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Russ.Chem.Bull., Int.Ed., Vol. 52, No. 2, February, 2003
Vinogradov et al.
NG 1.6, 6b 24.6; (S)ꢀ7b, 29.1; (R)ꢀ7b, 30.1; 145°C, NG, 1.3;
Nꢀacetylꢀ(S)ꢀ10, 33.7; Nꢀacetylꢀ(R)ꢀ10, 34.3. The conversions
of ketone 4d, 1ꢀindanone (6a), and imine 8 and the enantioꢀ
meric compositions of the products of their reduction, viz., 5d,
7a, and 9, respectively, were determined by HPLC on a
Laboratorny pristroje Praha chromatograph instrument; visualꢀ
ization was carried out with UV light, λ 254 nm, Chiralcel OD
(Daicel), 4.6 × 250 mm, the rate of elution was 1 mL min–1. The
compositions of the mobile phases (hexane : propanꢀ2ꢀol, v/v)
and retention times (min) were as follows: 95:5, 4d, 8.0; (S)ꢀ5d,
15.3; (R)ꢀ5d, 28; 6a, 6.4; (S)ꢀ7a, 6.7; (R)ꢀ7a, 7.3; 90 : 10, (R)ꢀ9,
6.64; 8, 8.0; (S)ꢀ9, 8.56. The assignment of the chromatographic
peaks of the products to the (R)ꢀ or (S)ꢀenantiomers was made
with the use of (R)ꢀ(+)ꢀ and (S)ꢀ(–)ꢀ5a (Aldrich), (R)ꢀ(–)ꢀ5h
(Fluka), (R)ꢀ(+)ꢀ and (S)ꢀ(–)ꢀ10 (Zeeland Chemicals). The
standards (R)ꢀ and (S)ꢀ9 were prepared by acylation of the corꢀ
responding enantiomerically pure amines 10 with Ph2P(O)Cl
(Aldrich). The assignment of the chromatographic peaks to the
(R)ꢀ or (S)ꢀenantiomers of 5b—f and 7a,b was made based on
the order in which they were eluted from the column by analogy
with alkanol 5a (see above). To determine the configuration of
the major enantiomer 5g, which was derived from ketone 4g in
entry 1 (see Table 2), alcohol 5g was isolated from the reaction
mixture by distillation after which the minus sign of the angle of
optical rotation was determined by polarimetry. This sign correꢀ
sponds to an enantiomeric excess of (R)ꢀ5g.13
Reduction of ketones 4 and 6 and imine 8 with complexes 2
and 3 prepared in situ in THF was carried out with the use of
the molar ratio NaAlH4(or AlH3) : TADDOL : substrate =
1.00 : 1.00 : 0.33 according to a procedure used for reduction of
compounds 4a,b with modified NaAlH4.1 A solution of AlH3 in
THF was prepared by the reaction of NaAlH4 with an equimolar
amount of HCl followed by separation of the precipitate of
NaCl by decantation.
In the experiments on hydride reduction of imine 8, unꢀ
consumed hydride was quenched by the dropwise addition of
water to the reaction mixture cooled to 0 °C. After separation of
aluminates, the reaction solution had an alkaline reaction. Unꢀ
der these condition, hydrolysis of unconsumed imine 8 and reꢀ
duction product 9 was not observed. To prepare amine 10, the
reaction mixture was treated with a solution of HCl in MeOH
and kept at ∼20 °C for 3 h. The enantiomeric composition of
amine 10 was determined by GLC.
Isolation of the solvate of sodium dihydrido(2,3ꢀisopropylꢀ
idenedioxyꢀ1,1,4,4ꢀtetraphenylꢀ1,4ꢀbutanediolato)aluminate with
THF, NaAl(IPTOLate)H2·THF. A solution of NaAlH4 (5 mmol,
270 mg) in anhydrous THF (9 mL) was added to a stirred soluꢀ
tion of IPTOL 1a (5 mmol, 2.33 g) in THF (20 mL) at ∼20 °C
through a rubber septum with the use of a syringe. The process
was accompanied by liberation of 223 mL of H2 (standard conꢀ
ditions; the theoretical yield was 224 mL). The reaction mixture
was stirred for 1 h and concentrated to ∼5 mL in vacuo at ∼20 °C.
Then hexane (10 mL) was added, a copious precipitate being
formed. The reaction mixture was concentrated to dryness as
described above to obtain the powdered complex, which was
dried in vacuo (1—2 Torr) at 40—45 °C for 1 h. The yield was
2.6 g (88%). According to the 1H NMR spectroscopic data, the
complex contained an equimolar amount of THF. Found (%):
C, 71.52; H, 5.74. C35H34AlNaO5. Calculated (%): C, 71.41;
H, 5.82. The operations with the solid complex (weighing, etc.)
should be carried out in air rather rapidly (5—10 min) to avoid
than the formation of (R)ꢀalkanol (cf. the structure
proꢀ(R)ꢀC″).
The stereochemistry of reduction of αꢀoxo ester 4h
corresponds to the models presented in Schemes 5 and 6
assuming that the polar CO2Et group possesses a more
substantial discriminating effect in the case of the hydride
attack of the oxo ester because of its better solvation in
solution compared to the (CH2)2Ph group.
To summarize, based on the consideration of the strucꢀ
tural models shown in Schemes 5 and 6, the results of
reduction of ketones with complexes 2 can be attributed
to the formation of cyclic TS B, whereas the stereochemiꢀ
cal result of reduction of ketones with reagents 3 can be
accounted for by the formation of acyclic TS C. Apparꢀ
ently, the higher level of asymmetric induction achieved
through TS B is associated with a more considerable steric
discrimination in the structures proꢀ(S)ꢀB´ and proꢀ(R)ꢀB´
(see Scheme 5) compared to the alternative structures
proꢀ(S)ꢀC″ and proꢀ(R)ꢀC″ (see Scheme 6).
Experimental
The NMR spectra were measured on a Bruker ACꢀ200 inꢀ
strument (200, 50.32, and 81.02 MHz for 1H, 13C, and 31P,
respectively). The following reagents were used: NaAlH4
(Zeeland Chemicals), ketones 4a,b and 6a,b, and LiAlH4
(Aldrich). The ligands (S,S)ꢀ1a 9 (m.p. 194—195 °C, [α]D25 +65
(c 1, CHCl3))9, (R,R)ꢀ1a 9 (m.p. 195—196 °C, [α]D –66
20
10
20
(c 1, CHCl3)), (S,S)ꢀ1b
(m.p. 179 °C, [α]D +80.5
(c 1, CHCl3)), (R,R)ꢀ1b 10 (m.p. 178—179 °C, [α]D –82
20
20
(c 1, CHCl3)), (S,S)ꢀ1c 11 (m.p. 173—174 °C, [α]D +38
(c 1, CHCl3)), (R,R)ꢀ1c 11 (m.p. 173—175 °C, [α]D –41
20
(c 1, CHCl3)), (S,S)ꢀ1d 9 (m.p. 198—199 °C, [α]D +70.6
25
(c 0.9, CHCl3)), (R,R)ꢀ1d 9 (m.p. 199—200 °C, [α]D –70.2
25
20
(c 1.8, CHCl3)), (R,R)ꢀ1e 10 (m.p. 152—154 °C, [α]D –55
20
(c 1, CHCl3)), (R,R)ꢀ1f 9 (m.p. 106 °C, [α]D –54.5 (c 1,
10
20
CHCl3)), (S,S)ꢀ1g
(m.p. 214—216 °C, [α]D +59 (c 1,
CHCl3)) and imine 8 12 (m.p. 135—137 °C; 31P NMR (CDCl3),
δ: 17.31; 1H NMR (CDCl3), δ: 2.98 (s, 3 H, Me); 7.30—7.60
(m, 10 H, Ar); 7.90—8.15 (m, 5 H, Ar); 13C NMR (CDCl3), δ:
22.97, 23.14 (d, Me, two signals due to coupling with 31P);
127.95—181.60 (15 signals, Ar, C=N))12 were synthesized acꢀ
cording to known procedures.
The compositions of the products of asymmetric hydrogenaꢀ
tion of ketones 4a—c,e,f were determined chromatographically
according to a procedure described earlier.1 The conversions of
carbonyl compounds 4g,h and 6b into the corresponding alkanols
and the enantiomeric compositions of reduction products 5g (as
acetate after esterification with Ac2O), 5h, and 7b and amine 10
(after its transformation into the acetyl derivative by the reacꢀ
tion with Ac2O) were determined by GLC on a Biokhromꢀ21
instrument equipped with a 30 m × 0.25 mm × 0.25 µm βꢀDEX
quartz capillary column (Supelco); the pressure was 1 atm, methꢀ
ane was used as the nonadsorbable gas (NG). The column temꢀ
peratures (°C) and retention times (min) were as follows: 50°C,
NG, 1.5; 4g, 3.6; (S)ꢀ and (R)ꢀ5g, 5.7 (enantiomers were not
separated); acetate of (S)ꢀ5g, 15.3; acetate of (R)ꢀ5g, 18.7;
145°C, NG, 2.2; 4h, 45.2; (R)ꢀ5h, 48.9; (S)ꢀ5h, 50.1; 130°C,
Vinogradov
