Chemistry of the diboron compounds

Chapter 1 Chemistry of the diboron compounds H. A b u Ali, V.M. Dembitsky a n d M. Srebnik Department o f Medicinal Chemistry & Natural Products, School o f Pharmacy, P.O. Box 12065, H e b r e w University o f Jerusalem, Jerusalem 91120, Israel Contents 1. I N T R O D U C T I O N .................................................................................................. 2 2. P R E P A R A T I O N O F D I B O R O N C O M P O U N D S A N D T H E I R P R O P E R T I E S ...................................................................................................... . ......... . ..................... 3 2.1. F o r m a t i o n of B - - B b o n d ..................................................................................... 3 2.2. Synthesis, s t r u c t u r e a n d p r o p e r t i e s of s o m e h a l o g e n a t e d d i b o r a n e s .............. 3 3. R E A C T I O N S O F D I B O R O N C O M P O U N D S ................................................... 16 3.1 M i s c e l l a n e o u s r e a c t i o n s ...................................................................................... 16 3.2. R e a c t i o n s with allenes ........................................................................................ 25 3.3. Synthesis of b i s d i b o r o n f r o m d i b o r o n c o m p o u n d s ......................................... 27 3.4. R e a c t i o n s w i t h diols a n d thiols ......................................................................... 28 3.5. Synthesis of a r y l b o r o n a t e s ................................................................................ 28 3.6. Synthesis a n d r e a c t i o n s of d i b o r a m e t a l c o m p l e x e s ......................................... 39 3.7. R e a c t i o n s w i t h dienes a n d alkenes ................................................................... 49 R E F E R E N C E S .......................................................................................................... 52

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H. Abu Ali et al.

1. INTRODUCTION Diborane reagents of the general formula B2(OR)4 have been utilized recently as reagents for a series of transition metal-catalyzed reactions. The first example of a reaction employing these reagents was reported in the early 1990's by Miyaura and co-workers, who described the diboration of alkynes catalyzed by Pt(PPh3)4 [1]. Metal-catalyzed diboration has since been extended to a useful methodology. Boron-containing compounds with a boron-boron single bond are important intermediates in structural complexity between simple monoboron derivatives and the polyhedral electron-deficient compounds of the element. The properties of diboron compounds, particularly the simple derivatives of the BzX4 type, have attracted the attention of many laboratories around the world since Stock's initial discovery of B2C14 nearly 80 years ago [2]. These boron-containing compounds provide the simplest examples of catenation in boron chemistry and offer suitable systems to study properties of the covalent B--B bond and the characteristic chemistry of compounds containing this linkage. Studies on the organic and inorganic chemistry of the B-B compounds have been reviewed [3]. Boronic acids and esters are used in a wide variety of research applications [4]. They also continue to attract attention as versatile functional group tolerant crosscoupling substrates in organic synthesis [5]. Synthetic methodology allowing for the direct attachment of boron to aromatics to afford arylboronates is thus an important challenge [6]. Arylboronic esters are generally purified more easily than arylboronic acids, can be synthesized without organolithium or Grignard reagents and promote one-pot cross-couplings [7]. Aryl borylation reactions, which directly afford arylboronic esters, have been successfully performed using aryl halides and triflates [6]. Two aspects of the boron chemistry of this class of compounds are particularly relevant: First, synthesis and properties of organodiboron derivatives, and, indeed, even authentic synthetic failure in this area, are of interest in comparison with the rich organic chemistry of monoboron derivatives. Second, the chemistry of subvalent boron compounds and their interactions with organic and organometallic systems can lead to novel reactions that make organoboron derivatives accessible. This chapter will concentrate primarily on features of the chemistry of diboron compounds of particular interest from the organometallic and biological point of view. While our limited scope does not permit a comprehensive review of all aspects of diboron chemistry, we will initially survey some general features of the subject, with emphasis on unique synthetic aspects and on properties particularly characteristic of compounds containing a simple electron-pair bond between boron atoms. Previously we published several review articles provided some aspects on boron chemistry [8-16], and including natural boron-containing compounds [17-18].

Chapter 1

3

2. PREPARATION OF DIBORON COMPOUNDS AND THEIR PROPERTIES 2.1. Formation of B---B bond

Synthesis of diboron compounds may involve either reductive coupling reactions of monoboron derivatives to form the boron-boron bond [ 19], or reactions of compounds possessing preformed B2 fragments [20]. The earliest synthesis of characterized diboron compounds was the preparation of B2C14 by Stock [1], using an electric discharge between zinc electrodes immersed in liquid BC13. Many discharge procedures have been reported for the synthesis of B2C14 [21-26]. Structures of some halogenated diboranes, 1, 2, and 3 are shown in Fig. 1. Diborane(6) 3 (or diboron hexahydride) has been reviewed [27-31 ].

Fig. 1. Structures of some halogenated diboranes, 1, 2, and 3. Adapted by authors 2.2. Synthesis, structure and properties of some halogenated diboranes

The first formation of B2Br4 and ]3214 from the trihalides by discharge methods has also been reported [32,33], but these boron halide sate rarely used in synthesis. Attempts to prepare B2F4 from BF3 in a discharge between mercury electrodes were unsuccessful [34]. Conventional chemical reduction of boron trihalides with active metals, metal borides, hydrogen plus metal, or other reducing agents is not a satisfactory route to the tetra(halo)diboranes [2,22]. Synthesis of BzC14 has been reported by Timms, who condensed BC13 at -196 ~ with copper atoms produced by vaporization of the metal [35], or high-temperature approach to the formation of B-B bonds by the insertion of BF (formed at 2000 ~ from boron and BF3) into the B-F bond [36]. Formation of tetra(methoxy)- and tetra(ethoxy)diborane(4) from the corresponding dialkoxychloroboranes and sodium was reported by Wiberg and Ruschmann [37], although later workers were unable to reproduce the synthesis of the ethoxy derivative [38]. Boron reacts vigorously with C12 and F2 to form BC13 and BF3 respectively, which when reacted with boron halides gave compounds 4 and 5 (Scheme 1). Synthesis of other diboron derivatives 6-10 have also been reported (Scheme 1) [38,39-50].

H. Abu Ali et al.

Scheme 1 Cl\ 2B + 3Cl 2 ~

zCl

2BCl 3 + BCl 3 Cl

Cl 4

2B + 3F 2 ~

F\ F B-B, F F

2BF 3 + BF

5

NR 2(R2N)2BCI + 2M

NR

NR

NR

R = Me, Et M = Na or K Me2 N,

NMe2

B-B~

2(Me2N)2BRX + 2M

R

R 7

R = Me, Et, Ph, Pr, n-Bu M = Na or K X = CI, Br

Et2 N, ,NEt2 B-B, Et2P 8 PEt2

2Et2NPBNEt2CI + 2M M = Na or K

Et2N, 2R10(R2N)BCI + 2M

~

,NEt2

R(~-B"oR~__

M = Na/K

9 PrO,

2(Rr20)2BCl + 2K

,,OPr

prdB-B"oPr 10

Diborane compounds with common structure 11 (Scheme 2) have been synthesized [46,49]. The synthesis of a series of bis(catecholato)diborane(4) compounds 12-16, B2[1,2-O2C6H412 12, B2[l,2-OEC6H3Me-412 13, B2[I,2O2C6H2Me2-3,512 14, BE[1,2-O2C6Ha-tBu-412 15, and B2[l,2-O2C6H2tBu2-3,512 16 (Scheme 2) have recently been reported [51]. The above compounds have been synthesized by reaction of 1% sodium/mercury amalgam with the corresponding halocatecholboranes, which are cleanly formed from the reaction of BCI3 or BBr3 and catechol. Combining these two steps in one pot, B2[ 1,2-O2C6HatBu-4)]2 was prepared from BCI3 and 4-tert-butylcatechol, and B2[1,2-O2C6H2tBu2-3,512 was prepared from 3,5-di-tert-butylcatechol and BBr3 on a multigram scale. Bis(pinacolato)diborane(4) was not formed from reaction of chloropinacolborane and Na/Hg, but it was formed by in situ addition of pinacol to either B2[I,2-O2C6H3tBu-4)]2 or B2[1,2-O2C6H2tBu23,512.

Chapter 1 Scheme 2 X

,X, Y\ ,B-CI X

X

Y~ ~B--B~ ~u X X

X = O, S, N(Me, Et, i-Pr) Y=(CH2)n n = 2 , 3

11

/O

Na/Hg, 90 ~ toluene, 3h

12, 42%

/o

ON

l

13,52%

/o

l/t,,

15, 96% l/t

~B-Cl .r Reaction of sodium naphthalide with B2C14 at room temperature was reported to give a liquid product with a suggested structure, 17. The compound 17 reacts with 4 equiv of (CH3)3N to form an adduct which decomposes above 100 ~ to give the bis(trimethylamine) adduct of BzC 14 and an unstable product that is thought to be 18 (Scheme 3). It was reported that the trimethylamine complex of tetra(methyl)diborane(4) was obtained from the reduction of bromodimethylborane with sodium or silver in trimethylamine [52].

H. Abu Ali et al.

Scheme 3

Na+

+

Cl,, /Cl B-B,, CI CI "~pOOm

erature B

[

NMe3

17

18

Scheme 4

Me2N

Me2N, 'B-CI

2
Me2 N

4K

-4KCI

.._ "-

NMe2

g--~~
\

Me2 N

NMe 2 19

Fisch et al. reported the synthesis of a 1,2,4,5-tetraborinane heterocyclic compound 19 which was stabilized by dimethylamino groups (Scheme 4) and showed a nido-structure, Fig. 2 [53]. Several transamination reactions of Bz(NMe2)4 20 with secondary amines have led to mixed tetra(amino)diborane(4) compounds Bz(NMez)4.n(NRz)n 24-26 (Scheme 5), and Bz0NCsH10)4 23 has been characterized by an X-ray structure analysis which reveals the presence of a rather long B-B bond, Fig. 3.

Chapter 1

7

Fig. 2. Crystal structure of novel 1,2,4,5-tetraborinane 19, B-B bond length 1.711 ,~. Adapted by the authors. Scheme 5

Et2N~B B~NEt2 Et2N NEt2

~'~N~B_B/

'N9

21, 25%

22, 46%

2 (R2N)2BCI

B-B'

2 Na/K - 2 MCI

Me2N,B_B~,NMe2 Me2N NMe2 20, > 80%

23

Me2N,B B, NMe2

~"~N\B_B,,N Me2

Me2N "B-B/ \NMe2

26

25

Me2N' 24

\

8

H. Abu Ali et al.

c7

cB'

Cll

c9

#~4~ ~ ' ~

-

~

~ c 5 "

0 BI ~ '

B _

2 ~

N

C9'

3

C5 C8 CII " C7

Fig. 3. View of the molecular structure of 22 showing the atom numbering scheme. Ellipsoids represent thermal displacement parameters at the 50% probability level. The molecules are located in the crystal on twofold symmetry axes; primed atoms are related to non-primed atoms by symmetry transformation: 1 - x, y, 11/2 - z. Selected bond distances (A) and angles (o) include: B l-B2 1.739(4), B l-N3 1.424(2), B l-N4 1.427(2), mean C-N 1.472, mean C-C 1.523, N4-BI-N4' 121.7(2), N3-B2-N3' 120.8(2), N4-BI-B2 119.1(1), N3-B2-B 1 1 i 9.6( 1), N4-B I-B2-N3 -103.6( 1), N4-B I-B2-N3' 76.4(1 ) However, tetra(amino)diboranes(4)of type R2N(Me2N)B-B(NMe2)NR2 are more readily accessible from LiNR2 and B2(NMe2)2CI2. Similarly, amination of B2(NMe2)2CI2 with N,N'-dimethylethylenediamine gives B[bis(dimethylamino)boryi]-N,N'-dimethyl-l,3,2-diazaborolidine 29, while reactions with Li(Me)N-CH2CH2-N(Me)Li also give 2,3-bis(dimethylamino)- 1,4-dimethyl- 1,2,3,4diazadiborinane 30 as the kinetically controlled product. Diborane(4) dihalides B2(NMe2)2X2 (X = C1, Br) 20a reacts only in a 1:1 ratio with TMP-B=N-CMe3 leading to 28 (molecular structure shown in Fig. 4 and 29 (Scheme 6) [54].

Chapter 1 Scheme

6

Me2N, NMe2 B-B" \ / m N N-\ /

"••lMe2)2

30

Me2N B B"NX2 ",

,

X2N (CH2NHMe2)2/ ~,//

NMe2 20a

~ .--

/---k N N~ " / B-B \ ~N N~ \ /

X= CI, Br

28

/,13~B NEt2 NEt2 29

27

Fig. 4. Molecular structure ofheterocyclic compound 28. Adapted by authors Heterocyclic organodiboron compounds 31 and 32 have been obtained by transamination of dialkylbis(dialkylamino)diborane(4) derivatives with o-diamines (Scheme 7) [49], and reaction of Bz[NMez]2(n-C4H9)2with o-aminophenol gave an unstable heterocycle 33. Organoboron heterocycles 34 and 35 containing the boronboron bond have been prepared by the reaction of N-lithio derivatives of alkylbis(alkylamino)boranes with 1,2-dichloro-l,2-bis (dimethyl-amino)diborane(4) [55].

10

H. A b u Ali et al.

Scheme 7 H

[~~

H I

32

I

N'B"R i

N-B-R

[~

I

H

N.B-.

HI N'B'BU o--B-Bu

I

H 31

NH2

H2 R,

,,R

/

/

35

~

"OH

,B"--B,, Me2N NMe2 R = alkyl, aryl, Cl a~

NLi

R1--B'., NLi

R.N~B"NMe2 Rf~

IB,

R

NMe2 34

+

R1 R Me2 . / B-~N~B"N ,-1--N~ g ' R1 R

NMe2

35

The synthesis and characterization of a series of bis(catecholato)diborane(4) compounds, B2(1,2-O2C6H4)2 38, B2(1,2-O2-3-MeC6H3)2 40, B2(1,2-O2-4-MeC6H3)2 41, B2(I,2-O2-4-tBu-C6H3)2 42, B2(1,2-O2-3,5-tBu2C6H2)2 43, B2(1,2-O2-3MeOC6H3)2 44, bis(dithiocatecholato)diborane(4) compounds, B2(1,2-S2C6H4)2 47, B2(1,2-S2-4-MeC6H3)2 48, and tetra(alkoxy)diborane(4) compounds, B2(OCH2CMe2CH20)2 45 and B2(OCMe2CMe20)2 46 from B2(NMe2)4 36 was described (Scheme 8). Compound 36 was synthesized by reductive coupling of BCI(NMe2)2, which in turn is prepared from reaction of BCI3 with B(NMe2)3 in a 1:2

Chapter 1

11

stoichiometry. Also were characterized [B2CI4-(NHMe2)2] 37 formed from addition of HC1 to 36 prior to complete reaction with diols, and the salt, [NHzMez]-[B(1,202C6H4)2], which arises from addition of catechol to B(NMe2)3. Thus, any B(NMe2)3 impurity present after the preparation of 36 needs to be removed by distillation prior to reaction with alcohols [56]. Scheme 8

BCl 3 +

2B(NMe2)3

~

Me2N , NMe2 ,B-B', Me2N NMe2 36

3BCI(NMe2) 2

I HCI O Rn

~

OH

Cl, Cl,~..[B

NMe2 R/ ,,t t

H4 3,5-t-Bu-4,6-H2 Rn = 3-Me-4,5,6-H3 Rn = 4-Me-3,5,6-H 3 Rn =4-t-Bu-3,5,6-H3 Rn = 3,5-t-Bu-2,4,6-H3 Rn = 3-MeO-4,5,6-H 3

38: Rn = 39: Rn =

40: 41: 42: 43:

44:

37

Rn

,,, / - - q

~ s Rn---~-' ~~s,B--B,s 47" Rn = 48: Rn =

s ~

45

~ ~ R n

H4 4-Me-3,5,6-H3

P--xt

% o,

,o ,"

The X-ray structures have been described for the bis(catecholato), bis(dithiocatecholato), and tetra(alkoxy)diborane(4) compounds B2(1,2-O2C6H4)2, B2(1,2-O2-4-/BuC6H3)2, B2( 1,2-O2-3,5-tBu2C6H2)2, B2(1,2-$2C6H4)2, B2(1,2-S2-4MeC6H3)2, and Bz(OCH2CMezCH20)2. In the solid state, all the compounds adopt planar structures for the B204 or B2S4 units, Fig. 5.

12

H. Abu Ali et al.

Fig. 5. Molecular structures of some diboron compounds. Structure of B2(1,2-O2-3Me2C6H3)2 45, B-B bond length was determined as 1.315/~; and structure of B2(1,2-02-3,5tBu2C6H2)2(NHMe2)2, B-B bond length was found as 1.788 /~; Structure of B2(1,2-S2-4MeC6H3)2 48, B-B length was determined as 1.737 Adapted by the authors A series of mixed tetra(amino)diborane(4) compounds bearing pyrrolyl, indolyl, and carbazolyl substituents besides dimethylamino groups has been prepared and subjected to reduction with elemental lithium in the presence of diethyl ether [60]. Tetra(amino)diborates(2-) are formed, which feature a boron-boron double bond (Scheme 9). The new diborates are isoelectronic with tetra(amino)ethylenes and are expected to be electron-transfer reagents [57]. X-ray crystal structures for 49 and 50 were studied and are depicted in Fig. 6.

13

Chapter 1 Scheme 9

\ CI\ N~ ,B-B"\ tN CI \

\ R2N +

LiNR2

~

N~ B-

~N'

B"

\

NR2

49: NR 2 = pyrrolyl

50:NR2 =

indolyl

Fig. 6. Molecular structures of 49 (A) and 50 (B) with B-B bonds 1.723 (A) and 1.718 (B) A respectively. Adapted by the authors Tetra(dimethylamino)diborane(4) was treated with o-phenylene isothiocyanato-boronate, to give an interesting reaction which involve not only disproportionation but also cleavage of the B-B bond giving compounds 51 and 52. The products were isolated in good agreement with this stoichiometry: 2-(1,3,2benzodioxaborolo)-l,3,2-benzodioxaborole 12, by comparison of its properties with those previously reported elsewhere [58] was indicated as the third product (Scheme 10).

14

H. Abu Ali et al.

Scheme 10

~~[~O

O'BNCS

+

Me2N'B_B,NMe2 Me2N' ~NMe2

~ O , , NMe2 ~[~~o,B-,NMe2 Me2NB(NCS)2 51

+

52

[~ o , B - - B , o ~ o,

o

~

12

The first synthesis of bis(pinacolato)diboron(4) 46 was reported more than 20 years ago by N6th [59], and the practical procedure is described below. A 2L, three-necked flask fitted with a mechanical stirrer, dropping funnel, and a reflux condenser connected to a nitrogen source and a bubbler is flushed with nitrogen. To the flask are added 53.7 g (0.271 mol) of tetra(dimethylamino)diborane(4) and 510 mL of toluene, and then a solution of 64.4 g (0.545 mol) of pinacol in 340 mL of toluene is added. The flask is immersed in an ice-water bath and a 5.4 M ethereal solution of hydrogen chloride (203 mL, 1.10 tool) is added dropwise during 2 h. As soon as the addition is started, a white precipitate of dimethylamine hydrochloride appears. The slurry is stirred at room temperature for an additional 4 h. The precipitate is removed by suction filtration, and the filtrate is concentrated on a rotary evaporator to give a white solid. The solid is dissolved in ca. 700 mL of pentane and the remaining solid is again removed by filtration. The filtrate is washed three times with 500 mL of water and dried over anhydrous MgSO4. The drying agent is removed by filtration and the filtrate is concentrated to ca. 150 mL. The flask is heated to dissolve the resulting precipitate, allowed to cool to room temperature, and then thoroughly chilled in a freezer (-30 ~ The first crop is collected by filtration and washed twice with 30 mL of cold pentane. The mother liquor is again concentrated to give another crop of crystals. The procedure is repeated two additional times. The combined crystals are dried under reduced pressure (0.1 mm) for 16 h at room temperature to give 54.3 g (79%) of 46 as colorless plates, mp 138 ~ [59] (Scheme 11).

Chapter 1 Scheme

15

11

BBr3 + Me2NH

pentane NMe2 NMe2 i BBr3 i - 78 ~ "Me2N'B"NMe2 - 78 ~ pentane Me2N"B"Br 2 Na toluene

~O"

B~.~

2 pinacol, benzene Me2N'B_gMe2 4 HCl/ether Me2N NMe2

46

Structural changes as a function of the torsional angle about the B-B bond angle have been studied for the diborane tetrahalides X2B-BX2 (X = F, C l, Br) by abinitio calculations [59]. The perpendicular structure with Ded symmetry was predicted to be the most stable conformation when the double-zeta basis 6-31 G* set was used in the calculations. A triple-zeta basis set augmented with diffuse functions and polarization functions of the type 6-311+G* showed that the planar D2h conformation is the most stable conformation for B2F4 which is in agreement with experimental results. Inclusion of correlation through the MP2 level of theory affects mostly the B-F bond length, and only to a small degree the barrier hight. For intermediate states with one X-B-B-X torsional angle constrained to lie between 0 and 90 ~ a pyramidal arrangement around the boron atoms is predicted with an overall symmetry of C2, and with two unequal B-X bond distances and two unequal B-B-X bond angles. Vibrational frequencies have been calculated and compared with experimental assignments [59]. As shown by Dewar et al. [60] the N atom of azoniaboratanaphthalenes can be lithiated, when the B atom is protected by an alkyl group. The B-tertbutyl derivative 53 was lithiated with LiMe in the presence of tetramethylethylenediamine (tmen). Subsequently, the N-lithio derivative 54 was borylated with the diborane C1-B(NMe2)-B(NMe2)-C1 and the corresponding 1,2-bis(azoniaborata- 1naphthyl)diborane 55 was obtained (Scheme 12) [61 ].

16

H. Abu Ali et al.

Scheme 12 H i B/t'Bu

1) MeLi, hexane,-30 ~ 2) (tmen), hexane, -78 ~ to rt, 3 h -CH4

Li(tmen) ~ B --t-Bu 53 t-BU~E~N ~

Li(tmen) /t-Bu

2

[~~B 55

B2CI2(NMe2) 2 (etheral solution) 0 ~ then rt, 6h 9~ - 2 LiCI - 2 (tmen)

(tmen) = tetramethylethylenediamine

Me2N, / ,-._, "B-B,, (('-~).~N / NMe2 ,k.y_~B_t_B u 54, 80%

3. REACTIONS OF DIBORON COMPOUNDS 3.1 Miscellaneous reactions

The insertion of CO into the B-B bond of 1,2-bis(diisopropylamino)-2,5dihydro-lH-1,2-diborole 60 and 1,2-bis(diisopropylamino)-3-methylidene-l,2diborolane 56 leads to the dimeric spiro products 1,7,9,14-tetrakis(diisopropylamino)-6,13-dioxa- 1,7,9,14-tetraboradispiro[4.2.4.2]tetradeca-2,10-diene 61 and 1,7,9,14-tetrakis(diisopropyl-amino)-bismethylidene-6,13-dioxa- 1,7,9,14-tetraboradispiro[4.2.4.2]-tetradecane 57. The reaction of 60 with tert-butyl isocyanide and 2,6dimethylphenyl isocyanide in THF leads to the formation of the monomeric insertion products 1,3-bis(diisopropylamino)-2-tert-butylimino-l,3-diboracyclohex-4-ene 62 and 1,3-bis-(diisopropylamino)-2-(29,69-dimethylphenylimino)-l,3-di-boracyclohex4-ene 63. Treatment of 56 with the isonitriles gives 2-tert-butylimino-l,3bis(diisopropylamino)-4-methylidene- 1,3-diboracyclohexane 58 and 1,3bis(diisopropylamino)-2-(29,69-dimethylphenylimino)-4-methylidene- 1,3-diboracyclohexane 59 (Scheme 13) [62]. Commercially available Pt(cod)Cl2 catalyzes the diboration of alkenes, alkynes, and aldimines using bis(catecholato)diborane(4) (cod = 1,5-cyclooctadiene). Catalyzed aldimine diboration provides the first direct route to r-aminoboronate esters. The diboration product from N-benzylidene-2,6-dimethylaniline was structurally characterized by physico-chemical methods (Scheme 14) [63].

17

Chapter 1

Scheme 13

N(i-Pr)2 (i-Pr)2~ ~ - O ' ~

2C'f

2CO

(/-Pr)2N=B-B=N(/-Pr)2 56

O-B

CN

(i-Pr)2N

N(i-Pr)2

57

(iPr)2~ N(/-Pr)2I B

N(i-p0~ y

N(i-Pr)2~B"~ B'N(i- Pr)2

2"

B

~ N(i-Pr)~

.@ 59

II \\

(i_Pr)2N

N(FPr)2

61

N(i-Pr)2~B" ~ B~N(i-Pr)2

58

62 N(i-Pr)~ B'~B'~N(i-Pr)2

63

2CO

CN (/-Pr)2N=B-B=N(i-Pr)2 60

The development of novel strategies for effectively linking organic compounds to solid supports has become essential as solid-phase chemistry and combinatorial technology have evolved into fundamental tools for drug discovery [64]. In principle, the ideal linker should provide effective loading onto the support, stability under a diverse variety of reaction conditions, and easy product removal without contamination from the linker [65].

18

H. Abu Ali et al.

Scheme 14

o

dB--B~o ~

O'

PtcodC,2,benzene,25~

/B'0

87%

~ ~ B ~ : ~

kP

O'l

/-Pr

/[~,.OMe

A novel linking strategy has been developed for synthesizing configurationally stable or-amino aldehyde on polymeric supports. Alkylation of Lalanine methyl ester with 9-bromo-9-p-bromophenylfluorenene, followed by ester hydrolysis and coupling to isoxazolidine, provided N-(9-p-bromophenylfluoren-9-yl)alanine isoxazolidide(5) 64, which was transformed into its corresponding boronate 65 by a palladium-catalyzed cross-coupling reaction with bis(pinacolato)-diborane(4). Boronate 65 was anchored to four different polymeric aryl halides Ra-d in 60-99% yields. Polymer-bound alaninal was then synthesized on non-cross-linked polystyrene by hydride reduction of isoxazolidide 66. Treatment of alaninal with phenylmagnesium bromide, cleavage of the resulting amino alcohol in a 1:2:2 TFA/CHaCl2/anisole cocktail, and acylation with di-tert-butyl dicarbonate furnished N-(BOC)norephedrines 67 that were demonstrated to be enantiopure by conversion to diastereomeric thioureas 68a (99%) and 68b (1%) (Scheme 15) [66].

19

Chapter I S c h e m e 15

B r ~

--•?

O

~---B

-•O'

0

B BO'~J~

N,,0

d - "o~\

PdCl2(dppf), KOAc, DMSO, 80 ~ 64

65 92%

OI

~

j

O

-

.,,c,,. .Br

Ra-d PdCI2(dppf), DMF 2M Na2CO3, 80 ~

Rb

Ra

~ O . . ~

I

"o ~

Rc

Rd

66a: 99%, 66b: 70% 66c: 78%, 66a: 60%

OH =.

AcO,.

S

NH

~co.~O s~ AcO ~

N

(1R,2S),

AcO,.

~CO~N

H OAc

Acu

68a

OAc

OH

CS

OH Et2N, CH2CI2

NH

6oc AcO.

S

A c O ~ o s~ OAc

(1 S,2S), 68b

NH

67

20

H. Abu Ali et aL

The solvent-free, microwave-assisted coupling of thienyl boronic acids and esters with thienyl bromides, using aluminum oxide as the solid support, served to rapidly check the reaction trends on changing times, temperature, catalyst, and base and easily optimize the experimental conditions to obtain the desired product in fair amounts. This procedure offers a novel, general, and very rapid route to the preparation of soluble thiophene oligomers. Quaterthiophene 69 was obtained in 6 min by reaction of 2-bromo-2,2'-bithiophene with bis(pinacolato)diborane(4) in 65% yield, whereas dithiophene 70 was obtained with 70% yield. The synthesis of new chiral 2,2'-bithiophenes also was reported. The detailed analysis of the byproducts of some reactions elucidates a few aspects of reaction mechanisms (Scheme 16) [67]. Scheme 16

AI203, PdCl2(dppf)/KF

+

~-

MW, 3min, 70 ~

S

S

Br

AI203' PdCI2(dppf)/KF MW, 3min, 70 ~

70

S

S

Br

Synthesis of chiral 2,2'-bithiophenes 72 and 73 have been reported [67]. The new methodology for the synthesis of the two enantiomers of bithiophene bearing R(-) and S(+) chiral groups at the terminal positions (compounds 72 and 73) presented here and the synthetic pattern is shown in (Scheme 17). As shown in the scheme, the monobrominated monomers were obtained by condensation of commercial 5-bromo-2-thiophene aldehyde with R(-) and S(+)l-phenylethylamine. Afterwards, they were reacted with bis(pinacolato)diborane(4) using the same experimental conditions employed for the preparation of quaterthiophene 71. After a few minutes of microwave irradiation, bithiophenes 72 and 73 were recovered in high yield (isolated yield in both compounds >70%).

21

Chapter 1

Scheme 17

Br/~ Ph,, H /

CHO

71

P4, , M e

H3N7

H

. .

Ph, H.N

Me

72

N~Ph H Me

Ph,

9 ,,,N~ -~ ~- ~ N ,---::v~Ph Me i~I 73 M~ "14

Free-base porphyrins react with haloboranes to give diborylporphyrins 74-76 in which the porphyrin ligands show marked rectangular distortions (Scheme 18) [68]. As for the biaryl ether containing macrocycles, an array of bioactive macrocycles with an endo aryl-aryl bond exists in nature. Recently a new palladium catalyzed, bis(pinacolato)diborane(4) mediated process has been developed to attain such a structural motif. The reaction consists of a domino process involving a Miyaura's arylboronic ester synthesis and an intramolecular Suzuki coupling. Synthesis of a bicyclic A-B-O-C ring system of RP-66453 77, a neurotensine receptor antagonist, with an endo aryl-aryl and an endo aryl-aryl ether bond was described (Scheme 19) [69].

--~

J

v~

Z

~_ -" ,aJ

r~v~

J

~mL

23

Chapter 1 Scheme 19

Me~~H

IN--:v~N'H'~ O COOMe o

t@,

:~QB--B'O~ PdCl2(dppf)KOAc OMe DMSO

BocHt~l ~N_.,~ N.~COOMe O OH

t HO~O

II _--

~

COOH

O

77,RP-66453 Diboration of a, fl-unsaturated ketones has been reported [70]. The diboration of enones with 78 gives 1,4-addition products 79-84 in the presence of a platinum(0) catalyst such as Pt(C2H4)(PPh3)2 at 80 ~ or Pt(dba)2 at room temperature (Scheme 20). The reaction catalyzed by Pt(C2H4)(PPh3)2 affords a single isomer which is assumed to be the Z-enolate. The hydrolysis of 79-84 with water gives fl-borylketones in high yields, the conversion of which is synthetically equivalent to the conjugate 1,4-addition of a boryl anion to enones. The diboration of a, fl-unsaturated esters and nitriles affords similar products [70].

24

H. Abu Ali et al.

Scheme 20

O

B-

O/B-O

O H20

R ~'-~-R1

R2

Pt(dba)2, toluene _ _ ~ B ~ , ~R2275-280 R1

274

275: R = Ph, R1 = H, R2 = Me, > 90%

276: R = H, R1 = R2 = Me, 64% 277: R = R2 = Me, R1 = H, 72% 278: R = R2 = Ph, R1 = H, > 90% 279: 2-cyclopentenone, 88% 280: 2-cyclohexenone, 61%

Methylenecyclopropane and its derivatives are of interest as the substrate for the transition metal-catalyzed addition reactions because of their high and unique reactivities originating from the highly strained structure. The platinum catalyzed reaction of bis(pinacolato)diboron(4), 46 proceeds through the proximal bond cleavage of the cyclopropane ring (Scheme 21) [71]. The catalytic cycle involving the insertion of methylenecyclopropane into the B-Pt bond of 86, followed by the rearrangement to a homoallylplatinum(II) species gives a ring-opening product 85. The selective formation of the cis-isomers for bicyclic methylenecyclopropane suggests a four-centered cyclic transition state for the ring-opening rearrangement. The results also provide information on the insertion mechanism of 86, i.e., the addition of the Pt-B bond to terminal alkene gives a primary alkyl-platinum intermediate, the selectivity being similar to that for the silylboration of alkenes [72].

Scheme 21 0

85 Pt(PPh3)4 Pt

25

Chapter 1 3.2. Reactions with allenes

Addition of bis(pinacolato)diborane(4) [(Me4C202)B-B(O2C2Me4)] to various allenes in the presence of Pt(PPh3)4 at 80 ~ or Pt(dba)2/(c-Hex)3P at 50 ~ gives compounds 87-100 in excellent yields. The addition to internal double bond was predominant for monosubstituted allenes, whereas the terminal diboration products were regioselectively obtained when a sterically bulky phosphine ligand of (c-Hex)3P and 1,1-disubstituted allenes were used [73] (Scheme 22). Scheme 22

87, 99% \

--C~-

/ gu

Bu BU~c--

\

H

/~B

/

\

/

88

Ph

89, 97%

Ph

~B'

B--

\

H

H

~B

--

/

\

/

91, 94%

cO2Et+

EtOO2C /~B H

90

'~

EtOOC~c ~

~B'

H

~B

B--

\

92

/

--

\

/ 93, 90%

Pt(PPh3)4, 80 ~ Me

Me~---C =

jB' \ 94

~B

B--

/

B--

\

/ 95, 98%

MeO tB

MeO,~___C__

/

H

MeS ,~B H

~(,SMe + MeS,)__C__

97

H

~

IB'

---C----

B--

\

.I \

99

IB

/

/B

96, 81%

__

\

~B

--

\

/

\

I

98,48%

100, 96%

26

H. Abu Ali et al.

Highly regio- and stereoselective acylboration of allenes 101a-e catalyzed by palladium complexes has been demonstrated by Cheng et al. [74], as the efficient route to a new class of 2-acylallylboronates 102-121 (Scheme 23). Scheme 23 Q

0

R

+ RCOCI R2

POCI2(MeCN,2, toluene, 80 ~

R2~-'B';~

101a: R1 = R2 = Me 101b: R1 = H, R2 = n-Bu 101c: R1 = H, R2 = Ph 101d: R1 = H, R2 = cyclohexyl 101e: R1 = H, R2 = t-Bu

102(101a): R = p-MeC6H4COCl, 72% 103(101a): R = C6HsCOCl, 68% 104(101a): R = CsHsCOCr, 67% 105(101a): R = p-MeO2CC6H4COCI, 67% 106(101a): R = p-NO2CsH4COCI, 77% 107(101a): R = p-MeOC6H4COCI, 61% 108(101a): R - m-MeOC6H4COCI, 75% 109(101a): R = o-MeOC6H4COCI, 57% 110(101a): R = 1-CloH7COCI, 92% 111(101a): R = t-BuCH2COCI, 80% 112(101a): R =/-PrCH2COCI, 63% 113(101a): R = C6H5CH2COCI, 57% 114(101b): R = t-BuCH2COCI, 91%, E/Z, 99:1 115(101c): R = t-BuCH2COCI, 77%, E/Z, 93:7 116(101d): R = t-BuCH2COCI, 88%, E/Z, 93:7 117(101b): R = p-MeOC6H4COCI, 70%, E/Z, 98:2 118(101b): R = 1-CloH7COCI, 71%, E/Z, 98:2 119(101e): R = p-MeOC6H4COCI, 50%, E/Z, 98:2

120a(101a): R _~/--COCI

71%

- ,k~...S

120b(101a): R = ~ ~-COCI

62%

N~O

A new efficient route for the synthesis of bis(diboranes) catalyzed by palladium complexes is diboration of allenes (Scheme 24) [75]. The stereochemistry of these bisboronic products was studied and the Z-isomer was also identified as the major product (93-95%).

27

Chapter 1 Scheme 24

O

RI~:C: R2

B--B" 0460 PdCI2(dba)2,toluene 80 ~ 4h 47

131-140

121-130

R1

o4

,B-O ~ "

142

o~

141

'o~

3.3. Synthesis of bisdiboron from diboron compounds Bisdiborane derivatives are an important class of compounds in boron chemistry. The addition of diboranes (X2B-BX2) to unsaturated hydrocarbons, first discovered by Schlesinger in 1954 [76], is an attractive and straightforward method to introduce two boryl units into organic molecules [2,42,52,77-79]. Diborane itself, B2I--I4, is stable only when complexed by Lewis base ligands such as amines or phosphines. Although the tetrahalides, BzX4 (X - F, C1, Br, I), have a reasonably well-established chemistry, they suffer from low thermal stability (with the exception of BzF4) and preparative difficulties. Tetraorganodiborane compounds, BzR4, are stable only when substituted with sterically demanding R groups such as t-Bu, CHz-t-Bu, and mesityl. The most stable derivatives are those in which good z-donor groups are present such as amido (NR2) or alkoxy (OR) [42,79]. More recently, as part of the interest in the oxidative addition chemistry of the B-B bond and metal-catalyzed diborations of alkenes [80-82] and alkynes [83-86] synthesis of stable, crystalline bis(pinacolato) and bis(catecholato) diborane(4) derivatives have been reported [9,87,88]. The development of new strategies in organic synthesis with a minimum of chemical steps is becoming more and more important for the efficient assembly of complex molecular structures [ 10,89]. The combination of multiple reactions in a single operation represents a particularly efficient approach. Among these strategies [90], geminated organobismetallic derivatives (1,1-bis anions) are becoming more and more useful [91 ]. During the past decades considerable efforts have been made to find new routes for the preparation of geminated sp 2 organobismetallic derivatives and for their

28

H. A b u Ali et al.

selective reactions with several electrophiles [91,92]. 3.4. Reactions with diols and thiols Homochiral diborane(4) compounds can be prepared via reaction with the appropriate homochiral diols (Scheme 25) [93]. Thiolate compound such as 2,2'-bis1,3,2-benzodithiaborole 47 was obtained from the reaction between diborane 20 and the appropriate thiole (Scheme 25) [56]. Scheme 25

Me02C',. 0

/0

C02Me

MeO2CIo'B-B~~',,CO2Me 53% 1)Et2O,rt, 12h 2) 1MHCI,Et20,rt, 12h

~leO2C',IOH

eoii.OH

1)Et2O,rt, 18h 1)Et20,rt, 18h Ph Ph~L~ B/O~.,Ph2) O,B_ 1MHCI,Et20,rt, 6h Me2NB-B,,,NMe2 2)lMHCI,Et20,rt,~ [1% B/O'~ ph,,."~0'

~01~ph 50%

2I Ph, OH ph4/IkOH

Me2N'

NMe2

2 .OH hi 0 p H

21)

ph4~O'

~0~ 60%

..,-%./SH Et20,then1MHCI,Et20,24h 2 ~ .,~'I SH V

S

\

$ / " , .~ 47, 76%

3.5. Synthesis of arylboronates Benzyl bromides and chlorides react with bis(pinacolato)diborane(4) in the presence of tetrakis(triphenylphosphine)palladium(0) and potassium carbonate to give the corresponding boronates 143-152 (Scheme 26) [94].

29

Chapter 1

Scheme 26

R,H_~x

~o

+

,o-..~

.. Pd(PPh3)4, 5mo1%, K2CO3 "-"~'[~~C).~B"O dioxane, 80-100 ~ 6 or 18h R1 143:R1 = H, X = Br, 79% 144: = 2-Me, X = Br, 74% 145: = 4-Me, X = Br, 83% 146: = 4-Me, X = Cl, 81% 147: = 2-F, X = Cl, 70% 148: = 3-Cl, X = Cl, 91% 149: = 3-CN, X = Br, 65% 150: = 4-OMe, X = Cl, 93% 151:= 3-COOMe, X = Br, 75%

Borylation at the benzyl position of alkylbenzenes with bis(pinacolato)diborane(4) is catalyzed by palladium on carbon. The method provides direct access to benzyl boronates 152-159 (Scheme 27) [95]. Scheme 27

[

~

cH3

CH3

B--O

H3C~~.J".~ _ [I "[ -B--O

H3C'~CH3

o,

H3C,~

OH3

H3C'~

CH3

~i~

o..~

o,B-B,o~

HsC~ ~

1i "T

153, 77%

154, 79%

6"g--o . ~ lss,72%

10% Pd/C, 100 ~ 16h

I \ H3C~ ~

11 "T

"B--O

c[~JH3 I

C ~

156, 64%

OH3 H [ ~

cH3

H3

TI "T

"B--O +H3C

C~H3 I

C,~

157,39% ~

OH3

"~ 159, 38% CHa

I

CH3

158, 15%

30

1t. Abu Ali et al.

Reduction of naphthoquinone 160 with sodium dithionite followed by methylation with dimethyl sulfate afforded naphthalene 161 in 64% yield. Triflate 161 was then heated with bis(pinacolato)diboron in dry dioxane in the presence of PdClz(dppf), dppf ligand and the weak base KOAc at reflux for 0.5 h to afford the boronate ester that was directly coupled with a further equivalent of triflate 161. This latter step was assisted with a second addition of the palladium catalyst and a stronger base, K3PO4 to drive the homocoupling reaction to completion furnishing binaphthyl 162 in 84% yields after purification by flash chromatography (Scheme 28) [96] Scheme 28

0

OMe

OMe 0 160

OMe OMe 161

OMe

oB-Bb

OMe OMe

OMe

OMe OMe 162, 84%

(i) CH2CI2-Et20 (1:3), Na2S204, H20, 20 rain, then dry acetone, K2CO3, Me2SO4, 60 ~ 23 h, 64%; (ii) bis(pinacolato)diboron (1.1 equiv.), PdCI2(dppf), dppf, KOAc, dioxane, reflux, 0.5 h, then triflate 161, PdCI2(dppf), K3PO4, dioxane, reflux, 2 h.

A highly efficient catalytic borylation process with aryldiazonium ions was developed using a carbene-palladium catalyst formed in situ to give arylpinacolatoborane products 164-175. The optimized reaction conditions with palladium acetate and imidazolium 163 as catalyst in THF at room temperature were applied to a variety of aryldiazonium tetrafluoroborate substrates (Scheme 29). Electron-rich and -deficient aryldiazonium ions all gave excellent yields of borylated products again used at l:l stoichiometry with bis(pinacolato)diborane(4). All yields reported are for isolated, chromatographically pure products [97]. Recently, natural products bearing a bis-naphthospiroketal structure have been attracting much attention because of their unique structures and biological activities. For instance, preussomerins were reported to show antibacterial, antifungal, and also ras farnesyl-protein transferase inhibitory activities [98]. Spiroxins A-E, isolated from a marine derived fungai strain LL-37H248, are another type of such compounds, in which, differently from preussomerins, two naphthoquinone moieties are directly connected by a C-C bond in place of one ether linkage, forming a unique bisnaphthospiroketal octacyclic ring system, Fig. 7.

I/

O-~--O

0")

-'-4

\ ...0

O-txA.O

0..

"q/

l

"--11

-11

~

z r,a

z r,a

--i'1 0a z

"-4

O.~-.O

Z

~Un

O-~--O

~

7-I

z

i~a

sO

CO 0

(3o (DO

O-~--O

~

I

O.!Ja-.o

O.ua

-'17

z

~

O-~--O

._~

77

z

0

CO O0

O.[XJ..O

o~ _~

0

"17

Z

~

. . . . . . . . .

"-~

z

z

3 o o-~

(Do ~

O.m..O

-rl

(DO O7

O-~--O

CD

-i-i

Z

(..0

O.~-.O

Z

~

O-txRO

__~

Z

l

(DO "-4

O-~--O

Z

m"

c~

32

H. Abu Ali et al.

R3 R2 OH

OY,I

~

O

0

OH

R1

i

R

0

/

le

O R5 Re K7 spiroxcin A-E

0 preussomerin G

R1 R2 R3 R4 R5 R0 R7 CI -O- H OH -OB CI -O- CI OH -OC H -O- H H -OD H OH H H H -OE CI -O- CI OH OH H

A

Fig. 7. Spiroxins A-E, isolated from a marine derived fungal strain LL-37H248 Spiroxin A, which is the major component produced in culture, was also reported to show antibacterial activity against Gram-positive bacteria and antitumor activity against ovarian carcinoma in nude mice, the mechanism of which was suggested to be due to its single-stranded DNA cleavage activity [99]. However, details of the DNA cleavage mechanism are not clear. A number of total syntheses of the preussomerins and related natural products have been reported [100]. However, synthesis of spiroxins requires an additional C-C bond formation to achieve the formation of the unique basic skeleton, and in fact, there is no report dealing with synthesis of spiroxins. The first total synthesis of racemic spiroxin C is described (Scheme 30). The generation of non-peptide small molecules by solid phase methods has proven to be a successful strategy in increasing the diversity of new pharmacologically active substance [101]. The Pd(0) catalyzed coupling reaction of resin-bound aryl triflate 176 with bis(pinacolato)borane(4), which proven to give the polymer-bound arylboronate from aryl alcohol (Scheme 31). This is a continuation to develop the non-peptide protein tyrosine kinases (PTK) inhibitors [ 102]. For naphthyl boronic acid inhibitor libraries, the solid phase synthetic methods of resin-bound naphthyl boronate 177 were developed [102,103]. Introduction of boron functional group to triflate of solid support was performed with application of Miyauras conditions (Scheme 31 ) [ 104].

33

Chapter I Scheme 30

OMe OMe

OMe OMe +

/~O

Of~

DMF, 80-90 ~

OMeBr

MeO

B 83% O" "O

OMe OTf / ~ I I [ ~ ~ Pd(PPh3)4, 4 too% THF, reflux

O

OPiv

O

BrBr~Br Br

0 O~Piv

~

Br CH2C 2,l0~ ~

a

~

93%

92%

[~

MOMO

I

(Piv) pivaloyl, (TBHP) tert-butyl hydroperoxide, (DBU) 1,8-diazabicyclo[5.4.0]undecF-ene, (NBS) N-bromosuccinimide, (AIBN) 2,2'-azobisisobutyronitrile. (a)PhI(OCOCF3)2, MeCN-THF-H20 (2:2:1), 0 ~ (b) Nail, THF then PivCI, 0 ~ (c) NBS, AIBN, benzene, reflux; (d) NaHCO3, DMSO, rt; (e) TBHP, DBU, CH2CI2, 0 ~ to rt.

b 87%

O

o;:'

OMeOMe

OPiv

I

O

c,d

~Br 27%

0 II

OPiv

OH

e 59%

~j

0 spiroxcin C

34

H. Abu Ali et al.

Scheme 31

OTf

OH 1) MeOH/HCI,reflux, 48h

Meo2cH~O

v~

H O ~

2)CH2Cl2,PhNTf/TFA,0~ l h MeO2C 93%

TMADWangresin Bu3P O'B'O MeO2C 177

0

OTf

0

PdCI2(dppf),dppf,KOAc 176

c

O,B,O Meo2cH~O 52%

Synthesis of arylboronates via the palladium(0)-catalyzed cross-coupling reaction of tetra(alkoxy)diboranes with aryl trifiates has been reported [104]. The cross-coupling reaction of (RO)2B-B(OR)2 (OR = methoxy and pinacolato) with aryl triflates to give arylboronates 178-189 was carried out at 80 ~ in the presence of PdCl2(dppf) (3 mol %), and KOAc (3 equiv) in dioxane. The reaction was generalized on various functional groups such as nitro, cyano, ester, and carbonyl groups (Scheme 32). Synthesis of pinacol arylboronates 190-200 via cross-coupling reaction of bis(pinacolato)diborane(4) with chloroarenes catalyzed by palladium(0)tricyclohexyl-phosphine complexes has been demonstrated by lshiyama et al. (Scheme 33) [ 105].

Chapter 1

35

Scheme 32

~>-o,,. _~~,_o~ ....PdCl2(dppf)/dppf L ~ KOAc/dioxane 80~ 7-18h

Ph-B..O~ 178

O2N--~~OTf

o~,-C~~~

,,~.86%

NO-C~--OT' OHO--CT--OT'

~c-C~~~

,,0,,,o~o

MeOC--~~OTf

o~c-CT-,~ MeOC~B'.~

,,,. ~ 182.92%

MeOOC~OTf MeO--~~OTf .1,..._ r

MeS~OTf

MeS~B'.O~

NO2 ~OTf OMe --OTf

OTf

o~ O

~ ~ / N OTf

185,81%

NO2

OMe ' ~ ' 0 ~ Bb

187,80%

Bb

188,84%

-~o O~

%%__~N

BO~ b 189,65%

36

H. Abu Ali et al.

Scheme 33

(~~~--CI

+ :~QB--"B'O~ PdCI2(dba)2 > Ph-B'.~)~ dioxane,80~ 7-18h 190,91% Nc~BO~ " 1 , 9,%

MeOOC--~~B',O~ 183,87% NO2 ~B'b~ NC ~ ' O ~ Bb Me

MeO--~~B'O~ 184,78% OMe

BOo

1.,,,o%

~B'.~~

194,92%

180,98%

186,72% 191,72~

MeO

. ~ ~

Me2

Bb

196,0% 0"~'@

,~

0-

197, 82%

=.;~

199,73%

0..0

198,77%

~~~

~oo,,~

h 2-Pyridylboronic esters 201 were generated by cross-coupling of 2bromopyridines with bis(pinacolato)diborane(4) in the presence of a base and palladium catalyst. The boronic esters reacted in situ with unreacted 2bromopyridines to afford high yields of 2,2'-bipyridines as homocoupled products. Depending upon the reaction conditions, varying amounts of protodeboronated products were also observed [106]. Masuda and co-workers successfully prepared an uncharacterized poly(pyridine) 203 in 88% yield by reacting 2,6-dibromopyridine

Chapter I

37

with 46 in the presence of NaOH and a palladium catalyst in DMF [107]. This polymeric product produced by homocoupling of dibromide and likely went through a 2-pyridyl-boronic ester intermediate 202 (Scheme 34). Under these conditions 2bromopyridine and bis(pinacolato)diborane(4) reacted to give bipyridine 204 in 78% yield. Scheme 34

R Q ~N~B r

O

PdCl2(dppf) NaOH, DMF 201

Br

Br

NaOH, DMF

1 ~,~

203

N I

204~ High yield synthesis of biphenylboronates 205 and also 206 have been demonstrated [ 108]. The directed ortho-lithiation to the synthesis ofborylated biaryls as an extension to the synthesis of (2-dialkylaminophenyl)-diarylboranes was published [109]. Reactions on 2-dimethylaminobiphenyl 207 gave a mixture of both possible lithiation products; therefore, a symmetrical terphenyl was introduced to give N,N-dimethyl-2-(o-dimesitylborylphenyl)-5-phenylanilin 208 as the sole product (Scheme 35). A new synthetic approach to fluorescent 4-amino-4'-boryl biaryls by a boronate selective Suzuki-coupling of p-(dimesitylboryl)phenylboronates with haloarenes under the employed reaction conditions has been reported. The triarylboryl unity is not attacked whereas non-sterically hindered triarylboranes like tri-1-naphthylborane gave coupling products in good yields 207 [ 110].

38

H. A b u Ali et al.

Scheme 35

PdCI2(dppf)

~OTf

O

205, 24%

KOAc/dioxane / L- O

0-_/

-

O~

206, 91%

NMe2

NMe2

1) OTf, NEt3, DCN.._ " 2)PdCI2(dppf) ,,,.._

0

0 ---/

B(Mes)2

208

,B-'O B(Mes)2

207

B(Mes)2 R = H, OH, OMe X=Br, I

PdCl2(dppf) B(Mes)2

B(Mes)2

The first synthesis of arylboronic esters 209-215 via the coupling of bis(pinacolato)diborane(4) with easily prepared aryldiazonium tetrafluoroborate salts was reported. The palladium-catalyzed borylation reaction proceeds efficiently under mild reaction conditions in the absence of a base to afford various functionalized arylboronic esters in moderate to high yields. (Scheme 36) [l 1 l]. The new methodology features relatively mild conditions, an environmentally benign alcohol solvent and no added base. This is the first example of a direct carbon-nitrogen to carbon boron bond transformation (Scheme 36) [11 l].

39

Chapter 1 Scheme 36

PdCI2(dppf) R~-/~N2BF4

MeOH, 40 ~ 212: R = p-COOMe, 81% 213: R = p-OMe, 51% 214: R = p-NO2, 61% 215: R = p-Br, o-Me, 42%

209: R = p-Br, 80% 210: R = p-Me, 87% 211: R = p-I, 58%

3.6. Synthesis and reactions of diborametal complexes The use of diborane(4) compounds to form metal bisboryl compounds has received considerable attention in recent years, since such compounds can be added catalytically to certain organic functional groups resulting in the formation of two carbon-boron bonds. The reaction of [RhCI(PPh3)3] with HBcat affords a rhodium bisboryl complex. However, reaction of [RhCI(PPh3)3] with Bzcat2 gives the Rh(III)bisboryl compound directly. This method of preparation has proven to be useful for the synthesis of a wide range of Rh-bisboryl compounds (Scheme 37) [112]. Scheme 37

t'Bu~o I

_

'..

II I

t-Bu

_-

Dph

t-Bu

Ph3P"

t-Bu

~O ~nk

.Rh\

0

/r

t-Bu

""~-~oOB"B;~~,. B /(~.'~ t-Bu t- u/O'B

Me

"~[]~Me t-gu Ph3P\ /

Ph3P MeO I? \/"~-~ /

B-O 0\/~

--

Ph-"Rh\B"~ .~P I

O ~ ,"~'~~

t-Buy ~ ~,'~"OO

~_./rr-"3 ~ Ph3P

w"--

B,, y

~, t-Bu- -

t-Bu

\\ //-'O

I'%I1\ /"

/Cl

Rh\-

~

/PPh3 ,.,,. ,.,Rh..o, i--ii31-. B):__.~,,

PPh3

~ ~

0

Me I

Me

u

o

~-'~'o'\RI~..,~162

MeO Ph3P' ~O.~~/

Oph3

Me

40

H. Abu Ali et al.

Recently, the structures of several bisboryl platinum compounds have been reported by Miyaura et al. [113]. The formation of cis-[Pt(PPh3)2(Bpin)2] presumably formed by dissociation of 2 equiv of PPh3 from [Pt(PPh3)4] followed by oxidative addition of Bzpin2 although the precise mechanism has not been established. Recently, the same authors have described the structure of this compound [63]. In addition, lverson and Smith [114] also reported that [Pt(PPh3)2(q-C2H4)] reacted with B2cat2 via the dissociation of ethylene. Dissociation of ethylene from [Pt(PPh3)2(qC2H4)] gives rise to highly reactive intermediates for oxidative addition. In fact, [Pt(PPh3)2(q-C2H4)] reacts with a wide range of diborane(4) compounds, which include both aryl- and alkyloxydiborane(4) compounds as well as B2(1,2-S2C6H4)2 [B2thiocat2], as shown in (Scheme 38) [115]. N6th has also reported the synthesis of cis-[Pt(PPh3)2{B(OMe)2}2] resulting from the oxidative addition of B2(OMe)4 which is the sole example of a nonchelating tetra(alkoxy)diborane(4) derivative involving a [Pt(PPh3)2] center [116]. Scheme 38 t-Bu. ~ O Y / ~ "-. ~ " I'~o't~" _ y

_

PhaP-Pt~B.O

Dph f ~) .Pt~,,

t-Bu J-

\\ / / - ' X "--~---I~..

"-r~, ~-"~

x"

~

Ph3P

/PPh3 Pt\

~

x

x=o,s

"'-?CH2

R

6 R

o

R = Me, OMe O

N R

I~

O

R

1,2-Bis(dimethylamino)- 1,2-dibora- [2]-ferrocenopane 216 was synthesized by the reaction of 1,1'-dilithioferocene with 1,2-dichlorobis(dimethylamino)-diborane(4) [117]. Conformation of 216 (a-c) has been studied. The staggered conformation causes non-equivalence of 2- and 5-, and 3and 4-positions at low temperature was shown (Scheme 39).

41

Chapter 1

Scheme 39

~

Li

CI \B,,NMe2

I

Fe

CI

/B,,

NMe2

hexane

THF

~.1~,"NMe2

~

Fe

I B'NMe2 216

~'N / \ N, / B--B

I

~N,

\N/ *

216b

/

\N /

I

i~~B~N~

216c

The 1,2-diaminodichlorodiboranes(4) and B2(NCsHI0)2CI2 served as starting materials for the syntheses of the iron diborane(4)yl complexes [CI(RzN)BB(NR2)Fe(CsHs)(CO)2] (217a, NRz=NC4H8, brown, and 217h, NRz=NCsH10, red colors, in 22% and 10% yields, respectively). Upon reaction with the anionic manganese hydride complex K[(CsH4Me)MnH(CO)2], the bridged borylene complexes [{(CsH4Me)Mn(CO)z}zBNR2] (218a, NRz=NC4H8, ; 218b, NR2=NCsH10, both obtained as dark red crystalline solids in 48%, and 40% yields, respectively) were obtained with cleavage of the boron-boron bond, hydrogen migration from manganese to boron, and formation of the corresponding diboranes(6) (HzBNR2)2 (Scheme 40) [118].

42

H. Abu Ali et al.

Scheme 40

C i ......._B-,.NR2

I

NaI

CI ~ B"N a 2

Oc,-Fe~co

- NaCl

R2N =

C

N

217a

I : ~ e \ B~,,N R2

oc" co

[

217b

CI/B"'-~N R 2 217

C I _.._B/.-N R 2

1 CI / B~NR

- KCl

2

R2N =

C

N

218a

218b

NR2

M~

~ OC

~

~ .==M e CO _ _ M n O(~

CO 218

Reaction of the diborane(4) B2(NMe2)212 with two equivalents of K[(r/5CsHs)M(CO)3] (M = Mo, W, Cr) yielded the dinuclear boryloxycarbyne complexes [{(rlS-CsHs)(OC)2M--CO}2-B2(NMe2)2] (219, M = Mo; 220, M = W; 221, M=Cr), which were fully characterized in solution by multinuclear NMR techniques (Scheme 41)[119].

43

Chapter 1 Scheme 41

NaI _ IM. +

I_B.NMe2

I I "B"N M e2

oC oCO

1

NaCI

oc--,r c-O. oc

O--C~

M

' oCO

g

//

Me2 N

2

219" M = Mo 220" M =W 221" M = Cr

Direct borylation of hydrocarbons catalyzed by a transition metal complex has been extensively studied by several groups and has become an economical, efficient, elegant, and environmentally benign protocol for the synthesis of a variety of organoboron compounds. The Rh-, It-, Re-, and Pd-catalyzed C-H borylation of alkanes, arches and benzylic positions of alkylarenes by bis(pinacolato)diborane(4) or pinacolborane provide alkyl-, aryl-, heteroaryl- and benzylboron compounds have recently been partly reviewed [120]. Rhodium-catalyzed 1,4-addition reactions of bis(pinacolato)diborane(4) and bis(neopentyl glycolato)diboron to a,fl-unsaturated ketones give the corresponding boron derivatives 222, 223 (Scheme 42a) and 224-230 (Scheme 42b) [121]. This is the first reported example in which a rhodium catalyst was used in addition reaction of diboron reagents to a,fl-unsaturated electron deficient alkenes. Scheme 42a

o 0

0

22' 78%

o

223, 75%

g~'~

44

H. Abu Ali et al.

Scheme 42b

~]~ o

0

24, 76% B..-O--.1

0.. / 0 0

0

0

225,

670/0

226, 63%

.•o

,o~ / ,

227, 64%

~

0

0.._...0 0

228, 62%

0

0.. 10 0

~-~ 0... B.-.O

1..,1-~,~0 N

229, 72%

.~....fCN 230, 65%

Ph"

~CN

O.B..O

..L_jcN

Ph"

Alkanes regiospecificaily reacted at the terminal carbon with pinB-Bpin at 150 ~ In the presence of Cp*Rh(q4-C6Me6) (4.0-6.0 mol%), one equivalent of pinBBpin afforded almost two equivalents of l-borylalkanes, thus indicating participation of pinBH in the catalytic cycle. Indeed, pinBH in n-octane gave pinacol noctylboronate in 65% yield (Scheme 43) [122]. Scheme 43

O.B,O

Cp*Rh(4_06Me6) ' 150 ~

~

0

~

O. ,O

Chapter 1

45

The C-H coupling of aromatic heterocycles with bis(pinacolato)diborane(4) was carried out in octane at 80-100 ~ in the presence of a 1/2 equiv [IrCI(COD)]2(4,4'-di-tert-butyl-2,2'-bipyridine) catalyst (3 mol%). The reactions of five-membered substrates such as thiophene, furan, pyrrole, and their benzo-fused derivatives exclusively produced 2-borylated products (Scheme 44), whereas those of sixmembered heterocycles including pyridine and quinoline selectively occurred at the 3-position (Scheme 45). Regioselective synthesis of bis(boryl)-heteroaromatics was also achieved by using an almost equimolar amount of substrates and the diborane [123]. Scheme 44

231, 83%

233, 67%

232, 83%

234, 79%

IrCl(COD)2 dtbpy octane, 80 ~

X = S, O, NH, NSi(/-Pr)3

IrCI(COD)2 dtbpy 1.1 equiv

235, 71%

octane, 80 ~

236, 80%

237, 80%

46

H. Abu Ali et al.

Scheme 45

238, 9 1 %

240, 9 2 %

239, 8 9 %

-~>(C)

241, 8 3 %

lrCI(COD)2

.o

o

dtbpy octane, 80 ~

X = S, O, NH, NSi(i-Pr)3

0 IrCI(COD)2 dtbpy octane, 80 ~

1.1 e q u i v N

242, 2 8 %

243, 14%

244, 8 4 %

A combination of a Cp*Ir complex and an electron-donating alkylphosphine such as P(Me)3 is effective for aromatic C-H borylation by pinBH gave good Irreagent (Scheme 46) [124]. Scheme 46

+ 6 ~H " Me3P "Cy

B-H Jr'"H Me3P / ~ B-O

'-d-

0

Ir- reagent

Chapter I

47

Further studies resulted in significant improvement in catalyst efficiency. A maximum turnover number (4500 TON) was achieved at 150 ~ when Ir(q 5C9H7)(COD) and a bidentate alkylphosphine such as dmpe (1,2bis(dimethylphosphino)ethane) were used at 150 ~ in a sealed ampule (Scheme 47) [125]. The orientation was kinetically determined, thus giving statistical meta/para isomers (ca. 2/1) for monosubstituted arenes. Borylation selectively occurred at the common meta-carbon for 1,3-disubstituted arenes, such as 1,3-dichlorobenzene and methyl 3-chlorobenzoate, since the reaction was more sensitive to steric hindrance than electronic effects of the substituents. Scheme 47

o#_

0

~B"o 245

MeO.

U"0 0 ~

MeOpX,~,

0

246

F3C,.

F3C__ c'

CI

\ @ 0 247 Ir(~15-C9H7)COD+ drape - Y " O . B ~ C I

150~ 61h or

IrCl(COD)2+ bpy 80~ 16h

v "CI

~0 Q~248 "

IZ

ii / 249

~

.~/OMe

{~

OMe

. •o B ~ / O M e 250

0

~OMe Br Br

251

48

H. Abu Ali et aL

Hartwig and co-workers [126] have shown that using photochemical activation of Cp*Re(CO)3 with irradiation from a 450-W medium-pressure mercury lamp, reaction ofbis(pinacolato)diborane(4) in alkane in the presence of Cp*Re(CO)3 (2.4-5.0 mol%) and CO (2 atm) produced the corresponding alkylboronates. Photochemical reaction of n-hexane with Cp*Re(CO)2(Bpin)2, prepared from Cp*Re(CO)3 and pin2B2, led to the regiospecific formation of l-borylpentane in quantitative yield (Scheme 48). Scheme 48

0

0

Cp*Re(CO)3 hv, 100%

+

...H

The catalyzed borylation of octane using rhodium complex 252 with bis(pinacolato)diborane(4) selectively adds at the terminal carbon of octane to give the borylated product in 88% yield. The product 253 can be converted into octylboronic acid 254 by hydrolysis (Scheme 49) [122,127]. Scheme 49

CH3(CH2)6CH3 +

~oB-B ~

/ 252 \

150~

0" B'~"~ 253, 88% hydrolysis "~'~6 B(OH)2 254

Chapter 1

49

3.7. Reactions with dienes and alkenes

The cross-coupling reaction of bis(pinacolato)diborane(4) [(Me4C202)BB(O2C2Me4)] with allyl acetates provided the pinacol esters of allylboronic acids with common structure 255 with regio- and E-stereoselectively in high yields 256-265 as have been reported (Scheme 50). The reaction was efficiently catalyzed by Pd(dba)2 in DMSO at 50 ~ [128]. Scheme 50

~

QB B'O'~ 0 -- 0 " ~

+

",v"~/R

Ph CF3CO2~,v~ Ph MeOCO~v~ Ph PhCO2 " V ~ Ph ArO,v~

Pd(dpa)2 DMSO, 50 ~

255 +

256, 86%

A

257, 3%

O

Ph

258, ,55% 259, 89%

ArO..

.•

ArO,,~

260, 16%

9

o-~ 261, 16%

ArO.~ v

ArO.~Ph

263, 26%

0 " ~

-@9

,._ O"B-,...,..--'~.~Ph 264, 24%

Ph 265, 16%

Ph

50

H. Abu Ali et al.

Commercially available Pt(cod)C12 catalyzes the diboration of terminal alkenes, vinylarenes, and alkynes using Bzcat2 to give compounds 266-270 in excellent yields (Scheme 51) [63]. The first metal-catalyzed diboration of aldimines to form R-amino boronate esters was also obtained when Pt(cod)Cl2 was used. Scheme 51

/~ M e O ~

Bcat

MeOz ~ ' ~ ~ / ~ _ _ B c a t 266, 96%

Bcat

cl-~

CI

~=/ L--Bcat 267, 93%

o, o..~

~~i~

o,B--B,o~ _~

,,,

Pt(cod)Cl2,benzene

,./',,v/-.,..,/~/~- Bcat Beat 268, 93% -,,.~.,~-,T~-~ Bcat 269, 92% Bcat Bcat\

-C}

/Bcat

- _C>-

Bis(pinacolato)diborane(4) was selectively added to alka-l,3-dienes in the presence of a catalytic amount of platinum(0) complexes [ 129] (Scheme 52). Scheme 52

R PPh3)4 RO,,

R R (RO)2BJ/X~N--B(OR)2 271

,OR

Ro-B-B-oR ,~._~'~ba)2 = (RO)2B/~/y 272

"%'"B(OR)2

Chapter I

51

Initial studies involving phosphine-containing bis(boryl) platinum compounds indicated no activity for the diboration of alkenes [130]. Subsequently however, Smith and co-workers demonstrated an immediate reaction between [Pt(nbe)3] (nbe = norbornene) and Bzcat2 (Scheme 53), providing the norbornene diboration product 273 in 88% yield [83a]. In this case, oxidative addition of Bzcat2, followed by insertion of norbornene into the Pt-B bond is a likely mechanism although there is no experimental data to support this. Theoretical studies of Pt-boron compound indicated that insertion of ethylene into the Pt-B bonds in [Pt(PH3){B(OH)2}2] was less favorable energetically compared to the reaction involving acetylene [131]. The substitution of a zc-bound ligand for a phosphine ligand should result in an overall reduction of the activation barrier to insertion of alkenes by destabilizing the bis(boryl) platinum complex prior to the insertion step. Scheme 53

nbe-Pt

r

.nbe "nbe

nbe

/nbe be/Pt"~B-O.)~__~

=~___~

B-O

273,88%

The palladium-catalyzed coupling reaction of bis(pinacolato)diborane(4) and vinyl halides or trifluoromethanesulfonates yields vinylboronates 274 (Scheme 54) [1321. Scheme 54

R • R 2

R3

X

~ O

+

/O~

"~o'B-B~o'~

PdCI2(PPh3) 2 KOPhl5equivt~176

274a: R 1 = 274b: R 1 = 274c: R1 = 274d: R 1 =

R1

.R2 --~~~

H, R 2 = CH3(CH2) 7, R 3 = H, X = Br, 92% H, R 2 = H, R 3 = CH3(CH2) 7, X = Br, 74% R2 = (CH2)4, R3 = H, X = Br, 99% R 2 = (CH2)4, R 3 = H, X =OTf, 88%

52

H. Abu Ali et al.

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[5] [6]

[7] [8] [9] [~o] [ll]

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54

[41]

[42] [43] [44] [45] [46] [47] [481 [49]

[SOl [51] [52] [53] [541

[55] [56] [57]

[S8l [59] [60] [61] [621 [63] [64] [65]

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