Synthesis of new chiral derivatives of N,N′-dimethylpropyleneurea (DMPU) and examination of their influence on the regio- and enantioselectivity of addition of 2-(1,3-dithianyl)lithium to cyclohex-2-en-1-one

Article abstract of DOI:10.1002/1522-2675(200207)85:7<1999::AID-HLCA1999>3.0.CO;2-K

The preparation of three new chiral derivatives of DMPU (N,N′-dimethylpropyleneurea) is described (Schemes 2-4); one type of derivative carries 1-phenylethyl or 1-cyclohexylethyl groups at the N-atoms of the tetrahydropyrimidin-2(1H)-one ring (2 and 4), a

Full text of DOI:10.1002/1522-2675(200207)85:7<1999::AID-HLCA1999>3.0.CO;2-K

Helvetica Chimica Acta Vol. 85 (2002)
1999
Synthesis of New Chiral Derivatives of N,N'-Dimethylpropyleneurea
(DMPU) and Examination of Their Influence on the Regio- and
Enantioselectivity of Addition of 2-(1,3-Dithianyl)lithium to
Cyclohex-2-en-1-one
by Eusebio Juaristi*, Marcos Herna¬ndez-RodrÌguez, Heraclio Lo¬pez-Ruiz, Judit Avinƒa, and
Omar Munƒoz-Munƒiz
¬
¬
Departamento de QuÌmica, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico
¬
¬
Nacional, Apartado Postal 14-740, 07000 Mexico, D.F., Mexico
and Michiya Hayakawa1) and Dieter Seebach
Department of Chemistry, Laboratorium f¸r Organische Chemie der Eidgenˆssischen Technischen Hochschule,
ETH-Hˆnggerberg, Wolfgang-Pauli-Strasse 10, CH-8093 Z¸rich
The preparation of three new chiral derivatives of DMPU (N,N'-dimethylpropyleneurea) is described
(Schemes 2 4); one type of derivative carries 1-phenylethyl or 1-cyclohexylethyl groups at the N-atoms of the
tetrahydropyrimidin-2(1H)-one ring (2 and 4), another type of derivative is substituted at C(4) and C(6) of the
heterocyclic ring (7). The potential of these chiral Lewis bases as promoters in the regio- and/or enantioselective
addition of 2-(1,3-dithianyl)lithium to cyclohex-2-en-1-one was explored; they are all unable to effect
enantioselective addition; the derivatives with branched substituents at the N-atoms do not shift the addition
mode from 1,2 to 1,4, while the 3,4,5,6-tetrahydro-1,3,4,6-tetramethylpyrimidin-2(1H)-one does (Scheme 5).
The results provide useful information regarding the nature of the nucleophilic organolithium reagent:
obviously, the steric hindrance to Li complexation on the CˆO O-atom of the tetrahydropyrimidin-2(1H)-one
by branched substituents at N-atoms (cf. X-ray crystal structure of 2 in the Fig.) prevents solvent-separated-ion-
pair (SSIP) formation; this was confirmed by PM3 and B3LYP/3-21-G(d)//PM3 calculations (Scheme 6).
Introduction. Hexamethylphosphoric triamide (HMPA) is a highly polar, aprotic
solvent that enhances the rates of numerous nucleophilic reactions [1]. Nevertheless,
HMPA is a known carcinogen, potentially hazardous for use either in industry or the
laboratory. N,N'-Dimethylpropyleneurea (ˆ 3,4,5,6-tetrahydro-1,3-dimethylpyrimidin-
2(1H)-one; DMPU) has been shown to be an excellent, nonmutagenic, and safe
replacement for HMPA [2]. Tetraalkylsulfamides [3] and quinuclidine N-oxide [4]
have also been proposed as substitutes for HMPA.
Recently, Denmark et al. [5] examined the effectiveness of chiral derivatives of
HMPA as Lewis base promoters2)3) in several enantioselective reactions, including the
so-called desymmetrization of meso-epoxides and aldol additions (Scheme 1,
Eqns. 1 and 2).
1
)
)
)
Part of the Ph. D. Thesis of M.H., Dissertation No. 10352, ETH-Zurich, 1993.
For a review article on organic catalysts, see [6].
Analogous phosphonamide catalysts were very recently reported by Buono et al., but the results could not
be reproduced [7].
2
3

2000
Helvetica Chimica Acta Vol. 85 (2002)
Scheme 1. HMPAand DMPU, and Their Chiral Analogs in Enantioselective Reactions
O
O
O
O
Me2N
Me2N
*R2N
*R2N
Me
Me
*R
R*
P
P
N
N
N
N
NMe2
NMe2
*
R
HMPA
DMPU
OSiCl3
O
chiral
R
(1)
+
+
SiCl4
* *
R
R
R
HMPA analog
Cl
OSiCl3
O
OSiCl3
chiral
*
*
Ph
(2)
PhCHO
HMPA analog
Motivated by Denmark×s work, we deemed it of interest to explore the potential of
chiral derivatives of DMPU as enantioselective promoters in the addition of 2-(1,3-
dithianyl)lithium to cyclohex-2-en-1-one to give either the 1,2- or 1,4-adduct, which are
both chiral.
Results and Discussion. Synthesis of Chiral Analogs of DMPU. C2-Symmetrical
diamines (R,R)-1 and (S,S)-1 were prepared from 1,3-dichloropropane and (R)- or
(S)-1-phenylethylamine4)5), respectively, according to the procedure of Feringa et al.
[10]. Subsequent reaction with triphosgene [11] produced the desired chiral DMPU
analogs (R,R)-2 and (S,S)-2 (Scheme 2)6). Recrystallization of (R,R)-2 afforded single
crystals suitable for X-ray analysis (see Fig.). Most interesting is the propeller-like
orientation of the 1-phenylethyl groups, which should lead to high enantioselectivities
in reactions taking place with suitable substrates coordinated to the CˆO O-atom [13].
The solid-state conformation adopted by (R,R)-2 (Fig.) is readily explained as a
consequence of allylic A1,3 strain, which would be present in the other possible
conformations around the NÀCHMePh bond [14]. This qualitative conclusion is
supported by theoretical calculations summarized in the Table.
Diamine (R,R)-3 was obtained in good yield from the reaction of commercial (R)-
1-cyclohexylethylamine and acrolein, followed by reduction with NaBH4 [16];
cyclization with carbonyldiimidazole gave the DMPU analog (R,R)-4 (−dodecahydro-
2×; Scheme 3).
4
)
For recent reviews on applications of 1-phenylethylamine in the preparation of enantiomerically pure
compounds, see [8].
For N-monoalkylations of 1-phenylethylamine in DMPU solution, see [9].
The moderate yield encountered in the cyclization reaction is a consequence of oligomer formation [12].
5
6
)
)

Helvetica Chimica Acta Vol. 85 (2002)
2001
Scheme 2. Preparation of the Chiral DMPU Analogs (S,S)-2 and (R,R)-2 from (S)- and (R)-1-Phenylethyl-
amine
O
Ph
NH2
*
Ph * NH HN * Ph
Ph
N
N * Ph
*
54%
93%
(S,S)-2 or (R,R)-2
(R) or (S)
(S,S)-1 or (R,R)-1
Figure. X-Ray crystal structure of the chiral DMPU analog (R,R)-2 (the crystallographic data have been
deposited with the Cambridge Crystallographic Data Centre, No. CCDC 177735)
Finally, the chiral DMPU derivatives (R,R)-7 and (S,S)-7, with stereogenic centers
in the heterocyclic ring, rather than on the N-substituents, were prepared from
acetylacetone as depicted in Scheme 4. 1,3-Dioxime 5 was obtained in good yield, and
reduction with Raney-Ni provided a mixture of meso- and rac-diamines 6 [17]. The
undesired meso-diastereoisomer was readily separated by flash-column chromatog-
raphy, and rac-6 was resolved by fractional crystallization of the dibenzoyl tartrate salt
[18]. Finally, cyclization with phosgene and N-methylation under Leuckart-Wallach
conditions [19] afforded (R,R)-7 and (S,S)-7 (Scheme 4).
Addition of 2-(1,3-Dithianyl)lithium to Cyclohex-2-en-1-one in the Presence of 2, 4 and
7. We examined the regio- and enantioselectivity of addition of 2-(1,3-dithianyl)lithium

2002
Helvetica Chimica Acta Vol. 85 (2002)
Table. Calculated (Gas-Phase) Conformational Preference of the N-(1-Phenylethyl) N-Substituents in (R,R)-2
[15]
H
O
H
O
H
Ph
N
Ph
Me
H
Ph
Me
Ph
Me
N
Me
N
N
A
B
Method
HF/6-311 ‡ G(d,p)//HF/6-31G(d)
B3LYP/6-311 ‡ G(d,p)//B3LYP/6-31G(d)
DE [kcal/mol] (A ! B)
‡ 2.35
‡ 2.59
Scheme 3. Preparation of the Chiral DMPU Analog (R,R)-4 from (R)-1-Cyclohexylethylamine (Im ˆ imida-
zol-1-yl)
H2C=CH–CHO
NH2
N
N
H
H
(not isolated)
(R)
NaBH4
90%
O
Im2CO
N
N
NH HN
78%
(R,R)-4
3
to cyclohex-2-enone, both in the absence and presence of Lewis base promoters
(Scheme 5). As expected [19], in the absence of HMPA or DMPU, the predominant
mode of reaction is 1,2-addition (! 8). When HMPA or DMPU is added (Entries 2
and 3 in Scheme 5) the 1,4-adduct 9 becomes the main product. Product 9 is also the
major regioisomer in the presence of chiral urea (S,S)-7 (Entry 6) but, to our surprise,
product 8 of 1,2-addition is highly predominant in the presence of (S,S)-2 or (R,R)-4
(Entries 4 and 5)7).
According to the models of Dolak and Bryson [20a], Cohen et al. [20b], and
Sikorski and Reich [20c], the regioselectivity of nucleophile addition to enones is a
function of the ion-pair structure of the Li reagent, where contact-ion pairs (CIP) with a
7
)
It has been established that the addition of 2-(1,3-dithianyl)lithium to cyclohex-2-en-1-one is irreversible
[19d].

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Scheme 4. Preparation of the Chiral DMPU Analogs (S,S)-7 and (R,R)-7 from Acetylacetone
O
O
NOH NOH
2 H2NOH
70%
5
O
NH2 NH2
N
N
d),e)
d),e)
(S,S)-7
(S,S)-6
a)-c)
O
5
NH2 NH2
N
N
(R,R)-6
(R,R)-7
a) Raney-Ni, NaOH. b) Flash column chromatography. c) Resolution with dibenzoyl tartaric acid. d) Phosgene.
e) Aq. H2CO/HCO2H
Scheme 5. Addition of 2-(1,3-Dithianyl)lithium to Cyclohex-2-en-1-one. Both adducts are racemic in all cases, as
determined by HPLC analysis on a teicoplanin (ChirobioticTTM) column and/or optical-rotation measurement.
The diastereoisomer ratio was determined by integration of corresponding signals in the 1H-NMR spectra.

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Helvetica Chimica Acta Vol. 85 (2002)
tight CÀLi association give 1,2-addition, whereas solvent-separated ion pairs (SSIP)
give predominantly 1,4-addition. In the system at hand, the contrasting effect of HMPA
and DMPU (giving 1,4-addition), and chiral derivatives 2 and 4 (affording 1,2-addition)
imply that the latter are unable to form complexes with the cation, probably due to
steric hindrance by the N-(1-phenylethyl) or N-(1-cyclohexylethyl) groups. Thus, CIP
2-(1,3-dithianyl)lithium, with an intact CÀLi association8), adds to the CˆO moiety
with negligible enantioselectivity (Entries 4 and 5 in Scheme 5).
By contrast, chiral DMPU derivative (S,S)-7 is obviously able to coordinate to the
Li-atom, so that an SSIP is formed, and the dithianyl nucleophile adds mainly in the 1,4-
fashion (Entry 6 in Scheme 5).
Nevertheless, product 9 is racemic, indicating that the stereogenic centers in (S,S)-7
are too far remote from the coordinating site to induce significant enantioselectivity of
the reaction. In an alternative interpretation, a −naked× carbanionic 2-(1,3-dithianyl)
species may be considered to add to cyclohex-2-en-1-one, with no effective
participation of the chiral Li-solvate in the transition state.
Computational Studies. A computational investigation was undertaken to gain
support for the speculative statements advanced in the previous section. The main
question is whether 2-(1,3-dithianyl)lithium is present as SSIP in THF/HMPA and
THF/DMPU solutions, but as CIP species in THF solution. To be able to keep the
model system as authentic as possible, with the available amount of computational
resources, we chose a combined semiempirical and density-functional approach. The
semiempirical PM3 method [22] with Li parameters of Anders et al. [23] has been
widely used in organolithium chemistry [24], and it has been shown to adequately
reproduce geometries of organolithium compounds; however, the energies obtained by
the PM3 method are usually not as accurate [25]. Recently, Abbotto, Streitwieser, and
Schleyer have demonstrated that energies obtained by means of density-functional
theory with the B3LYP hybrid function with standard basis sets [6-31 ‡ G(d), 6-311 ‡
G(d)] on the PM3-optimized geometries (B3LYP/6-31 ‡ G(d)//PM3) produce high-
level results (B3LYP/6-31 ‡ G(d)//B3LYP/6-31G(d)) of high accuracy [26]. Thus, we
applied this B3LYP//PM3 method for our calculations.
Cryoscopic measurements in THF have demonstrated that (2-(1,3-dithianyl)lithium
is monomeric in solution at low temperature [27], and it is well-established that the
most stable and common coordination sphere of Li is tetrahedral [28]. Therefore, the
energy associated with equilibria depicted in Scheme 6 was calculated at the B3LYP/3-
21G(d) level of theory with PM3-optimized geometries for the involved species and
ligand molecules. The most relevant result is that, in the presence of coordinating (L ˆ
‡
HMPA or DMPU), solvation of the Li cation to give an SSIP 2-(1,3-dithianyl)
carbanion is a highly exothermic (favorable) process (Entries 2 and 3 in Scheme 6). By
contrast, when L is THF or the chiral DMPU analog 2, formation of SSIP species is
calculated to be an endothermic (unfavorable) process (Entries 1 and 4). These
computational results are in line with the experimentally observed results discussed in
the previous section.
8
)
For crystal structures of Li dithianes, see [21].

Helvetica Chimica Acta Vol. 85 (2002)
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Scheme 6. Calculated Energies for Lithium Cation Solvation and Concomitant Formation of SSIP Species
(CIP ˆ contact ion pair, SSIP ˆ solvent-separated ion pair, L ˆ coordinating solvent THF, HMPA, DMPU, or
(S,S)-2)
Conclusions. The observations reported are best interpreted by assuming that the
DMPU derivatives 2 and 4 are unable to associate with the cation of 2-(1,3-
dithianyl)lithium, leading to nonenantioselective 1,2-addition products. In contrast,
‡
(R,R)-7 effectively solvates Li so that the organic anion adds to cyclohex-2-en-1-one
in a 1,4-fashion. The fact that no enantioselectivity was detected in this reaction is an
indication that the chiral promoter is not intimately involved in an enantioface-
differentiating step.
Experimental Part
General. Flasks, stirring bars, and hypodermic needles used for the generation and reactions or
organolithiums were dried for ca. 12 h at 1208 and allowed to cool in a desiccator over anh. CaSO4. Anh.
THF was obtained by distillation from benzophenone ketyl. DMPU and HMPA were dried over CaH2 and then
distilled at reduced pressure. 1,3-Dithiane was sublimed before use. The BuLi employed was titrated according
to the method we developed [29]. TLC: Merck DC-F254 plates, detection by UV light. Flash column
chromatography (FC): Merck silica gel (0.040 0.063 mm). HPLC: Waters 600 instrument fitted with UV/VIS
detector, and a chiral stationary phase of teicoplanin (Chirobiotic TTM) for the determination of enantiomeric
ratios. M.p.: not corrected. 1H-NMR Spectra: Jeol Eclipse-400 (400 MHz), Bruker Ultra Shield (300 MHz), and
Jeol GSX-270 (270 MHz) spectrometers. 13C-NMR Spectra: Jeol Eclipse-400 (100 MHz), Bruker Ultra Shield
(75 MHz), and Jeol GSX-270 (67.5 MHz). Chemical shifts (d) in ppm downfield from internal TMS reference;
the coupling constants (J) are given in Hz. MS: Hewlett Packard HP-5986 spectrometer. Elemental analyses
were obtained from Galbraith Laboratories, Inc., Knoxville, TN.
(R,R)- and (S,S)-N,N'-Bis(1-phenylethyl)propane-1,3-diamine ((R,R)- and (S,S)-1). The procedure
described by Feringa et al. [10] was followed, with 11.77 g (97.2 mmol) of (R)- or (S)-1-phenylethylamine and
3.07 ml (32.4 mmol) of 1,3-dichloropropane: (R,R)-1: 94% yield. [a]2D0 ˆ ‡65.4 (c ˆ 2.4, CHCl3). ([10]: [a]2D0
ˆ
À66.3 (c ˆ 0.55, CHCl3) for the (S,S) enantiomer). (S,S)-1: 93% yield. [a]2D0 ˆ À66.8 (c ˆ 4.2, CHCl3). ([10]:
[a]2D0 ˆ À66.3 (c ˆ 0.55, CHCl3)).
(R,R)- and (S,S)-3,4,5,6-Tetrahydro-1,3-bis(1-phenylethyl)pyrimidin-2(1H)-one ((R,R)- and (S,S)-2). The
starting diamine ((R,R)-1 or (S,S)-1; 7.12 g, 25.2 mmol), Et3N (7.02 ml, 50.4 mmol), and 250 ml of dry CH2Cl2
were placed in a round-bottom flask, and the resulting mixture was cooled to 08 before the dropwise addition of
a soln. of 2.65 g (8.9 mmol) of triphosgene in 150 ml of CH2Cl2 for 2 h. Stirring was continued at 08 for 3 h and
then at r.t. for 2 d. Then, 200 ml of 1n HCl was added at 08, the aq. phase was separated and extracted with two
100-ml portions of CH2Cl2, the combined org. phases were washed with brine soln., dried (Na2SO4), and
concentrated. The product was purified by FC (petroleum ether/AcOEt 9 :1).

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Helvetica Chimica Acta Vol. 85 (2002)
Data of (S,S)-2: 45% yield. M.p. 124 1258. [a]2D0 ˆ À125.5 (c ˆ 1.0, CHCl3). 1H-NMR (CDCl3, 300 MHz):
1.55 (d, J ˆ 7.1, 6 H); 1.67 1.80 (m, 2 H); 2.72 2.80 (m, 2 H); 3.00 3.08 (m, 2 H); 6.05 (q, J ˆ 7.1, 2 H); 7.20
7.40 (m, 1 0 H).13C-NMR (CDCl3, 75 MHz): 16.3; 22.8; 39.9; 51.7; 127.3; 128.0; 128.7; 142.1; 156.4. MS (20 eV):
‡
308 (M ), 293, 204, 203, 189, 162, 146, 120, 105, 91, 41. Anal. calc. for C20H24N2O (308.43): C 77.89, H 7.84,
N 9.08; found: C 77.84, H 7.88, N 9.11.
Data of (R,R)-2: 46% yield. M.p. 124 1258. [a]2D0 ˆ ‡125.5 (c ˆ 1, CHCl3).
(R,R)-N,N'-Bis(1-cyclohexylethyl)propane-1,3-diamine ((R,R)-3). A mixture of 44 ml (0.3 mol) of (R)-1-
cyclohexylethylamine, 60 ml (0.44 mol) of Et3N, and 8.0 g of K2CO3 was treated (dropwise addition) with
10.0 ml (0.15 mol) of acrolein at 48. The mixture was stirred for 3 h in an ice-bath, filtered over Celite, and the
collected solid material washed with 75 ml of MeOH. The filtrate was then treated with 8.36 g (0.23 mol) of
NaBH4 in 75 ml of MeOH at 48, and stirring was continued at r.t. for 1h. The mixture was heated to 50 8 for 2 h,
and then concentrated at r.t. The residue was rinsed with 100 ml of H2O and extracted with three 50-ml portions
of Et2O. The combined org. extracts were dried (MgSO4) and concentrated in the rotary evaporator to give
40.6 g (90% yield) of (R,R)-3 as a yellow oil. This product was characterized as the corresponding hydrochloride
(3 ¥ 2 HCl). [a]D25 ˆ ‡8.8 (c ˆ 0.625, H2O). IR (CHCl3): 3420, 2930, 2860, 2740, 1590, 1450, 1390, 1050. 1H-NMR
(CDCl3/D2O, 200 MHz): 3.31 3.07 ( m, 6 H); 2.12 (dt, J ˆ 7.5, 2 H); 1.9 1.6 (br, 12 H); 1.4 1.05 (br, 10 H); 1.3
(d, J ˆ 7.5, 6 H). Anal. calc. for C19H40Cl2N2 (367.45): C 62.11, H 10.97, N 7.62; found: C 61.83, H 10.82, N 7.52.
(R,R)-1,3-Bis(1-cyclohexylethyl)-3,4,5,6-tetrahydropyrimidin-2(1H)-one ((R,R)-4).
A soln. of 6.0 g
(20 mmol) of (R,R)-3 in 50 ml of THF was treated with 4.0 g (24 mmol) of carbonyldiimidazole at 48 (ice-
bath). The mixture was stirred at r.t. for 12 h, cooled to 48 (ice bath), and treated with 100 ml of 1n HCl. The
resulting mixture was extracted with three 100-ml portions of CH2Cl2, the combined org. extracts were dried
(MgSO4), and concentrated in the rotary evaporator to afford 5.0 g (78% yield) of (R,R)-4 as yellowish crystals,
which were recrystallized from t-BuOMe. M.p. 72 758. [a]2D5 ˆ À17.0 ( c ˆ 1.34, CHCl3). IR (CHCl3): 3370, 2980,
2830, 1700, 1650, 1600, 1500, 1450, 1380, 1170, 850. 1H-NMR (CDCl3, 300 MHz): 4.27 (dt, 1J ˆ 7, 2J ˆ 3, 2 H); 3.1
(dt, 1J ˆ 12, 2J ˆ 6, 2 H); 1.87 (quint., 2 H); 1.75 1.6 (m, 10 H); 1.3 0.9 (m, 12 H); 1.07 (d, J ˆ 7, 3 H ) . 13C-NMR
(CDCl3, 75 MHz): 156.0; 54.0; 40.6; 39.2; 30.4; 30.0; 26.4; 26.3; 26.2; 22.6; 16.0. Anal. calc. for C20H36N2O
(320.52): C 74.95, H 11.32, N 8.74; found: C 74.64, H 11.41, N 8.63.
(4S,6S)-3,4,5,6-Tetrahydro-1,3,4,6-tetramethylpyrimidin-2(1H)-one ((S,S)-7). (S,S)-Pentane-2,4-diamine
dihydrochloride [18] (32.1 g, 1.83 mmol) in 300 ml of toluene was added to 95 ml of H2O. The resulting
suspension was vigorously stirred at 48 (ice bath) before the dropwise addition of 337 ml of 4.5n NaOH
(1.5 mol) and 345 ml of a 20% soln. of phosgene in toluene (575 mmol). Stirring was continued for 4 h at r.t., and
then solvents were removed in a rotary evaporator. The residue was treated with 56.5 ml of 36% aq. soln. of
HCHO (732 mmol) and 188 ml of 98% HCOOH (5 mol). The mixture was heated under reflux for 12 h, and
then concentrated in the rotary evaporator. Compound (S,S)-7 (21.1 g, 74%) was obtained by distillation (b.p.
1028/1.5 mbar) over CaH2. Colorless oil. [a]2D5 ˆ ‡11.0 (c ˆ 1.18, CHCl3). IR (film): 3530, 2970, 1630, 1500, 1450,
1150. 1H-NMR (CDCl3, 200 MHz): 3.37 (ddq, 1J ˆ 6.4, 2J ˆ 3J ˆ 6.0, 2 H); 2.86 (s, 6 H); 1.76 (dd, 2 H); 1.15
(d, 6 H). 13C-NMR (CDCl3, 75 MHz): 156.3; 49.3; 36.8; 33.0; 10.6.
General Procedure for the Addition of 2-(1,3-Dithianyl)lithium to Cyclohex-2-en-1-one. A soln. of 0.12 g
(1.0 mmol) of 1,3-dithiane in 10 ml of dry THF was cooled to À788 under N2 before the dropwise addition of
0.4 ml of BuLi in hexane (2.4m, 1.0 mmol). The resulting mixture was stirred at À788 for 15 min and at 08 for 1h,
cooled again to À788, and treated with chiral urea (1.0 mmol) in 15 ml of THF. Stirring was continued for 25 min
at À788, and then the soln. was transferred via cannula to a flask containing 0.1ml (1.0 mmol) of cyclohex-2-en-
1-one in 5 ml of THF, also at À788. The mixture was stirred at this temp. for 4 h, before it was quenched with
3 ml of sat. aq. NH4Cl soln. The THF was removed at reduced pressure, and the residue was partitioned between
H2O and CH2Cl2. The org. phase was extracted with two portions of CH2Cl2, the combined org. extracts were
washed with 40 ml of H2O, dried, and concentrated. Final purification was accomplished by FC (hexane/AcOEt,
92 :8). 1,2-Adduct: 1-(1,3-Dithian-2-yl)cyclohex-2-en-1-ol (8): 1H-NMR (CDCl3 , 400 MHz): 1.60 2.10
(m, 8 H); 2.30 2.38 (br., 1H); 2.78 2.91 ( m, 4 H); 4.20 (s, 1H); 5.68 5.73 ( m, 1H); 5.89 5.93 ( m, 1 H).
‡
13C-NMR (CDCl3, 100 MHz): 18.6; 25.1; 25.9; 30.6; 30.8; 33.0; 59.8; 71.8; 129.4; 132.4. MS (20 eV): 216 (M ),
199, 119, 97, 79, 55, 41.
1,4-Adduct: 3-(1,3-Dithian-2-yl)cyclohexan-1-one (9): 1H-NMR (CDCl3, 400 MHz): 1.41 1.60 (m, 2 H);
1.63 1.76 (m, 1H); 1.90 2.44 ( m, 8 H); 2.72 2.75 (m, 4 H); 3.95 (d, J ˆ 5.1, 1 H). 13C-NMR (CDCl3,
‡
100 MHz): 24.7; 26.1; 28.4; 30.6; 41.1; 43.4; 45.1; 53.3; 210.1. MS (20 eV): 216 (M ), 142, 119, 110, 91, 79, 55, 41.
These spectroscopic data are similar to those reported previously by us [2a].

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2007
¬
Financial support from Conacyt, Mexico, via grant 33023-E is gratefully acknowledged. We are also
indebted to the reviewers and to Profs. Scott E. Denmark, University of Illinois, and Patrick J. Walsh, University
of Pennsylvania, for useful comments. We thank A. K. Beck and D. Kalbermatter for help in producing the
manuscript of this paper.
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Received March 9, 2002