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Cyclic and acyclic products from the addition of 1-aza-allyl anions to dienes and α,β-unsaturated ketones - regioselectivity
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TeulhcQon Lcttcn. Vol. 34. No. 2 Pp. 307314 1993 ~ladhGmtBlitain
Cyclic and Acyclic Products fkom the Addition of 1-Area-Ally1Anions to Dienes and u,HJnsaturated Ketones - Rc!gfo&dvity
Stefan Wegmam
&g~scb_cbanig&w
and Ernst-Ulrich W&thweia*
Iostitotc&r weafsbho
Manster, ollhhlg
wilhehs-uoiversilm
23. D-4400Maostrr
ln comparison with the widesptead use of enolates in organic synthesis, the application of their
nitrogen analogues, the I-aza-ally1 anions, has found relatively little attention in spite of several synthetic advantage ‘A The electronic natute of the nitrogen atom and the adjustable substitue-nton it ate the reasons for their enhanced selectivity, which allows to conduct teactions under milder and better controlled conditions, compared to enolates. Today, the sbucturai properties of I-aza-ally1 anions are well known, both expe&nentally 57 and theoretically from quautum chemical calculations 89. In this paper, we report on the dons
of the I-aza-allyl-lithium compound 1 withsimple dienes
and an a&unsaturated carbonyl compound. In 1975, TaLabe et al. lo briefly described a cycloalkenylation of lithiated N-isobutylidene-t-butylamiue with three dif&ent dienes (butadie~~, isopmne and mymene). They found cyclic and acyclic pmducts in varying amounts as de&ted by glc. Our intemst in this field concentrates on the ngio- and skreoselectivity of polyfunctional aza-substituted auions and their possible control in organic synthesis “*12. Starting from the com?sponding aldimine, we prepa& the l-aza-allyl-lithium compound 1 in situ by depmto&on
in THF at -7PC using litbium-diisopropylamide &DA) as base.kopmc was addedto the
307
deeply colond solution of 1 at low tempemture. Depending on reaction time and tempemmre open chain (3) and cyclic (4) products were isolated after NaHC$ THF reflux tempera=
(4 days) a 955 mixm
hydrolysis and ch~~matographic workup 13. Thus, at
of 4a aod 4b was obtained in 47% yield. At -1OT however
(4 days), a 8020 mixtme of 3a and 3b was isolated in 40% yield; further hydrolysis during flash chroma-
tography on wet silica gel leads to the ~&unsaturated
aldehydes SI and Sb. Mechanistically, the formation
of the cyclic products 4 takes place via a two step mechanism, involving the ally1 anions 2 as key intermediates; they can be trapped at low temperature during the workup giving the imines 3; under more severe conditions at higher temperatmw the aaions 2 cycke
yield&
the amino-cyclohexene derivatives 4.
The isolation of the acyclic products 3 is our main argument against an one-step cycloaddition mechanism of the Diels-Alder type.
3b
(95:5;
47%)
5b
The addition of isopnme to 1 is not completely regioselective; however, the formation of the adduct 2a with the more favorable ally1 anion intermediate dominates smgly. Reaction of 1 with 2,Mimethylbutadiene
(3 days, 50°C) yields open chain pmducts 6 exclusively;
no cyclic isomers were detected. Differing from the isoprene adducta. the imines 6 are formed as an E/Zmixture (72~28; 41% yield); the E-isomer seems to pndominate.
309
tau
E-6 (72:28;
41%)
Z-6
Other dienes (1,3-cyclohexadiene.
lS-cyclooctadime,
cyclopenbxkne,
I&diphenylbutadiene
and
anthmcene) did not react even under man vigomus conditions (see howewr ‘4.
6a
6b (55:45;
Additionally, the
mctionof
72%)
the oxygen analogue of isopnme, methyivinylketone,
with 1 was in-
vestigated (compare 15).After ddition at -78°C warming up to mom tempefatum, sthring for 4 days and hydrolytic workup, a reaction mixtum (72%) was obtained consistig resulting &om 18 and 1Maack
of the two ~oisomers
74~ (55:45),
at the Michael acceptor. 7a could be isolated by distillation, but complete
separation of both isomers was not possible due to their low stability. Hydrolysis (acetate buffer, pH - 4.5) gives access to the corrwponding aldehydes (compan? ‘5. The intermediate adducts can also be trapped by uimethylsilyl chloride, which yields the siloxy compounds 8 (55:45; 72% yield). Rue 8b was obtained after Kugeh.ohr distillation. Aldehyde derived I-aza-aIlyl-lithium
compounds like 1 am obviously interesting synthetic building
blocks; their special reactivity allows not only addition to carbonyl compounds (‘U&ted
aldol reaction” 2).
310
but also to simple dienes, a reaction type, which is not known from enolate analogues. Key step in these teactions is the intermediate formation of a stabilized allylic anion species, which uuder the don conditions does not react with dienes and methylvinylketone. Therefore. anionic polymerization as a side teaction is not observed. Sometimes however, the low stability of some of the aldehydes requhes special cate during wokup aud pmifkation. Am: The financial support of this work by the Deutsche Forschungsgemeinschaft (DFG) and the Fonds der Chemischen Indumie is gratefully acknowledged.
1 2 3 4 5 6 7 8 9 10 11 12 13
14 15 16
Whitesell,J.K.; Whitesell,M.A. Syntksis 1983,517-X%. Wit&G.; R&R., &ew.Chem. l%& 80.8-15; Angcw.Chem.Znt.EaEngl. l!M8, 7.7. IUukaiy~T.. Org&act. 1982,28.203-331. Ahlhht,H.; v.Daacke,A., Synthesis 1987.24-28. Dietrich,H.; Mahdi,W.; Knotr,R., JAm.Chem.Suc. 1966,108,2462-2464. Knorr,R.; DietrichsI; hIahdi,W., Ckm.kr. 1991,124,2057-2063 and mferences therein. Schkyer,P.v.R.; Hacker,R.; Dieuich,H.; Mahdi,W., J.Ch.Suc. ChCommrcn. l!M5,622-624. Glaaer,R.; Streitwieser,A., J.Org.Chem. 1991,56,6612-6624. Glascr,R.; Hadad,C.M.; W&erg&B.; St&wieser,A., J.&g.Chem. 1!D91,56,6625-6637. TakabeJc; Fujiwara,H.; Katagi&T.; Tanaka&, Tetruhedron L&r. 1975,1239-1240. W0lf.G.; Wtkthwein,B.-U., Ckn.kr. 1991,124; 889-896. Baumatm,F.; WUrthwein,B.-U., Tea-M Lat. l9!bl,32,4683-4686. Allcompounds wete completely characterized by spectroscopic methods and gave satisfactory C!,H,N analyses. For exampk c:colorless liquid bp. 65 VY1.5 Torr. ‘H-NMR (300 MHz, CDC+): & 0.80 (s, 3H, CIQ, 0.90 (s, 3H, CM& 1.05 (s, 9H, C(CH&). 1.59 (s, 3H. C-C-C&), 1.65-1.75 (m, lH, J-7.40 Hz, J-18.02 Hz, HC-C-C-II), 1.75-1.85 (III, 2H, C-CH-CHZ), 2.12-2.22 (m, lH, J-4.6 Hz, J-17.58 Hz, HC-C-C-H), 2.40 (dd, lH, J-7.70 Hz, J-5.20 Hz, N-C-H), 5.22-5.27 (m, lH, C-C-H). ‘3C-NMR (90.56 MHz. CDC13): b 21.97 (CH3). 23.38 (CH3), 28.17 (GC-CH,), 30.53 (C(CH,),). 32.86 (CH3-C-CH,), 39.19 (CIQ, 39.4!t(CHz), 50.48 (C(CH,),), 54.39 (N-C-H), 120.1 (C-C-H), 131.9 (C-C-H). IR v~_~ 3m3200 cm . 5a:colorless liquid b.p. 55 ?I!/6 Torr. ‘H-NMR (300 MHz, CDC13): 8- 1.02 (s, 6H, C(CH3)3, 1.58 (s, 3H, C-C-C!H3), 1.67 (s, 3H, C-C-CH,), 2.12 (d, 2H, J-7.70 Hz, C!H$, 5.05 (t, IH, J- 7.80 Hz, C-C-H), 9.45 (s, lH, G-C-H). ‘3C-NMR (75.47 MHz, CDC13): & 21.07 (C(CH3)i), 25.87 (C-CCH3), 35.52 (CH& 46.55 (OHC-C-(CH,), 118.7 (CH-C-CH,), 134.6 (CH+CH3), 206.3 (CHO). 1720 cm”. mvo,o Mightgteen oil b.p. 60 “C/O.01 Tocr (Kugekohr distillation). ‘H-NMR (300 MHz, CDC13): & 0.07 (s, 9H, Si(C!H3)3), 0.90 (I, 6H, C(CH3)?), 1.12 (s, 9H. C(CH3)3). 1.23 (s. 3H. C-CH,), 5.00-5.10 (m, 2H, J-17.5 Hz, J-11.0 Hz, CH-CIQ, 5.90 (dd, lH, J-17.8 Hz, J-10.4 Hz, C%C!H& 7.64 (s, lH, N-C-H). t3C-NMR (75.47 MHz, CDC13): 8- 2.34 (Si(CHjj3), 20.43 (C(CH3)2), 22.12 (CH3), 29.73(C(CH3),). 45.88 (C(CH3)2>, 56.42 (C(CH3)3). 79.78 (CH3-C-G!%), 113.6 (CH_GH2), 142.8 (CH_cH2), 164.2 (N-C-H). JR vGN 1660 cm-t. Wit&G.; FischeqS.; Tanaka,M., Lie&~ Ann.Chem. 1973, 1075. Cotey,BJ.; Bnders,D., Chem.Ber. 1978,111. 1362-1383. Pfau,M.; Ughetto-MonfrinJ.; Jo-., BuU.soC.Chim.Fr. l-,627-632.
(Received in Germany 18 September 1992)
TeulhcQon Lcttcn. Vol. 34. No. 2 Pp. 307314 1993 ~ladhGmtBlitain
Cyclic and Acyclic Products fkom the Addition of 1-Area-Ally1Anions to Dienes and u,HJnsaturated Ketones - Rc!gfo&dvity
Stefan Wegmam
&g~scb_cbanig&w
and Ernst-Ulrich W&thweia*
Iostitotc&r weafsbho
Manster, ollhhlg
wilhehs-uoiversilm
23. D-4400Maostrr
ln comparison with the widesptead use of enolates in organic synthesis, the application of their
nitrogen analogues, the I-aza-ally1 anions, has found relatively little attention in spite of several synthetic advantage ‘A The electronic natute of the nitrogen atom and the adjustable substitue-nton it ate the reasons for their enhanced selectivity, which allows to conduct teactions under milder and better controlled conditions, compared to enolates. Today, the sbucturai properties of I-aza-ally1 anions are well known, both expe&nentally 57 and theoretically from quautum chemical calculations 89. In this paper, we report on the dons
of the I-aza-allyl-lithium compound 1 withsimple dienes
and an a&unsaturated carbonyl compound. In 1975, TaLabe et al. lo briefly described a cycloalkenylation of lithiated N-isobutylidene-t-butylamiue with three dif&ent dienes (butadie~~, isopmne and mymene). They found cyclic and acyclic pmducts in varying amounts as de&ted by glc. Our intemst in this field concentrates on the ngio- and skreoselectivity of polyfunctional aza-substituted auions and their possible control in organic synthesis “*12. Starting from the com?sponding aldimine, we prepa& the l-aza-allyl-lithium compound 1 in situ by depmto&on
in THF at -7PC using litbium-diisopropylamide &DA) as base.kopmc was addedto the
307
deeply colond solution of 1 at low tempemture. Depending on reaction time and tempemmre open chain (3) and cyclic (4) products were isolated after NaHC$ THF reflux tempera=
(4 days) a 955 mixm
hydrolysis and ch~~matographic workup 13. Thus, at
of 4a aod 4b was obtained in 47% yield. At -1OT however
(4 days), a 8020 mixtme of 3a and 3b was isolated in 40% yield; further hydrolysis during flash chroma-
tography on wet silica gel leads to the ~&unsaturated
aldehydes SI and Sb. Mechanistically, the formation
of the cyclic products 4 takes place via a two step mechanism, involving the ally1 anions 2 as key intermediates; they can be trapped at low temperature during the workup giving the imines 3; under more severe conditions at higher temperatmw the aaions 2 cycke
yield&
the amino-cyclohexene derivatives 4.
The isolation of the acyclic products 3 is our main argument against an one-step cycloaddition mechanism of the Diels-Alder type.
3b
(95:5;
47%)
5b
The addition of isopnme to 1 is not completely regioselective; however, the formation of the adduct 2a with the more favorable ally1 anion intermediate dominates smgly. Reaction of 1 with 2,Mimethylbutadiene
(3 days, 50°C) yields open chain pmducts 6 exclusively;
no cyclic isomers were detected. Differing from the isoprene adducta. the imines 6 are formed as an E/Zmixture (72~28; 41% yield); the E-isomer seems to pndominate.
309
tau
E-6 (72:28;
41%)
Z-6
Other dienes (1,3-cyclohexadiene.
lS-cyclooctadime,
cyclopenbxkne,
I&diphenylbutadiene
and
anthmcene) did not react even under man vigomus conditions (see howewr ‘4.
6a
6b (55:45;
Additionally, the
mctionof
72%)
the oxygen analogue of isopnme, methyivinylketone,
with 1 was in-
vestigated (compare 15).After ddition at -78°C warming up to mom tempefatum, sthring for 4 days and hydrolytic workup, a reaction mixtum (72%) was obtained consistig resulting &om 18 and 1Maack
of the two ~oisomers
74~ (55:45),
at the Michael acceptor. 7a could be isolated by distillation, but complete
separation of both isomers was not possible due to their low stability. Hydrolysis (acetate buffer, pH - 4.5) gives access to the corrwponding aldehydes (compan? ‘5. The intermediate adducts can also be trapped by uimethylsilyl chloride, which yields the siloxy compounds 8 (55:45; 72% yield). Rue 8b was obtained after Kugeh.ohr distillation. Aldehyde derived I-aza-aIlyl-lithium
compounds like 1 am obviously interesting synthetic building
blocks; their special reactivity allows not only addition to carbonyl compounds (‘U&ted
aldol reaction” 2).
310
but also to simple dienes, a reaction type, which is not known from enolate analogues. Key step in these teactions is the intermediate formation of a stabilized allylic anion species, which uuder the don conditions does not react with dienes and methylvinylketone. Therefore. anionic polymerization as a side teaction is not observed. Sometimes however, the low stability of some of the aldehydes requhes special cate during wokup aud pmifkation. Am: The financial support of this work by the Deutsche Forschungsgemeinschaft (DFG) and the Fonds der Chemischen Indumie is gratefully acknowledged.
1 2 3 4 5 6 7 8 9 10 11 12 13
14 15 16
Whitesell,J.K.; Whitesell,M.A. Syntksis 1983,517-X%. Wit&G.; R&R., &ew.Chem. l%& 80.8-15; Angcw.Chem.Znt.EaEngl. l!M8, 7.7. IUukaiy~T.. Org&act. 1982,28.203-331. Ahlhht,H.; v.Daacke,A., Synthesis 1987.24-28. Dietrich,H.; Mahdi,W.; Knotr,R., JAm.Chem.Suc. 1966,108,2462-2464. Knorr,R.; DietrichsI; hIahdi,W., Ckm.kr. 1991,124,2057-2063 and mferences therein. Schkyer,P.v.R.; Hacker,R.; Dieuich,H.; Mahdi,W., J.Ch.Suc. ChCommrcn. l!M5,622-624. Glaaer,R.; Streitwieser,A., J.Org.Chem. 1991,56,6612-6624. Glascr,R.; Hadad,C.M.; W&erg&B.; St&wieser,A., J.&g.Chem. 1!D91,56,6625-6637. TakabeJc; Fujiwara,H.; Katagi&T.; Tanaka&, Tetruhedron L&r. 1975,1239-1240. W0lf.G.; Wtkthwein,B.-U., Ckn.kr. 1991,124; 889-896. Baumatm,F.; WUrthwein,B.-U., Tea-M Lat. l9!bl,32,4683-4686. Allcompounds wete completely characterized by spectroscopic methods and gave satisfactory C!,H,N analyses. For exampk c:colorless liquid bp. 65 VY1.5 Torr. ‘H-NMR (300 MHz, CDC+): & 0.80 (s, 3H, CIQ, 0.90 (s, 3H, CM& 1.05 (s, 9H, C(CH&). 1.59 (s, 3H. C-C-C&), 1.65-1.75 (m, lH, J-7.40 Hz, J-18.02 Hz, HC-C-C-II), 1.75-1.85 (III, 2H, C-CH-CHZ), 2.12-2.22 (m, lH, J-4.6 Hz, J-17.58 Hz, HC-C-C-H), 2.40 (dd, lH, J-7.70 Hz, J-5.20 Hz, N-C-H), 5.22-5.27 (m, lH, C-C-H). ‘3C-NMR (90.56 MHz. CDC13): b 21.97 (CH3). 23.38 (CH3), 28.17 (GC-CH,), 30.53 (C(CH,),). 32.86 (CH3-C-CH,), 39.19 (CIQ, 39.4!t(CHz), 50.48 (C(CH,),), 54.39 (N-C-H), 120.1 (C-C-H), 131.9 (C-C-H). IR v~_~ 3m3200 cm . 5a:colorless liquid b.p. 55 ?I!/6 Torr. ‘H-NMR (300 MHz, CDC13): 8- 1.02 (s, 6H, C(CH3)3, 1.58 (s, 3H, C-C-C!H3), 1.67 (s, 3H, C-C-CH,), 2.12 (d, 2H, J-7.70 Hz, C!H$, 5.05 (t, IH, J- 7.80 Hz, C-C-H), 9.45 (s, lH, G-C-H). ‘3C-NMR (75.47 MHz, CDC13): & 21.07 (C(CH3)i), 25.87 (C-CCH3), 35.52 (CH& 46.55 (OHC-C-(CH,), 118.7 (CH-C-CH,), 134.6 (CH+CH3), 206.3 (CHO). 1720 cm”. mvo,o Mightgteen oil b.p. 60 “C/O.01 Tocr (Kugekohr distillation). ‘H-NMR (300 MHz, CDC13): & 0.07 (s, 9H, Si(C!H3)3), 0.90 (I, 6H, C(CH3)?), 1.12 (s, 9H. C(CH3)3). 1.23 (s. 3H. C-CH,), 5.00-5.10 (m, 2H, J-17.5 Hz, J-11.0 Hz, CH-CIQ, 5.90 (dd, lH, J-17.8 Hz, J-10.4 Hz, C%C!H& 7.64 (s, lH, N-C-H). t3C-NMR (75.47 MHz, CDC13): 8- 2.34 (Si(CHjj3), 20.43 (C(CH3)2), 22.12 (CH3), 29.73(C(CH3),). 45.88 (C(CH3)2>, 56.42 (C(CH3)3). 79.78 (CH3-C-G!%), 113.6 (CH_GH2), 142.8 (CH_cH2), 164.2 (N-C-H). JR vGN 1660 cm-t. Wit&G.; FischeqS.; Tanaka,M., Lie&~ Ann.Chem. 1973, 1075. Cotey,BJ.; Bnders,D., Chem.Ber. 1978,111. 1362-1383. Pfau,M.; Ughetto-MonfrinJ.; Jo-., BuU.soC.Chim.Fr. l-,627-632.
(Received in Germany 18 September 1992)