硼氢化钠还原

www.elsevier.nl:locate:jorganchem Journal of Organometallic Chemistry 609 (2000) 137–151 Methods of enhancement of reactivity and selectivity of sodium borohydride for applications in organic synthesis Mariappan Periasamy *, Muniappan Thirumalaikumar School of Chemistry, Uni6ersity of Hyderabad, Central Uni6ersity PO, Hyderabad 500 046, India Received 29 February 2000; received in revised form 16 April 2000 Abstract NaBH4 does not reduce carboxylic acids, esters, amides and nitriles under ambient conditions. However, the reactivity of NaBH4 can be enhanced by the addition of certain additives. For example, addition of iodine to NaBH4 in THF provides H3B–THF that is useful for hydroborations and reductions of various functional groups. The aldehydes and ketones are reduced in a fast manner by the NaBH4 reagent. Even so, the selectivities realised in such reductions can be enhanced using NaBH4 along with another additive. In this article, various methods used for the enhancement of reactivity and selectivity of NaBH4 in organic synthesis are described. © 2000 Elsevier Science S.A. All rights reserved. Keywords: Sodium borohydride; Enhancement of reactivity; Additives; Reduction of organics 1. Introduction Metal hydrides are valuable reagents in modern or- ganic chemistry. The most frequently used hydride is the NaBH4 reagent. It is a mild, inexpensive and invalu- able reagent for applications in a wide range of reduc- tion processes. It is the reagent of choice for the reduction of aldehydes and ketones to alcohols [1] and imines [2] or iminium salts [3] to amines with protic solvents [4]. The carboxylic acids, esters, amides and nitriles are more resistant towards NaBH4 [1]. How- ever, the reactivity of NaBH4 can be enhanced by carrying out the reaction in the presence of certain additives. In this article, various methods of enhance- ment of reactivity and selectivity of NaBH4 using addi- tives for applications in organic synthesis are described. 2. Hydroboration of alkenes and alkynes Hydroboration of carbon�carbon multiple bonds provides a method for the synthesis of the valuable organoborane intermediates with high regio- and stereospecificities [5]. Historically, Brown and Subba Rao discovered the hydroboration reaction during their investigation of the activation of NaBH4 for the reduc- tion of esters using AlCl3 [6]. The use of BF3 in the place of AlCl3 led to more effective utilisation of the hydride for the generation of diborane, B2H6 and bo- rane Lewis base complexes (Eqs. 1–3) [7]. 9RCH�CH2�AlCl3 ���� diglyme 3(RCH2CH2)3B�AlH3�3NaCl (1) 12RCH�CH2�3NaBH4�4BF3 ���� diglyme 4(RCH2CH2)3B�3NaBF4 (2) (RCH2CH2)3B�3H2O2�NaOH “3RCH2CH2OH�NaB(OH)4 (3) Although several of these borane complexes are com- mercially available (e.g. H3B–THF, H3B–SMe2 and H3B–NR3), there have been sustained efforts towards the development of alternative, simple and convenient methods of generation of boranes in situ for hydrobo- ration. In 1963, it was reported that a 1:1 mixture of NaBH4 and CH3COOH hydroborates alkenes [8a]. Later, a modified procedure for hydroboranes using NaBH4–CH3COOH was reported (Eq. (4)) [8b]. * Corresponding author. Tel.: �91-40-3010904; fax: �91-40- 3010120. E-mail address: mpsc@uohyd.ernet.in (M. Periasamy) 0022-328X:00:$ - see front matter © 2000 Elsevier Science S.A. All rights reserved. PII: S0022-328X(00)00210-2 Administrator 高亮 Administrator 高亮 Administrator 高亮 Administrator 高亮 Administrator 高亮 Administrator 高亮 M. Periasamy, M. Thirumalaikumar : Journal of Organometallic Chemistry 609 (2000) 137–151138 NaBH4�CH3COOH“CH3COOBH3Na ������������� 1. n-C4H9CH�CH2 2. H2O2�OH� n-C4H9CH2CH2OH 75% (4) Selective hydroboration of olefinic moiety in the pres- ence of carboxylic acid group was reported from this laboratory (Eq. (5)) [9]. (5) Also, a new method of conversion of olefins to dialkyl ketone was developed (Eq. (6)) [10]. NaBH4������������� 1. AcOH–THF 2. n-C8H17CH�CH2 25°C, 12 h ������������� 1. CHCl3–NaOMe 2. H2O2–OH� (n-C8H17CH2CH2)2 80% C�O (6) A method of conversion of terminal alkenes to car- boxylic acids through hydroboration of olefins was also developed (Eq. (7)) [11]. This method provides a simple, one-pot synthesis of carboxylic acids from terminal alkenes. (7) Also, various combinations of metal salts and borohy- drides, such as SnCl4–NaBH4 [12], TiCl4–NaBH4 [13], TiCl4–PhCH2N�(Et)3BH4� [14] and CoCl2–NaBH4 [15] have been reported to effect hydroboration of olefins. Whereas the CoCl2–NaBH4 combination behaves as a hydroborating agent when the reaction is carried out with THF for 2 h at room temperature (r.t.) before the addition of alkene, it works as a hydrogenating agent [15] in methanol (Eq. (8)). This method has some advantages over the reported method using alcoholic medium [16]. (8) Chiral semicorrin 1–3 cobalt complexes can be pre- pared readily using CoCl2 and the corresponding free ligands. These complexes are efficient enantioselective catalysts for the conjugate reduction of a,b-unsaturated carboxylates (Eq. (9)) [17] and a,b-unsaturated carbox- amides [18] using NaBH4. (9) Chalcones undergo facile reduction on reaction with NiCl2–NaBH4 system to afford dihydrochalcones (Eq. (10)) [19]. The use of copper or cobalt chloride in place of NiCl2 is not as efficient for this application. (10) The NaBH4 reacts with I2 to give diborane (Eq. (11)) [20a]. 2NaBH4�I2“B2H6�H2�2NaI (11) The reactive ‘H3B–THF’ species can be easily generated in situ by mixing NaBH4 and I2 in THF [20b]. Hydro- boration of alkenes using this NaBH4–I2 system in THF followed by oxidation gives the corresponding anti- Markovnikov alcohols (Eqs. (12) and (13)) in good yields [21,22]. n-C8H17CH�CH2������� NaBH4–I2 THF ����� H2O2 NaOH n-C8H17CH2CH2OH 92% (12) (13) Later, it was reported that electrochemical oxidation of NaBH4 using catalytic amounts of sodium iodide gives diborane that hydroborates olefins (Eq. (14)) [23]. (14) The Me3SiCl–PhCH2N�(Et)3BH4� reagent system has been reported to effect hydroboration of olefins to give anti-Markovnikov alcohols after oxidation (Eq. (15)) [24]. CH3(CH2)6CH�CH2 ����������� 1. PhCH2N�(Et3)B�H4 Me3SiCl, CH2Cl2 2. H2O2�OH� CH3(CH2)7CH2OH 72% (15) M. Periasamy, M. Thirumalaikumar : Journal of Organometallic Chemistry 609 (2000) 137–151 139 Very recently, it has been reported that the tetrabutyl- ammonium borohydride liberates diborane in solvents such as CH2Cl2, CHCl3 and CCl4. A number of terminal, internal and cyclic alkenes were hydroborated using this borohydride (Eq. (16)) [25]. (16) The 1-alkynes undergo dihydroboration to yield the corresponding terminal alcohols after oxidation. Gener- ally, the disubstituted alkynes give vinyl boranes that on oxidation offord ketones as the major product (Eqs. (17) and (18)) [25,26]. However, the diphenyl acetylene yields 1,2-diphenylethanol as the major product through dihy- droboration under these conditions. C6H5C�CC6H5������������� NaBH4�Bu4N�Cl� CHCl3 C6H5CH(OH)CH2C6H5 83% (17) CH3CH2C�CCH2CH3������������� NaBH4�Bu4N�Cl� CHCl3 CH3CH2CO(CH2)2CH3 90% (18) The PdCl2–NaBH4–polyethyleneglycol (PEG)– CH2Cl2 system is effective for hydrogenation of car- bon�carbon triple bonds to the corresponding cis-alkenes (Eq. (19)) [27]. This reagent has advantages of faster rates and higher selectivity. (19) 3. Reduction of carboxylic acids The NaBH4 gives acyloxyborohydride species on reac- tion with carboxylic acids in THF that hydroborate olefins. The acyloxy moieties in such acyloxyborohydrides remain unchanged under ambient conditions. However, one half of the acyloxy moiety undergoes reduction upon heating to give the corresponding alcohol (Eq. (20)) [28]. (20) A similar reaction was also observed using NaBH4, RCOOH and catechol at 25°C (Eq. (21)) [29]. (21) Aliphatic carboxylic acids are reduced by NaBH4 to the corresponding alcohols in good yields when RCOOH and CF3COOH are used in 1:1 ratio under ambient conditions (Eq. (22)). However, the aromatic acids give poor yields (e.g. benzoic acid 20%). Also, the NaBH4– CF3COOH combination is good for the reduction of aliphatic carboxylic acids (65–95% yields). Again, aro- matic acids give poor results under these conditions (30%). (22) The ZnCl2–NaBH4 reagent system readily reduces both aliphatic and aromatic acids to the corresponding alcohols in refluxing THF (Eq. (23)) [30]. The reaction requires only stoichiometric quantities of hydride for this conversion. Also, dicarboxylic acids are reduced to the corresponding diols under these conditions. RCOOH��������� NaBH4�ZnCl2 THF, D RCH2OH R�alkyl:aryl 70�95% (23) The reagent prepared using ZrCl4 and NaBH4 reduces the carboxylic acids in excellent yields under mild condi- tions (Eq. (24)) [31]. PhCOOH��������� NaBH4�ZrCl4 THF, rt, 5 h PhCH2OH 85% (24) Carboxylic acids are reduced to the corresponding alcohols under ambient conditions by the NaBH4–I2 reagent system in very good yields with some selectivities (Eqs. (25) and (26)) [32]. CH3(CH2)8COOH�������� NaBH4–I2 THF 0–25°C CH3(CH2)8CH2OH 95% (25) (26) M. Periasamy, M. Thirumalaikumar : Journal of Organometallic Chemistry 609 (2000) 137–151140 Further, selective reduction of the carboxylic acid group in an olefinic acid has also been achieved by forming the corresponding acyloxyborohydride before the addition of I2 (Eq. (27)) [32]. (27) Cyanuric chloride–NaBH4 reagent system has also been used to effect the reduction of carboxylic acids to alcohols under mild conditions (Eq. (28)) [33]. (28) Facile, chemoselective reduction of carboxylic acids to alcohols using a phosphonium hexafluorophosphate (BOP reagent)–NaBH4 reagent system has been reported (Eqs. (29) and (30)) [34]. Also, this method is convenient, rapid and chemoselective in several cases. For example, functional groups such as nitro, nitrile, azido and ester are unaffected under these conditions. (29) (30) 4. Reduction of amino acids and their derivatives Chiral amino alcohols are important class of com- pounds. They are useful in asymmetric transformations, synthesis of pharmaceuticals [35], resolution of racemic mixtures [36] and in synthesis of insecticides [37]. Obvi- ously, several reagents are available (e.g. LiAlH4 [38], DIBAL [39], H3B–THF [40]) for the reduction of free as well as protected amino acids to the corresponding amino alcohols. However, these reagents suffer from disadvan- tages of cost, inflammability and tedious isolation proce- dures. Meyers and coworkers examined the reduction of amino acids using the NaBH4–I2 reagent system. The results indicate that it is an excellent reagent system for the conversion of amino acids to amino alcohols (Eq. (31)) [41]. (31) The N-acyl amino acids give the corresponding N- alkyl amino alcohols under these conditions (Eq. (32)) [41]. (32) However, the N-carbamate protecting group is unaf- fected under these conditions [41]. Also, the reductions of pentachlorophenyl esters of the Boc protected amino acids and peptides to the corresponding alcohols have been reported (Eq. (33)) [42]. (33) The NaBH4–I2 reagent system is safe, simple and inexpensive. Hence, it is useful, especially in the large scale synthesis of chiral amino alcohols. Amino acids are also reduced using the inexpensive NaBH4–H2SO4 reagent system in THF (Eq. (34)) [43]. It is of interest to note that no racemization occurs in the reduction of amino acids using NaBH4–I2 or NaBH4– H2SO4. (34) 5. Reduction of carboxylic acid esters The NaBH4–ZnCl2 reagent system exhibits powerful reducing properties in the presence of a tertiary amine. The carboxylic esters were smoothly reduced by this reagent to their corresponding alcohols (Eq. (35)) [44]. Further, the reduction does not take place without the amine under these conditions. (35) M. Periasamy, M. Thirumalaikumar : Journal of Organometallic Chemistry 609 (2000) 137–151 141 The NaBH4–I2 reagent system has also been used for this application. It readily reduces carboxylic acid esters under reflux conditions in good yields (Eq. (36)) [21]. PhCH2COOEt ��������� NaBH4–I2, THF 70°C, 0.5 h ���� H2O PhCH2CH2OH 85% (36) 6. Reduction of carboxylic acid amides Numerous chemicals of importance in medicinal chemistry have been prepared through reduction of amides [45]. It was found that the amides can be easily reduced to primary amines using NaBH4–CoCl2 system in good yields in hydroxylic as well as in non-hydrox- ylic solvents (Eq. (37)) [46]. n-C3H7CONH2���������� NaBH4–CoCl2 n-C3H7CH2NH2 70% (37) The NaBH4–I2 system is also useful for the reduction of amides (Eqs. (38)–(40)) [21]. PhCONH2 ������� NaBH4–I2 THF, D ���� NaOH PhCH2NH2 70% (38) PhNHCOCH3“PhNHCH2CH3 75% (39) Ph(CH3)NCOCH3“Ph(CH3)NCH2CH3 74% (40) Further, reduction of amides containing sensitive functional groups can also be carried out using NaBH4–I2 reagent system under ambient conditions (Eq. (41)) [47]. (41) A new procedure for the highly selective reduction of tertiary amides to amines using NaBH4–bis(2-bro- moethyl)selenium dibromide 4 has been reported (Eq. 42) [48a,b]. (42) At a higher temperature, this reaction takes place smoothly in a shorter period. However, reduction of secondary and primary amides with this system in THF failed. Also, without the selenium compound, the reac- tion did not take place. It has been observed that the reaction of NaBH4 with 4 produces borane (5) and bis(2-bromoethyl)selenide (6). (BrCH2CH2)2Se–BH3 (BrCH2CH2)2Se 5 6 7. Reduction of nitriles The CoCl2–NaBH4 reagent system effectively re- duces the nitriles in good yields [46] in hydroxylic as well as non-hydroxylic solvents (Eq. (43)). C6H5CH(OH)CN���������� NaBH4–CoCl2 C6H5CH(OH)CH2NH2 80% (43) Mandelonitrile is smoothly reduced using the NaBH4–CoCl2 system [49]. It is of interest to note that reduction by LiAlH4 gives the a-hydroxy-b-phenylethyl- amine in low yields. Cupric salts–NaBH4 combinations are also effective for reduction of nitriles. The halo- genides, sulfates, carboxylates of cobalt, nickel, iridium, rhodium, osmium and platinum were also used along with NaBH4 in several applications. Also, ZrCl4– NaBH4 reagent system has been used for the reduction of nitriles in excellent yields (Eq. (44)) [31]. PhCH2CN���������� NaBH4–ZrCl4 THF, r.t. PhCH2CH2NH2 91% (44) Nitriles are also reduced by NaBH4–I2 system in THF under refluxing conditions (Eq. (45)) [21]. PhCN������ NaBH4–I2 THF ������ NaOH PhCH2NH2 72% (45) Also, nitriles on reaction with a mixture of NaBH4 and bis(2-bromoethyl)selenium dibromide (4), in boil- ing THF give the corresponding primary amines (Eq. (46)) [48]. RCN������������ 1. NaBH4–4, THF 2. HCl RCH2NH2.HCl R�alkyl:aryl 35–73% (46) This reagent system does not affect many other sub- stituents that are susceptible to H3B–THF [48b]. 8. Reduction of acid chlorides The acyl chlorides are efficiently reduced to the cor- responding alcohols on reaction with Zn(BH4)2 in pres- ence of TMEDA (Eq. (47)) [50]. Electron withdrawing group in the substrates enhances the rate of reduction. It is of interest to note that the selective reduction of acyl chlorides in the presence of other functional groups, such as chloro, nitro, ester and conjugated double bond can be achieved using this reagent system. RCOCl��������� NaBH4–ZnCl2 TMEDA RCH2OH R�alkyl:aryl 86–98% (47) M. Periasamy, M. Thirumalaikumar : Journal of Organometallic Chemistry 609 (2000) 137–151142 9. Reduction of nitro compounds Nitro compounds are reduced to the corresponding amino compounds effectively using the NaBH4–CuSO4 system (Eq. (48)) [51]. It was reported that this system also reduces ketones, aliphatic esters, olefins and nitriles. (48) A novel reagent system, prepared using BiCl3 and NaBH4, reduces aromatic nitro compounds to the cor- responding amines in good yields (Eq. (49)) [52]. The functional groups such as Me, OH, NH2, OMe, Cl in the aromatic ring do not have any marked effect on the rate of the reaction. Moreover, these functional groups survive during the reduction, making this process fairly general and selective. RNO2��������� NaBH4–BiCl3 THF RNH2 R�alkyl:aryl 35–90% (49) The aromatic nitro compounds are also reduced in good yields to the corresponding N-aryl hydroxyl- amines using NaBH4 in the presence of catalytic amounts of metallic selenium (Eq. (50)) [53]. (50) These selenium catalysed reductions were accelerated by electron withdrawing groups. The aliphatic nitro compounds gave the corresponding oximes under these conditions. The active species in this system is the hydrogen selenide anion [54]. Hence, this method opens up a new way to the use of selenium as a redox catalyst in organic synthesis. The N-aryl hydroxylamines have been also prepared through antimony catalysed NaBH4 reduction of ni- troarenes (Eq. (51)) [55]. (51) The novel NaBH4–(NH4)2SO4 reagent system has been used for the selective, rapid reduction of nitro compounds to the corresponding amino derivatives in good yields (Eq. (52)) [56]. RNO2���������������� NaBH4–(NH4)2SO4 EtOH, r.t., 30–120 min RNH2 R�aryl (70–90%) (52) 10. Reduction of aldehydes and ketones The NaBH4 is a reagent of choice for the reduction of aldehydes and ketones. The reactivity of NaBH4 can be readily modified through its reaction with acetic acid (Eq. 53) [2,57]. With excess of acetic acid, triacyloxy borohydride is formed. The NaBH4–CH3COOH reagent system has been used for reductions of enam- ines, imines, vinylogous carbamates, aromatic and aliphatic a,b-unsaturated tosylhydrazones, pyrylium salts [58]. It has been also used for the reduction or reductive N-alkylation of amines, oximes [59] and ni- trogen containing heterocycles [2]. (53) The NaBH(OAc)3 reagent has been used for the chemoselective reduction of aldehydes in the presence of ketones [2]. Also, selective reduction of ketones using NaBH4 in glacial acetic acid solvent or NaBH4 in THF using 3 equivalents of acetic acid were reported [60]. Further, highly stereoselective reduction of ketones was also achieved using NaBH(OAc)3 in acetic acid (Eq. 54) [61]. (54) In the presence of ZrCl4, NaBH4 reduces the alde- hydes selectively in high yields (Eq. (55)) [31]. PhCHO��������� NaBH4�ZrCl4 THF, r.t., 5 h PhCH2OH 95% (55) Aromatic aldehydes are more selectively reduced than the related ketones by the reducing system consist- ing of NaBH4 and SnCl2 in THF (Eq. (56)) [62]. It may of interest to note that selective reduction of aldehydes in the presence of ketones is ordinarily impracticable using the reducing agents such as alkali metal borohy- drides, aluminohydrides and diborane [63]. PhCHO���������� NaBH4–SnCl2 PhCH2OH 96.8% �PhCOPh 92% (56) M. Periasamy, M. Thirumalaikumar : Journal of Organometallic Chemistry 609 (2000) 137–151 143 The NaBH4 in combination with anhydrous AlCl3 conveniently reduces diaryl and aryl alkyl ketones to methylenic hydrocarbons (Eq. (57)) [64]. (57) Although alkali metal borohydrides have received much attention in organic synthesis, the studies on the use of alkaline earth metals are limited. For example, a,b-unsaturated ketones more readily converted to allylic alcohols selectively using NaBH4 in the presence of CaCl2 (Eq. (58)) [65]. Among the alkaline earth metal chlorides examined, CaCl2 gives the best combination of good yields and selectivities in the NaBH4 reduction of 2-cyclo- hexen-1-one. Further, this method provides a simple, inexpensive alternative procedure for the selective 1,2-re- duction of a,b-unsaturated ketones. (58) Metal salts mediated NaBH4 reduction of a-alkyl-b- keto esters leads to different stereochemical control depending on the nature of the metal atom. For example, the strongly chelating TiCl4 led to the syn isomer while non-chelating CeCl3 [66] gave anti isomer [67]. The keto esters are also reduced using the ZnCl2–NaBH4 system to afford