Reversal of π-facial diastereoselection in the hydride reduction of selenanones. Further application of the exterior frontier orbital extension model

Article abstract of DOI:10.1016/S0040-4039(00)00641-9

Reversal of π-facial diastereoselection in the hydride reduction of 2- phenyl-4-selenanone (1b) and 6-phenyl-3-selenanone (2b) has been rationalized by the exterior frontier orbital extension model (EFOE model). (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00641-9

Tetrahedron Letters 41 (2000) 4597±4601
Reversal of p-facial diastereoselection in the hydride
reduction of selenanones. Further application of the exterior
frontier orbital extension model
Shuji Tomoda,a,* Jian Zhang,a Daisuke Kaneno,a Masahito Segib,* and Aojia Zhoub
aDepartment of Life Sciences, Graduate School of Arts and Sciences, Komaba, Meguro-Ku, Tokyo 153-8902, Japan
bDepartment of Chemistry and Chemical Engineering, Faculty of Engineering, Kanazawa University, Kodatsuno, Kanazawa,
Ishikawa 920-8667, Japan
Received 9 March 2000; revised 12 April 2000; accepted 14 April 2000
Abstract
Reversal of p-facial diastereoselection in the hydride reduction of 2-phenyl-4-selenanone (1b) and 6-phenyl-
3-selenanone (2b) has been rationalized by the exterior frontier orbital extension model (EFOE model).
# 2000 Elsevier Science Ltd. All rights reserved.
Keywords: diastereoselection; selenanone; hydride reduction; EFOE model.
It has long been known that replacement of C3 of a cyclohexanone ring with a sulfur atom
causes diastereofacial reversal in nucleophilic carbonyl addition. Two remarkable examples have
been reported.1,2 While common six-membered ketones containing one or two second-raw hetero-
atom(s) (O, N) undergo preferential axial attack, a predominant equatorial attack has been
observed for the nucleophilic addition to 3-thianones1 and 1,3-dithian-5-one.2 The unusual facial
diastereoselection has been explained in terms of the transition state hyperconjugative stabilization
model of Cieplak assuming the order of the electron-donating property of antiperiplanar bond(s)
to be C±S>C±H>C±C.3
Recently, we proposed a new theoretical model (the exterior frontier orbital extension model;
the EFOE model) to explain and predict p-facial diastereoselection of the nucleophilic carbonyl
addition.4 The simple semi-quantitative model has been successfully applied to a variety of cyclic
ketones5 including 1,3-diheteran-5-ones (heteroatom=O or S).6 Herein, we show by theory and
experiment that facial diastereoselection of selenanone reduction is dictated by ground-state
properties of the ketones rather than by transition state e€ects which have been emphasized in the
previous intuitive models.3,7
The model compounds chosen are 4-selenanones (1) and 3-selenanones (2). The EFOE model
predicts opposite p-facial diastereoselection for the model selenanones: preferential axial attack
* Corresponding authors. E-mail: tomoda@selen.c.u-tokyo.ac.jp, segi@t.kanazawa-u.ac.jp
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00641-9

4598
for 1 and equatorial attack for 2 (RHF/6-31G(d) level8 using the Huzinaga basis set for selenium9).
This model is based on the simple assumption that the p-facial di€erence in the reaction driving
force must be the origin of the p-facial diastereoselection. It is assumed that the p-facial di€erence
in frontier orbital (LUMO) and conformational (steric) properties of a ground-state ketone should
be the origin of the facial selection. Two quantities corresponding to the ®rst term (exchange
repulsions; steric e€ect) and the third term (donor±acceptor stabilizing interactions) of the Salem±
Klopman equation10 were de®ned in the exterior of the van der Waals surface of a ketone sub-
strate: p-plane-divided accessible space (PDAS)11 and p-plane-divided exterior frontier orbital
electron density (EFOE density). 12
Table 1 collects the data of EFOE analysis for the model selenanones along with those of cyclo-
hexanone for comparison. It is clear that both EFOE density and PDAS values of 4-selenanones
(1a, 1b) behave in a manner similar to those of cyclohexanone except that the former prefers
greater equatorial attack than the latter due to larger values of EFOE density (0.482%, 0.470%)
and PDAS (53.0 au3, 55.8 au3) in the equatorial face of 1 than those of cyclohexanone (EFOE
density=0.249%; PDAS=47.2 au3). Hence, the diastereoselection of 4-selenanones is orbital-
controlled rather than steric-controlled like that of cyclohexanone.12 On the other hand, the
magnitudes of the EFOE densities of 3-selenanones (2a, 2b) over the axial face are lower (0.125%,
0.297%) than those of the equatorial face (0.568%, 0.459%). The origin of such reversal of the
order of the values of the EFOE density compared with those of cyclohexanone may be due to
signi®cant out-of-phase (antibonding) mixing of the selenium lone pair orbital to the p*CˆO
orbital thus causing appreciable reduction in the EFOE density over the axial face of the carbonyl
plane of 2a, whereas there is no such signi®cant antibonding contribution in 1a (Fig. 1). Further-
more, the equatorial faces of 3-selenanones (PDAS=57.9 au3 for 2a, 59.2 au3 for 2b) are much
Table 1
EFOE analysis of the p*CˆO orbitals of 4-selenanones (1) and 3-selenanones (2)a

4599
Figure 1. Side views of the LUMOs of 4-selenanone (1a) and 3-selenanone (2a) (HF/3-21G*)
more sterically relaxed than the axial faces (PDAS=13.0 au3 for 1a, 12.2 au3 for 1b). Consequently,
the facial diastereoselection of 3-selenanones is both orbital- and steric-controlled. It is noted that
phenyl substitution at C4 does not a€ect this conclusion. Hence, the EFOE model predicts
moderate axial preference for 1 and high equatorial preference for 2. The following experimental
results strongly support the above conclusions drawn from the EFOE analysis.
The syntheses of conformationally anchored selenanones (1b and 2b) began with the synthesis
of the Diels±Alder adduct between anthracene and selenobenzaldehyde generated using bis-
(dimethylaluminum)selenide13 in the presence of benzaldehyde (Scheme 1). The labile seleno-
aldehyde, thermally generated by the retro-Diels±Alder reaction of the adduct, was trapped in
situ with 2-trimethylsiloxy-1,3-butadiene to a€ord 1b and 2b in a 57:43 ratio after hydrolysis with
tri¯uoroacetic acid. Each ketone was reduced with three common hydride reagents (LiAlH4,
LiBH4, NaBH4). Their diastereoselectivities were determined by 1H NMR at 500 MHz.14 The last
column of Table 1 shows the results. It is interesting to note that 4-selenanone (1b) behaves
normally to undergo predominant axial hydride attack (68±81%), whereas an equatorial hydride
attack is favored for 3-selenanone (2b) (88±95%). The latter observation is surprising since one
might a priori expect steric relaxation owing to the lack of one of the axial hydrogens at C3 and
C5 of the cyclohexanone moiety. Among the three hydrides employed, NaBH4 seems the most
sterically demanding (less axial attack).
Scheme 1. Synthesis of 1b and 2b. (a) PhCHO, (Me2Al)2Se, toluene±dioxane, 100ꢀC, 5 h (82% yield); (b) 2-tri-
methylsiloxy-1,3-butadiene, toluene, 100ꢀC, 5 h (78% yield); (c) CF3CO2H, 25ꢀC, 30 min (95% yield).
To evaluate whether or not the antiperiplanar hyperconjugative stabilization e€ects (hereafter
called `the AP e€ect') in the transition state might dictate in the facial diastereoselection in these
systems, transition structures of LiAlH4 reduction were located using the two parent selenanones
(1a and 2a) at the B3LYP/6-31G(d) level8 using the Huzinaga basis for Se.15 The transition states
(TS) of 1a show signi®cant di€erences in percent elongation (%BE) 16 of the antiperiplanar bonds

4600
vicinal to the incipient bond (C3±Hax/C5±Hax for ax-TS or C3±C2/C5±C6 for eq-TS) due to the AP
e€ect between the ax-TS (%BE=+0.04%) and eq-TS (%BE=+0.05%) relative to the ground-
state 1a optimized at the same level. The magnitudes of the AP e€ects are virtually the same over
both p-faces. This is not consistent with the observed facial selection of 1a. In consonant with
these results, the di€erence in NBO bond population for the antiperiplanar bonds between the
17
transition state and the ground state (ÁBP) was ^0.0076 e (electrons) for ax-TS and ^0.0074 e
for eq-TS (B3LYP/6-31G(d)). Fig. 2 shows the LiAlH4 transition structures of 3-selenanone (2a).
In agreement with the experiment, the ZPVE-corrected total electronic energy of the eq-TS is
indeed lower by 1.2 kcal mol^1 than that of the ax-TS. The AP e€ects evaluated by %BE and
ÁBP, averaged for the two antiperiplanar bonds (C2±Hax/C4±Hax for ax-TS or Se1±C2/C4±C5
for eq-TS), are +0.21%/+0.20% and ^0.0150 e/^0.0170 e for ax-TS and +0.13%/+0.03% and
^0.0075 e/^0.0057 e for eq-TS. Evidently, the AP e€ects operate against the observed diastereo-
selection in 2a. Hence, the AP e€ects cannot account for the observed facial stereoselectivity of 1b
and 2b.
Figure 2. Transition structures of LiAlH4 reduction of 3-selenanone (2a) (B3LYP method with Huzinaga basis for Se9
and 6-31G(d) basis sets for other elements). (Left: ax-TS; Right: eq-TS; bond lengths in A and bond angles in degrees)
These conclusions are entirely consistent with our previous ones for the LiAlH4 reductions of
cyclohexanone, adamantan-2-ones, 1,3-diheteran-4-ones (heteroatom=O, S).5,6,18 It should be
stressed here again that the AP e€ects are regarded merely as a major internal energy relaxation
mechanism that operates against the direction of the bond formation process.3
In conclusion, it is demonstrated that the ground-state steric and frontier orbital properties
must be responsible for p-facial diastereoselection in the reduction of selenones.
Acknowledgements
The authors express their gratitude to Dr. M. Iwaoka for computational assistance. We thank
the Ministry of Education, Culture and Sports for ®nancial support through Grants-in-Aid for
Scienti®c Research (Project Nos. 09440215 and 09239207) and the Institute for Molecular Science
for generous assignment of computational time.

4601
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„
EFOE density (%)=100Â É2FMO dꢀ
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