Preparation and reactions of 2,2-dimethyl-1,3-dioxan-5-one-SAMP-hydrazone: A versatile chiral dihydroxyacetone equivalent

Article abstract of DOI:10.1055/s-2002-33646

The SAMP-hydrazone of 2,2-dimethyl-1,3-dioxan-5-one represents a valuable chiral dihydroxyacetone equivalent. Asymmetric mono- or α,α′-bisalkylations followed by auxiliary cleavage leads to the corresponding mono- or α,α′-disubstituted, acetonide protected ketodiols in excellent diastereo- and enantiomeric excesses.

Full text of DOI:10.1055/s-2002-33646

PRACTICAL SYNTHETIC PROCEDURES
1775
Preparation and Reactions of 2,2-Dimethyl-1,3-dioxan-5-one-SAMP-Hydra-
zone: A Versatile Chiral Dihydroxyacetone Equivalent
2
, 2-Dimethyl-1,3-
i
e
5-one-SA
M
t
P-Hyd
e
razone r Enders,* Matthias Voith, Stuart J. Ince
PSP
Institut für Organische Chemie, Rheinisch-Westfälische Technische Hochschule,
Professor-Pirlet-Straße 1, 52074 Aachen, Germany
Fax +49(241)8092127; E-mail: enders@rwth-aachen.de
Received 5 April 2002
No
4
Abstract: The SAMP-hydrazone of 2,2-dimethyl-1,3-dioxan-5-one represents a valuable chiral dihydroxyacetone equivalent. Asymmetric
mono- or , -bisalkylations followed by auxiliary cleavage leads to the corresponding mono- or , -disubstituted, acetonide protected
ketodiols in excellent diastereo- and enantiomeric excesses.
Key words: asymmetric synthesis, ketodiols, alkylations, hydrazones, chiral dihydroxyacetone equivalent
1. 2,2-DMP, CSA,
DMF, r.t., 40 h,
OCH3
Et3N, EtOAc
N
O
O
N
2. NaIO4, KH2PO4,
H2O, 5-10 °C, 3 h,
to r.t. over 15 h
HO
NH2·HCl
SAMP, benzene,
reflux, 20 h
Procedure 1
OH OH
O
O
90%
O
58%
H3C CH3
H3C CH3
1
2
(S)-3
OCH3
1. t-BuLi, THF, −78 °C, 2 h,
RX, −100 °C, 2 h,
to r.t. over 15 h
N
O
N
O
R
2. O3, CH2Cl2, −78 °C, 15 min
Procedure 2
O
O
O
25-95%
H3C CH3
H3C CH3
(S)-3
4
1. t-BuLi, THF, −78 °C, 2 h,
R1X, −100 °C, 2 h,
to r.t. over 15 h
OCH3
2. t-BuLi, THF, −78 °C, 2 h,
R2X, −100 °C, 2 h,
to r.t. over 15 h
N
O
N
O
R2
R1
3. O3, CH2Cl2, −78 °C, 15 min
Procedure 3
O
O
O
30-87%
H3C CH3
H3C CH3
(S)-3
5
Scheme 1
Introduction
many groups have focused on broadening the scope of
these enzyme-catalyzed aldol reactions.1 On the other
Nature employs dihydroxyacetone phosphate (DHAP) as hand, the development of a chiral DHAP equivalent for
a C3-building block for carbohydrate synthesis via asym- chemical asymmetric synthesis would open up not just the
metric enzyme-catalyzed aldol reactions. Consequently possibility of asymmetric aldol reactions but also of other
electrophilic substitutions in -position such as asymmet-
ric alkylations as well, drastically increasing the scope
Synthesis 2002, No. 12, 06 09 2002. Article Identifier:
and utility. Whilst a chiral 4-subsituted 2,2-dimethyl-1,3-
1437-210X,E;2002,0,12,1775,1779,ftx,en;Z06102SS.pdf.
dioxan-5-one derivative, prepared from D-glucose, has
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

1776
D. Enders et al.
PRACTICAL SYNTHETIC PROCEDURES
been employed in an asymmetric aldol reaction,2 the de- by a modification of the method of Woodward and Vor-
velopment of a chiral dihydroxyacetone equivalent for brüggen reported by Hoppe et al.4 As shown in Table 1 a
general asymmetric synthesis has not been realized. In large range of electrophiles are compatible with the asym-
1989 we reported that conversion of 2,2-dimethyl-1,3-di- metric alkylation of the SAMP-hydrazone of dioxanone
oxan-5-one (2) to the corresponding SAMP-hydrazone (S)-3 (Procedure 2, Scheme). Smooth reaction of the aza-
(S)-3 proved an excellent platform for asymmetric alkyla- enolate, generated by deprotonation with tert-butyllithi-
tions.3 In this ‘Practical Synthetic Procedure’ we will um at low temperature, occurred with aziridines5 (Entry
show that the broad tolerance of a variety of electrophiles 1), Michael acceptors6 (Entry 2), a range of alkyl
in electrophilic -substitution reactions and the ease of halides3,7–10 (Entries 3–13) and a silyl triflate11 (Entry 14).
auxiliary cleavage under a range of conditions make this Auxiliary cleavage was achieved with either ozone, aque-
chiral DHAP equivalent a valuable C3-building block for ous oxalic acid, or aqueous copper(II) chloride to give the
a broad range of asymmetric syntheses.
-substituted ketones 4 in excellent enantiomeric excesses
(ee = 89 to 98%). The yield over two steps was 25–95%.
Of all the alkyl halides examined, the worst cases were
methyl (Entry 3) and allyl (Entry 9) yielding the ketones
in 45% and 25% yield, respectively, after ozonolytic
Scope and Limitations
The preparation of 2,2-dimethyl-1,3-dioxan-5-one- cleavage. These relatively low yields may be explained by
SAMP-hydrazone [(S)-3] is detailed in Procedure 1 the high volatility of the ketones and competitive cleavage
(Scheme 1). The preparation of the parent 2,2-dimethyl- of the double bond in the allyl case. To avoid ozonolytic
1,3-dioxan-5-one (2) starting from the aminotriol 1, both cleavage of double bond containing substituents, cleavage
of which are commercially available, was accomplished conditions can be switched to aqueous copper (II) chloride
(Entries 10 and 11).8 Moreover the reaction was tolerant
to O-protected -hydroxy7 (Entry 6), -hydroxy9,10 (En-
Table 1 Examples for Asymmetric Synthesis of 4-Subtituted 2,2-
Dimethyl-1,3-dioxan-5-ones 4
tries 7,12, and 13) and -hydroxy alkyl halides8 (Entry 8),
an -bromo ester3 (Entry 15), as well as the secondary iso-
Entry
1
R
Yielda (%) de (%) ee (%)
propyl iodide3 (Entry 4).
(CH2)2NHTs
CH(Me)CH2CO2Bu-t
Me
70b
–
98
96
93
95
94
94
96
96
95
96
96
98
The methodology was further extended to , -bisalkyla-
tions (Procedure 3). When the same electrophile is used
twice, then after cleavage, C2-symmetric bisalkylated ke-
tones 5 (R1 = R2) result (Table 2).12–14 The exclusively
1,3-trans substituted products were isolated in 58–83%
yield and enantiomeric excesses greater than 98%. In the
unsymmetrical series (Table 3),10,15,16 yields over three
steps were 30–87% with enantiomeric excesses greater
than 96% in all cases. Once again, only the 1,3-trans sub-
stituted products were observed. The functional group tol-
erance was broadened to alkyl halides containing epoxy
functionality10 (Entries 5 and 10) and three further sec-
ondary alkyl halides, -methylbenzyl15 (entry 7),
cyclopentyl15 (Entry 8) and cyclohexyl15 (Entry 9). Cleav-
age of the auxiliary was accomplished either using ozone
or aqueous oxalic acid.
2
79c
96
–
3
45c
4
i-Pr
60c
–
5
(CH2)2Ph
71c
–
6
CH2OBn
84d,e
95d
–
7
(CH2)2OTBS
(CH2)3OTBS
CH2CH=CH2
(CH2)2CH=CH2
(CH2)3CH=CH2
–
8
52b,e
25c
–
9
–
10
11
12
62b,e
90b,e
59c
–
–
Table 2 Examples for Asymmetric Synthesis of C2-Symmetric, 4,6-
Disubtituted 2,2-Dimethyl-1,3-dioxan-5-ones 5
89
O
O
Entry
Ra
X
Yieldb
(%)
de
(%)
ee
(%)
CH3
H3CH3
13
61c
87
98
1
2
3
4
5
Pr
I
68
83
68
58
64
96
96
96
96
96
>99
98
O
O
i-Pr
I
CH3
H3CH3
Bn
Br
I
98
14
15
SiMe2Hex-t
80c
45c
–
–
96
89
Et
>98
>99
CH2CO2CH3
(CH2)2Ph
I
a Overall yield starting from (S)-3.
b Auxiliary cleavage utilizing aq CuCl2.
c Ozonolytic cleavage.
a R = R1 = R2.
b Overall yield starting from (S)-3.
d Auxiliary cleavage utilizing aq oxalic acid.
e Yield of the auxiliary cleavage step.
Synthesis 2002, No. 12, 1775–1779 ISSN 0039-7881 © Thieme Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
2,2-Dimethyl-1,3-dioxan-5-one-SAMP-Hydrazone
1777
Table 3 Examples for Asymmetric Synthesis of 4,6-Disubtituted
2,2-Dimethyl-1,3-dioxan-5-ones 5
Procedures
Herein we describe the synthesis of SAMP-hydrazone
(S)-3 and two typical procedures for monosubstituted as
well as for , -disubstituted dioxanones 4 and 5. In the
first procedure (Procedure 1) the two step synthesis of 2,2-
dimethyl-1,3-dioxan-5-one (2) starting from the commer-
cially available aminotriol 1 followed by condensation
with (S)-1-amino-2-methoxymethylpyrrolidine (SAMP)
to afford the title compound (S)-3 in an overall yield of
52% is described. Procedures 2 and 3 show the mono- and
, -bisalkylation of SAMP-hydrazone (S)-3 and the oxi-
dative cleavage to give the monsubstituted dioxanone 4
(71%, 2 steps) or the , -disubstituted dioxanone 5 (86%,
3 steps), respectively.
En- R1
try
R2
Yielda de
ee
(%)
(%)
76
83
70
43
(%)
1
2
3
4
Me
i-Pr
96
96
96
81
>99
>99
>99
98
Me
Me
Me
CH2OBn
CH2CO2CH3
O
O
CH3
H3CH3
5
Me
51
98
98
O
6
7
Me
Me
Me
Me
Bn
86
70b
71
40
30
96
96
96
96
91
>99
>99
>99
>99
98
2,2-Dimethyl-1,3-dioxan-5-one (2)
CH(Me)Ph
cy-Pent
A 2 L round-bottom flask, equipped with a magnetic stirring bar,
was filled with 2-amino-2-hydroxymethyl-1,3-propandiol hydro-
chloride (1; 78.0 g, 500 mmol), DMF (160 mL), 2,2-dimethoxypro-
pane (2,2-DMP, 63.8 g, 600 mmol) and camphorsulfonic acid
(CSA, 4.18 g, 25 mmol). The mixture was stirred at r.t. for 40 h.
Et3N (4.2 mL) was added followed by removal of the solvent under
reduced pressure. The residue was dissolved in EtOAc (1.2 L) and
Et3N (67 mL) and stirred at r.t. for 10 min. The precipitate was fil-
tered and the solvent was removed under reduced pressure. The
crude -amino alcohol (50.0 g, 310 mmol) was then transferred to a
2 L three necked round-bottom flask, equipped with an overhead
stirrer, dropping funnel and thermometer and was dissolved in H2O
(450 mL). KH2PO4 (42.4 g, 310 mmol) was added and the solution
was cooled to 5 °C. Then, an aq NaIO4 solution (924 mL, 0.5 M)
was added dropwise over 3 h while the temperature was maintained
at 5–10 °C. The cooling bath was removed and the mixture was
stirred at r.t. for 15 h. The aqueous solution was extracted with
CH2Cl2 (15 70 mL). The combined organic layers were washed
with brine (70 mL), dried (MgSO4) and concentrated in vacuo. The
crude product was purified by distillation using a Vigreux column
to afford 2,2-dimethyl-1,3-dioxan-5-one (2) as a colorless oil
(25.3 g, 58%; 2 steps); bp 50–54 °C/11 Torr.
8
9
cy-Hex
10
O
O
O
CH3
H3CH3
11 Bn
CH2OBn
87c
96
96
a Overall yield starting from (S)-3 utilizing ozone for auxiliary cleav-
age.
b All diastereoisomers.
c Auxiliary cleavage utilizing aq oxalic acid.
A limitation of the methodology appears to be the reaction
of the azaenolates of the SAMP-dioxanone with alde-
hydes.17 A solution to this problem has been to employ the
-silyldioxanone (Entry 14, Table 1) as an alternative
chiral DHAP equivalent for aldol reactions.11
IR (CHCl3): 3472, 2991, 2941, 2893, 2538, 1801, 1753, 1445, 1425,
1378, 1338, 1270, 1222, 1153, 1121, 1093, 1052, 1029, 1007, 975,
918, 849, 832, 733, 715, 664, 624, 572, 559, 515, 477 cm–1.
1H NMR (CDCl3, 300 MHz): = 4.16 (s, 4 H, CH2), 1.45 (s, 6 H,
CH3).
13C NMR (CDCl3, 75 MHz): = 208.0 (CO), 100.1 (CCH3), 66.8
(2 C, CH2), 23.5 (2 C, CH3).
The utility of this methodology has been further demon-
strated in target oriented synthesis. The applications are
varied and include such topics as piperidine synthesis (via
reductive amination),18 C5- to C9-deoxy sugar synthesis
(via diastereoselective reduction)10 and the synthesis of
HIV-1 protease inhibitors.13 Furthermore, the total syn-
thesis of the natural products (+)-aspicillin (via the corre-
sponding RAMP hydrazone),19 L-threosphingosine,20 as
well as both enantiomers of streptenol A9 have also been
accomplished. Majeswki et al. have also used the SAMP-
dioxanone (S)-3 in a total synthesis of (+)-frontalin.21
MS (EI, 70 eV): m/z (%) = 130 (M+, 63), 115 (65), 10 (67), 73 (5),
72 (100), 59 (17), 58 (18), 57 (6).
Anal. Calcd for C6H10O3: C, 55.37; H, 7.74. Found: C, 55.14;
H, 7.71.
(S)-(+)-1-(2,2-Dimethyl-1,3-dioxan-5-ylidenamino)-2-methoxy-
methylpyrrolidine [(S)-3]
In a flask equipped with a Dean–Stark trap (for azeotropic removal
of H2O) and a reflux condenser, dioxanone 2 (8.45 g, 65 mmol) and
In summary, 2,2-dimethyl-1,3-dioxan-5-one-SAMP-hy-
drazone [(S)-3] has proven to be a very versatile chiral
DHAP equivalent for asymmetric synthesis. We are con-
tinuing to examine new electrophiles in the alkylation re-
actions (such as epoxides for example), as well as new
ways of functionalising the final products (such as meth-
ylenation and hydrogenation)14 and new applications
(such as quaternary centre construction).22
(S)-1-amino-2-methoxymethylpyrrolidine
(SAMP)
(8.46 g,
65 mmol) in benzene (80 mL) were refluxed for 20 h. After cooling,
Et2O (200 mL) was added and the mixture was washed with H2O
(2 10 mL). The organic layer was dried (MgSO4) and the solvent
was removed under reduced pressure. The crude hydrazone was pu-
rified by distillation under reduced pressure to give (S)-3 as a pale
yellow oil (14.2 g, 90%); bp 82–88 °C/0.05 Torr; 23 +230° (neat).
D
Synthesis 2002, No. 12, 1775–1779 ISSN 0039-7881 © Thieme Stuttgart · New York

1778
D. Enders et al.
PRACTICAL SYNTHETIC PROCEDURES
IR (CHCl3): 1460, 1450, 1380, 1370, 1340, 1220, 1155–1040, 835
cm–1.
r.t. over 15 h. The mixture was quenched with pH 7 buffer solution
(2 mL) and diluted with Et2O (80 mL). The organic layer was
washed with pH 7 buffer solution (10 mL) and brine (2 10 mL).
The organic layer was dried (MgSO4) and concentrated in vacuo.
The resulting monsubstituted SAMP-hydrazone was alkylated
again at the -position using benzyl bromide as the electrophile fol-
lowing the procedure described above. The obtained 4,6-disubsti-
tuted SAMP-hydrazone was dissolved in CH2Cl2 (50 mL) and
flushed with ozone (60 Lh–1) at –78 °C for 15 min. The reaction
mixture was allowed to warm to r.t. and flushed with argon. After
removal of the solvent under reduced pressure the crude product
was purified by flash chromatography (silica gel, n-pentane–Et2O,
20:1) to afford (S,S)-5 as a colorless oil (2.01 g, 86%); [ ]D25 –198.3
(c = 1.05, CHCl3).
1H NMR (CDCl3, 300 MHz): = 4.21–4.58 (m, 4 H, CNCOCH2),
3.35 (s, 3 H, OCH3), 3.04–3.46 (m, 4 H, CHHN, CH, CH2OCH3),
2.50 (q, J = 8.3 Hz, 1 H, CHHN), 1.95–2.06 (m, 1 H, CHCHH),
1.80–1.89 (m, 2 H, NCH2CHH, CHCHH), 1.60–1.71 (m, 1 H,
NCH2CHH), 1.43 (s, 3 H, CCH3), 1.40 (s, 3 H, CCH3).
13C NMR (CDCl3, 75 MHz): = 160.0 (C=N), 99.9 [C(CH3)2],
75.4 (CH2OCH3), 66.6 (CH), 62.6, 60.3 (2 C, CNCH2), 59.2
(OCH3), 55.4 (NCH2), 24.5 (CCH3), 23.2 (CCH3), 22.7
(NCH2CH2).
MS (EI, 70 eV): m/z (%) = 242 (M+, 1.5), 139 (43), 98 (60), 70
(100), 43 (30).
IR (CHCl3): 3016, 2966, 2958, 2927, 2855, 1745, 1497, 1455, 1377,
1217, 1174, 1122, 1076, 1031, 968, 944, 835, 758, 700, 699 cm–1.
Anal. Calcd for C12H22N2O3: C, 59.48; H, 9.15; N, 11.56. Found:
C, 59.47; H, 9.36; N, 11.34.
1H NMR (CDCl3, 400 MHz): = 7.18–7.30 (m, 5 H, C6H5), 4.44
(ddd, J = 1.4, 3.3, 8.8 Hz, 1 H, CH2CH), 4.29 (qd, J = 1.4, 6.9 Hz, 1
H, CH3CH), 3.23 (dd, J = 3.2, 15.0 Hz, 1 H, CHH), 2.80 (dd,
J = 9.1, 14.8 Hz, 1 H, CHH), 1.43 (d, J = 0.6 Hz, 3 H, CCH3), 1.33
(d, J = 0.6 Hz, 3 H, CCH3), 1.29 (d, J = 6.9 Hz, 3 H, CHCH3).
13C NMR (CDCl3, 100 MHz): = 210.7 (CO), 137.6 (CPh), 129.0,
128.0 (4 C, OCH, m-CH), 126.2 (p-CH), 101.0 [C(CH3)2], 75.0,
70.6 (2 C, CH), 34.8 (CH2), 24.0 (CH3), 23.9 (CH3), 14.4 (CHCH3).
MS (EI, 70 eV): m/z (%) = 234 (M+, 12), 190 (25), 176 (83), 162
(27), 147 (33), 147 (16), 133 (33), 132 (90), 131 (81), 119 (18), 119
(48), 114 (26), 105 (20), 104 (100), 103 (23), 91 (23), 86 (83), 78
(14), 77 (18), 65 (10), 59 (31), 58 (94), 56 (17), 56 (64), 51 (14), 45
(13).
(S)-(–)-2,2-Dimethyl-4-phenethyl-1,3-dioxan-5-one [(S)-4]
[R = (CH2)2Ph]
A dry, argon flushed, 100 mL Schlenk round-bottom flask,
equipped with a magnetic stirring bar, was filled with SAMP-hydra-
zone (S)-3 (2.42 g, 10 mmol) and anhyd THF (40 mL). Then,
t-BuLi (7.5 mL, 15% in n-pentane, 11 mmol) was added dropwise
by syringe at –78 °C. After stirring for 2 h at this temperature, the
mixture was cooled to –100 °C and 2-phenylethyl iodide (1.59 mL,
11 mmol), dissolved in anhyd THF (2 mL) was added slowly. After
further stirring for 2 h at –100 °C, the mixture was allowed to warm
to r.t. over 15 h. The mixture was quenched with pH 7 buffer solu-
tion (2 mL) and diluted with Et2O (80 mL). The organic layer was
washed with pH 7 buffer solution (10 mL) and brine (2 10 mL).
The combined organic layers were dried (MgSO4) and concentrated
in vacuo. The obtained monoalkylated SAMP-hydrazone was dis-
solved in CH2Cl2 (50 mL) and flushed with ozone (60 Lh–1) at
–78 °C for 15 min. The reaction mixture was allowed to warm to r.t.
and flushed with argon. After removal of the solvent under reduced
pressure, the crude product was purified by flash chromatography
(silica gel, n-pentane–Et2O; 30:1) to afford (S)-4 as a colorless oil
(1.66 g, 71%); [ ]D27 –189.0 (c = 1.02, CHCl3).
Anal. Calcd for C14H18O3: C, 71.77; H, 7.74. Found: C, 71.45;
H, 7.74.
References
(1) For a recent example and review see: (a) Shoevaart, R.; van
Rantwijk, F.; Sheldon, R. A. J. Org. Chem. 2000, 65, 6940.
(b) Machajewski, T. D.; Wong, C.-H. Angew. Chem., Int.
Ed. 2000, 39, 1352; Angew. Chem. 2000, 112, 1406.
(2) Hirama, M.; Noda, T.; Itô, S.; Kabuto, C. J. Org. Chem.
1988, 53, 706.
(3) Enders, D.; Bockstiegel, B. Synthesis 1989, 493.
(4) (a) Hoppe, D.; Schmincke, H.; Kleemann, H.-W.
Tetrahedron 1989, 45, 687. (b) For an alternative synthesis
of 2 starting with nitromethane on a 1 mol scale, see Ref.3
(5) Enders, D.; Janeck, C. F.; Raabe, G. Eur. J. Org. Chem.
2000, 3337.
IR (CHCl3): 3473, 3086, 3063, 3028, 2989, 2936, 2865, 2633, 2157,
1951, 1875, 1801, 1746, 1604, 1585, 1497, 1455, 1432, 1379, 1323,
1250, 1225, 1173, 1105, 1071, 1036, 991, 974, 918, 867, 853, 774,
750, 701, 623, 605, 582, 538, 517, 490 cm–1.
1H NMR (CDCl3, 400 MHz): = 7.16–7.29 (m, 5 H, C6H5), 4.24
(dd, J = 1.5, 16.9 Hz, 1 H, COCHH), 4.15 (ddd, J = 1.5, 3.6, 9.1 Hz,
1 H, COCH), 3.95 (d, J = 17.0 Hz, 1 H, COCHH), 2.80 (m, 1 H, Ph-
CHH), 2.68 (m, 1 H, PhCHH), 2.20 (m, 1 H, CHCHH), 1.86 (m, 1
H, CHCHH), 1.45 (s, 3 H, CH3), 1.42 (s, 3 H, CH3).
(6) Enders, D.; Kownatka, D.; Hundertmark, T.; Prokopenko,
O. F.; Runsink, J. Synthesis 1997, 649.
(7) Enders, D.; Hundertmark, T.; Lazny, R. Synlett 1998, 721.
(8) Enders, D.; Hundertmark, T.; Lazny, R. Synth. Commun.
1999, 29, 27.
(9) Enders, D.; Hundertmark, T. Eur. J. Org. Chem. 1999, 751.
(10) Enders, D.; Jegelka, U. Tetrahedron Lett. 1993, 34, 2453.
(11) Enders, D.; Prokopenko, O. F.; Raabe, G.; Runsink, J.
Synthesis 1996, 1095.
13C NMR (CDCl3, 100 MHz): = 209.8 (CO), 141.2 (CPh), 128.3,
128.6 (4 C, OCH, m-CH), 126.3 (p-CH), 101.1 (CCH3), 73.8
(CHO), 66.7 (COCH2), 31.2, 30.4 (2 C, CH2), 24.4, 24.1 (2 C, CH3).
MS (CI, Isobutane): m/z (%) = 236 (15), 235 (M+ + 1, 100), 218 (7),
217 (64), 178 (11), 177 (93), 176 (14), 159 (36), 134 (11), 133 (11),
131 (5), 130 (6).
Anal. Calcd for C14H18O3: C, 71.77; H, 7.74. Found: C, 71.50;
H, 7.89.
(12) Enders, D.; Gatzweiler, W.; Jegelka, U. Synthesis 1991,
1137.
(S,S)-(–)-4-Benzyl-2,2,6-trimethyl-1,3-dioxan-5-one [(S,S)-5]
[R1 = CH3, R2 = Bn]
(13) Enders, D.; Jegelka, U.; Dücker, B. Angew. Chem., Int. Ed.
1993, 32, 423; Angew. Chem. 1993, 105, 423.
(14) Enders, D.; Voith, M. Synlett 2002, 29.
(15) Enders, D.; Voith, M., unpublished results.
(16) Enders, D.; Hundertmark, T. Tetrahedron Lett. 1999, 40,
4169.
A dry, argon flushed, 100 mL Schlenk round-bottom flask,
equipped with a magnetic stirring bar, was filled with (S)-3 (2.42 g,
10 mmol) and anhyd THF (40 mL). Then, t-BuLi (7.5 mL, 15% in
n-pentane, 11 mmol) was added dropwise by syringe at –78 °C. Af-
ter stirring for 2 h, the mixture was cooled to –100 °C and a solution
of MeI (0.68 mL, 11 mmol) in anhyd THF (2 mL) was added slow-
ly. After further stirring for 2 h, the mixture was allowed to warm to
(17) Bockstiegel, B. Ph.D. Thesis; Aachen University: Germany,
1988.
Synthesis 2002, No. 12, 1775–1779 ISSN 0039-7881 © Thieme Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
2,2-Dimethyl-1,3-dioxan-5-one-SAMP-Hydrazone
1779
(18) (a) Enders, D.; Jegelka, U. Synlett 1992, 999. (b) Enders,
D.; Kirchhoff, J. H. Synthesis 2000, 2099.
(19) Enders, D.; Prokopenko, O. F. Liebigs. Ann. Chem. 1995,
1185.
(21) Majewski, M.; Nowak, P. Tetrahedron: Asymmetry 1998, 9,
2611.
(22) Enders, D.; Nühring, A.; Runsink, J.; Raabe, G. Synthesis
2001, 1406.
(20) Enders, D.; Whitehouse, D.; Runsink, J. Chem.–Eur. J.
1995, 1, 382.
Synthesis 2002, No. 12, 1775–1779 ISSN 0039-7881 © Thieme Stuttgart · New York