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Density functional computations of enantioselective alkynylation of aldehydes catalyzed by oxazaborolines. Part 2. Structures of transition states and the mechanism of enantioselective reduction
Journal of Molecular Structure (Theochem) 629 (2003) 209–221 www.elsevier.com/locate/theochem
Density functional computations of enantioselective alkynylation of aldehydes catalyzed by oxazaborolines. Part 2. Structures of transition states and the mechanism of enantioselective reduction Ming Li*, Rongxing He Department of Chemistry, Southwest-China Normal University, Chongqing 400715, People’s Republic of China Received 28 November 2002; accepted 17 February 2003
Abstract Quantum chemical computations of the enantioselective alkynylation of aldehyde with alkynylborane catalyzed by chiral oxazaborolidine are performed by means of the density functional theory method. All the transition states for the alkynylation are optimized completely at the B3LYP/6-31G(d) level and the mechanism of the enantioselective alkynylation is studied. As demonstrated, the enantioselective alkynylation of aldehyde is exothermic and includes the formation of the catalystalkynylborane adduct, the formation of the catalyst-alkynylborane-aldehyde adduct, the transfer of alkynyl to the carbonyl carbon of the aldehyde moiety, and the decomposition of the catalyst-alkoxyborane adduct leading to the regeneration of the catalyst. There are four reduction paths for the alkynylation reduction. The transfer of the alkynyl moiety is the controlling-velocity step for this reduction and the alkynylation results mainly in R-chiral alcohols that are in correspondence to the experiment. q 2003 Elsevier B.V. All rights reserved. Keywords: Enantioselective alkynylation; Mechanism; Chiral oxazaborolidine; Transition states; Density functional theory
1. Introduction In 1994, Corey and Cimprich [1] reported the enantioselective alkynylation reduction of aldehyde with alkynylborane catalyzed by chiral oxazaborolidine. In their experiment, Corey et al. used the oxazaborolidine C, as a catalyst, and the alkynylborane D, as an alkynyl donor, to reduce the aldehyde B and obtained the chiral alcohol A (Scheme 1). Compared with the traditional nucleophilic alkynylation of carbonyl compounds, this method has rapid reaction velocity and high enantioselectivity. Corey et al. * Corresponding author. E-mail address: [email protected] (M. Li).
pointed out that there is an analogy in manner between the enantioselective alkynylation of aldehyde with alkynylborane and the asymmetric reduction of prochiral ketone with borane promoted by oxazaborolidine. According to the mechanism of the enantioselective reduction of prochiral ketone with borane catalyzed by the CBS catalysts suggested by Corey et al. [2], therefore, the enantioselective alkynylation of aldehyde with alkynylborane catalyzed by oxazaborolidine goes mainly through the following steps: (1) coordination of the alkynylborane D as an alkyne moiety donor to the oxazaborolidine catalyst C, (2) coordination of the carbonyl oxygen in the aldehyde B to the boron of C, (3) shift of the alkynyl moiety of the alkynylborane D toward the carbonyl carbon to lead to
0166-1280/03/$ - see front matter q 2003 Elsevier B.V. All rights reserved. doi:10.1016/S0166-1280(03)00142-8
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Scheme 1.
the reduced carbonyl carbon, (4) regeneration of the catalyst C and formation of the chiral alcohol A. However, the sufficient theoretical evidence must be obtained to verify the rightness of Corey’s speculation about this process. Therefore, it is useful to investigate this enantioselective alkynylation in detail by means of the quantum chemical method. Some successful modeling studies on the enantioselective reduction of prochiral ketone with borane catalyzed by oxazaborolidine have been carried out by means of the ab initio molecular orbital methods [3 – 21]. They support the Corey’s mechanism of catalysis. However, quantum chemical studies on the enantioselective alkynylation of aldehyde with alkynylborane catalyzed by chiral oxazaborolidine have not been reported yet. In the first part of this work, the structures and properties of the catalyst and all the intermediary states for the alkynylation are studied by means of the density functional theory (DFT) method. The aim of this part is to investigate the structures and properties of all the transition states and the mechanism of the enantioselective alkynylation by means of the DFT method.
2. Model and computations In the first part of this work, some modeling molecules are employed to replace oxazaborolidine,
alkynylborane, and aldehyde. As presented in Scheme 1, the molecule 1 is used as the modeling for the oxazaborolidine catalyst C, the molecule 2 as the modeling for the alkynylborane D, and the molecule 3 as the modeling for the aldehyde B. The modeling molecule 1 keeps the chirality of the chiral carbon in the oxazaborolidine C. The plausible path of the enantioselective alkynylation of the aldehyde 3 with the alkynylborane 2 catalyzed by the chiral oxazaborolidine 1 is shown in Scheme 2. TS1, TS2, and TS3 are the transition states leading to the catalyst-alkynylborane adduct 4, the catalyst-alkynylborane-aldehyde adduct 5, and the catalyst-alkoxyborane adduct 6, respectively. TS4 is the transition state for the decomposition of the adduct 6. In the present work, all the structures of these transition states are optimized completely by means of the DFT method at the B3LYP/6-31G(d) level and their vibrational analysis and natural bond orbital (NBO) analysis [22,23] are performed at the same computational level. The total energies E, the activating energies DE– ; and the vibrational frequencies n for all the transition states are summarized in Table 1. The selected bond lengths and their Mulliken overlap populations are shown in Tables 2 and 3, respectively. The selected atomic charges are listed in Table 4. The selected stabilization interaction
M. Li, R. He / Journal of Molecular Structure (Theochem) 629 (2003) 209–221
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Scheme 2.
energies obtained from the second-order perturbative theory [22] are illustrated in Table 5. The optimized structures of the transition states TS1, TS2, TS3, and TS4 are illustrated in Figs. 1, 2, 3, and 4, respectively.
M1 before the formation of the catalyst-alkynylborane adduct 4. This intermediary state is stable and its lowest vibrational frequency is 20.0 cm21. It is illustrated in Table 1 that the total energy for M1 is 2 494.7984 a.u. and is lower than
3. Discussion
Table 1 Dipole moments D (Debye), total energies E (a.u.), activating energies DE– (kJ/mol), and vibrational frequencies n (cm21)
3.1. Structures of transition states 3.1.1. Transition state TS1 The optimized structure of the transition state TS1 for the formation of the catalyst-alkynylborane adduct 4 is presented in Fig. 1. As shown in Table 1, its sole imaginary frequency is 2 98.3 cm21 and corresponds to the B2 – N(3) stretching vibration. It is obvious that TS1 is a transition state. The total energy E for TS1 is 2 494.7968 a.u. and is lower than 2 494.7944 a.u. of the sum of energy for the catalyst 1 and the alkynylborane 2. This result implies that TS1 is not the transition state for the directly reaction of the catalyst 1 with the alkynylborane 2 to form the catalyst-alkynylborane adduct 4. As indicated in the first part of this work, there is an intermediary state
TS1 TS2a TS2b TS2c TS2d TS3a TS3b TS3c TS3d TS4a TS4b TS4c TS4d M1 M2a M2b M2c M2d
D
E
DE–
n1
n2
3.18 3.71 6.01 4.72 3.95 3.31 2.95 3.03 3.33 3.58 3.72 3.38 4.11 2.46 2.93 6.76 3.39 2.91
2494.7968 2648.6283 2648.6266 2648.6196 2648.6269 2648.6217 2648.6156 2648.6030 2648.6164 2648.6614 2648.6600 2648.6653 2648.6614 2494.7984 2648.6309 2648.6286 2648.6300 2648.6308
4.20 6.83 5.25 27.31 10.24 44.63 48.83 47.26 47.78 37.81 42.27 35.71 41.75
298.3 250.4 264.1 2121.8 286.7 2343.8 2287.7 2261.7 2335.8 2158.1 262.7 2170.4 2170.3 20.0 19.9 16.0 22.1 20.6
24.3 22.4 31.1 26.9 38.2 46.9 47.6 19.6 40.1 31.0 23.3 33.0 40.2 27.1 28.8 22.3 24.9 24.2
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Table 2 Selected bond lengths (nm) for the transition states
B2 –C1p B2 –N(3) N(3)– B(2) B(2)–OCyO OCyO –CCyO B2 –OCyO CCyO –C1p
p
B2 –C1 B2 –N(3) N(3)– B(2) B(2)–OCyO OCyO –CCyO B2 –OCyO CCyO –C1p
TS1
TS2a
TS2b
TS2c
TS2d
TS3a
TS3b
0.1549 0.2296 0.1447
0.1580 0.1762 0.1516 0.2443 0.1215 0.3422 0.3703
0.1576 0.1769 0.1516 0.2294 0.1219 0.3349 0.4452
0.1582 0.1728 0.1552 0.1893 0.1221 0.3089 0.3618
0.1583 0.1747 0.1528 0.2181 0.1219 0.3231 0.3596
0.1743 0.1607 0.1645 0.1509 0.1311 0.2831 0.1845
0.1719 0.1614 0.1638 0.1484 0.1320 0.3097 0.1804
TS3c
TS3d
TS4a
TS4b
TS4c
TS4d
2
0.1731 0.1611 0.1642 0.1477 0.1325 0.3101 0.1796
0.1722 0.1613 0.1645 0.1515 0.1307 0.2821 0.1877
0.1932 0.1480 0.2551 0.1418 0.1450 0.1476
0.1794 0.1497 0.2754 0.1414 0.1465 0.1479
0.2037 0.1474 0.2482 0.1418 0.1442 0.1475
0.1932 0.1487 0.2398 0.1418 0.1452 0.1477
0.1527
2 494.7968 a.u. for TS1. Therefore, the activating energy DE– for TS1 is 4.20 kJ/mol. Obviously, the formation of the catalyst-alkynylborane adduct 4 is easily because of a low activating energy. In the transition state TS1, the distance between N(3) and B2 is 0.2296 nm and is much longer than 0.1789 nm in the adduct 4. The B2 – N(3) – B(2) and B2 – N(3) – C(4) angles and the B2 – N(3) – B(2) – O(1) torsion angle are 106.4, 117.7, and 110.18,
respectively (B2 is the boron atom of the alkynylborane 2 and B(2) is the boron atom of the catalyst 1). As shown in Tables 2 and 3, the B2 –C1p bond for TS1 is 0.1549 nm, which longer than 0.1527 nm for the free alkynylborane 2, and its Mulliken overlap population is 0.525, which smaller than 0.555 for 2. It is obvious that the B2 – C1p bond in the transition state TS1 is weaken. In addition, it is clear in Table 4 that the positive charges of B2 and the negative charge of N(3)
Table 3 Selected Mulliken overlap populations for the transition states
B2 –C1p B2 –N(3) N(3)–B(2) B(2)–OC – O OC – O – CC – O B2 –OC – O CC – O –C1p
B2 –C1p B2 –N(3) N(3)–B(2) B(2)–OC – O OC – O – CC – O B2 –OC – O CC – O –C1p
TS1
TS2a
TS2b
TS2c
TS2d
TS3a
TS3b
0.525 0.074 0.389
0.507 0.121 0.307 0.055 0.552 0.005 0.002
0.506 0.117 0.319 0.070 0.529 0.004 0.000
0.500 0.142 0.301 0.098 0.513 0.003 0.002
0.505 0.124 0.299 0.084 0.535 0.003 0.002
0.287 0.232 0.234 0.260 0.340 0.004 0.175
0.303 0.234 0.231 0.304 0.317 20.009 0.204
TS3c
TS3d
TS4a
TS4b
TS4c
TS4d
2
0.297 0.233 0.227 0.316 0.345 20.010 0.192
0.304 0.229 0.232 0.256 0.369 0.004 0.170
0.095 0.319 0.044 0.247 0.358 0.323
0.124 0.308 0.028 0.257 0.359 0.309
0.088 0.333 0.049 0.271 0.360 0.320
0.098 0.316 0.058 0.241 0.352 0.331
0.555
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Table 4 Selected atomic charges for the transition states
O(1) B(2) N(3) B2 OCyO CCyO C1p
O(1) B(2) N(3) B2 OCyO CCyO C1p
TS1
TS2a
TS2b
TS2c
TS2d
TS3a
TS3b
TS3c
20.428 0.422 20.633 0.295
20.423 0.495 20.678 0.378 20.342 0.264 0.088
20.448 0.503 20.674 0.384 20.330 0.249 0.089
20.461 0.541 20.670 0.390 20.319 0.257 0.089
20.439 0.522 20.685 0.389 20.334 0.265 0.087
20.493 0.573 20.690 0.567 20.419 0.156 20.110
20.533 0.590 20.677 0.540 20.408 0.133 20.040
20.531 0.577 20.675 0.551 20.413 0.121 20.058
TS3d
TS4a
TS4b
TS4c
TS4d
1
2
20.497 0.578 20.694 0.566 20.415 0.153 20.105.
20.424 0.471 20.679 0.691 20.526 0.041
20.408 0.448 20.665 0.695 20.538 0.045
20.432 0.468 20.683 0.684 20.519 0.061
20.436 0.485 20.690 0.689 20.523 0.042
0.074
in the transition state TS1 are 0.295 and 2 0.633, respectively. They are larger than 0.213 of B2 in the free alkynylborane 2 and 2 0.569 of N(3) in the free catalyst 1. The increase in the charges of B2 and N(3) for TS1 causes the interaction between the alkynylborane 2 and the catalyst 1 to be strengthened. The weakening of the B2 – C1p bond and the strengthened interaction between 2 and 1 are of advantage to the succeeding reactions. 3.1.2. Transition State TS2 The transition state TS2 for the formation of the catalyst-alkynylborane-aldehyde adduct 5 involves four structures such as TS2a, TS2b, TS2c and TS2d. These structures are in one-to-one correspondence to four structures 5a, 5b, 5c and 5d of the adduct 5. Their sole imaginary frequencies are, respectively, 2 50.4 for TS2a, 2 64.1 for TS2b, 2 121.8 for TS2c, and 2 86.7 cm21 for TS2d. These imaginary frequencies all correspond to the B(2) – O C – O stretching vibrations. Their total energies are 2 648.6283 for TS2a, 2 648.6266 for TS2b, 2 648.6196 for TS2c, and 2 648.6269 for TS2d. It has been pointed out in the first part of this work that four intermediary states M2a, M2b, M2c and M2d exist before the formation of the catalyst-alkynylborane-aldehyde adduct 5. As illustrated in Table 1, the lowest vibrational frequencies of these intermediary states are 19.9 for M2a,
20.569 0.213
16.0 for M2b, 22.1 for M2c, and 20.6 cm21 for M2d and thus they are stable. The intermediary states M2a, M2b, M2c and M2d are also in one-to-one correspondence to the transition states TS2a, TS2b, TS2c and TS2d. The total energies for these intermediary states are also shown in Table 1. As a result, the activating energies for TS2a, TS2b, TS2c and TS2d are 6.83, 5.25, 27.31, and 10.24 kJ/mol. The optimized structures of TS2a, TS2b, TS2c and TS2d are illustrated in Fig. 2. In these transition states, the B(2) – OC – O bonds are 0.2443 for TS2a, 0.2294 for TS2b, 0.1895 for TS2c, and 0.2181 nm for TS2d, respectively. The B2 –N(3) – B(2) –O(1) and OC – O –B(2) – N(3) –C(4) torsion angles are, respectively, 127.4, 2 100.9 for TS2a, 123.1, 2 113.5 for TS2b, 114.2, 2 134.0 for TS2c, and 126.68, 2 108.38 for TS2d. The CC – O – OC – O – B(2), OC – O – B(2) – N(3), and B2 –N(3) – B(2) angles are 129.9, 105.0, 123.7 for TS2a, 113.9, 108.3, 123.7 for TS2b, 147.7, 105.6, 125.3 for TS2c, and 132.88, 103.78, 125.48 for TS2d. It must be emphasized that the formation of the transition state TS2 leads to the increased carbonyl bond of TS2. The CC – O – OC – O bond in the free aldehyde 3 is 0.1210 nm, whereas the CC – O – OC – O bonds in the transition states TS2a, TS2b, TS2c and TS2d are 0.1215, 0.1219, 0.1221, and 0.1219 nm, respectively. The corresponding Mulliken overlap populations are decreased from 0.625 for 3 to 0.552
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Table 5 Selected stabilization interaction energies Eð2Þ (kJ/mol) for TS3a, TS3b, TS3c and TS3d Donor NBO TS3a
TS3b
TS3c
TS3d
3 2
Acceptor NBO p
Eð2Þ p
C20–B23 O18
BD (s) BDp(s)
CCyO –C1 CCyO –C1p
C20–C24 C24
BDp(s) BDp(s)
C1p –B2 C1p –B2
B23–C20 C20–C26
BDp(p) BDp(p)
CCyO –OCyO CCyO –OCyO
C20–B23 O18 C24
BDp(s) BDp(s) BDp(s)
CCyO –C1p CCyO –C1p CCyO –C1p
C20–C24 C24
BDp(s) BDp(s)
C1p –B2 C1p –B2
C20–C24 O18–C19
BDp(p) BDp(p)
CCyO –OCyO CCyO –OCyO
BD(s) LP(p) LP(s) P Eð2Þ BD(s) LP(s) P Eð2Þ BD(s) CR(s) P Eð2Þ
C20–B23 O18 C24
BDp(s) BDp(s) BDp(s)
CCyO –C1p CCyO –C1p CCyO –C1p
C20–C24 C24
BDp(s) BDp(s)
C1p –B2 C1p –B2
C20–B23 C23
p
BD (p) BDp(p)
CCyO –OCyO CCyO –OCyO
BD(s) LP(p) LP(s) P Eð2Þ BD(s) LP(s) P Eð2Þ BD(s) P Eð2Þ P Eð2Þ P Eð2Þ
C20–B23 O18 C24
BDp(s) BDp(s) BDp(s)
CCyO –C1p CCyO –C1p CCyO –C1p
C20–C24 C24
BDp(s) BDp(s)
C1p –B2 C1p –B2
O18–C19
BDp(p)
CCyO –OCyO
BD(sp) LP(p) P Eð2Þ BD(s) LP(s) P Eð2Þ BD(s) BD(p) P Eð2Þ BD(s) LP(p) LP(s) P Eð2Þ BD(s) LP(s) P Eð2Þ BD(s) BD(s) P Eð2Þ
38.28 160.67 198.95 66.07 30.71 96.78 58.45 29.12 87.57 61.30 96.32 84.98 242.60 54.60 30.08 84.68 51.97 41.25 93.22 53.26 89.16 68.62 211.04 48.91 37.87 86.78 79.91 17.15 97.06 65.44 105.35 86.82 257.61 58.12 27.99 86.11 77.36 77.36 39.83 57.74
for TS2a, 0.529 for TS2b, 0.513 for TS2c, and 0.535 for TS2d. It is clear that the carbonyl bonds in these transition states are weakened. In addition, the formation of the transition state TS2 also leads to the increased B2 – C1p bond. As shown in Tables 2 and 3, the B2 –C1p bonds in the transition states TS2a,
Fig. 1. The optimized structure of TS1.
TS2b, TS2c and TS2d are much longer than the B2 – C1p bond in the free alkynylborane 2 and their Mulliken overlap populations are smaller than the overlap population in 2. Therefore, the B2 –C1p bonds in these transition states are also weakened. The weakening of the B2 –C1p and CC – O – OC – O bonds is of advantage to the transfer of the alkynyl from the alkynylborane moiety to the carbonyl carbon of the aldehyde moiety. 3.1.3. Transition state TS3 Through the transfer of the alkynyl of the alkynylborane moiety, the catalyst-alkynylboranealdehyde adduct 5 is transformed into the catalystalkoxyborane adduct 6. TS3 is the transition state for the transfer of the alkynyl from the alkynylborane moiety to the carbonyl carbon of the aldehyde moiety. It also involves four structures such as TS3a, TS3b, TS3c and TS3d, which are in one-to-one correspondence to four structures 6a, 6b, 6c and 6d of the adduct 6. The sole imaginary frequencies, which correspond to the B2 – C1p – CC – O stretching vibrations, for TS3a, TS3b, TS3c and TS3d are 2 343.8 for TS3a, 2 287.7 for TS3b, 2 261.7 for TS3c, and 2 335.8 cm21 for TS3d, respectively. The total energies and the activating energies are 2 648.6217, 44.63 for TS3a, 2 648.6156, 48.83 for TS3b, 2 648.6030, 47.26 for TS3c, and 2 648.6164 a.u., 47.78 kJ/mol for TS3d. The optimized structures of the transition states TS3a, TS3b, TS3c and TS3d are illustrated in Fig. 3. In these transition states, the B2 –N(3), B(2) – OC – O,
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Fig. 2. The optimized structures of TS2a, TS2b, TS2c, and TS2d.
and N(3) –B(2) bonds are 0.1607, 0.1509, 0.1645 for TS3a, 0.1614, 0.1484, 0.1638 for TS3b, 0.1611, 0.1477, 0.1642 for TS3c, and 0.1613 nm, 0.1515 nm, 0.1645 nm for TS3d. The B2 –N(3) –B(2) –O(1) and OC – O – B(2) – N(3) – C(4) torsion angles are 128.8, 2 117.8 for TS3a, 87.0, 2 159.6 for TS3b, 89.5, 2 161.8 for TS3c, and 128.88, 2 116.28 for TS3d. The OC – O – B(2) – N(3), and B2 – N(3) – B(2) angles are 104.2, 119.9 for TS3a, 110.2, 121.8 for TS3b, 109.8, 122.2 for TS3c, and 130.18, 120.38 for TS3d. It is emphasized here that the B2 – C1p and OC – O – CC – O bonds in the transition states are changed considerably. As demonstrated in Tables 2 and 3, the B2 –C1p and OC – O – CC – O bonds are 0.1743, 0.1311 for TS3a,
0.1719, 0.1320 for TS3b, 0.1731, 0.1325 for TS3c, and 0.1722 nm, 0.1307 nm for TS3d. The Mulliken overlap populations for the B2 – C1p and OC – O – CC – O bonds are 0.287, 0.340 for TS3a, 0.303, 0.317 for TS3b, 0.297, 0.345 for TS3c, and 0.304, 0.369 for TS3d. Obviously, the B2 – C1p and OC – O – CC – O bonds in the transition states are much longer than those in the four structures of the catalyst-alkynylborane-aldehyde adduct 5 (0.1596, 0.1240 for 5a, 0.1586, 0.1233 for 5b, 0.1595, 0.1243 for 5c, and 0.1595 nm, 0.1242 nm for 5d), whereas their Mulliken overlap populations are smaller than those for 5a, 5b, 5c, and 5d (0.488, 0.466 for 5a, 0.499, 0.468 for 5b, 0.487, 0.459 for 5c, and 0.484, 0.464 for 5d).
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Fig. 3. The optimized structures of TS3a, TS3b, TS3c, and TS3d.
Therefore, the B2 –C1p and OC – O – CC – O bonds for the transition states TS3a, TS3b, TS3c and TS3d are weakened greatly. The weakening of the B2 – C1p and OC – O – CC – O bonds is of advantage to the transfer of the alkynyl from the alkynylborane moiety to the carbonyl carbon of the aldehyde moiety and thus to the reduction of the aldehyde. It is found, especially, that the distances between C1p and CC – O in the transition states TS3a, TS3b, TS3c and TS3d (0.1845, 0.1804, 0.1796, and 0.1877 nm) are decreased considerably, compared with those in
5a, 5b, 5c, and 5d (0.2886, 0.3746, 0.2815, and 0.2802 nm). The corresponding Mulliken overlap populations are increased from 0 to 0.175, 0.204, 0.192, and 0.170. These results imply that in the transition states for the alkynyl transfer, there is the remarkable interaction between the C1p and CC – O atoms. This remarkable interaction leads to the formation of the B2 – N(3) – B(2) – OC – O –CC – O – C1p 6-membered rings in the transition states TS3a, TS3b, TS3c and TS3d. As shown in Fig. 3, a twisted chair structure is formed by
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Fig. 4. The optimized structures of TS4a, TS4b, TS4c, and TS4d.
the B2 –N(3) – B(2) – OC – O –CC – O – C1p 6-membered ring and the oxazaborolidine ring in TS3a or TS3d, whereas a twisted boat structure is formed in TS3b or TS3c. In addition, the B2 – OC – O distances for the four transition states are shortened, compared with those for 5a, 5b, 5c, and 5d (0.3017, 0.3131, 0.3259, and 0.2953 nm). They are 0.2831 for TS3a, 0.3097 for TS3b, 0.3101 for TS3c, and 0.2821 nm for TS3d, respectively.
The change in the atomic charges for the transition states TS3a, TS3b, TS3c and TS3d is considerable. As presented in Table 4, the positive charges of the carbonyl carbons for these transition states are 0.156 for TS3a, 0.133 for TS3b, 0.121 for TS3c, and 0.153 for TS3d. They are much smaller than those for the adducts 5a, 5b, 5c, and 5d (0.277, 0.255, 0.262, and 0.2525). As discussed earlier, the remarkable interaction between C1p and CC – O leads
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to the formation of the B2 – N(3) – B(2) – OC – O –CC – p O – C1 6-membered rings in the transition states for the transfer of the alkynyl. Therefore, partial electrons arising from the C1p atom are transferred to the CC – O atom. In addition, the positive charges of B2 and the negative charges of OC – O in the transition states are increased considerably, compared with those in 5a, 5b, 5c, and 5d (0.408 and 2 0.342, 0.385 and 2 0.297, 0.387 and 2 0.322, 0.415 and 2 0.338). They are 0.567, 2 0.419 for TS3a, 0.540, 2 0.408 for TS3b, 0.551, 2 0.413 for TS3c, and 0.566, 2 0.415 for TS3d. It is clear that the increase in the positive charges of B2 and the negative charges of OC – O results in the strengthened interaction between B 2 and O C – O , which is of advantage to the formation of the B – O – B –N 4-membered ring in the catalyst-alkoxyborane adduct 6. The NBO analysis [22,23] for the transition states TS3a, TS3b, TS3c and TS3d is carried out. Selected stabilization interaction energies Eð2Þ obtained from the second-order perturbative theory are summarized in Table 5, where BD and BDp represent, respectively, bonding and antibonding NBO and LP and CR are lone pairs and core electrons. In the NBO analysis, Eð2Þ is used to describe the interaction between the donor bond and the acceptor bond of an intramolecule or to describe the delocalization trend of electrons from a donor bond to an acceptor bond. As presented in Table 5, for the transition state P TS3, the total stabilization interaction energies Eð2Þ between all other bonding orbitals and the s B2 –C1p antibonding orbital, BDp(s)B2 – C1p, are 96.78 for TS3a, 84.68 for TS3b, 86.78 for TS3c, and 86.11 kJ/mol for TS3d. They are much larger than 57.74 kJ/mol for the free alkynylborane 2. This result shows that there is the strong trend of the electron transfer from other bonding orbitals to the s B2 – C1p antibonding orbital in all the transition states TS3a, TS3b, TS3c and TS3d. As a result, the B2 – C1p bonds in these transition states are weakened greatly. Further, it is found that the trend of transfer of electrons to the s B2 – C1p antibonding orbital for TS3a is the strongest among these transition states. In other words, the s B2 – C1p bond for TS3a is the weakest and thus is broken down much more easily than the s B2 –C1p bonds for TS3b, TS3c and TS3d. In P addition, the total stabilization interaction energies Eð2Þ between
all other bonding orbitals and the s CC – O – C1p antibonding orbital, BDp(s)CO – C1p, are 198.95 for TS3a, 242.60 for TS3b, 211.04 for TS3c, and 257.61 kJ/mol for TS3d. Apparently, this value for TS3a is the smallest among all the values, which implies that the interaction between CC – O and C1p in TS3a is the strongest. The stabilization interaction energies between all other bonding orbitals and the p CC – O – OC – O antibonding orbital, BDp(p)C – O, are 87.57 for TS3a, 93.22 for TS3b, 97.06 for TS3c, and 77.36 kJ/mol for TS3d. They are much larger than 39.83 kJ/mol for the free aldehyde 3. It is obvious that the p CC – O – OC – O bonds in the transition states TS3a, TS3b, TS3c and TS3d are weakened considerably. 3.1.4. Transition state TS4 As illustrated in Scheme 2, the decomposition of the B – O – B –N 4-membered ring in the catalystalkoxyborane adduct 6 goes through the transition state TS4. TS4 has four structures such as TS4a, TS4b, TS4c and TS4d. They are in one-to-one correspondence to the four structures 6a, 6b, 6c and 6d of the adduct 6. The sole imaginary frequencies for these transition states, which correspond to the B2 – N(3) and B(2) – OC – O stretching vibrations, are, respectively, 2 158.1 for TS4a, 2 62.7 for TS4b, 2 170.4 for TS4c, and 2 170.3 cm21 for TS4d. The total energies E and the activating energies DE– are 2 648.6614, 37.81 for TS4a, 2 648.6600, 42.27 for TS4b, 2 648.6653, 35.71 for TS4c, and 2 648.6614 a.u., 41.75 kJ/mol for TS4d. The optimized structures of the transition states TS4a, TS4b, TS4c and TS4d are shown in Fig. 4. In these transition states, the N(3) –B(2) –OC – O – CC – O and N(3) – B 2 – O C – O – CC – O torsion angles are 2 143.6, 123.3 for TS4a, 2 148.2, 137.7 for TS4b, 132.7, 2 139.4 for TS4c, and 114.98, 2 118.18 for TS4d, respectively. The B2 – N(3) –B(2), N(3) –B(2) – OC – O and B(2) –OC – O – B2 angles are, 101.0, 74.8, 99.1 for TS4a, 107.7, 64.9, 70.9 for TS4b, 100.6, 78.6, 83.5 for TS4c, and 99.18, 79.38, 81.78 for TS4d. As presented in Table 2, the OC – O –CC – O and CC – O – C1p bonds for these transition states are 0.1418, 0.1476 for TS4a, 0.1414, 0.1479 for TS4b, 0.1418, 0.1475 for TS4c, and 0.1418 nm, 0.1477 nm for TS4d, and they are almost transformed into normal s single bonds. By Comparison with the adducts 6a,
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6b, 6c and 6d, the most remarkable characteristics of the transition states TS4a, TS4b, TS4c and TS4d is the considerably increase in their B2 –N(3) and B(2) – OC – O bonds. They are 0.1932, 0.2551 for TS4a, 0.1794, 0.2754 for TS4b, 0.2037, 0.2482 for TS4c, and 0.1932 nm, 0.2398 nm for TS4d. As illustrated in Table 3, the Mulliken overlap populations for these bonds are decreased from those for the catalyst-alkoxyborane adducts (0.234, 0.183 for 6a, 0.231, 0.179 for 6b, 0.231, 0.178 for 6c, and 0.232, 0.178 for 6d) to 0.095, 0.044 for TS4a, 0.124, 0.028 for TS4b, 0.088, 0.049 for TS4c, and 0.098, 0.058 for TS4d. It is clear that the B2 –N(3) and B(2) –OC – O interactions are weakened considerably. These results imply that during the decomposition of the B –O –B – N 4-membered rings in the adducts 6a, 6b, 6c and 6d, the B2 –N(3) bonds and the B(2) – OC – O bonds are broken down simultaneously, which leads to the directly formation of the alkoxyborane 7 shown in Scheme 2 and the regeneration of the catalyst 1. The present conclusion is different from the mechanism of the enantioselective reduction of prochiral ketone with borane catalyzed by the CBS catalysts suggested by Corey et al. [2]. According to the Corey’s mechanism, there are two reaction steps during the decomposition of the B – O –B – N 4-membered ring. The first one is the fracture of the B(2) –OC – O bonds and the second is the fracture of the B2 – N(3) bonds. 3.2. Mechanism of reduction As illustrated earlier, there are four reaction paths for the enantioselective alkynylation of aldehyde with alkynylborane catalyzed by oxazaborolidine. There are two paths through which R-chiral alcohols are generated. One is the path, 1 ! 4a ! 5a ! 6a ! 7a, and it passes through the transition states TS1, TS2a, TS3a, and TS4a. The other is the path, 1 ! 4 c ! 5c ! 6c ! 7c, and it passes through the transition states TS1, TS2c, TS3c, and TS4c. S-chiral alcohols are obtained through the reduction paths, 1 ! 4b ! 5 b ! 6b ! 7b and 1 ! 4d ! 5d ! 6d ! 7d, respectively. The later two paths pass through the transition states TS1, TS2b, TS3b, and TS4b and the transition states TS1, TS2d, TS3d, and TS4d. The total energies E and the activating energies DE– for all the transition states are summarized in Table 1.
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The energy relation for the enantioselective alkynylation of the aldehyde 3 with the alkynylborane 2 catalyzed by the chiral oxazaborolidine 1 is illustrated in Fig. 5, where the energies of all the intermediary states for the alkynylation are taken from the first part of this work. As shown in Fig. 5, the enantioselective alkynylation of the aldehyde 3 is exothermic. The activating energy DE– for the formation of the catalystalkynylborane adduct 4 is 4.20 kJ/mol and that for the corresponding reverse reaction is 6.04 kJ/mol. The activating energies for the formation of the catalystalkynylborane-aldehyde adduct 5 are 6.83 for TS2a, 5.25 for TS2b, 27.31 for TS2c, and 10.24 kJ/mol for TS2d and those for the corresponding reverse reactions are 27.31, 19.95, 3.68, and 20.22 kJ/mol. The activating energies for the transfer of alkynyl leading to the catalyst-alkoxyborane adduct 6 are 44.63 for TS3a, 48.83 for TS3b, 47.26 for TS3c, and 47.78 kJ/mol for TS3d and those for the corresponding reverse reactions are 142.04, 158.84, 199.28, and 159.89 kJ/mol. The activating energies for the decomposition of the B – O – B –N 4-membered ring in 6 are 37.81 for TS4a, 42.27 for TS4b, 35.71 for TS4c, and 41.75 kJ/mol for TS4d and those for the corresponding reverse reactions are 30.46, 34.13, 20.22, and 30.46 kJ/mol. Obviously, the activating energies for the transfer of alkynyl from alkynylborane to the carbonyl carbon of aldehyde in the catalystalkynylborane-aldehyde adduct 5 and those for the reverse reactions are the highest among the transition states TS1, TS2, TS3, and TS4. Therefore, the transfer of alkynyl is the controlling-velocity step for the enantioselective alkynylation of aldehyde with alkynylborane catalyzed by chiral oxazaborolidine. Further, it is found that among the transition states TS3a, TS3b, TS3c and TS3d, the activating energies DE– for TS3a is the lowest. Because of this reason, the enantioselective alkynylation of aldehyde with alkynylborane catalyzed by oxazaborolidine goes mainly through the reduction path, 1 ! 4a ! 5a ! 6a ! 7a, which leads to R-chiral alcohols. This result is in agreement with the experiment [1] and the normal consequences for the enantioselective reduction of prochiral ketones with borane catalyzed by chiral oxazaborolidines [24,25]. In addition, as demonstrated earlier, the transition state TS3a for the alkynyl transfer, 5a ! 6a, is
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Fig. 5. The energy relation for the enantioselective alkynylation. DE– ðTS1Þ ¼ 4:20; DE– ðTS2aÞ ¼ 6:83; DE– ðTS2bÞ ¼ 5:25; DE– ð TS2cÞ ¼ 27:31; DE– ðTS2dÞ ¼ 10:24; DE– ðTS3aÞ ¼ 44:63; DE– ðTS3bÞ ¼ 48:83; DE– ðTS3cÞ ¼ 47:26; DE– ðTS3dÞ ¼ 47:78; DE– ðTS4aÞ ¼ 37:81; DE– ðTS4bÞ ¼ 42:27; DE– ðTS4cÞ ¼ 35:71; DE– ðTS4dÞ ¼ 41:75 kJ=mol:
a twisted chair structure and involves a B2 – N(3) – B(2) – OC – O – CC – O – C1p 6-membered ring. Therefore, the enantioselective alkynylation of aldehyde with alkynylborane catalyzed by oxazaborolidine has a twisted chair transition state.
4. Conclusions All the results for this work imply that the enantioselective alkynylation of aldehyde with alkynylborane catalyzed by chiral oxazaborolidine is exothermic and goes mainly through the formation of the catalyst-alkynylborane adduct, the formation of the catalyst-alkynylborane-aldehyde adduct, the transfer of alkynyl from the alkynylborane moiety to the carbonyl carbon of the aldehyde moiety, and the decomposition of the catalyst-alkoxyborane adduct leading to the regeneration of the catalyst. There are four reduction paths for the alkynylation reduction,
two of which lead to R-chiral alcohols and others to Schiral alcohols. The transfer of the alkynyl moiety is the controlling-velocity step for the enantioselective alkynylation of aldehyde and the alkynylation reduction results mainly in R-chiral alcohols that are in correspondence to the experiment. The transition state for the transfer of the alkynyl moiety involves a B2 – N(3) – B(2) – OC – O – CC – O – C1p 6-membered ring. During the decomposition of the catalystalkoxyborane adduct with a B –O – B –N 4-membered ring, the B –N and B – O bonds in the B – O – B –N 4membered ring are broken down simultaneously.
Acknowledgements This work is supported by the Science Foundation of National Education Ministry, People’s Republic of China.
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References [1] E.J. Corey, K.A. Cimprich, J. Am. Chem. Soc. 116 (1994) 3151. [2] E.J. Corey, R.K. Bakshi, S. Shibata, J. Am. Chem. Soc. 109 (1987) 5551. [3] M. Li, R. Xie, C. Hu, X. Wang, A. Tian, Int. J. Quantum Chem. 78 (2000) 245. [4] M. Li, R. Xie, S. Tian, A. Tian, Int. J. Quantum Chem. 78 (2000) 252. [5] M. Li, R. Xie, H. Hu, A. Tian, Int. J. Quantum Chem. 78 (2000) 261. [6] M. Li, W. Zheng, F. Yang, A. Tian, Int. J. Quantum Chem. 81 (2001) 291. [7] V. Nevalainen, Tetrahedron: Asymmetry 2 (1991) 429. [8] V. Nevalainen, Tetrahedron: Asymmetry 2 (1991) 827. [9] V. Nevalainen, Tetrahedron: Asymmetry 3 (1992) 921. [10] V. Nevalainen, Tetrahedron: Asymmetry 3 (1992) 1441. [11] V. Nevalainen, Tetrahedron: Asymmetry 3 (1992) 1563. [12] V. Nevalainen, Tetrahedron: Asymmetry 4 (1993) 1565. [13] V. Nevalainen, Tetrahedron: Asymmetry 4 (1993) 1597.
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[14] V. Nevalainen, Tetrahedron: Asymmetry 4 (1993) 2001. [15] V. Nevalainen, Tetrahedron: Asymmetry 5 (1994) 903. [16] L.P. Linney, C.R. Self, I.H. Williams, Tetrahedron: Asymmetry 5 (1994) 813. [17] G.J. Quallich, J.F. Blake, T.M. Woodll, J. Am. Chem. Soc. 116 (1994) 8516. [18] V. Nevalainen, R. Uggla, M.R. Sundberg, Tetrahedron: Asymmetry 6 (1995) 1431. [19] R. Uggla, V. Nevalainen, M.R. Sundberg, Tetrahedron: Asymmetry 7 (1996) 2725. [20] V. Nevalainen, Tetrahedron: Asymmetry 7 (1996) 1449. [21] V. Nevalainen, Tetrahedron: Asymmetry 8 (1997) 2241. [22] A.E. Reed, R.B. Weinstock, F. Weinhold, J. Chem. Phys. 83 (1985) 735. [23] A.E. Reed, L.A. Curtiss, F. Weinhold, Chem. Rev. 88 (1988) 899. [24] M. Felder, G. Giffels, C. Wandrey, Tetrahedron: Asymmetry 8 (1997) 1975. [25] G.B. Jones, S.B. Heaton, B.J. Chapman, M. Guzel, Tetrahedron: Asymmetry 8 (1997) 3625.
Density functional computations of enantioselective alkynylation of aldehydes catalyzed by oxazaborolines. Part 2. Structures of transition states and the mechanism of enantioselective reduction Ming Li*, Rongxing He Department of Chemistry, Southwest-China Normal University, Chongqing 400715, People’s Republic of China Received 28 November 2002; accepted 17 February 2003
Abstract Quantum chemical computations of the enantioselective alkynylation of aldehyde with alkynylborane catalyzed by chiral oxazaborolidine are performed by means of the density functional theory method. All the transition states for the alkynylation are optimized completely at the B3LYP/6-31G(d) level and the mechanism of the enantioselective alkynylation is studied. As demonstrated, the enantioselective alkynylation of aldehyde is exothermic and includes the formation of the catalystalkynylborane adduct, the formation of the catalyst-alkynylborane-aldehyde adduct, the transfer of alkynyl to the carbonyl carbon of the aldehyde moiety, and the decomposition of the catalyst-alkoxyborane adduct leading to the regeneration of the catalyst. There are four reduction paths for the alkynylation reduction. The transfer of the alkynyl moiety is the controlling-velocity step for this reduction and the alkynylation results mainly in R-chiral alcohols that are in correspondence to the experiment. q 2003 Elsevier B.V. All rights reserved. Keywords: Enantioselective alkynylation; Mechanism; Chiral oxazaborolidine; Transition states; Density functional theory
1. Introduction In 1994, Corey and Cimprich [1] reported the enantioselective alkynylation reduction of aldehyde with alkynylborane catalyzed by chiral oxazaborolidine. In their experiment, Corey et al. used the oxazaborolidine C, as a catalyst, and the alkynylborane D, as an alkynyl donor, to reduce the aldehyde B and obtained the chiral alcohol A (Scheme 1). Compared with the traditional nucleophilic alkynylation of carbonyl compounds, this method has rapid reaction velocity and high enantioselectivity. Corey et al. * Corresponding author. E-mail address: [email protected] (M. Li).
pointed out that there is an analogy in manner between the enantioselective alkynylation of aldehyde with alkynylborane and the asymmetric reduction of prochiral ketone with borane promoted by oxazaborolidine. According to the mechanism of the enantioselective reduction of prochiral ketone with borane catalyzed by the CBS catalysts suggested by Corey et al. [2], therefore, the enantioselective alkynylation of aldehyde with alkynylborane catalyzed by oxazaborolidine goes mainly through the following steps: (1) coordination of the alkynylborane D as an alkyne moiety donor to the oxazaborolidine catalyst C, (2) coordination of the carbonyl oxygen in the aldehyde B to the boron of C, (3) shift of the alkynyl moiety of the alkynylborane D toward the carbonyl carbon to lead to
0166-1280/03/$ - see front matter q 2003 Elsevier B.V. All rights reserved. doi:10.1016/S0166-1280(03)00142-8
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Scheme 1.
the reduced carbonyl carbon, (4) regeneration of the catalyst C and formation of the chiral alcohol A. However, the sufficient theoretical evidence must be obtained to verify the rightness of Corey’s speculation about this process. Therefore, it is useful to investigate this enantioselective alkynylation in detail by means of the quantum chemical method. Some successful modeling studies on the enantioselective reduction of prochiral ketone with borane catalyzed by oxazaborolidine have been carried out by means of the ab initio molecular orbital methods [3 – 21]. They support the Corey’s mechanism of catalysis. However, quantum chemical studies on the enantioselective alkynylation of aldehyde with alkynylborane catalyzed by chiral oxazaborolidine have not been reported yet. In the first part of this work, the structures and properties of the catalyst and all the intermediary states for the alkynylation are studied by means of the density functional theory (DFT) method. The aim of this part is to investigate the structures and properties of all the transition states and the mechanism of the enantioselective alkynylation by means of the DFT method.
2. Model and computations In the first part of this work, some modeling molecules are employed to replace oxazaborolidine,
alkynylborane, and aldehyde. As presented in Scheme 1, the molecule 1 is used as the modeling for the oxazaborolidine catalyst C, the molecule 2 as the modeling for the alkynylborane D, and the molecule 3 as the modeling for the aldehyde B. The modeling molecule 1 keeps the chirality of the chiral carbon in the oxazaborolidine C. The plausible path of the enantioselective alkynylation of the aldehyde 3 with the alkynylborane 2 catalyzed by the chiral oxazaborolidine 1 is shown in Scheme 2. TS1, TS2, and TS3 are the transition states leading to the catalyst-alkynylborane adduct 4, the catalyst-alkynylborane-aldehyde adduct 5, and the catalyst-alkoxyborane adduct 6, respectively. TS4 is the transition state for the decomposition of the adduct 6. In the present work, all the structures of these transition states are optimized completely by means of the DFT method at the B3LYP/6-31G(d) level and their vibrational analysis and natural bond orbital (NBO) analysis [22,23] are performed at the same computational level. The total energies E, the activating energies DE– ; and the vibrational frequencies n for all the transition states are summarized in Table 1. The selected bond lengths and their Mulliken overlap populations are shown in Tables 2 and 3, respectively. The selected atomic charges are listed in Table 4. The selected stabilization interaction
M. Li, R. He / Journal of Molecular Structure (Theochem) 629 (2003) 209–221
211
Scheme 2.
energies obtained from the second-order perturbative theory [22] are illustrated in Table 5. The optimized structures of the transition states TS1, TS2, TS3, and TS4 are illustrated in Figs. 1, 2, 3, and 4, respectively.
M1 before the formation of the catalyst-alkynylborane adduct 4. This intermediary state is stable and its lowest vibrational frequency is 20.0 cm21. It is illustrated in Table 1 that the total energy for M1 is 2 494.7984 a.u. and is lower than
3. Discussion
Table 1 Dipole moments D (Debye), total energies E (a.u.), activating energies DE– (kJ/mol), and vibrational frequencies n (cm21)
3.1. Structures of transition states 3.1.1. Transition state TS1 The optimized structure of the transition state TS1 for the formation of the catalyst-alkynylborane adduct 4 is presented in Fig. 1. As shown in Table 1, its sole imaginary frequency is 2 98.3 cm21 and corresponds to the B2 – N(3) stretching vibration. It is obvious that TS1 is a transition state. The total energy E for TS1 is 2 494.7968 a.u. and is lower than 2 494.7944 a.u. of the sum of energy for the catalyst 1 and the alkynylborane 2. This result implies that TS1 is not the transition state for the directly reaction of the catalyst 1 with the alkynylborane 2 to form the catalyst-alkynylborane adduct 4. As indicated in the first part of this work, there is an intermediary state
TS1 TS2a TS2b TS2c TS2d TS3a TS3b TS3c TS3d TS4a TS4b TS4c TS4d M1 M2a M2b M2c M2d
D
E
DE–
n1
n2
3.18 3.71 6.01 4.72 3.95 3.31 2.95 3.03 3.33 3.58 3.72 3.38 4.11 2.46 2.93 6.76 3.39 2.91
2494.7968 2648.6283 2648.6266 2648.6196 2648.6269 2648.6217 2648.6156 2648.6030 2648.6164 2648.6614 2648.6600 2648.6653 2648.6614 2494.7984 2648.6309 2648.6286 2648.6300 2648.6308
4.20 6.83 5.25 27.31 10.24 44.63 48.83 47.26 47.78 37.81 42.27 35.71 41.75
298.3 250.4 264.1 2121.8 286.7 2343.8 2287.7 2261.7 2335.8 2158.1 262.7 2170.4 2170.3 20.0 19.9 16.0 22.1 20.6
24.3 22.4 31.1 26.9 38.2 46.9 47.6 19.6 40.1 31.0 23.3 33.0 40.2 27.1 28.8 22.3 24.9 24.2
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Table 2 Selected bond lengths (nm) for the transition states
B2 –C1p B2 –N(3) N(3)– B(2) B(2)–OCyO OCyO –CCyO B2 –OCyO CCyO –C1p
p
B2 –C1 B2 –N(3) N(3)– B(2) B(2)–OCyO OCyO –CCyO B2 –OCyO CCyO –C1p
TS1
TS2a
TS2b
TS2c
TS2d
TS3a
TS3b
0.1549 0.2296 0.1447
0.1580 0.1762 0.1516 0.2443 0.1215 0.3422 0.3703
0.1576 0.1769 0.1516 0.2294 0.1219 0.3349 0.4452
0.1582 0.1728 0.1552 0.1893 0.1221 0.3089 0.3618
0.1583 0.1747 0.1528 0.2181 0.1219 0.3231 0.3596
0.1743 0.1607 0.1645 0.1509 0.1311 0.2831 0.1845
0.1719 0.1614 0.1638 0.1484 0.1320 0.3097 0.1804
TS3c
TS3d
TS4a
TS4b
TS4c
TS4d
2
0.1731 0.1611 0.1642 0.1477 0.1325 0.3101 0.1796
0.1722 0.1613 0.1645 0.1515 0.1307 0.2821 0.1877
0.1932 0.1480 0.2551 0.1418 0.1450 0.1476
0.1794 0.1497 0.2754 0.1414 0.1465 0.1479
0.2037 0.1474 0.2482 0.1418 0.1442 0.1475
0.1932 0.1487 0.2398 0.1418 0.1452 0.1477
0.1527
2 494.7968 a.u. for TS1. Therefore, the activating energy DE– for TS1 is 4.20 kJ/mol. Obviously, the formation of the catalyst-alkynylborane adduct 4 is easily because of a low activating energy. In the transition state TS1, the distance between N(3) and B2 is 0.2296 nm and is much longer than 0.1789 nm in the adduct 4. The B2 – N(3) – B(2) and B2 – N(3) – C(4) angles and the B2 – N(3) – B(2) – O(1) torsion angle are 106.4, 117.7, and 110.18,
respectively (B2 is the boron atom of the alkynylborane 2 and B(2) is the boron atom of the catalyst 1). As shown in Tables 2 and 3, the B2 –C1p bond for TS1 is 0.1549 nm, which longer than 0.1527 nm for the free alkynylborane 2, and its Mulliken overlap population is 0.525, which smaller than 0.555 for 2. It is obvious that the B2 – C1p bond in the transition state TS1 is weaken. In addition, it is clear in Table 4 that the positive charges of B2 and the negative charge of N(3)
Table 3 Selected Mulliken overlap populations for the transition states
B2 –C1p B2 –N(3) N(3)–B(2) B(2)–OC – O OC – O – CC – O B2 –OC – O CC – O –C1p
B2 –C1p B2 –N(3) N(3)–B(2) B(2)–OC – O OC – O – CC – O B2 –OC – O CC – O –C1p
TS1
TS2a
TS2b
TS2c
TS2d
TS3a
TS3b
0.525 0.074 0.389
0.507 0.121 0.307 0.055 0.552 0.005 0.002
0.506 0.117 0.319 0.070 0.529 0.004 0.000
0.500 0.142 0.301 0.098 0.513 0.003 0.002
0.505 0.124 0.299 0.084 0.535 0.003 0.002
0.287 0.232 0.234 0.260 0.340 0.004 0.175
0.303 0.234 0.231 0.304 0.317 20.009 0.204
TS3c
TS3d
TS4a
TS4b
TS4c
TS4d
2
0.297 0.233 0.227 0.316 0.345 20.010 0.192
0.304 0.229 0.232 0.256 0.369 0.004 0.170
0.095 0.319 0.044 0.247 0.358 0.323
0.124 0.308 0.028 0.257 0.359 0.309
0.088 0.333 0.049 0.271 0.360 0.320
0.098 0.316 0.058 0.241 0.352 0.331
0.555
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Table 4 Selected atomic charges for the transition states
O(1) B(2) N(3) B2 OCyO CCyO C1p
O(1) B(2) N(3) B2 OCyO CCyO C1p
TS1
TS2a
TS2b
TS2c
TS2d
TS3a
TS3b
TS3c
20.428 0.422 20.633 0.295
20.423 0.495 20.678 0.378 20.342 0.264 0.088
20.448 0.503 20.674 0.384 20.330 0.249 0.089
20.461 0.541 20.670 0.390 20.319 0.257 0.089
20.439 0.522 20.685 0.389 20.334 0.265 0.087
20.493 0.573 20.690 0.567 20.419 0.156 20.110
20.533 0.590 20.677 0.540 20.408 0.133 20.040
20.531 0.577 20.675 0.551 20.413 0.121 20.058
TS3d
TS4a
TS4b
TS4c
TS4d
1
2
20.497 0.578 20.694 0.566 20.415 0.153 20.105.
20.424 0.471 20.679 0.691 20.526 0.041
20.408 0.448 20.665 0.695 20.538 0.045
20.432 0.468 20.683 0.684 20.519 0.061
20.436 0.485 20.690 0.689 20.523 0.042
0.074
in the transition state TS1 are 0.295 and 2 0.633, respectively. They are larger than 0.213 of B2 in the free alkynylborane 2 and 2 0.569 of N(3) in the free catalyst 1. The increase in the charges of B2 and N(3) for TS1 causes the interaction between the alkynylborane 2 and the catalyst 1 to be strengthened. The weakening of the B2 – C1p bond and the strengthened interaction between 2 and 1 are of advantage to the succeeding reactions. 3.1.2. Transition State TS2 The transition state TS2 for the formation of the catalyst-alkynylborane-aldehyde adduct 5 involves four structures such as TS2a, TS2b, TS2c and TS2d. These structures are in one-to-one correspondence to four structures 5a, 5b, 5c and 5d of the adduct 5. Their sole imaginary frequencies are, respectively, 2 50.4 for TS2a, 2 64.1 for TS2b, 2 121.8 for TS2c, and 2 86.7 cm21 for TS2d. These imaginary frequencies all correspond to the B(2) – O C – O stretching vibrations. Their total energies are 2 648.6283 for TS2a, 2 648.6266 for TS2b, 2 648.6196 for TS2c, and 2 648.6269 for TS2d. It has been pointed out in the first part of this work that four intermediary states M2a, M2b, M2c and M2d exist before the formation of the catalyst-alkynylborane-aldehyde adduct 5. As illustrated in Table 1, the lowest vibrational frequencies of these intermediary states are 19.9 for M2a,
20.569 0.213
16.0 for M2b, 22.1 for M2c, and 20.6 cm21 for M2d and thus they are stable. The intermediary states M2a, M2b, M2c and M2d are also in one-to-one correspondence to the transition states TS2a, TS2b, TS2c and TS2d. The total energies for these intermediary states are also shown in Table 1. As a result, the activating energies for TS2a, TS2b, TS2c and TS2d are 6.83, 5.25, 27.31, and 10.24 kJ/mol. The optimized structures of TS2a, TS2b, TS2c and TS2d are illustrated in Fig. 2. In these transition states, the B(2) – OC – O bonds are 0.2443 for TS2a, 0.2294 for TS2b, 0.1895 for TS2c, and 0.2181 nm for TS2d, respectively. The B2 –N(3) – B(2) –O(1) and OC – O –B(2) – N(3) –C(4) torsion angles are, respectively, 127.4, 2 100.9 for TS2a, 123.1, 2 113.5 for TS2b, 114.2, 2 134.0 for TS2c, and 126.68, 2 108.38 for TS2d. The CC – O – OC – O – B(2), OC – O – B(2) – N(3), and B2 –N(3) – B(2) angles are 129.9, 105.0, 123.7 for TS2a, 113.9, 108.3, 123.7 for TS2b, 147.7, 105.6, 125.3 for TS2c, and 132.88, 103.78, 125.48 for TS2d. It must be emphasized that the formation of the transition state TS2 leads to the increased carbonyl bond of TS2. The CC – O – OC – O bond in the free aldehyde 3 is 0.1210 nm, whereas the CC – O – OC – O bonds in the transition states TS2a, TS2b, TS2c and TS2d are 0.1215, 0.1219, 0.1221, and 0.1219 nm, respectively. The corresponding Mulliken overlap populations are decreased from 0.625 for 3 to 0.552
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Table 5 Selected stabilization interaction energies Eð2Þ (kJ/mol) for TS3a, TS3b, TS3c and TS3d Donor NBO TS3a
TS3b
TS3c
TS3d
3 2
Acceptor NBO p
Eð2Þ p
C20–B23 O18
BD (s) BDp(s)
CCyO –C1 CCyO –C1p
C20–C24 C24
BDp(s) BDp(s)
C1p –B2 C1p –B2
B23–C20 C20–C26
BDp(p) BDp(p)
CCyO –OCyO CCyO –OCyO
C20–B23 O18 C24
BDp(s) BDp(s) BDp(s)
CCyO –C1p CCyO –C1p CCyO –C1p
C20–C24 C24
BDp(s) BDp(s)
C1p –B2 C1p –B2
C20–C24 O18–C19
BDp(p) BDp(p)
CCyO –OCyO CCyO –OCyO
BD(s) LP(p) LP(s) P Eð2Þ BD(s) LP(s) P Eð2Þ BD(s) CR(s) P Eð2Þ
C20–B23 O18 C24
BDp(s) BDp(s) BDp(s)
CCyO –C1p CCyO –C1p CCyO –C1p
C20–C24 C24
BDp(s) BDp(s)
C1p –B2 C1p –B2
C20–B23 C23
p
BD (p) BDp(p)
CCyO –OCyO CCyO –OCyO
BD(s) LP(p) LP(s) P Eð2Þ BD(s) LP(s) P Eð2Þ BD(s) P Eð2Þ P Eð2Þ P Eð2Þ
C20–B23 O18 C24
BDp(s) BDp(s) BDp(s)
CCyO –C1p CCyO –C1p CCyO –C1p
C20–C24 C24
BDp(s) BDp(s)
C1p –B2 C1p –B2
O18–C19
BDp(p)
CCyO –OCyO
BD(sp) LP(p) P Eð2Þ BD(s) LP(s) P Eð2Þ BD(s) BD(p) P Eð2Þ BD(s) LP(p) LP(s) P Eð2Þ BD(s) LP(s) P Eð2Þ BD(s) BD(s) P Eð2Þ
38.28 160.67 198.95 66.07 30.71 96.78 58.45 29.12 87.57 61.30 96.32 84.98 242.60 54.60 30.08 84.68 51.97 41.25 93.22 53.26 89.16 68.62 211.04 48.91 37.87 86.78 79.91 17.15 97.06 65.44 105.35 86.82 257.61 58.12 27.99 86.11 77.36 77.36 39.83 57.74
for TS2a, 0.529 for TS2b, 0.513 for TS2c, and 0.535 for TS2d. It is clear that the carbonyl bonds in these transition states are weakened. In addition, the formation of the transition state TS2 also leads to the increased B2 – C1p bond. As shown in Tables 2 and 3, the B2 –C1p bonds in the transition states TS2a,
Fig. 1. The optimized structure of TS1.
TS2b, TS2c and TS2d are much longer than the B2 – C1p bond in the free alkynylborane 2 and their Mulliken overlap populations are smaller than the overlap population in 2. Therefore, the B2 –C1p bonds in these transition states are also weakened. The weakening of the B2 –C1p and CC – O – OC – O bonds is of advantage to the transfer of the alkynyl from the alkynylborane moiety to the carbonyl carbon of the aldehyde moiety. 3.1.3. Transition state TS3 Through the transfer of the alkynyl of the alkynylborane moiety, the catalyst-alkynylboranealdehyde adduct 5 is transformed into the catalystalkoxyborane adduct 6. TS3 is the transition state for the transfer of the alkynyl from the alkynylborane moiety to the carbonyl carbon of the aldehyde moiety. It also involves four structures such as TS3a, TS3b, TS3c and TS3d, which are in one-to-one correspondence to four structures 6a, 6b, 6c and 6d of the adduct 6. The sole imaginary frequencies, which correspond to the B2 – C1p – CC – O stretching vibrations, for TS3a, TS3b, TS3c and TS3d are 2 343.8 for TS3a, 2 287.7 for TS3b, 2 261.7 for TS3c, and 2 335.8 cm21 for TS3d, respectively. The total energies and the activating energies are 2 648.6217, 44.63 for TS3a, 2 648.6156, 48.83 for TS3b, 2 648.6030, 47.26 for TS3c, and 2 648.6164 a.u., 47.78 kJ/mol for TS3d. The optimized structures of the transition states TS3a, TS3b, TS3c and TS3d are illustrated in Fig. 3. In these transition states, the B2 –N(3), B(2) – OC – O,
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215
Fig. 2. The optimized structures of TS2a, TS2b, TS2c, and TS2d.
and N(3) –B(2) bonds are 0.1607, 0.1509, 0.1645 for TS3a, 0.1614, 0.1484, 0.1638 for TS3b, 0.1611, 0.1477, 0.1642 for TS3c, and 0.1613 nm, 0.1515 nm, 0.1645 nm for TS3d. The B2 –N(3) –B(2) –O(1) and OC – O – B(2) – N(3) – C(4) torsion angles are 128.8, 2 117.8 for TS3a, 87.0, 2 159.6 for TS3b, 89.5, 2 161.8 for TS3c, and 128.88, 2 116.28 for TS3d. The OC – O – B(2) – N(3), and B2 – N(3) – B(2) angles are 104.2, 119.9 for TS3a, 110.2, 121.8 for TS3b, 109.8, 122.2 for TS3c, and 130.18, 120.38 for TS3d. It is emphasized here that the B2 – C1p and OC – O – CC – O bonds in the transition states are changed considerably. As demonstrated in Tables 2 and 3, the B2 –C1p and OC – O – CC – O bonds are 0.1743, 0.1311 for TS3a,
0.1719, 0.1320 for TS3b, 0.1731, 0.1325 for TS3c, and 0.1722 nm, 0.1307 nm for TS3d. The Mulliken overlap populations for the B2 – C1p and OC – O – CC – O bonds are 0.287, 0.340 for TS3a, 0.303, 0.317 for TS3b, 0.297, 0.345 for TS3c, and 0.304, 0.369 for TS3d. Obviously, the B2 – C1p and OC – O – CC – O bonds in the transition states are much longer than those in the four structures of the catalyst-alkynylborane-aldehyde adduct 5 (0.1596, 0.1240 for 5a, 0.1586, 0.1233 for 5b, 0.1595, 0.1243 for 5c, and 0.1595 nm, 0.1242 nm for 5d), whereas their Mulliken overlap populations are smaller than those for 5a, 5b, 5c, and 5d (0.488, 0.466 for 5a, 0.499, 0.468 for 5b, 0.487, 0.459 for 5c, and 0.484, 0.464 for 5d).
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Fig. 3. The optimized structures of TS3a, TS3b, TS3c, and TS3d.
Therefore, the B2 –C1p and OC – O – CC – O bonds for the transition states TS3a, TS3b, TS3c and TS3d are weakened greatly. The weakening of the B2 – C1p and OC – O – CC – O bonds is of advantage to the transfer of the alkynyl from the alkynylborane moiety to the carbonyl carbon of the aldehyde moiety and thus to the reduction of the aldehyde. It is found, especially, that the distances between C1p and CC – O in the transition states TS3a, TS3b, TS3c and TS3d (0.1845, 0.1804, 0.1796, and 0.1877 nm) are decreased considerably, compared with those in
5a, 5b, 5c, and 5d (0.2886, 0.3746, 0.2815, and 0.2802 nm). The corresponding Mulliken overlap populations are increased from 0 to 0.175, 0.204, 0.192, and 0.170. These results imply that in the transition states for the alkynyl transfer, there is the remarkable interaction between the C1p and CC – O atoms. This remarkable interaction leads to the formation of the B2 – N(3) – B(2) – OC – O –CC – O – C1p 6-membered rings in the transition states TS3a, TS3b, TS3c and TS3d. As shown in Fig. 3, a twisted chair structure is formed by
M. Li, R. He / Journal of Molecular Structure (Theochem) 629 (2003) 209–221
217
Fig. 4. The optimized structures of TS4a, TS4b, TS4c, and TS4d.
the B2 –N(3) – B(2) – OC – O –CC – O – C1p 6-membered ring and the oxazaborolidine ring in TS3a or TS3d, whereas a twisted boat structure is formed in TS3b or TS3c. In addition, the B2 – OC – O distances for the four transition states are shortened, compared with those for 5a, 5b, 5c, and 5d (0.3017, 0.3131, 0.3259, and 0.2953 nm). They are 0.2831 for TS3a, 0.3097 for TS3b, 0.3101 for TS3c, and 0.2821 nm for TS3d, respectively.
The change in the atomic charges for the transition states TS3a, TS3b, TS3c and TS3d is considerable. As presented in Table 4, the positive charges of the carbonyl carbons for these transition states are 0.156 for TS3a, 0.133 for TS3b, 0.121 for TS3c, and 0.153 for TS3d. They are much smaller than those for the adducts 5a, 5b, 5c, and 5d (0.277, 0.255, 0.262, and 0.2525). As discussed earlier, the remarkable interaction between C1p and CC – O leads
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to the formation of the B2 – N(3) – B(2) – OC – O –CC – p O – C1 6-membered rings in the transition states for the transfer of the alkynyl. Therefore, partial electrons arising from the C1p atom are transferred to the CC – O atom. In addition, the positive charges of B2 and the negative charges of OC – O in the transition states are increased considerably, compared with those in 5a, 5b, 5c, and 5d (0.408 and 2 0.342, 0.385 and 2 0.297, 0.387 and 2 0.322, 0.415 and 2 0.338). They are 0.567, 2 0.419 for TS3a, 0.540, 2 0.408 for TS3b, 0.551, 2 0.413 for TS3c, and 0.566, 2 0.415 for TS3d. It is clear that the increase in the positive charges of B2 and the negative charges of OC – O results in the strengthened interaction between B 2 and O C – O , which is of advantage to the formation of the B – O – B –N 4-membered ring in the catalyst-alkoxyborane adduct 6. The NBO analysis [22,23] for the transition states TS3a, TS3b, TS3c and TS3d is carried out. Selected stabilization interaction energies Eð2Þ obtained from the second-order perturbative theory are summarized in Table 5, where BD and BDp represent, respectively, bonding and antibonding NBO and LP and CR are lone pairs and core electrons. In the NBO analysis, Eð2Þ is used to describe the interaction between the donor bond and the acceptor bond of an intramolecule or to describe the delocalization trend of electrons from a donor bond to an acceptor bond. As presented in Table 5, for the transition state P TS3, the total stabilization interaction energies Eð2Þ between all other bonding orbitals and the s B2 –C1p antibonding orbital, BDp(s)B2 – C1p, are 96.78 for TS3a, 84.68 for TS3b, 86.78 for TS3c, and 86.11 kJ/mol for TS3d. They are much larger than 57.74 kJ/mol for the free alkynylborane 2. This result shows that there is the strong trend of the electron transfer from other bonding orbitals to the s B2 – C1p antibonding orbital in all the transition states TS3a, TS3b, TS3c and TS3d. As a result, the B2 – C1p bonds in these transition states are weakened greatly. Further, it is found that the trend of transfer of electrons to the s B2 – C1p antibonding orbital for TS3a is the strongest among these transition states. In other words, the s B2 – C1p bond for TS3a is the weakest and thus is broken down much more easily than the s B2 –C1p bonds for TS3b, TS3c and TS3d. In P addition, the total stabilization interaction energies Eð2Þ between
all other bonding orbitals and the s CC – O – C1p antibonding orbital, BDp(s)CO – C1p, are 198.95 for TS3a, 242.60 for TS3b, 211.04 for TS3c, and 257.61 kJ/mol for TS3d. Apparently, this value for TS3a is the smallest among all the values, which implies that the interaction between CC – O and C1p in TS3a is the strongest. The stabilization interaction energies between all other bonding orbitals and the p CC – O – OC – O antibonding orbital, BDp(p)C – O, are 87.57 for TS3a, 93.22 for TS3b, 97.06 for TS3c, and 77.36 kJ/mol for TS3d. They are much larger than 39.83 kJ/mol for the free aldehyde 3. It is obvious that the p CC – O – OC – O bonds in the transition states TS3a, TS3b, TS3c and TS3d are weakened considerably. 3.1.4. Transition state TS4 As illustrated in Scheme 2, the decomposition of the B – O – B –N 4-membered ring in the catalystalkoxyborane adduct 6 goes through the transition state TS4. TS4 has four structures such as TS4a, TS4b, TS4c and TS4d. They are in one-to-one correspondence to the four structures 6a, 6b, 6c and 6d of the adduct 6. The sole imaginary frequencies for these transition states, which correspond to the B2 – N(3) and B(2) – OC – O stretching vibrations, are, respectively, 2 158.1 for TS4a, 2 62.7 for TS4b, 2 170.4 for TS4c, and 2 170.3 cm21 for TS4d. The total energies E and the activating energies DE– are 2 648.6614, 37.81 for TS4a, 2 648.6600, 42.27 for TS4b, 2 648.6653, 35.71 for TS4c, and 2 648.6614 a.u., 41.75 kJ/mol for TS4d. The optimized structures of the transition states TS4a, TS4b, TS4c and TS4d are shown in Fig. 4. In these transition states, the N(3) –B(2) –OC – O – CC – O and N(3) – B 2 – O C – O – CC – O torsion angles are 2 143.6, 123.3 for TS4a, 2 148.2, 137.7 for TS4b, 132.7, 2 139.4 for TS4c, and 114.98, 2 118.18 for TS4d, respectively. The B2 – N(3) –B(2), N(3) –B(2) – OC – O and B(2) –OC – O – B2 angles are, 101.0, 74.8, 99.1 for TS4a, 107.7, 64.9, 70.9 for TS4b, 100.6, 78.6, 83.5 for TS4c, and 99.18, 79.38, 81.78 for TS4d. As presented in Table 2, the OC – O –CC – O and CC – O – C1p bonds for these transition states are 0.1418, 0.1476 for TS4a, 0.1414, 0.1479 for TS4b, 0.1418, 0.1475 for TS4c, and 0.1418 nm, 0.1477 nm for TS4d, and they are almost transformed into normal s single bonds. By Comparison with the adducts 6a,
M. Li, R. He / Journal of Molecular Structure (Theochem) 629 (2003) 209–221
6b, 6c and 6d, the most remarkable characteristics of the transition states TS4a, TS4b, TS4c and TS4d is the considerably increase in their B2 –N(3) and B(2) – OC – O bonds. They are 0.1932, 0.2551 for TS4a, 0.1794, 0.2754 for TS4b, 0.2037, 0.2482 for TS4c, and 0.1932 nm, 0.2398 nm for TS4d. As illustrated in Table 3, the Mulliken overlap populations for these bonds are decreased from those for the catalyst-alkoxyborane adducts (0.234, 0.183 for 6a, 0.231, 0.179 for 6b, 0.231, 0.178 for 6c, and 0.232, 0.178 for 6d) to 0.095, 0.044 for TS4a, 0.124, 0.028 for TS4b, 0.088, 0.049 for TS4c, and 0.098, 0.058 for TS4d. It is clear that the B2 –N(3) and B(2) –OC – O interactions are weakened considerably. These results imply that during the decomposition of the B –O –B – N 4-membered rings in the adducts 6a, 6b, 6c and 6d, the B2 –N(3) bonds and the B(2) – OC – O bonds are broken down simultaneously, which leads to the directly formation of the alkoxyborane 7 shown in Scheme 2 and the regeneration of the catalyst 1. The present conclusion is different from the mechanism of the enantioselective reduction of prochiral ketone with borane catalyzed by the CBS catalysts suggested by Corey et al. [2]. According to the Corey’s mechanism, there are two reaction steps during the decomposition of the B – O –B – N 4-membered ring. The first one is the fracture of the B(2) –OC – O bonds and the second is the fracture of the B2 – N(3) bonds. 3.2. Mechanism of reduction As illustrated earlier, there are four reaction paths for the enantioselective alkynylation of aldehyde with alkynylborane catalyzed by oxazaborolidine. There are two paths through which R-chiral alcohols are generated. One is the path, 1 ! 4a ! 5a ! 6a ! 7a, and it passes through the transition states TS1, TS2a, TS3a, and TS4a. The other is the path, 1 ! 4 c ! 5c ! 6c ! 7c, and it passes through the transition states TS1, TS2c, TS3c, and TS4c. S-chiral alcohols are obtained through the reduction paths, 1 ! 4b ! 5 b ! 6b ! 7b and 1 ! 4d ! 5d ! 6d ! 7d, respectively. The later two paths pass through the transition states TS1, TS2b, TS3b, and TS4b and the transition states TS1, TS2d, TS3d, and TS4d. The total energies E and the activating energies DE– for all the transition states are summarized in Table 1.
219
The energy relation for the enantioselective alkynylation of the aldehyde 3 with the alkynylborane 2 catalyzed by the chiral oxazaborolidine 1 is illustrated in Fig. 5, where the energies of all the intermediary states for the alkynylation are taken from the first part of this work. As shown in Fig. 5, the enantioselective alkynylation of the aldehyde 3 is exothermic. The activating energy DE– for the formation of the catalystalkynylborane adduct 4 is 4.20 kJ/mol and that for the corresponding reverse reaction is 6.04 kJ/mol. The activating energies for the formation of the catalystalkynylborane-aldehyde adduct 5 are 6.83 for TS2a, 5.25 for TS2b, 27.31 for TS2c, and 10.24 kJ/mol for TS2d and those for the corresponding reverse reactions are 27.31, 19.95, 3.68, and 20.22 kJ/mol. The activating energies for the transfer of alkynyl leading to the catalyst-alkoxyborane adduct 6 are 44.63 for TS3a, 48.83 for TS3b, 47.26 for TS3c, and 47.78 kJ/mol for TS3d and those for the corresponding reverse reactions are 142.04, 158.84, 199.28, and 159.89 kJ/mol. The activating energies for the decomposition of the B – O – B –N 4-membered ring in 6 are 37.81 for TS4a, 42.27 for TS4b, 35.71 for TS4c, and 41.75 kJ/mol for TS4d and those for the corresponding reverse reactions are 30.46, 34.13, 20.22, and 30.46 kJ/mol. Obviously, the activating energies for the transfer of alkynyl from alkynylborane to the carbonyl carbon of aldehyde in the catalystalkynylborane-aldehyde adduct 5 and those for the reverse reactions are the highest among the transition states TS1, TS2, TS3, and TS4. Therefore, the transfer of alkynyl is the controlling-velocity step for the enantioselective alkynylation of aldehyde with alkynylborane catalyzed by chiral oxazaborolidine. Further, it is found that among the transition states TS3a, TS3b, TS3c and TS3d, the activating energies DE– for TS3a is the lowest. Because of this reason, the enantioselective alkynylation of aldehyde with alkynylborane catalyzed by oxazaborolidine goes mainly through the reduction path, 1 ! 4a ! 5a ! 6a ! 7a, which leads to R-chiral alcohols. This result is in agreement with the experiment [1] and the normal consequences for the enantioselective reduction of prochiral ketones with borane catalyzed by chiral oxazaborolidines [24,25]. In addition, as demonstrated earlier, the transition state TS3a for the alkynyl transfer, 5a ! 6a, is
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Fig. 5. The energy relation for the enantioselective alkynylation. DE– ðTS1Þ ¼ 4:20; DE– ðTS2aÞ ¼ 6:83; DE– ðTS2bÞ ¼ 5:25; DE– ð TS2cÞ ¼ 27:31; DE– ðTS2dÞ ¼ 10:24; DE– ðTS3aÞ ¼ 44:63; DE– ðTS3bÞ ¼ 48:83; DE– ðTS3cÞ ¼ 47:26; DE– ðTS3dÞ ¼ 47:78; DE– ðTS4aÞ ¼ 37:81; DE– ðTS4bÞ ¼ 42:27; DE– ðTS4cÞ ¼ 35:71; DE– ðTS4dÞ ¼ 41:75 kJ=mol:
a twisted chair structure and involves a B2 – N(3) – B(2) – OC – O – CC – O – C1p 6-membered ring. Therefore, the enantioselective alkynylation of aldehyde with alkynylborane catalyzed by oxazaborolidine has a twisted chair transition state.
4. Conclusions All the results for this work imply that the enantioselective alkynylation of aldehyde with alkynylborane catalyzed by chiral oxazaborolidine is exothermic and goes mainly through the formation of the catalyst-alkynylborane adduct, the formation of the catalyst-alkynylborane-aldehyde adduct, the transfer of alkynyl from the alkynylborane moiety to the carbonyl carbon of the aldehyde moiety, and the decomposition of the catalyst-alkoxyborane adduct leading to the regeneration of the catalyst. There are four reduction paths for the alkynylation reduction,
two of which lead to R-chiral alcohols and others to Schiral alcohols. The transfer of the alkynyl moiety is the controlling-velocity step for the enantioselective alkynylation of aldehyde and the alkynylation reduction results mainly in R-chiral alcohols that are in correspondence to the experiment. The transition state for the transfer of the alkynyl moiety involves a B2 – N(3) – B(2) – OC – O – CC – O – C1p 6-membered ring. During the decomposition of the catalystalkoxyborane adduct with a B –O – B –N 4-membered ring, the B –N and B – O bonds in the B – O – B –N 4membered ring are broken down simultaneously.
Acknowledgements This work is supported by the Science Foundation of National Education Ministry, People’s Republic of China.
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