上原記念生命科学財団研究報告集, 34 (2020)ୖཎグᛕ⏕࿨⛉Ꮫ㈈ᅋ◊✲ሗ࿌㞟, 34㸦2020㸧

8. ๰⸆໬Ꮫࢆᚿྥࡋࡓࣟࣂࢫࢺ࡞㔠ᒓゐ፹཯ᛂࡢ㛤Ⓨ⁪⏣ Ⰻᮾி኱Ꮫ ኱Ꮫ㝔⸆Ꮫ⣔◊✲⛉ ࣡ࣥࢫࢺࢵࣉ๰⸆ඹ⏝ࣇ࢓ࢩࣜࢸ࢕ࢭࣥࢱ࣮
Key words㸸ඖ⣲≉ᛶ㸪ࢡࣟࢫ࢝ࢵࣉࣜࣥࢢ཯ᛂ㸪㑏ඖ཯ᛂ㸪཯ᛂᶵᵓ㸪⌮ㄽィ⟬⥴ ゝ᭷ᶵ㔠ᒓ໬ᏛࡢⓎᒎࡣࠊ᭷ᶵ໬Ꮫศ㔝࡟࠾࠸࡚኱ࡁ࡞㈉⊩ࢆᯝࡓࡋࠊ㧗ᗘ࡞ศᏊኚ᥮࣭⢭ᐦ᭷ᶵྜᡂࢆྍ⬟࡟ࡋ࡚ࡁࡓࠋࡋ࠿ࡋ࡞ࡀࡽࠊ๰⸆໬Ꮫ࡟࠾࠸࡚‶㊊ࡣ࡞ࡃࠊ≉࡟᭷⏝ᐁ⬟ᇶࡢ㎿㏿࣭ຠ⋡ⓗ࣭㑅ᢥⓗᑟධἲࡢ㛤ᣅࡣ୍ᒙ୙ྍḞ࡛࠶ࡿࠋ౛࠼ࡤࠊࢡࣟࢫ࢝ࢵࣉࣜࣥࢢ཯ᛂࡢฟ⌧࡟ࡼࡾⰾ㤶⎔㐃⤖ࡢ໬Ꮫࡣ኱ࡁࡃ㐍ᒎࡋࠊ๰⸆ࡢࡳ࡞ࡽࡎࠊከᵝ࡞᭷ᶵᮦᩱ➼ࡢᶵ⬟ᛶศᏊࡢ⛉Ꮫࡀ኱ࡁࡃ㐍ᒎࡋࡓࠋ୍᪉࡛⛉Ꮫࡢ㐍ᒎ࡟ࡼࡾࠊᙜ↛ᖖ࡟᪂ࡓ࡞ᵓ㐀ࡀồࡵࡽࢀࠊࡑ࠺ࡋࡓศᏊタィ࣭⤖ྜᙧᡂࢆᐇ⌧ࡍࡿᙉຊ࡞ᡭἲࡢ㛤Ⓨࡀồࡵࡽࢀ࡚࠸ࡿࠋࡲࡓࠊ㧗౯࠶ࡿ࠸ࡣẘᛶࡢ㧗࠸㔠ᒓ࣭㓄఩Ꮚࡢ౑⏝ࠊཝᐦ↓Ỉ࣭↓㓟⣲᮲௳ࡀᚲせ࡞࡝ࠊࠕ౑࠸᫆ࡉࠖࠕᐇ⏝ᛶࠖࡢ㠃ࡶ኱ࡁ࡞ㄢ㢟࡛࠶ࡿࠋᮏ◊✲࡛ࡣࠊ≉࡟ඖ⣲ࡢ≉ᛶࢆά⏝ࡍࡿࡇ࡜࡛ࠊ᭷ᶵ㔠ᒓヨ⸆ࡀά㌍ࡍࡿ᭷ᶵ཯ᛂ࡟࠾ࡅࡿ᪂ࡓ࡞཯ᛂᛶ࣭㑅ᢥᛶࡢᐇ⌧ࢆ┠ᣦࡋࡓࠋ཯ᛂࡢ㛤Ⓨ࡜࡜ࡶ࡟ࡑ࠺ࡋࡓ཯ᛂᛶ࣭㑅ᢥᛶࡢ㉳※ࢆ᫂ࡽ࠿࡟ࡍࡿࡇ࡜࡛ࠊᮏ◊✲ࢆጞཎ࡜ࡋ࡚ࡉࡽ࡞ࡿ໬Ꮫࡢᒎ㛤ࢆ┠ㄽࡴࡶࡢ࡛࠶ࡿࠋ᪉ἲ࠾ࡼࡧ⤖ᯝ1㸬 㔠ᒓ㸫㔠ᒓ㛫┦஫స⏝ࢆά⏝ࡍࡿᙉຊ࡞ࢡࣟࢫ࢝ࢵࣉࣜࣥࢢ཯ᛂࡢ㛤Ⓨ୕ḟඖⓗ࡟ᔞ㧗࠸Ⅳ⣲㦵᱁ࡣᵝࠎ࡞ศᏊᶵ⬟࡟㈉⊩ࡋ࡚࠾ࡾࠊ㏆ᖺࡑࡢά⏝ࡀࡼࡾ኱ࡁ࡞ὀ┠ࢆ㞟ࡵ࡚࠸ࡿࠋ≉࡟་⸆ရ࡟࠾࠸࡚ࡣ⁐ゎᛶࠊ௦ㅰᏳᐃᛶࡢྥୖ࡟ᐤ୚ࡋࠊࡲࡓ᭷ᶵⰍ⣲࡞࡝࡟࠾࠸࡚ࡣศᏊྠኈࡢࢫࢱࢵ࢟ࣥࢢࢆᢚไࡍࡿࠋࡑࡢ௚࡟ࡶ㓄఩Ꮚࡶྵࡵࡓゐ፹ࡸศᏊᶵᲔࡢ㔜せ࡞ࣔࢳ࣮ࣇ࡜ࡋ࡚ከᵝ࡞ᙺ๭ࢆᯝࡓࡍ㸦ᅗ 1㸧ࠋࢡࣟࢫ࢝ࢵࣉࣜࣥࢢ཯ᛂࡣᶵ⬟ᛶศᏊࡢⅣ⣲㦵᱁ࡢྜᡂἲ࡜ࡋ࡚ᗈࡃά⏝ࡉࢀ࡚࠸ࡿࠋ㏆ᖺ࡛ࡣࠊ≉࡟㓄఩Ꮚࡢ㛤Ⓨ࡟ࡼࡾᇶ㉁ࡢ㐺⏝⠊ᅖ࣭཯ᛂάᛶࡢྥୖࡀሗ࿌ࡉࢀ࡚࠸ࡿࠋࡋ࠿ࡋ࡞ࡀࡽࠊ❧య㞀ᐖࡀ኱ࡁࡃ཯ᛂࡀ㜼ᐖࡉࢀࡸࡍ࠸ᔞ㧗࠸Ⅳ⣲㦵᱁࡬ࡢ㐺⏝ࡣᴟࡵ࡚ไ㝈ࡉࢀ࡚࠾ࡾࠊ❧య㞀ᐖ࡟ࡶᙉ࠸ᙉຊ࡞ࢡࣟࢫ࢝ࢵࣉࣜࣥࢢ཯ᛂࡢ㛤Ⓨࡣ㔜せ࡞ㄢ㢟࡛࠶ࡗࡓࠋ୍᪉ࠊᮏሗ࿌⪅ࡽࡣ monocarba-closo-dodecaborate ࡢⅣ⣲㡬Ⅼୖ࡟࠾ࡅࡿࢡࣟࢫ࢝ࢵࣉࣜࣥࢢ཯ᛂࡢ㛤Ⓨ࡟࠾࠸࡚ࠊ᭷ᶵ㖡ヨ⸆ࡢά⏝ࢆ㘽࡜ࡋ࡚ࠊ≉␗ⓗ࡟㧗࠸཯ᛂᛶࢆ♧ࡍࡇ࡜ࢆぢฟࡋ࡚࠸ࡓࠋᮏ◊✲࡛ࡣࠊ᭷ᶵ㖡ヨ⸆ࡢ≉ᛶࢆά⏝ࡍࡿࡇ࡜࡛ᵝࠎ࡞ᔞ㧗࠸Ⅳ⣲㦵᱁࡟㐺⏝ྍ⬟࡞ᙉຊ࡞ࢡࣟࢫ࢝ࢵࣉࣜࣥࢢ཯ᛂࢆ㛤Ⓨࡋࠊࡑࡢ㧗࠸཯ᛂᛶࡢ㉳※࡟ᐇ㦂࡜⌮ㄽィ⟬ࡢ୧㠃࠿ࡽ㏕ࡗࡓࠋᅗ 1㸬ᔞ㧗࠸Ⅳ⣲㦵᱁ࢆ᭷ࡍࡿᶵ⬟ᛶศᏊ

1ୖཎグᛕ⏕࿨⛉Ꮫ㈈ᅋ◊✲ሗ࿌㞟, 34㸦2020㸧㻌཯ᛂ᮲௳ࢆ⢭ᰝࡋࡓ⤖ᯝࠊ᭷ᶵ㖡ヨ⸆ࢆ⏝࠸ࡿࡇ࡜࡛ከᵝ࡞Ⅳ⣲㦵᱁࡟࠾࠸࡚Ⅳ⣲㸫Ⅳ⣲⤖ྜᙧᡂࢆᐇ⌧ࡍࡿࢡࣟࢫ࢝ࢵࣉࣜࣥࢢ཯ᛂࢆ㛤Ⓨࡋࡓ㸦ᅗ 2㸧ࠋศᏊᶵᲔ࣭ࢭࣥࢧ࣮࡞࡝ࡢࢥ࢔࡜ࡋ࡚㔜せ࡞ࢺࣜࣉࢳࢭࣥ㦵᱁ࡢ 9 ఩࡟࠾ࡅࡿࢡࣟࢫ࢝ࢵࣉࣜࣥࢢ཯ᛂࢆᐇ⌧ࡋࠊᵝࠎ࡞ⰾ㤶⎔ࠊ࣊ࢸࣟⰾ㤶⎔ࠊ࢔ࣝ࢟ࢽࣝ໬ྜ≀ࠊ࢔ࣝ࢟ࣝ໬ྜ≀ࡢᑟධࡀᐜ᫆࡟ྍ⬟࡛࠶ࡿࡇ࡜ࢆ♧ࡋࡓࠋ୍᪉࡛ྠᵝࡢ཯ᛂࢆࢡࣟࢫ࢝ࢵࣉࣜࣥࢢ཯ᛂ࡟࠾࠸࡚ỗ⏝ࡉࢀࡿ᭷ᶵள㖄ヨ⸆ࡸ᭷ᶵ࣍࢘⣲ヨ⸆ࢆ⏝࠸ࡓሙྜ࡟ࡣ඲ࡃ཯ᛂࡀ㐍⾜ࡋ࡞࠿ࡗࡓࠋᮏ཯ᛂ᮲௳ࡣࠊ௚ࡢᔞ㧗࠸ sp㸱-Ⅳ⣲㦵᱁࡛࠶ࡿࠊ࢔ࢲ࣐ࣥࢳࣝᇶࠊ

tert-ࣈࢳࣝᇶ࡞࡝ࡶ㐺⏝ྍ⬟࡛࠶ࡗࡓࠋࡉࡽ࡟࣓ࢩࢳࣝᇶࢆࡣࡌࡵ࡜ࡍࡿ❧య㞀ᐖࡢ኱ࡁ࡞ⰾ㤶⎔࡟࠾࠸࡚ࡶ⤖ྜᙧᡂྍ⬟࡛࠶ࡗࡓࠋࡇࢀࢆά⏝ࡍࡿࡇ࡜࡛࢟ࣗࣂࣥ㦵᱁࡬ࡢⰾ㤶⎔ᑟධࡶᐇ⌧࡛ࡁࡓࠋࡇࡢࡼ࠺࡟࡯ࡰྠᵝࡢ᮲௳࡛ sp㸰࠾ࡼࡧ sp㸱-Ⅳ⣲ࢆ᭷ࡍࡿᵝࠎ࡞ᔞ㧗࠸ᇶ㉁࡟㐺⏝ྍ⬟࡞ࢡࣟࢫ࢝ࢵࣉࣜࣥࢢ཯ᛂ࡛࠶ࡿࡇ࡜ࢆᐇドࡋࡓ㹙1㹛ࠋRCu+FG

X(1.0 eq.)

Pd(OAc)2 (5 mol%)
L1 (15 mol%)R

THF(-toluene)
Temp., 4–48 h(1.1 eq.)

MeO PCy2

FGPP
3MeO

MeO

L1O
3

L3

L2A 䝖 䝸 䝥 䝏䝉䞁 ㄏᑟయ (཯ᛂ ᗘ㻌80 ºC – 140 ºC)
X ⥺⤖ᬗᵓ㐀

MeO2C
CO2Me
3 : X = I, 83%
X =Br, 69%a

CF3
4 : X = I, 83%

MeO

SFe
10 : X = I, 31%aAc
6 : X = I, 81%CN
5 : X = I, 83%

SAc

11 : X = Br, 39% (66%)aOMe
8 : X = I, 82%

7 : X = I, 53% (77%)

NN

N

EtO2C

12 : X = Br, 66%

13 : X = Br, 60%

9 : X = I, 67%a

14 : X = I, 64%N

15 : X = I, 45%

16 : X = I, 73%

17 : X = Br, 74%

B 䛭䛾௚䛾 sp3–Ⅳ⣲䛷 䛾཯ᛂ (཯ᛂ ᗘ100 ºC)
MeMeO

O

CO2MeHO

O H

NMeO
MeOO

CO2MePh

18 : X = Br, 90%

HHMeMeO

MeO

19 : X = I, 24%

20 : X = Br, 76%a,b

22 : X = I, 79%c

21 : X = I, 43%c

23 : X = I, 54% (70%)b

C sp2–Ⅳ⣲䛷䛾཯ᛂ (཯ᛂ ᗘ rt – 120 ºC)
CO2MeCO2MeCO2MeOMe

CO2Me
24 : X = I, 55%d

25 : X = I, 88%c

26 : X = I, 97%: X = Br, 77%

27 : X = I, 55%a

CO2Me

28 : X = I, p-, 96%
29: X = I, o-, 91%

CO2MeN32 : X = Br, 58%a

MeMeEtEt
Et
Et

33 : X = Br, 41%a

34 : X = I, 85%

35 : X = I, 34%a

30 : X = Br, 71%a

CO2Me

31 : X = Br, 31%aONMeMe36 : X = I, 53%a

37 : X = I, 31% (49%)a,eᅗ 2㸬᭷ᶵ㖡ヨ⸆ࢆ⏝࠸ࡿࢡࣟࢫ࢝ࢵࣉࣜࣥࢢ཯ᛂ
a L2 was used instead of L1. b Ni(acac)2 was used instead of Pd(OAc)2. c L2 was used instead of L1and 3 eq. of TMEDA were added. d L3 was used instead of L1 at –20 °C and 3 eq. of TMEDA wereadded. e 10 mol% of Pd catalyst and 30 mol% L2 were used.

2ୖཎグᛕ⏕࿨⛉Ꮫ㈈ᅋ◊✲ሗ࿌㞟, 34㸦2020㸧㻌ᮏ཯ᛂࡢ㧗࠸཯ᛂᛶࡢ㉳※ࢆ᫂ࡽ࠿࡟ࡍ࡭ࡃࠊ཯ᛂᶵᵓࡢゎ᫂࡟ྲྀࡾ⤌ࢇࡔࠋᮏ཯ᛂࡣୖ㏙ࡢࡼ࠺࡟᭷ᶵ㔠ᒓヨ⸆ࡢ≉ᛶࡀ኱ࡁࡃᙳ㡪ࡍࡿࡇ࡜࡟ຍ࠼࡚ࠊゐ፹ࡢ Pd(OAc)2 ↓ࡋ࡛ࡣ඲ࡃ཯ᛂࡀ㐍⾜ࡋ࡞࠸ࡇ࡜ࠊᑐᛂࡍࡿ᭷ᶵ㖡ヨ⸆࡜࢔࣮ࣜࣝࣃࣛࢪ࣒࢘㘒య࠿ࡽ⏕ᡂ≀ࢆ୚࠼ࡿ࡞࡝ࡢᑐ↷ᐇ㦂࠿ࡽࠊࢺࣛࣥࢫ࣓ࢱࣝ໬ẁ㝵ࡀ㧗࠸཯ᛂᛶ࡟࠾࠸࡚㔜せ࡛࠶ࡿࡇ࡜ࡀ᫂ࡽ࠿࡜࡞ࡗࡓࠋࡑࡇ࡛ࠊࣔࢹࣝ཯ᛂ࡟ࡘ࠸࡚ DFT ィ⟬㸦ȰB97X-D/SDD&6-31+G*㸧࡟ࡼࡿゎᯒࢆ⾜ࡗࡓ㸦ᅗ 3㸧ࠋࡣࡌࡵ࡟ࢺࣜࣉࢳࢭࣥ㖡ヨ⸆࡜࢔࣮ࣜࣝࣃࣛࢪ࣒࢘㘒య㸦trans-Pd(Ph)Br(PMe3)㸧࡜ࡢ㓄఩࡟ࡼࡾࠊཎ⣔࡜ẚ㍑ࡋ࡚኱ࡁࡃᏳᐃ໬㸦㸫31.4 kcal/mol㸧ࡋࡓ୰㛫య㸦IINT1㸧ࢆ୚࠼ࡓࠋ㖡࡜ࣃࣛࢪ࣒࢘㛫ࡢ㊥㞳ࡣ 2.69 Å ࡜ࡑࢀࡒࢀࡢ van der Waals ༙ᚄࡢ࿴㸦3.03 Å㸧ࡼࡾࡶ▷ࡃࠊ㖡−ࣃࣛࢪ࣒࢘㛫ࡢᙉ࠸┦஫స⏝ࡀ♧၀ࡉࢀࡓࠋ⥆ࡃ㑄⛣≧ែ 㸦TTS1㸧࡟࠾࠸࡚ࡶࠊ㖡−ࣃࣛࢪ࣒࢘㛫ࡢཎᏊ㛫㊥㞳ࡣ 2.52 Å ࡜▷ࡃࠊᙉ࠸㔠ᒓ−㔠ᒓ㛫┦஫స⏝ࡀ☜ㄆࡉࢀࡓࠋࡑࡢ⤖ᯝࠊ㑄⛣≧ែࡢᵓ㐀ࡣࢺࣛࣥࢫ࣓ࢱࣝ໬࡟࠾࠸࡚ᗈࡃぢࡽࢀࡿᅄ୰ᚰ㑄⛣≧ែ࡜ࡣ␗࡞ࡾࠊ┦஫స⏝࡟㉳ᅉࡋ࡚㖡࡜ࣃࣛࢪ࣒࢘ඖ⣲ࡀ㏆᥋ࡍࡿࢥࣥࣃࢡࢺ࡞୕୰ᚰ㑄⛣ᵓ㐀࡜࡞ࡿࠋࡇࢀ࡟ࡼࡾᔞ㧗࠸ࢺࣜࣉࢳࢭࣥ㓄఩Ꮚࡢ㖡࠿ࡽࣃࣛࢪ࣒࢘࡬ࡢ㌿⛣ࡀ㸩21.4 kcal/mol ࡜ప࠸άᛶ໬࢚ࢿࣝࢠ࣮࡛㐍⾜ࡋࠊ㑏ඖⓗ⬺㞳࡬࡜⥆ࡃ୰㛫య㸦IINT2㸧ࢆ୚࠼ࡿࡇ࡜ࡀ᫂ࡽ࠿࡜࡞ࡗࡓࠋ୍᪉ࠊࢺࣜࣉࢳࢭࣥள㖄࠾ࡼࡧ࣍࢘⣲ヨ⸆ࢆ⏝࠸ࡓሙྜࡣࠊṍࢇࡔᅄ୰ᚰ㑄⛣ᵓ㐀࡜࡞ࡾࠊࢺࣛࣥࢫ࣓ࢱࣝ໬࡟ࡣ㖡ヨ⸆࡜ẚ㍑ࡋ࡚㧗࠸άᛶ໬࢚ࢿࣝࢠ࣮ࢆᚲせ࡜ࡍࡿࡇ࡜ࡀ♧၀ࡉࢀࡓࠋ

2.52∆G (kcal/mol)

PdCu0RT–10–20–30

PhBr

Pd+Pd

2.75

Pd PMe3
Cu
BrCu
BrTS2

TS1(–5.8)(–10.0)–31.4–15.6+21.4

PMe3

PMe3

INT1+19.8

INT2

–51.3

(–25.6)2.45(–31.4)

–40
–50
–60

BrCu

Cu

Pd

PMe3

Br

2.69

CuPd䝖 䝷 䞁 䝇䝯 䝍 䝹໬ẁ㝵

Pd
PMe3
Cu
BrCu

Pd

PdCu

PMe3

INT3
(–57.1)㑏ඖⓗ⬺㞳ẁ㝵ᅗ 3㸬ࢺࣜࣉࢳࢭࣥ㖡ヨ⸆࡜࢔࣮ࣜࣝࣃࣛࢪ࣒࢘㘒య࡜ࡢ཯ᛂࡘ࠸࡚ࡢ DFT ィ⟬⤖ᯝEnergy changes and bond lengths at the ȰB97X-D/SDD (for Pd, Cu, and Br) & 6-31+G*(for other atoms) level of theory are shown in kcal/mol and Å, respectively.

2㸬ⰾ㤶᪘໬ྜ≀ࡢࣟࣂࢫࢺ࡞㖡ゐ፹ᐁ⬟ᇶᑟධἲ࢔ࢽࣜࣥㄏᑟయࠊࣇ࢙ࣀ࣮ࣝㄏᑟయࡣ་⸆ရ࡞࡝ࡢᶵ⬟ᛶศᏊ࡟ᗈࡃぢࡽࢀࡿᵓ㐀࡛࠶ࡾࠊࡑࡢྜᡂἲࡢ㛤ᣅࡣ㔜せ࡛࠶ࡿࠋࡇࡢⅣ⣲㸫❅⣲⤖ྜࠊⅣ⣲㸫㓟⣲⤖ྜࡢᙧᡂ࡟ࡶࢡࣟࢫ࢝ࢵࣉࣜࣥࢢ཯ᛂࡣ኱ࡁ࡞㈉⊩ࢆᯝࡓࡋ࡚࠾ࡾࠊᵝࠎ࡞᪉ἲㄽࡀ㛤Ⓨࡉࢀ࡚ࡁࡓࠋ≉࡟๓⪅ࡣ Buchwald-Hartwig ࢔࣑ࣀ໬཯ᛂ࡜࿧ࡤࢀࠊ୺࡟ࣃࣛࢪ࣒࢘ࡸࢽࢵࢣࣝゐ፹ࢆ⏝࠸࡚ࠊ2 ⣭࢔࣑ࣥࢆ୰ᚰ࡜ࡍࡿᇶ㉁࡟㐺⏝ྍ⬟࡞཯ᛂ⣔ࡀከࡃ☜❧ࡉࢀ࡚࠸ࡿࠋ୍᪉࡛ࠊ❅⣲※࡜ࡋ࡚᭱ࡶỗ⏝ᛶࡀ㧗ࡃࢩࣥࣉࣝ࡞࢔ࣥࣔࢽ࢔ࡢ┤᥋ࡢά⏝ࡣࠊ㔠ᒓゐ፹୰ᚰ࡬ᙉࡃ㓄఩ࡋ࡚ࡋࡲ࠸ᮃࡳࡢ཯ᛂࢆ㜼ᐖࡍࡿࡇ࡜ࠊ
N–H ⤖ྜࡀᙉᅛ࡛࠶ࡾษ᩿ࡀᅔ㞴࡞ࡇ࡜ࠊ⏕ᡂࡍࡿࣔࣀ࢔࣮ࣜࣝ࢔࣑ࣥࡀࡼࡾ཯ᛂᛶࡀ㧗ࡃ๪཯ᛂࢆᘬࡁ㉳ࡇࡋ࡚ࡋࡲ࠺ࡇ࡜ࠊ࡞࡝ࡢ⌮⏤࠿ࡽᴟࡵ࡚㝈ࡽࢀ࡚࠸ࡓࠋᮏሗ࿌⪅ࡽࡣࡇ࠺ࡋࡓ⌧≧ࢆཷࡅࠊࡇࢀࡲ࡛࡟࢔ࣥࣔࢽ࢔Ỉࢆ၏୍ࡢ⁐፹࡜ࡋ࡚⏝࠸ࡿࡇ࡜࡛㖡ゐ፹࡟ࡼࡿⰾ㤶᪘໬ྜ≀ࡢ࢔࣑ࣀ໬཯ᛂࢆ㛤Ⓨࡋࡓࠋᮏ཯ᛂ࡛ࡣࠊ࢔ࣥࣔࢽ࢔Ỉࡀ཯ᛂヨ⸆࣭㓄఩Ꮚ࣭⁐፹ࡢ୕ᙺࢆᢸ࠺ࡇ࡜࡛ຠ⋡ⓗ࡟཯ᛂࡀ㐍⾜ࡍࡿࡇ࡜ࢆᐇ㦂ࢹ࣮ࢱ࡜⌮ㄽィ⟬ࡼࡾ᫂ࡽ࠿࡟ࡋࡓ㹙2㹛ࠋࡇࢀࡽࡢ⤖ᯝࢆᇶ࡟Ỉࢆ㓟⣲※࡜ࡍࡿỈ㓟ᇶᑟධ཯ᛂࡢ㛤Ⓨ࡟ྲྀࡾ⤌ࢇ࡛࠸ࡿࠋᙜึࡢ᳨ウ࡟ࡼࡾࠊ࢔࣑ࣀ໬཯ᛂࡢ㝿࡜␗࡞ࡾỈࢆ၏୍ࡢ⁐፹࡜ࡍࡿࡓࡵࠊ㖡ゐ፹ࡢ཯ᛂᛶࡢపࡉ࡜ᇶ㉁ࡢ⁐ゎᛶࡢపࡉࡀㄢ㢟࡛࠶ࡿࡇ࡜ࡀุ᫂ࡋࡓࠋࡑࡇ࡛㓄఩Ꮚࡸ⏺㠃άᛶ๣࡞࡝ࡢῧຍຠᯝࢆከゅⓗ࡟᳨ウࡋࡓࠋࡑࡢ⤖ᯝࠊࢫࢡ࣮ࣟࢫࢆῧຍࡋࡓ㝿࡟኱ࡁ࡞ຍ㏿ຠᯝࡀぢࡽࢀࠊ┠ⓗࡢࣇ࢙ࣀ࣮ࣝㄏᑟయࡀ㧗཰⋡࡟࡚ᚓࡽࢀࡿࡇ࡜ࢆぢฟࡋࡓ㸦ᅗ 4㸧ࠋᮏ཯ᛂ⣔ࡣ✀ࠎࡢ㸦࣊ࢸࣟ㸧ⰾ㤶᪘3ୖཎグᛕ⏕࿨⛉Ꮫ㈈ᅋ◊✲ሗ࿌㞟, 34㸦2020㸧㻌໬ྜ≀࡟㐺⏝ྍ⬟࡛࠶ࡾࠊ✵Ẽ୰࡛ࡶ཯ᛂࡀ⾜࠼ࡿࠋࡲࡓࢢ࣒ࣛࢫࢣ࣮࡛ࣝࡢ཯ᛂࡶၥ㢟࡞ࡃ㐍⾜ࡍࡿ࡞࡝ࠊሀ∼࡞཯ᛂ࡛࠶ࡿࠋ≉࡟ࢫࢡ࣮ࣟࢫࡢᙺ๭ࢆ᫂ࡽ࠿࡟ࡍ࡭ࡃࠊ཯ᛂᶵᵓࡢゎᯒ࡟ྲྀࡾ⤌ࢇࡔࠋ⌮ㄽィ⟬ࡼࡾࠊࢫࢡ࣮ࣟࢫࡢ㒊ศᵓ㐀ࡀ㓄఩ࡋࡓ㖡㘒యࡣ㓟໬ⓗ௜ຍẁ㝵ࢆಁ㐍ࡍࡿࡇ࡜ࡀ♧၀ࡉࢀ࡚࠾ࡾࠊ㓄఩Ꮚ࡜ࡋ࡚ാࡁࠊ㖡ゐ፹ࡢ཯ᛂᛶࢆ
ྥୖࡉࡏ࡚࠸ࡿࡇ࡜ࡀ᫂ࡽ࠿࡜࡞ࡗࡓࠋࡲࡓᇶ㉁ࡢ⁐ゎᛶࡢྥୖ࡟ࡶᐤ୚ࡋ࡚࠸ࡿࡇ࡜ࡀ♧ࡉࢀࠊᮏ㖡ゐ፹཯ᛂ࡟࠾ࡅࡿࢫࢡ࣮ࣟࢫࡢᙺ๭ࡀ᫂ࡽ࠿࡜࡞ࡗࡓࠋᅗ 4㸬Ỉࢆ㓟⣲※࡜ࡍࡿ㖡ゐ፹Ỉ㓟ᇶᑟධ཯ᛂ࡜཯ᛂ౛3㸬N,N-ࢪ࢔ࣝ࢟ࣝ࢔࣑ࢻࡢ㑏ඖ཯ᛂࡢ㑅ᢥᛶ㸸DIBAL ࡟ࡼࡿ཯ᛂࡢሙྜ࢔࣑ࢻᵓ㐀ࡶ་⸆ရ࡞࡝࡟ᗈࡃ⏝࠸ࡽࢀࡿ㔜せ࡞ᵓ㐀࡛࠶ࡿ࡜࡜ࡶ࡟ࠊ౛࠼ࡤࣄࢻࣜࢻ㑏ඖ཯ᛂ࡟ࡼࡾᑐᛂࡍࡿ࢔࣑ࣥࠊ࢔ࣝࢥ࣮ࣝࠊ࢔ࣝࢹࣄࢻ㢮ࢆ୚࠼ࡿࡓࡵࠊྜᡂᡓ␎ୖࠊຠ⋡ⓗ࡞㑅ᢥⓗ㑏ඖ཯ᛂࡢ㛤Ⓨࡣ㔜せ࡞ㄢ㢟࡛࠶ࡿࠋࢩ࣏࣮ࣥ࢞ࣝ༡ὒ⌮ᕤ኱Ꮫࡢ༓ⴥಇ௓ᩍᤵࢢ࣮ࣝࣉ࡜ࡢඹྠ◊✲ࢆᒎ㛤ࡋ࡚࠾ࡾࠊࡈࡃ᭱㏆ࠊள㖄ࣄࢻࣜࢻ✀࡟ࡼࡿ㑅ᢥⓗ࢔࣑ࢻ㑏ඖ཯ᛂࢆ㛤Ⓨࡋࡓ㹙3㹛ࠋࡑࡢ୍㐃ࡢ◊✲ࡢ୰࡛ࠊ࣓ࢱࣝࣄࢻࣜࢻヨ⸆ࡢ୰࡛ࡶ᭱ࡶᗈࡃ⏝࠸ࡽࢀࡿ௦⾲ⓗ࡞ヨ⸆࡛࠶ࡿ Diisobutylaluminum
hydride (DIBAL) ヨ⸆࡟╔┠ࡋࡓࠋ୍⯡ⓗ࡟ࡣࠊN,N-ࢪ࢔ࣝ࢟ࣝ࢔࣑ࢻࡢ㑏ඖ཯ᛂ࡟࡚ᑐᛂࡍࡿ࢔࣑ࣥࢆ୚࠼ࡿ࡜ࡉ
ࢀࡿࠋࡋ࠿ࡋ࡞ࡀࡽࠊྂࡃ࠿ࡽ౑ࢃࢀࡿヨ⸆࡟ࡶ㛵ࢃࡽࡎࠊࡑࡢ཯ᛂᶵᵓ࡟ࡘ࠸࡚࡯࡜ࢇ࡝᳨ウࡀ࡞ࡉࢀ࡚࠸࡞࠸ࠋࡑ
ࡇ࡛ࡇࡢ㔜せ࡞཯ᛂࡢ㑅ᢥᛶࡢ㉳※ࢆ᫂ࡽ࠿࡟ࡍ࡭ࡃࠊࣔࢹࣝ࡜ࡋ࡚࢔࣑ࢻࡢ㑏ඖ࡟࠾ࡅࡿ 1 ẁ㝵┠ࡢࣄࢻࣜࢻ㌿⛣࡟ࡼࡗ࡚⏕ࡌࡿ࢔ࢽ࢜ࣥᛶࡢ࢝ࣝࣅࣀ࣮ࣝ୰㛫య I ࠿ࡽࡢ཯ᛂ࡟ࡘ࠸࡚ DFT ィ⟬(ȰB97X-D/6-311+G**/SMD(THF)//Ȱ
B97X-D/6-31+G*/SMD(THF)) ࢆ⾜ࡗࡓ㸦ᅗ 5㸧ࠋࡑࡢ⤖ᯝࠊ஧㔞యᵓ㐀ࢆ᭷ࡍࡿヨ⸆ࡢ 2 ᰾࢔࣑ࣝࢽ࣒࢘୰ᚰࡀຠ⋡ⓗ࡟Ⅳ⣲㸫㓟⣲⤖ྜࢆάᛶ໬ࡍࡿࡇ࡜࡟ࡼࡾࠊࡑࡢษ᩿ࡀ㏿ࡸ࠿࡟㐍⾜ࡍࡿ㸦ǼG ‡ 㸻 㸩13.7 kcal/mol㸧ࡇ࡜ࡀ᫂ࡽ࠿࡜࡞ࡗࡓ㸦ᅗ 5C㸧ࠋ୍᪉ࠊᑐᛂࡍࡿ࢔ࣝࢹࣄࢻ㸦࠶ࡿ࠸ࡣ࢔ࣝࢥ࣮ࣝ㸧ࢆ୚࠼ࡿⅣ⣲㸫❅⣲⤖ྜࡢษ᩿࡟ࡣࡼࡾ
኱ࡁ࡞࢚ࢿࣝࢠ࣮ࡀᚲせ࡛࠶ࡾ㸦ᅗ 5D㸧
ࠊDIBAL ヨ⸆࡟ࡼࡿ㑏ඖ࡛ࡣ࢔࣑ࣥࢆ୚࠼ࡿࡇ࡜ࢆ♧ࡍࠋࡲࡓヨ⸆ࡢ஧㔞యᵓ㐀ࡣ㔜せ࡛࠶ࡾࠊ༢᰾ࡢࣔࢹ࡛ࣝࡣୖ㏙ࡢⅣ⣲㸫㓟⣲⤖ྜࡢษ᩿ࡣ඲ࡃ㐍⾜ࡋ࡞࠸ࠋࡉࡽ࡟ࠊ࢔ࣝࢹࣄࢻࢆ୚࠼ࡿ
NaH-NaI ヨ⸆ࡢ཯ᛂ㸦ᅗ 5B㸧࡟ࡘ࠸࡚ࡶྠᵝࡢ⌮ㄽィ⟬ࢆ⾜࠺࡜ࠊࢼࢺ࣒ࣜ࢘୰ᚰ࡛ࡣຠ⋡ⓗ࡟άᛶ໬ࡉࢀࡎࠊࡸࡣ
ࡾⅣ⣲㸫㓟⣲⤖ྜษ᩿࡟ࡣ኱ࡁ࡞࢚ࢿࣝࢠ࣮ࡀᚲせ࡛࠶ࡿࡇ࡜ࡀุ᫂ࡋࡓࠋࡍ࡞ࢃࡕࠊDIBAL ヨ⸆࡟ࡼࡿ㑏ඖ཯ᛂ࡟࠾࠸࡚ࠊ஧㔞యᵓ㐀࡜㧗࠸ Lewis 㓟ᛶࢆ᭷ࡍࡿ࢔࣑ࣝࢽ࣒࢘ඖ⣲ࡢ≉ᛶࡀࡑࡢ཯ᛂᛶ࣭㑅ᢥᛶࢆไᚚࡋ࡚࠸ࡿࡇ࡜ࢆ
᫂ࡽ࠿࡟ࡋࡓ㹙4㹛ࠋ4ୖཎグᛕ⏕࿨⛉Ꮫ㈈ᅋ◊✲ሗ࿌㞟, 34㸦2020㸧㻌ᅗ 5㸬DIBAL ヨ⸆ࡢᵓ㐀࡜࢔࣑ࢻࡢ㑏ඖ཯ᛂC, D) Energy changes and bond lengths at the ȰB97X-D/6-311+G**/SMD(THF)//ȰB97X-D/631+G*/SMD(THF) level of theory are shown in kcal/mol and Å, respectively.

⪃ ᐹᮏ◊✲࡛ࡣࠊ᭷ᶵ㔠ᒓヨ⸆ࢆ⏝࠸ࡿ᭷ᶵ཯ᛂ࡟࠾ࡅࡿ᪂ࡓ࡞཯ᛂᛶ࣭㑅ᢥᛶࡢᐇ⌧ࢆ┠ᣦࡋࡓࠋ࠸ࡎࢀ࡟࠾࠸࡚ࡶࠊ཯ᛂᶵᵓࡢ⢭ᰝ࡟ࡼࡾࠊ≉࡟ඖ⣲ࡢ≉ᛶࡀ㔜せ࡞ᙺ๭ࢆᯝࡓࡋࠊ≉␗࡞཯ᛂᛶ࣭㑅ᢥᛶࡢ⋓ᚓ࡟ᐤ୚ࡋ࡚࠸ࡿࡇ࡜ࡀ᫂ࡽ࠿࡟࡞ࡗࡓࠋඹྠ◊✲⪅࣭ㅰ㎡ᮏ◊✲ࡢඹྠ◊✲⪅ࡣࠊᮾி኱Ꮫ኱Ꮫ㝔⸆Ꮫ⣔◊✲⛉࣡ࣥࢫࢺࢵࣉ๰⸆ඹ⏝ࣇ࢓ࢩࣜࢸ࢕ࢭࣥࢱ࣮ࡢΏ㑓ᗣᖹ  ≉௵ຓᩍ࡛࠶ࡿࠋᩥ ⊩1㸧 Oi M, Takita R, Kanazawa J, Muranaka A, Wang C, Uchiyama M. Organocopper Cross-coupling Reaction for
C–C Bond Formation on Highly Sterically Hindered Structures. Chem Sci. 2019 May 10;10(24):6107-6112.
PMID: 31360416 DOI: 10.1039/c9sc00891h
2㸧 Takagi M, Watanabe M, Murata S, Takita R. Copper-catalyzed Arene Amination in Pure Aqueous Ammonia.
Org Biomol Chem. 2019 Feb 13;17(7):1791-1795. PMID: 30489597 DOI: 10.1039/C8OB02708K
3㸧 Ong DY, Yen Z, Yoshii A, Revillo Imbernon J, Takita R, Chiba S. Controlled Reduction of Carboxamides toAlcohols or Amines by Zinc Hydrides. Angew Chem Int Ed Engl. 2019 Apr 1;58(15):4992-4997. Epub 2019 Mar
5. PMID: 30761712 DOI: 10.1002/anie.201900233.
4㸧 Ong DY, Watanabe K, Takita R, Chiba S. Mechanistic Insights on Reduction of Carboxamides byDiisobutylaluminum Hydride and Sodium Hydride-Iodide Composite. Helv Chim Acta. 2019 Jul 30;102(9). pii:
e1900166. DOI: 10.1002/hlca.201900166
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