Hydrogen-bonding as a stereocontrolling element in free-radical C-allylation reactions: Vicinal, proximal, and remote asymmetric induction in the amino acid series

Full text of DOI:10.1021/ja953913f

J. Am. Chem. Soc. 1996, 118, 2507-2508
2507
Scheme 1a
Hydrogen-Bonding as a Stereocontrolling Element
in Free-Radical C-Allylation Reactions: Vicinal,
Proximal, and Remote Asymmetric Induction in the
Amino Acid Series
Stephen Hanessian,* Hua Yang, and Robert Schaum
Department of Chemistry, UniVersite´ de Montre´al
P.O. Box 6128, Station Centre-Ville
Montre´al, Quebec, Canada H3C 3J7
ReceiVed NoVember 21, 1995
Stereocontrolled bond-forming reactions by free-radical pro-
cesses in acyclic molecules are currently among the more
challenging areas in asymmetric synthesis.1 Recent advances
in this area have generally focused on the utilization of
derivatives of carboxylic acids with appropriate chiral auxilia-
ries2 and on exploiting the presence of â-alkoxy substituents
and other resident groups.3 A model for the transition state in
such reactions involving 1,2-asymmetric induction has been
proposed by Hart and Krishnamurthy4 and further elaborated
upon by Curran and co-workers.5 The general consensus is that,
with few exceptions, the high diastereoselectivity is the result
of a combination of minimized allylic 1,3-strain and torsional
strain6 and of stereoelectronic effects.7,8 The notion that
intramolecular H-bonding might play a role in the C-deuteration9
and C-allylation2d of â-hydroxycarbalkoxy and amide R-radicals
has been alluded to and experimentally tested with unrewarding4
or inconclusive results.5
a Reaction conditions: (a) LDA, PhSeBr, THF, -78 °C; (b)
allyltributylstannane, AIBN, hν, toluene or dichloromethane, -40 °C
or -20 °C.
examples of remarkably high stereoselectivity in 1,2-induction2,3
and unprecedented 1,3-, 1,4-,12 and 1,5-asymmetric inductions
in the free-radical C-allylation of R-acyl radicals derived from
a series of N-substituted acyclic amino acid derivatives (Scheme
1),13 by exploiting intramolecular H-bonding as a stereocon-
trolling element.
Treatment of the readily available R-selenophenyl or R-iodo
esters or amides of â-N-substituted amino acid derivatives with
allytributylstannane14 led to a quasi exclusive formation of the
anti-C-allyl derivatives, regardless of the nature of the â-alkyl
(aryl) substituent tested so far (Scheme 1, series A; Table 1,
entries 1-3).15 Changing the â-substituent to a carbomethoxy
group resulted in a complete reversal of selectivity, giving the
syn-C-allylated product, while maintaining high stereoselectivity
(Scheme 1, series B; Table 1, entries 4 and 5).15
Continuing our studies10 on the reactivity and stereochemical
issues related to R-carbalkoxy radicals,11 we report herein
(1) For recent reviews on stereochemical control in free radical reactions
in acyclic systems, see: (a) Smadja, W. Synlett 1994, 1. (b) Porter, N. A.;
Giese. B. and Curran. D. P. Acc. Chem. Res. 1991, 24, 296. (c) Giese, B.
Angew. Chem. Int. Ed. Engl. 1989, 28, 969. For general reviews, see: (d)
Curran, D. P. Synthesis 1988, 417; 489. (e) Giese, B. Radicals in Organic
Synthesis. Formation of Carbon-Carbon Bonds; Pergamon Press: Oxford,
1986.
(2) For recent examples in acyclic substrates with chiral auxilaries, see:
(a) Nishida, M.; Ueyama, E.; Hayashi, H.; Ohyake, Y.; Yamura, Y.;
Yanaginuma, E.; Yonemitsu, O.; Nishida, A.; Kawahara, N. J. Am. Chem.
Soc. 1994, 116, 6455. (b) Yamamoto, Y.; Onuki, S.; Yumoto, M.; Asao,
N. J. Am. Chem. Soc. 1994, 116, 421. (c) Porter, N. A.; Rosenstein, I. J.;
Breyer, R. A.; Bruhnke, J. D.; Wu, W.-X.; McPhail, A. T. J. Am. Chem.
Soc. 1992, 114, 7664 and previous papers. (d) Hamon, D. P. G.; Massy-
Westropp, R. A.; Razzino, P. J. Chem. Soc., Chem. Commun. 1991, 332;
722. (e) Giese, B.; Zehnder, M.; Roth, M. and Zeitz H.-G.J. Am. Chem.
Soc. 1990, 112, 6741.
Using DMSO instead of toluene as solvent resulted in an
erosion or reversal of selectivity,15 thus demonstrating the role
of the polarity of the solvent4 on the prevailing conformers in
the transition state of these reactions and the dominant role that
intramolecular H-bonding may play in controlling conforma-
tional mobility.
In an effort to study the influence of intramolecular H-bonding
on the stereoselectivity of C-allylation, we extended the reaction
to a series of γ-, δ-, and ω-amino acid derivatives (Scheme 1,
series C, D). Unprecedented levels of proximal 1,3-induction
were obtained with the N-trifluoroacetyl and N,N-dimethyl or
N-methoxy-N-methyl amide derivatives (Table 1, entries 6-10).
The selectivity was somewhat lower in the case where R1 )
Me and Ph (Table 1, entries 9 and 10). However, extending
the distance between the electronically most favored hydrogen-
bonding partners (N-TFA and CONMe2) led to surprisingly good
1,4-anti- and 1,5-syn selectivity (Table 1, entries 11 and 12;
Scheme 1, series D, n ) 2, 3, respectively).
(3) For recent examples in acyclic substrates with a chiral resident group,
see: (a) Kundig, E. P.; Xu, L.-H.; Romanens P. Tetrahedron Lett. 1995,
36, 4047. (b) Murakata, M.; Tsutsui, H.; Hoshino, O. J. Chem. Soc., Chem.
Commun. 1995, 481. (c) Giese, B.; Buliard, M.; Dickhaut, J.; Halbach, R.;
Hassler, C.; Hoffmann, U.; Hinzen, B.; Senn, M. Synlett 1995, 116. d)
Guindon, Y.; Gue´rin, B.; Chabot, C.; Mackintosh, N. and Ogilvie, W. W.
Synlett 1995, 449 and previous papers. (e) Ogura, K.; Kayano, A.; Sumitani,
N.; Akazome, M.; Fujita, M. J. Org. Chem. 1995, 60, 1106. (f) Nagano,
H.; Kuno, Y. J. Chem. Soc., Chem. Commun. 1994, 987. (g) Morikawa,
T.; Washio, Y.; Shiro, M.; Taguchi, T. Chem. Lett. 1993, 249. (h) Curran,
D. P.; Abaraham, A. C.; Liu, H. J. Org. Chem. 1991, 56, 4335.
(4) Hart, D.; Krishnamurthy, R. J. Org. Chem. 1992, 57, 4457; Synlett
1991, 412.
(5) (a) Curran, D. P.; Abraham, A. Tetrahedron 1993, 49, 4821. (b)
Curran, D. P.; Ramamoorthy, P. S. Tetrahedron 1993, 49, 4841.
(6) (a) Giese, B.; Damm, W.; Wetterich, F.; Zeitz, H.-G.; Rancourt, J.;
Guindon, Y. Tetrahedron Lett. 1993, 5885. (b) Thoma, G.; Curran, D. P.;
Geib, S. V.; Giese, B.; Damm, W.; Wetterich, F. J. Am. Chem. Soc. 1993,
115, 8585.
(11) (a) Belletire, J. L.; Mahmoudi, N. O. Tetrahedron Lett. 1989, 30,
4363. (b) Surzur, J.-M.; Bertrand, M. P. Pure Appl. Chem. 1988, 60, 1659.
See also: Clough, J. M.; Pattenden, G.; Wight, P. G. Tetrahedron Lett.
1989, 30, 7469.
(12) For a different type of 1,4-induction originating from a chiral
auxiliary, see: Stacker, J. G.; Curran, D. P.; Rebek, J., Jr.; Ballester, P. J.
Am. Chem. Soc. 1991, 113, 5918. See also ref 2e.
(7) (a) Guindon, Y.; Slassi, A.; Rancourt, J.; Bantle, G.; Bencheqroun,
M.; Wurtagh, L.; Ghiro, E.; Jung, G. J. Org. Chem. 1995, 60, 288. (b)
Durkin, K.; Liotta, D.; Rancourt, J.; Lavalle´e, J.-F.; Boisvert, L.; Guindon,
Y. J. Am. Chem. Soc. 1992, 114, 4912.
(8) For theoretical and mechanistic insights, see: (a) Spellmeyer, D. C.;
Houk, K. N. J. Org. Chem. 1987, 52, 959. (b) Curran, D. P.; Sun, S.
Tetrahedron Lett. 1993, 34, 6181. (c) Giese, B.; Damm, W.; Martin, R.;
Zehnder, M. Synlett 1992, 441. See also ref 6a.
(13) For the application of radical chemistry to amino acid and related
derivatives, see: (a) Easton, C. J.; Hutton, C. A.; Rositano, G.; Tan, E. W.
J. Org. Chem. 1991, 56, 5614. (b) Barton, D. H. R.; Herve´, Y.; Potier, P.;
Thierry, J. Tetrahedron 1988, 44, 5479. See also: Crich, D.; Quintero, L.
Chem. ReV. 1989, 89, 1413. See also ref 2.
(14) Keck, G. E.; Yates, J. B. J. Am. Chem. Soc. 1982, 104, 5829.
(15) For details, see supporting information. Anti/syn designations refer
to the relative orientations of substituents in an extended zig-zag chain.
(9) Hamon, D. P. G.; Massy-Westropp, R. A.; Razzino, P. Tetrahedron
1993, 49, 6419. See also ref 2d.
(10) Hanessian, S.; Di Fabio, R.; Marcoux, J.-F.; Prud’homme, M. J.
Org. Chem. 1990, 55, 3436 and references therein.
0002-7863/96/1518-2507$12.00/0 © 1996 American Chemical Society

2508 J. Am. Chem. Soc., Vol. 118, No. 10, 1996
Communications to the Editor
Scheme 2a
Table 1
a Reaction conditions: (a) allyltributylstannane, AIBN, hν, toluene,
-40 °C; (b) TBAF, THF; (c) peptide formation, PyBOP, i-Pr2NEt,
CH3CN, with the corresponding amine salt (ref 15).
in iterative, and one-step, multiple C-allylation protocols leading
to the tripeptide congener 2 (Scheme 2). Thus, C-allylation of
the (2S)-tri-R-phenylseleno peptide derivative 1 gave a major
product 2, whose structure and stereochemistry was confirmed
by an independent stepwise synthesis via amide coupling of
enantiopure C-allyl precursors. Alternatively, C-allylation of
3, amide formation, and iteration of the process on the
R-phenylseleno dipeptide ester 4 also gave 2 (Scheme 2).15,17,18
We have shown that H-bonding can be a strong stereocon-
trolling element in the free-radical C-allylation of a variety of
acyclic amino acid derivatives. The diastereomerically pure or
enriched products are versatile chirons for further manipula-
tions19 and for the design of unnatural oligomeric amino acid
motifs with potentially interesting three-dimensional arrays.20
Results pertaining to these and related studies will be com-
municated in due course.
1
a Ratio determined by H NMR of the crude sample. Entries 3, 9,
11, and 12 correspond to racemic products. b Isolated yield. c Stereo-
chemistry determined by analogy to entry 3, and by NOE studies of
the corresponding N-Boc-pyrrolidine derivative after cyclization with
Hg(OAc)2; see ref 15. d Stereochemistry determined by converting into
N-Piv product, which was proved by X-ray single crystal analysis.e Ratio
determined by HPLC analysis. f Ratio for NMe2 amide remained
unchanged at 30 °C. g Stereochemistry correlated by chemical means;
see ref 15. h The nitrogen atom was protected with Cbz instead of TFA.
i Stereochemistry by analogy to the product in entry 8. j Anti/syn 86:
14, 64% for N,N-dimethyl derivative. k X-ray single crystal analysis.
l Reaction done at 0 °C.
Acknowledgment. We thank NSERC and Bio-Me´ga/Boehringer
Ingelheim Research Inc. for generous financial assistance through the
Medicinal Chemistry Chair program. We thank Dr. Michel Simard
for X-ray crystallographic analyses.
Supporting Information Available: Physical constants, chemical
correlations, experimental procedures, NMR and FT-IR spectra, and
HPLC and X-ray analyses for the compounds described herein (36
pages). This material is contained in many libraries on microfiche,
immediately follows this article in the microfilm version of the journal,
can be ordered from the ACS, and can be downloaded from the Internet;
see any current masthead page for ordering information and internet
access instructions.
JA953913F
(16) Gardner, R. R.; Gellman, S. H. J. Am. Chem. Soc. 1995, 117, 10411
and previous papers.
(17) Extensive intramolecular H-bonding in 1 and 2 is evident from FT-
IR and 1H NMR data. The nature of the prevailing conformers in solution
is presently under study.
Figure 1. Proposed H-bonded radical intermediates favoring anti attack
in 1,2-asymmetric induction (series A). Shaded lobe indicates preferred
side of attack by allylstannane.
(18) For isolated examples of free-radical reactions in peptides, see: (a)
Easton, C. J.; Scharfbilling, I. M.; Tan, E. W. Tetrahedron Lett. 1988, 29,
1565. See also ref 13a. (b) Apitz, G.; Jager, M.; Jaroch, S.; Kratzel, M.;
Schaffeler, L.; Steglich, W. Tetrahedron 1993, 49, 8223.
(19) For a recent review on the utility of amino acid derivatives, see
Duthaler, R. O. Tetrahedron, 1994, 50, 539.
(20) (a) Lokey, R. S.; Iverson, B. L. Nature 1995, 375, 303. (b) Ghadiri,
R. M.; Granja, J. R.; Milligan, R. A.; McLee, D. E.; Khazannovich, N.
Nature 1993, 366, 324. (c) Kerfeld, K. S. A.; Kim, R. M.; Camac, D.;
Groves, J. T.; Lear, J. D.; DeGrado, W. F. J. Am. Chem. Soc. 1992, 114,
9656.
The quasi exclusive formation of anti-products in series A
(1,2-induction) can be interpreted on the basis of the prevalence
of ground state and transition state conformations, in which
H-bonding plays a dominant role in favoring a pseudo six-
membered ring. Interestingly, the (2S)-anti isomer A (Figure
1), with a distinctive FT-IR H-bonding band at 3293 cm-1 16
,
reacted faster than the (2R)-syn isomer B (FT-IR 3410 cm-1).
Finally, we demonstrate the versatility of the methodology