)
A solution of th e 1,2-diam in e 17 (2.50 g, 5 m m ol) in an h ydrous tetrah ydrofuran (20 m l)
was cooled to –78 °C. After 10 m in MeLi (1.6 M in eth er, 6.3 m l, 10 m m ol) was added un der
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1538
Martelli, Savoia:
stirrin g durin g 15 m in . Th e m ixture was stirred for an oth er 2 h , wh ile allowin g th e tem pera-
ture to rise slowly to –30 °C, th en quen ch ed with degassed water (10 m l). Th e organ ic ph ase
was extracted with eth er (3 × 20 m l), th e collected eth ereal layers were dried with an h ydrous
3
sodium sulfate an d con cen trated to give 18 as an oil: 2.49 g (100%), (E,E)-(4R,5R)/
(E,E)-(4S,5S) = 90:10 (GC-MS an d 1H NMR). Separation of th e diastereom ers was previously
described3.
Syn th esis of Un sym m etrically 1,2-Disubstituted Diam in es 19
A solution of th e 1,2-diam in e 17 (2.50 g, 5 m m ol) in an h ydrous tetrah ydrofuran (20 m l)
was cooled to –78 °C. After 10 m in th e organ olith ium reagen t (15 m m ol) was added un der
stirrin g durin g 15 m in . Th e m ixture was stirred for an oth er 2 h , wh ile allowin g th e tem pera-
ture to rise slowly to –30 °C, th en quen ch ed with degassed water (10 m l). Th e organ ic ph ase
was extracted with eth er (3 × 20 m l), th e collected eth ereal layers were dried with an h ydrous
sodium sulfate an d con cen trated to give an oily residue. Ch rom atograph y on an silica gel
colum n , elutin g with cycloh exan e–eth yl acetate m ixtures, allowed to separate th e 1,2-di-
am in es.
(E)-(4R,5R)- and (E)-(4S,5S)-1-Phenyl-N,N′-bis[(S)-1-phenylethyl]non-4-ene-4,5-diamine (19a):
yellowish th ick oil, 1.36 g (62%), (E)-(4R,5R)/(E)-(4S,5S) > 90:10 by 1H NMR. [α]20 –144.0
D
(c 0.5, ch loroform ). For C31H40N2 (440.7) calculated: 84.49% C, 9.15% H, 6.36% N; foun d:
84.52% C, 9.10% H, 6.33% N. 1H NMR (200 MHz): 0.75 t, 3 H, J = 7.4 (CH3); 0.83 m , 2 H
(CH2CH3); 1.09 m , 2 H (CH2CH2CH3); 1.31 d, 3 H, J = 6.6 (CHCH3); 1.33 d, 3 H, J = 6.6
(CHCH3); 1.43 m , 4 H (CHCH2 an d NH); 2.09 m , 1 H (CHN); 2.24 m , 3 H (CHN an d
CH2CH=CH); 3.78 q, 1 H, J = 6.6 (CHCH3); 3.85 q, 1 H, J = 6.6 (CHCH3); 5.71 dt, 1 H, J = 16
an d 7.2 (CH2CH=CHPh ); 5.88 d, 1 H, J = 16 (CH=CHPh ); 7.05–7.20 m , 10 H (Ph ).
(E)-(4R,5R)- and (E)-(4S,5S)-1,5-Diphenyl-N,N′-bis[(S)-1-phenylethyl]pent-1-ene-4,5-diamine (19b):
yellowish th ick oil, 1.59 g (69%), (E)-(4R,5R)/(E)-(4S,5S) = 85:15 by 1H NMR. [α]20 –55.1
D
(c 0.48, ch loroform ). For C33H36N2 (460.6) calculated: 86.04% C, 7.88% H, 6.08% N; foun d:
86.10% C, 7.89% H, 6.05% N. 1H NMR (200 MHz): 1.25 d, 3 H, J = 6.6 (CHCH3); 1.33 d,
3 H, J = 6.6 (CHCH3); 1.92 broad, 2 H (NH); 2.09 m , 1 H (CHN); 2.04 m , 1 H (CH2CH=CH);
2.24 m , 1 H (CH2CH=CH); 2.51 dt, 1 H, J = 7.0 an d 6.1 (CHCHCH2); 3.20 d, 1 H, J = 7.0
(NCHPh ); 3.42 q, 1 H, J = 6.6 (CHCH3); 3.88 q, 1 H, J = 6.6 (CHCH3); 5.82 dt, 1 H, J = 16.0
an d 7.2 (CH2CH=CHPh ); 6.10 d, 1 H, J = 16.0 (CH=CHPh ); 7.05–7.40 m , 20 H (Ph ).
Syn th esis of C2-Sym m etric 1,2-Disubstituted 1,2-Diam in es 2
An organ olith ium reagen t RLi (10 m m ol) was added durin g 15 m in to th e stirred solution of
1,2-diam in e 17 (2.50 g, 5 m m ol) in an h ydrous tetrah ydrofuran (20 m l) at –78 °C. After 1.5 h
an oth er 10 m m ol of RLi was slowly added. Th e m ixture was furth er stirred wh ile allowin g
th e tem perature to rise slowly to –30 °C (R = allyl) or 0 °C durin g 1 h . Usual work-up gave
th e products 2a, 2c–2e as m ixture of diastereom ers (see Sch em e 4), th en ch rom atograph ic
separation afforded th e pure m ain diastereom ers, wh ich were iden tified by com parison of
th eir ph ysical an d spectral properties with th ose reported for th e auth en tic m aterials.
(5R,6R)-N,N′-Bis[(S)-1-phenylethyl]decane-5,6-diamine (2a ): yellowish oil, 1.30 g (68%).
[α]20 –138.8 (c 1.0, ch loroform ); ref.3: [α]20 –122.2 (c 1.3, ch loroform ).
D
D
(2R,3R)-N,N′-Bis[(S)-1-phenylethyl]butane-2,3-diamine (2c): yellowish oil, 0.80 g (54%).
[α]20 –106.2 (c 0.41, ch loroform ); ref.1 for th e en an tiom er of 2c: [α]20 +128 (c 0.84, ch lo-
D
D
roform ).
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

Chiral Masked Form of Glyoxal Diimine
1539
(3R,4R)-2,2,5,5-Tetramethyl-N,N′-bis[(S)-1-phenylethyl]hexane-2,3-diamine (2d ): yellowish oil,
1.18 g (62%). [α]20 +55.6 (c 0.68, ch loroform ); ref.3: [α]20 +73.4 (c 1.8, ch loroform ); ref.7:
D
D
[α]20 +31.6 (c 0.364, ch loroform ).
D
(4R,5R)-N,N′-Bis[(S)-1-phenylethyl]octa-1,7-diene-4,5-diamine (2e): wh ite solid, 1.10 g (63%)
after ch rom atograph y (silica gel colum n ) an d crystallization (m eth an ol); m .p. 67–68 °C.
[α]20 –120 (c 1.1, ch loroform ); ref.4: [α]20 –126.8 (c 2.04, ch loroform ).
D
D
Syn th esis of Un sym m etrically 1,2-Disubstituted Diam in es 5
A solution of 1,2-diam in e 17 (2.50 g, 5 m m ol) in an h ydrous tetrah ydrofuran (20 m l) was
cooled to –78 °C. After 10 m in an R1Li (15 m m ol) was added un der stirrin g durin g 15 m in .
Th e m ixture was stirred for an oth er 2 h , wh ile allowin g th e tem perature to rise slowly to
–30 °C. Th en th e m ixture was cooled again to –78 °C, an R2Li (10 m m ol) was slowly added
an d th e stirred m ixture was allowed to reach –30 °C (R2 = allyl) or 0 °C durin g 1–2 h . After
quen ch in g with degassed water an d usual work-up, th e products were isolated by colum n
ch rom atograph y, elutin g with cycloh exan e–eth yl acetate m ixtures.
(2R,3R)- and (2S,3S)-N,N′-Bis[(S)-1-phenylethyl]heptane-2,3-diamine (5a): yellowish oil, 2.05 g
(41%) (ca 8% of an im purity was detected by GC-MS an d 1H NMR), (2R,3R)/(2S,3S) = 90:10
by GC-MS. [α]20 –121.8 (c 0.42, ch loroform ). 1H NMR (300 MHz): 0.83 t, 3 H, J = 7.2
D
(CH2CH3); 0.88 d, 3 H, J = 6.3 (CHCH3); 0.98 m , 2 H (CH2CH3); 1.20 m , 2 H (CH2C2H5);
1.27 s, 2 H (NH); 1.31 d, 3 H, J = 6.6 (CHCH3); 1.32 d, 3 H, J = 6.6 (CHCH3); 1.45 m , 2 H
(CHCH2); 2.0 q, 1 H, J = 4.8 (CHCHCH3); 2.19 m , 1 H (CHCH2); 3.79 q, 1 H, J = 6.6
(Ph CHCH3); 3.81 q, 1 H, J = 6.6 (Ph CHCH3); 7.18–7.42 m , 10 H (Ph ). EI-MS, m/z (rel.%): 190
(100) [M+ – 148], 105 (81), 86 (48), 191 (16), 77 (15), 148 (14) [M+ – 190].
(1R,2R)- and (1S,2S)-N,N′-Bis[(S)-1-phenylethyl]propane-1,2-diamine (5b): yellowish oil, 1.04 g
(58%) (2–3% of an im purity was detected by GC-MS an d 1H NMR), (1R,2R)/(1S,2S) = 92:8 by
1H NMR. [α]20 –219.7 (c 0.34, ch loroform ). For C25H30N2 (358.5) calculated: 83.75% C,
D
8.43% H, 7.81% N; foun d: 83.85% C, 8.48% H, 7.78% N. 1H NMR (300 MHz): 0.67 d, 3 H,
J = 6.6 (CHCH3); 1.24 d, 3 H, J = 6.6 (NCHCH3); 1.38 d, 3 H, J = 6.9 (NCHCH3); 1.82 br, 2 H
(NH); 2.43 dq, 1 H, J1 = 9.0, J2 = 6.6 (CHCHCH3); 3.0 d, 1 H, J = 9.0 (CHPh ); 3.41 q, 1 H, J =
6.6 (Ph CHCH3); 3.86 q, 1 H, J = 6.9 (Ph CHCH3); 7.02 m , 2 H (Ph ); 7.18–7.42 m , 13 H (Ph ).
(1R,2R)- and (1S,2S)-1-Phenyl-N,N′-bis[1(S)-phenylethyl]pent-4-ene-1,2-diamine (5c): oil, 1.25 g
(65%), (1R,2R)/(1S,2S) = 90:10 by 1H NMR. [α]20 –185.4 (c 0.6, ch loroform ). For C27H32N2
D
(384.5) calculated: 84.33% C, 8.39% H, 7.29% N; foun d: 84.35% C, 8.40% H, 7.28% N.
1H NMR (300 MHz): 1.24 d, 3 H, J = 6.6 (CHCH3); 1.35 d, 3 H, J = 6.6 (CHCH3); 1.81 m , 1 H
(CHCH2); 2.0 bs, 2 H (NH); 2.16 m , 1 H (CHCH2); 2.49 m , 1 H (CHCH2); 3.16 d, 1 H, J =
7.8 (NCHCHCH2); 3.41 q, 1 H, J = 6.6 (CHCH3); 3.86 q, 1 H, J = 6.6 (CHCH3); 4.85 d, 1 H,
Jtran s = 15.6 (CH=CH2); 4.93 d, 1 H, Jcis = 9.0 (CH=CH2); 5.58 ddt, 1 H, J = 9.0, 15.6 an d 6.3
(CH=CH2); 7.10 m , 2 H (Ph ); 7.20–7.40 m , 13 H (Ph ). GC-MS (partial decom position ) EI-MS,
m/z (rel.%): 105 (100), 174 (90), 70 (34), 106 (22), 79 (12), 77 (10), 210 (6), 135 (4), 343 (3).
Financial support from the Ministero dell’Istruzione, dell’Università e della Ricerca, Roma (FIRB
funds), and The University of Bologna is gratefully acknowledged.
Collect. Czech. Chem. Commun. (Vol. 68) (2003)

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Martelli, Savoia:
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Collect. Czech. Chem. Commun. (Vol. 68) (2003)