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Unusual reactions of secondary amino acids with trifluoroacetic anhydride: A novel access to α-trifluoromethylated acyloins
TetrWm
oo40-4039/94$6.clo+ .al
Letters,Vol. 35, No. 1, pp. 149-152 1994
Perp~PESSLSd
PhtedinGreatBritain
Unusual Reactions of Secondary Amino Acids with Trifluoroacetic Anhydride: A Novel Access to a-Trifluoromethylated
Absbuct:
A new kagmentation reaction of acumdaq
Acyloins
u-amino acids with trifluoroacetic
anhydride under Dakin-West reaction conditions proceeds intumaliatcs followed by ring cleavage to form a-uifl~ethylatcd
through oxazolium salt acyloins in go& yields.
Thereacti~ofu-aminoacidswithaccticanh;ydrideinthtprurenctofabPsctogivea-scttaminoalkyl ketones is known as the Dakin-West (D-W) reaction and haa received much attention.’ Sccon&ry
amino
acids am likewise known to undergo the D-W reaction employing acetic anhydride at slightly higher temperatures and its mechanism lliflIloroEeticanhydridc
has been studied in &tail.’
(TFAA)has gainedFencwcdintuestin
Recently, the D-W reaction employing thepmpanuionoftlifluoNmlethylkc~s,2
an important class of inhibitors of a variety of hydrolytk ct~xymes.~ However, out rtccnt discovery4 ofthc unusualformation af S-tritluur0tnethyloxazolcs (3) fram N-acylprolincs (1) or IV-acyl-N-bcnzyl-u-amino
a: R=Ph, b: R-eMcOQH,,
c: R=+CQH,,
sdle!mel
& R=Bu’
150
uifluoromethyhued acyloins (2 and 5) as main p&ucts.
l%ese compounds possess a unique suuctuml
feahmz and are ofgreatsynthetic intent6 aa novel trifhmmethylao#i building blocks’ which ate subject of &Xive hlvestigaticQ. Table 1. Mans Run
Aminoacid
of Sewndury Amino Acids and TFAA Methoda
PlDduct (yield %)b
1
la
A
2
lb
A
h (88) 2b (85)
3
lc
A
2~ (81)
4
Id
A
2d (6% 3d (12)
5
4a
A
!%I(54). 6a (11). 7a (5)
6
4a
B
5a (50), 6a (14). 7a (13)
7
4b
A
5a (27), 6a (23), 7a (1)
8
4b
B
So (17), 6a (43). 7a (16)
9
4c
A
Sp (41), 6a (lo), 7a (33)
10
4d
A
5b (68). 6b (8). 7b 02)
11
4e
A
6c (43), 7c (2)c
a) Method A: The addition
ofTWA
was done at 100 OC,according to general procedure described in
the text. Method B: The addition of TPAA was done at 0 “C, according to the procedure described in ref. 4. b) Satisfactory spectral and analytical (combustion and/or high resolution mass) data were obtained for all new compounds. c) No isolation of !k is probably due to the loss during extraction because the product may bc water-soluble.
R’CHQH 1 NCOPh L2
TFAA
R’
R
cF3
CPI OH
+
8 R1yms
R’ + Ph$x
OCOPh
0
(3F3
41: R’=PhC&, R2=Me
Sa: R’=PhC!Hz
6a: R’ =PhCH2
7a: R’=PhCH2
4b: R1=PhCH2, R’=Et 4c: R1=R2=PhCH2 4d: R’=Ph. R’=lvIe
SIX R’=Ph SC: R’=Me
6b: R’=Ph 6c: R’=lvIe
7b: R’=Ph
4e:
R’=R’=ti
7c: Rt=Me
Scheme 2
According to a previous ~~port,~the reaction was initially carried out by the addition of TFAA at 0 ‘C to a solution of N-acylpro~me (1) and pyridine in benzene and gave 5-triflwaomethyloxazole
(3) in good yield
(Scheme 1). In contrast, when addition of TPAA was done at 100 “C, the results were quite different. Thus, TPAA (0.64 ml, 4.5 mmol) was added to a refluxing solution of la (313.5 mg, 1.5 mmol) and pyridine (0.73 mI, 9 mmol) in dry benzene (6 ml) and the mixture was fmther rtfluxed for 1 h. The mixture was evapmated
151
inwc~dthcrcsiducwastakcnupin 109bHC1~~(~:1,6ml);tbesolu~wess~M60’Cfor2 h. After workup. the product WIUpurified by column cluomatognpby on silica gel elutiag with EtOAcThe mason why the rcuction affds
bcxane (1:l) to give 2a (383.1 mg, 88%).8
product depending on the tcmpcxatum of the maction mixture is still unclear. applicable tu not only IV-acylprolincr (1) but also other N-acyl-IV-alkyl-a-ami
a compkely
fliffeIent
This reaction is generally &da (4). as shown in
Schcme2andTablcl. IntheccueobIa,thetemperuureatadditionofTFMdoesaothavea~o~ effect on product distributions (Table 1, NII 5 and 6). R1
1
O-
H-
R’f-M D
NCOF%
i2
Ph 8
4
9
I- [ a
’
[Rpj
I
-R2%
5
scheme3
I 6
H+ -R2NH2
Although~ia#mtchrnistic~nsedyettobe~~~tbe~tionapperntoproceadviaa similar mechanism
to that &scribed
in the reaction of N-acylprolines.4
Several oboervationr help to
152
delineate the gtoss mechanistic details of the way how 4 is converted to $6. and 7, respectively. First, in the mactkm of 4c (Table 1, run 9). bumoic acid (40%). bcnzylaminc(35%, isolated as N-acetyl derivative) and benzylalcohol(1346)~iso~urtheacidicandbasicfrrctionrafaesCXmcti~ofdre~.
Second,
itwaspnrvcdthotSMd6~notthedirtct~productr,buttheywGlcfamed~acidh~y~sof the maction mixture. Gn the other hand, oxaxoles (‘7) were formed befae the acid hydrolysis. pnwedthatSwrsnotderivedfiomthehydrolysisof6,becw~#6as
Third, we
recoveredunchangedundcrthesame
reaction conditions as 4a. In Scheme 3. key intermediate oxazolium ion 10. the postulated common intermediate
for the formation
of oxaxoles,’
could have three sites which could be attacked by
trifluoroacetate anion. KutlK!rUMiou of triflllcmacctaicaniontoin-11couhilc8dtol2andacid hydrolysis of 12 via a-amino trifluoromethyl ketones (13)9 may account for the formation of 5. In summary, this work describes the unusual 6ngmentation reaction of secondary amino acids, which provides an access to synthetically usefill uiflucrometllylatal
acyloins. studies am in progress to e&idate
the precise mechanism of this reaction and to fully explore the synthetic potential
of these
producm.
Refereucaa and Notes 1. Buchanan, G. L. Chem. Sot. Rev. 1988,17,91. 2. The D-w neaction of aminoacids with -mAA yields the tzorlegponding a-amide uiRuaometby1 ketones. See: (a) Kolb, M.; N&es, B.; Gerkt, An@astro, M. R.; Gii,
F. Liebig Ann. Chem. 1990. 1; (b) Pcet, N. P.; Burkkt,
J. P.;
E. L.; Mehdi, S.; Bey, P.; Kolb, M.; Neises, B.; SchirIin, D. J. Med. C&m.
1!Bo, 33,394 and refeWlces cited therein. 3. (a) Begue. J. P.: Bonnet-Delpon. D. Tetrahedron 1991,47,3Un, Tetrahedron Lett. 1992,33,1285;
(c) Edwa&
(b) Boivin. J.; Kaim, L. El.; Zani, S. Z
P. D. Tetrahedron ht.
1992.33.4279.
4. (a) Kawase, M.; Miyamae, I-I.;Narita, M.; Kuribara, T. TetrahedronLett. 1993.34.859;
(b) Kawase, M.
Heterocycles 1993,36,2441. 5. It is reported that Wacyl-N-phenylglycines am treated witb TPAA at room temperatme to tiord anhydro~-aiflu~~ld-hydroxy-13-oxazolonium
hydroxides. This is the case hitherto reported, to our
knowledge, concernin g reaction of secondary amino acids and TFAA in the absence of a base. See: (a) Sk@. G.; Singb, S. TetrahedronLm.
1964.3789;
(b) Greco, C. V.; Gray, R. P.; Grosso, V. G. J. J. Org.
Chem. 1%7,32,4101. 6. The usefulness of acyloins in synthetic organic chemistry has been weII recognized. M.; Berglund, B. A.; Fenmasta, R. Tetrahedron L&t. 1992,33,606!5 7. (a) Fuchikami, T. J. Synrk Org. C&m. Jpn. 1984,42,775;
and refuenas
See: Moriarty, R. cited therein.
(b) Tanaka, K. J. Synch.Org. Chem.Jpn.
1990,48,16. 8. The acyloins (2 and 5) were isolated as a single isomer. Par 2rr: bp2 235 “C (bath temp.); ‘H NMR (CDC13): 6 1.84-2.01 (m. 2H), 2.64-2.85 (m. 2H), 3.31-3.47 (m, 2H), 4.51 (q. J-7.9 Hz, lH), 5.00 (d, Jr6.4 Hx, lH, D20 changeable), 6.96-7.00 (br, lH, D20 changeable), 7.33-7.49 (m, 3H), 7.70-7.73 (m, 2H); 13C NMR (CDC13): 6 23.21 (t), 36.65 (t). 39.15 (t). 75.11 (q,2Jc_ps31.1 Hx ), 122.70 (q, Jc_+84.0 Hz), 126.94 (d), 128.64 (d), 131.74 (d), 134.13 (s), 168.62 (s), 203.82 (8); JR (oil): 3325, 1730,164O cm-‘. 9. It is suggested that a-amino trifluoromethyl ketones am easily hydrolyzed to a-hydroxy ketones via the enolic form of the ketones. See: Begue, J. P.; Bonnet-Delpon, D.; Sdassi, H. Tetmhedron Lett. 1992,33. 1879.
(Received in Japan 13 September 1993; accepted 27 October 1993)
oo40-4039/94$6.clo+ .al
Letters,Vol. 35, No. 1, pp. 149-152 1994
Perp~PESSLSd
PhtedinGreatBritain
Unusual Reactions of Secondary Amino Acids with Trifluoroacetic Anhydride: A Novel Access to a-Trifluoromethylated
Absbuct:
A new kagmentation reaction of acumdaq
Acyloins
u-amino acids with trifluoroacetic
anhydride under Dakin-West reaction conditions proceeds intumaliatcs followed by ring cleavage to form a-uifl~ethylatcd
through oxazolium salt acyloins in go& yields.
Thereacti~ofu-aminoacidswithaccticanh;ydrideinthtprurenctofabPsctogivea-scttaminoalkyl ketones is known as the Dakin-West (D-W) reaction and haa received much attention.’ Sccon&ry
amino
acids am likewise known to undergo the D-W reaction employing acetic anhydride at slightly higher temperatures and its mechanism lliflIloroEeticanhydridc
has been studied in &tail.’
(TFAA)has gainedFencwcdintuestin
Recently, the D-W reaction employing thepmpanuionoftlifluoNmlethylkc~s,2
an important class of inhibitors of a variety of hydrolytk ct~xymes.~ However, out rtccnt discovery4 ofthc unusualformation af S-tritluur0tnethyloxazolcs (3) fram N-acylprolincs (1) or IV-acyl-N-bcnzyl-u-amino
a: R=Ph, b: R-eMcOQH,,
c: R=+CQH,,
sdle!mel
& R=Bu’
150
uifluoromethyhued acyloins (2 and 5) as main p&ucts.
l%ese compounds possess a unique suuctuml
feahmz and are ofgreatsynthetic intent6 aa novel trifhmmethylao#i building blocks’ which ate subject of &Xive hlvestigaticQ. Table 1. Mans Run
Aminoacid
of Sewndury Amino Acids and TFAA Methoda
PlDduct (yield %)b
1
la
A
2
lb
A
h (88) 2b (85)
3
lc
A
2~ (81)
4
Id
A
2d (6% 3d (12)
5
4a
A
!%I(54). 6a (11). 7a (5)
6
4a
B
5a (50), 6a (14). 7a (13)
7
4b
A
5a (27), 6a (23), 7a (1)
8
4b
B
So (17), 6a (43). 7a (16)
9
4c
A
Sp (41), 6a (lo), 7a (33)
10
4d
A
5b (68). 6b (8). 7b 02)
11
4e
A
6c (43), 7c (2)c
a) Method A: The addition
ofTWA
was done at 100 OC,according to general procedure described in
the text. Method B: The addition of TPAA was done at 0 “C, according to the procedure described in ref. 4. b) Satisfactory spectral and analytical (combustion and/or high resolution mass) data were obtained for all new compounds. c) No isolation of !k is probably due to the loss during extraction because the product may bc water-soluble.
R’CHQH 1 NCOPh L2
TFAA
R’
R
cF3
CPI OH
+
8 R1yms
R’ + Ph$x
OCOPh
0
(3F3
41: R’=PhC&, R2=Me
Sa: R’=PhC!Hz
6a: R’ =PhCH2
7a: R’=PhCH2
4b: R1=PhCH2, R’=Et 4c: R1=R2=PhCH2 4d: R’=Ph. R’=lvIe
SIX R’=Ph SC: R’=Me
6b: R’=Ph 6c: R’=lvIe
7b: R’=Ph
4e:
R’=R’=ti
7c: Rt=Me
Scheme 2
According to a previous ~~port,~the reaction was initially carried out by the addition of TFAA at 0 ‘C to a solution of N-acylpro~me (1) and pyridine in benzene and gave 5-triflwaomethyloxazole
(3) in good yield
(Scheme 1). In contrast, when addition of TPAA was done at 100 “C, the results were quite different. Thus, TPAA (0.64 ml, 4.5 mmol) was added to a refluxing solution of la (313.5 mg, 1.5 mmol) and pyridine (0.73 mI, 9 mmol) in dry benzene (6 ml) and the mixture was fmther rtfluxed for 1 h. The mixture was evapmated
151
inwc~dthcrcsiducwastakcnupin 109bHC1~~(~:1,6ml);tbesolu~wess~M60’Cfor2 h. After workup. the product WIUpurified by column cluomatognpby on silica gel elutiag with EtOAcThe mason why the rcuction affds
bcxane (1:l) to give 2a (383.1 mg, 88%).8
product depending on the tcmpcxatum of the maction mixture is still unclear. applicable tu not only IV-acylprolincr (1) but also other N-acyl-IV-alkyl-a-ami
a compkely
fliffeIent
This reaction is generally &da (4). as shown in
Schcme2andTablcl. IntheccueobIa,thetemperuureatadditionofTFMdoesaothavea~o~ effect on product distributions (Table 1, NII 5 and 6). R1
1
O-
H-
R’f-M D
NCOF%
i2
Ph 8
4
9
I- [ a
’
[Rpj
I
-R2%
5
scheme3
I 6
H+ -R2NH2
Although~ia#mtchrnistic~nsedyettobe~~~tbe~tionapperntoproceadviaa similar mechanism
to that &scribed
in the reaction of N-acylprolines.4
Several oboervationr help to
152
delineate the gtoss mechanistic details of the way how 4 is converted to $6. and 7, respectively. First, in the mactkm of 4c (Table 1, run 9). bumoic acid (40%). bcnzylaminc(35%, isolated as N-acetyl derivative) and benzylalcohol(1346)~iso~urtheacidicandbasicfrrctionrafaesCXmcti~ofdre~.
Second,
itwaspnrvcdthotSMd6~notthedirtct~productr,buttheywGlcfamed~acidh~y~sof the maction mixture. Gn the other hand, oxaxoles (‘7) were formed befae the acid hydrolysis. pnwedthatSwrsnotderivedfiomthehydrolysisof6,becw~#6as
Third, we
recoveredunchangedundcrthesame
reaction conditions as 4a. In Scheme 3. key intermediate oxazolium ion 10. the postulated common intermediate
for the formation
of oxaxoles,’
could have three sites which could be attacked by
trifluoroacetate anion. KutlK!rUMiou of triflllcmacctaicaniontoin-11couhilc8dtol2andacid hydrolysis of 12 via a-amino trifluoromethyl ketones (13)9 may account for the formation of 5. In summary, this work describes the unusual 6ngmentation reaction of secondary amino acids, which provides an access to synthetically usefill uiflucrometllylatal
acyloins. studies am in progress to e&idate
the precise mechanism of this reaction and to fully explore the synthetic potential
of these
producm.
Refereucaa and Notes 1. Buchanan, G. L. Chem. Sot. Rev. 1988,17,91. 2. The D-w neaction of aminoacids with -mAA yields the tzorlegponding a-amide uiRuaometby1 ketones. See: (a) Kolb, M.; N&es, B.; Gerkt, An@astro, M. R.; Gii,
F. Liebig Ann. Chem. 1990. 1; (b) Pcet, N. P.; Burkkt,
J. P.;
E. L.; Mehdi, S.; Bey, P.; Kolb, M.; Neises, B.; SchirIin, D. J. Med. C&m.
1!Bo, 33,394 and refeWlces cited therein. 3. (a) Begue. J. P.: Bonnet-Delpon. D. Tetrahedron 1991,47,3Un, Tetrahedron Lett. 1992,33,1285;
(c) Edwa&
(b) Boivin. J.; Kaim, L. El.; Zani, S. Z
P. D. Tetrahedron ht.
1992.33.4279.
4. (a) Kawase, M.; Miyamae, I-I.;Narita, M.; Kuribara, T. TetrahedronLett. 1993.34.859;
(b) Kawase, M.
Heterocycles 1993,36,2441. 5. It is reported that Wacyl-N-phenylglycines am treated witb TPAA at room temperatme to tiord anhydro~-aiflu~~ld-hydroxy-13-oxazolonium
hydroxides. This is the case hitherto reported, to our
knowledge, concernin g reaction of secondary amino acids and TFAA in the absence of a base. See: (a) Sk@. G.; Singb, S. TetrahedronLm.
1964.3789;
(b) Greco, C. V.; Gray, R. P.; Grosso, V. G. J. J. Org.
Chem. 1%7,32,4101. 6. The usefulness of acyloins in synthetic organic chemistry has been weII recognized. M.; Berglund, B. A.; Fenmasta, R. Tetrahedron L&t. 1992,33,606!5 7. (a) Fuchikami, T. J. Synrk Org. C&m. Jpn. 1984,42,775;
and refuenas
See: Moriarty, R. cited therein.
(b) Tanaka, K. J. Synch.Org. Chem.Jpn.
1990,48,16. 8. The acyloins (2 and 5) were isolated as a single isomer. Par 2rr: bp2 235 “C (bath temp.); ‘H NMR (CDC13): 6 1.84-2.01 (m. 2H), 2.64-2.85 (m. 2H), 3.31-3.47 (m, 2H), 4.51 (q. J-7.9 Hz, lH), 5.00 (d, Jr6.4 Hx, lH, D20 changeable), 6.96-7.00 (br, lH, D20 changeable), 7.33-7.49 (m, 3H), 7.70-7.73 (m, 2H); 13C NMR (CDC13): 6 23.21 (t), 36.65 (t). 39.15 (t). 75.11 (q,2Jc_ps31.1 Hx ), 122.70 (q, Jc_+84.0 Hz), 126.94 (d), 128.64 (d), 131.74 (d), 134.13 (s), 168.62 (s), 203.82 (8); JR (oil): 3325, 1730,164O cm-‘. 9. It is suggested that a-amino trifluoromethyl ketones am easily hydrolyzed to a-hydroxy ketones via the enolic form of the ketones. See: Begue, J. P.; Bonnet-Delpon, D.; Sdassi, H. Tetmhedron Lett. 1992,33. 1879.
(Received in Japan 13 September 1993; accepted 27 October 1993)