References and Notes
Percent review of aza-Claisen rearrangement:
1a
Majumdar KC.
Bhattacharyya T.
Chattopadhyay B.
Sinha B.
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2009,
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1b
Davies SG.
Garner AC.
Nicholson RL.
Osborne J.
Roberts PM.
Savory ED.
Smith AD.
Thomson JE.
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2009,
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1c
Castro AMM.
Chem. Rev.
2004,
104:
2939
1d
Nubbemeyer U.
Synthesis
2003,
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2a
Tsunoda T.
Sakai M.
Sasaki O.
Sako Y.
Hondo Y.
Itô S.
Tetrahedron
Lett.
1992,
33:
1651
2b
Tsunoda T.
Tatsuki S.
Shiraishi Y.
Akasaka M.
Itô S.
Tetrahedron Lett.
1993,
34:
3297
2c
Itô S.
Tsunoda T.
Pure Appl. Chem.
1994,
66:
2071
2d
Tsunoda T.
Nishii T.
Yoshizuka M.
Yamasaki C.
Suzuki T.
Itô S.
Tetrahedron Lett.
2000,
41:
7667
2e
Nishii T.
Suzuki S.
Yoshida K.
Arakaki K.
Tsunoda T.
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2003,
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2f
Tsunoda T.
Tatsuki S.
Kataoka K.
Itô S.
Chem. Lett.
1994,
543
2g
Tsunoda T.
Ozaki F.
Shirakata N.
Tamaoka Y.
Yamamoto H.
Itô S.
Tetrahedron Lett.
1996,
37:
2463
2h
Inai M.
Nishii T.
Mukoujima S.
Esumi T.
Kaku H.
Tominaga K.
Abe H.
Horikawa M.
Tsunoda T.
Synlett
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3 The stereochemistry of the products
was determined by the comparison with the samples, which had been
obtained by the rearrangement of 1a; see
ref. 2a.
4 It was suspected that the basicity
of LHMDS was not sufficient to deprotonate the amides, and stronger
bases must be required. However, the reaction with LDA gave lower yields
and stereoselectivities; see ref. 2a. Furthermore, the reaction
of 9a utilizing s-BuLi
(1.5 equiv) gave the same results as with LHMDS (1.5 equiv).
5
Typical Procedure
for the Aza-Claisen Rearrangement
To a solution of
LHMDS (1.0 M in toluene, 5.0 mL) in toluene (3 mL) was added a toluene
solution (3 mL) of carboxamide 9d (231
mg, 1.0 mmol) at -78 ˚C under an argon
atmosphere in a pressure tube.6 After 30 min with stirring,
the reaction mixture was allowed to warm to r.t. and was sealed.
After heating of the sealed solution at 120 ˚C
for 24 h, a sat. aq NaHCO3 (24 mL) was added, and the
mixture was extracted with CH2Cl2 (30 mL),
dried (Na2SO4), and evaporated.7 The
residual mixture was purified by SiO2 column chromatography
(n-hexane-EtOAc = 3:1)
to give 156 mg (68%) of 11d and
39 mg (17%) of a mixture of 10d and 11d as colorless needles, respectively.
Compound 10d: mp 84.5-85.5 ˚C
(n-hexane-EtOAc). [α]D
²¹ -94.7
(c 0.65, CHCl3). ¹H
NMR (400 MHz, CDCl3): δ = 7.40-7.20
(m, 5 H), 5.65 (br d, J = 7.2
Hz, 1 H), 5.13 (quin, J = 7.6
Hz, 1 H), 4.76 (m, 1 H), 4.73 (m, 1 H), 2.45-2.30 (m, 2
H), 2.09 (ddd, J = 12.5,
5.2, 0.8 Hz, 1 H), 1.72 (dd, J = 1.2,
0.8 Hz, 3 H), 1.47 (d, J = 6.8
Hz, 3 H), 1.11 (d, J = 6.8
Hz, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 174.9, 143.24,
143.21, 128.6, 127.3, 126.2, 112.4, 48.5, 42.2, 39.6, 22.4, 21.6,
17.6. IR (ATR): 3269, 2970, 1637, 1542, 1450 cm-¹.
MS (CI): m/z = 232 [M + H]+ (base
peak), 231 [M]+, 128, 105.
HRMS (CI): m/z [M + H]+ calcd
for C15H22ON: 232.1701; found: 232.1701.
Compound 11d: mp 54.2-55.5 ˚C
(n-hexane-EtOAc); [α]D
²¹ -84.6
(c 0.43, CHCl3). ¹H
NMR (400 MHz, CDCl3): δ = 7.40-7.20
(m, 5 H), 5.66 (br d, J = 6.8
Hz, 1 H), 5.13 (quin, J = 7.2
Hz, 1 H), 4.74 (br s, 1 H), 4.68 (br s, 1 H), 2.45-2.30
(m, 2 H), 2.07 (dd, J = 17.2,
10.8 Hz, 1 H), 1.67 (s, 3 H), 1.48 (d, J = 6.8
Hz, 3 H), 1.14 (d, J = 6.8
Hz, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 175.0,
143.2, 143.1, 128.6, 127.3, 126.2, 112.4, 48.4, 42.1, 39.6, 22.3,
21.5, 17.6. IR (ATR): 3285, 2970, 1639, 1538, 1450 cm-¹.
MS (CI):
m/z = 232 [M + H]+ (base
peak), 231 [M]+, 128, 105.
HRMS (CI): m/z [M + H]+ calcd
for C15H22ON: 232.1701; found: 232.1701.
6 An air-tight cylinder for high-pressure
experiments is available at Alltech Associates, Inc.
7 At this point, the diastereomeric ratio
was determined by GLC or LC.
8
Determination of
the Stereochemistry of the Products
A 88:12 mixture
of 10b and 11b was
subjected to hydroboration(disiamylborane), oxidation (aq NaOH-H2O2),
and heating with PTSA to give 3-methylvalero-lactone whose specific
rotation {[α]D
²³ -19.8
(c 4.5, CHCl3)} was
compared with its 3R-isomer {[α]D
²5 +27.6
(c 5.6, CHCl3)}.9 Thus,
the major product 10b was determined to have
the S configuration at the C-3 position.
9
Konoike T.
Araki Y.
J. Org. Chem.
1994,
59:
7849
10
Determination
of the Stereochemistry of the Products
A: A 91:9 mixture
of 10c and 11c was
subjected to hydroboration(disiamylborane), oxidation (aq NaOH-H2O2),
and heating with PTSA to give 2-methylvalero-lactone whose specific
rotation {[α]D
²² -56.3
(c 2.48, MeOH)} was compared
with its 2S-isomer {[α]D
²5 +67.3
(c 6.59, CHCl3)}.¹¹ Thus,
the major product 10c was determined to
have the R configuration at the C-2 position.
B:
The stereochemistry of the major product 10d was confirmed
by X-ray analysis as shown in Figure
[¹]
. Crystallographic
data (excluding structure factors) for this structure have been
deposited with the Cambridge Crystallo-graphic Data Centre as supplementary
publication numbers CCDC 832610. Copies of the data can be obtained,
free of charge, on application to CCDC, 12 Union Road, Cambridge,
CB2 1EZ, UK [fax: +44(1223)336033 or
e-mail:
deposit@ccdc.cam.ac.uk].
C: The stereochemistries
of the major products 10e and 10f were estimated
empirically.
Figure 1 The crystallographic
analysis of 10d
11
Evans DA.
Ennis MD.
Mathre DJ.
J. Am. Chem. Soc.
1982,
104:
1737
12 It was reported that enolates of esters
decomposed completely to ketene at 0 ˚C; see ref.
11.
13 Although it was suspected that there
were several decomposition pathways, we could not isolate any meaningful
compounds, not even Claisen-type condensation products, from the
reaction mixtures.
14
Ireland RE.
Mueller RH.
Willard AK.
J. Am. Chem. Soc.
1976,
98:
2868
