Allylboration - ACS Symposium Series (ACS Publications)

Chapter 3

Allylboration

Downloaded by UNIV OF FLORIDA on December 6, 2016 | http://pubs.acs.org Publication Date (Web): November 30, 2016 | doi: 10.1021/bk-2016-1236.ch003

Subash C. Jonnalagadda,*,1,2 Pathi Suman,1 Amardeep Patel,1 Gayathri Jampana,1 and Alexander Colfer1 1Department

of Chemistry and Biochemistry, Rowan University, Glassboro, New Jersey 08028, United States 2Department of Biomedical and Translational Sciences, Rowan University, Glassboro, New Jersey 08028, United States *E-mail: [email protected]

Allylboration involves the addition of “allyl” boron species across multiple bonds (most commonly aldehydes, ketones, and imines). This chapter will focus on the recent advances in the area of stereoselective allylboration with a main emphasis on the boranes derived from chiral auxiliaries such as α-pinene, tartrate, borabicylo[3.3.2]decane, and camphor. Other topics include catalytic enantioselective allylboration and the chemistry of chiral α–substituted allylboranes. Allylboration of other functional groups including epoxides, nitriles, lactams, and heteroaromatics are also discussed.

Introduction Allylboration is a carbon-carbon bond forming reaction that deals with the addition of an “allyl” boron species across a multiple bond (e.g. C=O, C=N, C=C, N=N, S=O, C≡N, C≡C, etc.) or even a strained single bond. While this reaction is routinely observed with carbonyl compounds such as aldehydes, ketones, and the corresponding imines, there are several instances in which these reactions happen with substrates such as alkenes, alkynes, allenes, amides, lactams, nitriles, pyrazines, pyridines, pyrroles, etc. Allylboration of aldehydes and ketones using B-allyl dialkylboranes as the allylating reagents is known to be a very fast reaction and it proceeds even at very low temperatures (-100 °C). This has subsequently led to the development © 2016 American Chemical Society Coca; Boron Reagents in Synthesis ACS Symposium Series; American Chemical Society: Washington, DC, 2016.


of several chiral allylboranes for the stereoselective allylboration of aldehydes and ketones. The stereoselectivity could in general be enhanced by lowering the temperature of these reactions. In most cases, allylboration is predicted to occur via an allylic rearrangement involving a six-membered chair-like transition state. While several allyl metal reagents have been developed for the allylation of carbonyl compounds, allylboron reagents hold a special place in organic chemistry and synthesis owing to multiple reasons. Firstly, boron offers an environmental-friendly alternative to most other toxic metals that are routinely used for this reaction. Secondly, allylboranes provide very high levels of stereocontrol as these reactions proceed via a rigid six-membered chair-like transition state. Accordingly, there have been extensive investigations on the use of chiral auxiliaries for carrying out enantio- and diastereoselective allylboration reactions. Finally, many of the allyl boron reagents are economical as they can be readily accessed from simple precursors such as sodium borohydride, and chiral pool materials such as camphor, α-pinene, tartaric acid, etc. Owing to their importance, utility, and applications, thousands of papers dealing with the preparation of new allylboron reagents and their use in natural product syntheses have appeared in the past four decades and it would be impractical to cover all aspects of this topic in one chapter. Needless to mention, allylation of carbonyl compounds using boron reagents has been extensively reviewed (1–6). Due to the extensive amount of research that has been undertaken in this area, it is prohibitive to cover all topics in a single chapter and we apologize in advance for any unintentional omissions due to oversight. This chapter will primarily deal with the preparation of various highly functionalized chiral allylboranes (with particular emphasis on α-pinene based chiral auxiliaries), along with a few of the recent developments on the design of catalytic enantioselective allylboration and a brief discussion on α-substituted chiral allylboranes.

Stereoselective Allylboration of Carbonyl Compounds Mikhailov and Bubnov first reported the synthesis of triallylborane (7) and its further reaction with carbonyl compounds (8–10). The reaction of aldehydes and ketones with allylboranes involves the addition of an allyl group via allylic rearrangement and most commonly, the γ-carbon in the allylborane adds to the carbonyl carbon (8–10). Hoffmann introduced the first chiral allylborane (1) (11, 12) derived from camphor for the enantioselective synthesis of homoallylic alcohols which was then utilized for the stereoselective synthesis of natural products (13–15). Apart from camphor, Hoffmann also introduced several chiral vicinal diol based boronates (2) (16) for allylboration. Corey was able to improve the stereoselectivity of these boronates further by the introduction of chiral vicinal sulfonamide derived allylboranes (17). Yamamoto introduced tartarate ester based allenylboronate and 68 Coca; Boron Reagents in Synthesis ACS Symposium Series; American Chemical Society: Washington, DC, 2016.


propargylboronate for the stereoselective synthesis of homopropargylic alcohols and homoallenyl alcohols respectively (18, 19). Roush developed this area in a significant manner and he was able to synthesize a diverse scaffold of higher order allylborane reagents derived from chiral tartrate esters (3) (20, 21) and tartaramide (22). Brown discovered the α-pinene based B-allyldiisopinocampheylborane (4) in 1983 and ever since, these reagents have been very well studied (23). These reagents have attained immense significance owing to the excellent levels of reagent-based stereocontrol observed during their reactions with aldehydes and imines. Reetz introduced chiral diamine-derived 1,3,2-dizaboroles (5) as stereoselective allylborating agents (24, 25) and Itsuno was further able to develop these reagents for solid phase applications (26). Masamune introduced chiral borolane (6) prepared via kinetic resolution methodology for chiral allylation (27, 28). Soderquist was further able to extend the stereoselective allylation to ketones and ketimines via the introduction of borabicyclo[3.3.2]decane (7) as the chiral auxiliary (29). Kauffman (30) introduced binaphthol based allylborane (8) for the allylboration of carbonyl compounds (Figure 1).

Figure 1. Chiral auxiliary-based allylboranes.

Based on the exceptional success of α-pinene, Brown investigated the use of several terpenoid allylboranes derived from β-pinene (9), ethylapopinene (10), limonene (11), 2-carene (12), 3-carene (13), and longifolene (14) (Figure 2) (31–34). While 2-carene and 3-carene based reagents do often provide higher levels of enantioselectivity, α–pinene has still proven to be the most popular chiral auxiliary because of the excellent levels of stereocontrol that it offers in addition to being cost-effective as both antipodes of this compound are abundantly available from pine trees. 69 Coca; Boron Reagents in Synthesis ACS Symposium Series; American Chemical Society: Washington, DC, 2016.


Figure 2. Chiral terpenoid-derived allylboranes.

Preparation of Allylboranes via “Allyl”transmetalations Standard methods for the preparation of allylboranes involve the generation of allyl metal species (via deprotonation or dehalogenation) and subsequent transmetalation with dialkylborinates or trialkylborates. Alternatively, allylboranes could also be synthesized via hydroboration of 1,2-dienes (allenes) or 1,3-dienes. Another method of preparation includes homologation of vinylboranes or boronates. This section has been categorized based on the method of preparation of the chiral allylboranes. Most of the functionalized allylboranes reported below have been prepared using chiral auxiliaries derived from α-pinene as well as tartarate esters. In order to avoid redundancy, for the most part, we have focused on functionalized B-“Allyl”diisopinocampheylboranes.

(B)-Allyldiisopinocampheylborane Introduced by Brown and Jadhav (35), B-Allyldiisopinocampheylborane 4 has attracted significant attention from the organic chemistry community. This reagent is prepared by the reaction of B-chloro or B-methoxydiisopinocampheylborane (Ipc2BCl 16 or Ipc2BOMe 17) with allyl Grignard, followed by the filtration of the magnesium salts under inert-atmosphere. Ipc2BCl 16 and Ipc2BOMe 17 are in turn obtained from diisopinocampheylborane Ipc2BH 15 upon treatment with HCl and MeOH respectively (Scheme 1). Ipc2BH is easily obtained via hydroboration of α-pinene. Allylborane 4 reacts with a wide variety of aldehydes to provide the homoallylic alcohols in excellent enantiomeric excess (ee). As mentioned earlier, α-pinene provides exceptional levels of stereocontrol independent of the inherent chirality of the substrates. As both enantiomers of α-pinene are readily available, it is possible to obtain both enantiomers of the homoallylic alcohols with the appropriate choice of the stereoisomer of α-pinene. The high levels of selectivity can be explained based on the rigid six-membered chair like transition states (TS1 & TS2). The 1,3-diaxial 70 Coca; Boron Reagents in Synthesis ACS Symposium Series; American Chemical Society: Washington, DC, 2016.


strain forces the aldehyde to approach the allylborane preferentially from one side (TS2). These reagents are quite stable and they are even commercially available as 1M solutions in pentane (36). They could be stored under an inert atmosphere for longer periods of time without appreciable decomposition or loss of enantioselectivity (35). Recently Singaram et al. were able to show that even indium is able to promote the formation of B-allyldiisopinocampheylborane 4 upon reaction with allyl bromide (37).

Scheme 1. Allylboration of aldehydes with B-allyldiisopinocampheylborane.

Allylation of Imines Using B-Allyldiisopinocampheylborane Itsuno reported the allyboration of N-silylaldimines and N-aluminoaldimines 20 with a variety of allylborane reagents, and it was noticed that the allylboration with allylborane 4 seemed to provide lower enantioselectivities (38–40). Brown demonstrated that the reaction of N-silyl imines with 4 was indeed taking place during work up (as observed by the exothermicity during work up). Accordingly, Brown et al. were able to enhance the enantioselectivity of this reaction by the addition of a stoichiometric amount of water to the reaction mixture at low temperature (-78 °C) (Scheme 2) (41). Later Ramachandran and co-workers applied this methodology for the synthesis of diverse homoallylic amines and azaheterocyclic compounds (42–44). 71 Coca; Boron Reagents in Synthesis ACS Symposium Series; American Chemical Society: Washington, DC, 2016.


Scheme 2. Allylboration of aldimines and acylsilanes.

Allylation of Acylsilanes Using B-Allyldiisopinocampheylborane Asymmetric allylboration of acylsilanes 22 has also been reported with Ballyldiisopinocampheylborane 4 furnishing the tertiary homoallylic alcohols 23 in varying levels of enantioselectivity (2-90% ee) (Scheme 2) (45).

(B)-(Z or E)-γ-Methylallyldiisopinocampheylborane (B)-(Z or E)-γ-Methylallyldiisopinocampheylborane reagents are obtained by the deprotonation of cis or trans 2-butene respectively, using Schlosser’s base (nBuLi, KOtBu) followed by transmetallation with Ipc2BOMe 17 or Ipc2BCl 16. Temperature plays a critical role in this reaction as the cis and trans crotyl anions Z-25 and E-25 undergo rapid interconversion at higher temperature, which leads to scrambling of the reagent stereochemistry. The potassium counter ion is required for maintaining the integrity of the double bond because of its ability to form a stable η3 linkage with crotyl anion at lower temperature. The reaction of crotylboranes 26 with aldehydes results in the formation of homoallylic alcohols 27a-d in high diastereomeric excess (de) and enantiomeric excess (ee) (46, 47). Crotylboration offers a valuable tool to the synthetic chemist for the synthesis of all four diastereomers of the propionate motif in the homoallylic alcohols 27a-d, via an appropriate choice of (Z or E)-2-butene and (+ or -) α-pinene (Scheme 3).

72 Coca; Boron Reagents in Synthesis ACS Symposium Series; American Chemical Society: Washington, DC, 2016.


Scheme 3. Crotylboration of aldehydes.

(B)-β-Methylallyldiisopinocampheylborane (B)-β-Methylallyldiisopinocampheylborane is prepared by the reaction of 2-methylpropene 28 with n-butyl lithium and subsequent treatment with Ipc2BOMe 17 (48, 49). The resulting “ate” complex is treated with BF3.Et2O to release the methallylborane 30, which upon reaction with aldehydes furnishes the β-methylhomoallylic alcohols 31 in very good ee (Scheme 4).

Scheme 4. β-Methylallylboration of aldehydes. 73 Coca; Boron Reagents in Synthesis ACS Symposium Series; American Chemical Society: Washington, DC, 2016.

1,3-Bis(diisopinocampheylboryl)-2-methylenepropane


Barrett et al. demonstrated the synthesis of bis-allylborane 33 via a double deprotonative lithiation of 2-methylpropene 28 with excess n-butyl lithium and treatment with Ipc2BCl 16. This reagent furnished, upon reaction with two equivalents of aldehyde followed by oxidative work up, the C2-symmetric bis homoallylic alcohols 34 in good yields and selectivity (Scheme 5) (50, 51).

Scheme 5. 1,3-Bis(diisopinocampheylboryl)-2-methylenepropane. (B)-γ,γ-Dimethylallyldiisopinocampheylborane Brown and Jadhav reported the synthesis of γ,γ-dimethylallyldiisopinocampheylborane 36 via the hydroboration of 1,1-dimethylallene 35 with Ipc2BH 15, however this method required the use of expensive dimethylallene reagent, thus rendering it difficult for large scale applications (52). We then demonstrated the use of 4-chloro-2-methylbut-2-ene 37 (readily obtained from inexpensive prenyl alcohol) for the preparation of 36. Thus, the conversion of 37 into the corresponding Grignard and subsequent treatment with Ipc2BOMe 17 provided ready access to the allylborane 36, which upon reaction with aldehydes yielded β,β-dimethyl homoallyl alcohols 38 in high ee (Scheme 6) (53, 54).

Scheme 6. γ,γ-Dimethylallylboration of aldehydes. 74 Coca; Boron Reagents in Synthesis ACS Symposium Series; American Chemical Society: Washington, DC, 2016.

(B)-Isoprenyldiisopinocampheylborane


Brown and Randad reported the preparation of B-isoprenylborane 42 via the deprotonation of isoprene 39 with potassium tetramethylpiperidide 40 followed by the addition of Ipc2BOMe 17 to the resulting allylpotassium 41. These reagents were then used for the synthesis of ipsenol 43 and ipsdienol 44 by reaction with appropriate aldehydes (Scheme 7) (55, 56).

Scheme 7. Isoprenylboration of aldehydes.

(B)-(Z)-γ-Alkoxyallyldiisopinocampheylborane The reaction of allyl alkyl ethers 45 with sbutyl lithium results in the formation of (Z)-olefinyl anion 46 due to the strong coordination between ether oxygen and lithium (57, 58). Brown et al. were able to convert 46 to (Z)-γ-alkoxyallylborane reagent 47 upon further treatment with Ipc2BOMe 17 (59). Allylboration of aldehydes with 47 provides excellent de and ee for the corresponding syn β-alkoxyhomoallylic alcohol 48. While this reagent was initially developed using allyl methyl ether 47a, subsequently, several new reagents have also been prepared using different alcohol protecting groups such as methoxymethyl (MOM) 47b, 2-(trimethylsilyl)ethoxymethyl (SEM) 47c, methoxyethoxymethyl (MEM) 47d, p-methoxyphenyl (PMP) 47e, tetrahydropyranyl (THP) 47f, etc. (Scheme 8). These protecting groups offer greater versatility for further chemical manipulations of the syn β-alkoxyalcohols (60–63). 75 Coca; Boron Reagents in Synthesis ACS Symposium Series; American Chemical Society: Washington, DC, 2016.


Scheme 8. (Z)-γ-Alkoxyallylboration of aldehydes.

(B)-(E)-γ-Methoxyallyldiisopinocampheylborane

While the deprotonative lithiation of allyl methyl ethers provides the (Z)-stereochemistry for the methoxyallyl anion as mentioned above (Scheme 8), Hoffmann was able to show that reduction of (E)-1-methoxy-3-(phenylthio)propene 49 with two equivalents of potassium naphthalenide 50 at -120 °C, afforded the potassium (E)-alkoxyallyl anion 51 (64, 65). Ganesh and Nicholas trapped the allyl anion 51 with Ipc2BOMe 17 to provide the elusive (E)-γ-alkoxyallylborane reagent 52 (66). As expected, this reagent provided anti stereochemistry for the homoallylic alcohols 53 upon reaction with aldehydes (Scheme 9).



Scheme 9. (E)-γ-Alkoxyallylboration of aldehydes.

(B)-(Z)-γ-Chloroallyldiisopinocampheylborane Hertweck carried out the deprotonation of allyl chloride 54 with lithium dicyclohexylamide (Chx2NLi) which resulted in the formation of (Z)-olefin 55, because of the Li-Cl coordination as seen above (Scheme 8) during the deprotonation of allyl alkyl ethers. Treatment of 55 with Ipc2BOMe 17 yielded the requisite allylborane which upon reaction with aldehydes resulted in the syn β-chlorohomoallyl alcohols 58 (67, 68). It should be noted that the regular alkaline peroxide work up of this reaction would lead to the epoxidation to produce the vinyloxiranes. Accordingly, mild work up with 8-hydroxyquinoline is typically employed to obtain β-chloro-homoallylic alcohols (Scheme 10).

Scheme 10. (Z)-γ-Chloroallylboration of aldehydes.


(B)-(E)-γ-(N,N-Diphenylamino)allyldiisopinocampheylborane


Lithiation of allyl diphenylamine 59 with n-butyl lithium in the presence of tetramethylethylenediamine was effective in the preparation of (E)- anion 60, which upon sequential treatment with Ipc2BOMe 17, aldehyde, and alkaline peroxide workup produced anti β-diphenylaminohomoallyl alcohols 63 (Scheme 11) (69).

Scheme 11. (E)-γ-(Diphenylamino)allylboration of aldehydes.

(B)-(E)-γ-(Diphenylmethyleneamino)allyldiisopinocampheyl Borane While the allyl diphenylamine based allylborane 61, was useful for the synthesis of β-diphenylaminoalcohol 63, Barrett and co-workers were able to extend this methodology for the preparation of β-amino homoallylic alcohols 69 as well (70, 71). Accordingly, they initiated their synthesis with the deprotonation of benzophenone-allylimine 64, with LDA followed by the addition of Ipc2BCl 16 to yield the allylborane 66. This reagent upon addition of aldehyde, alkaline work up and deprotection of the imine yielded the expected anti β-amino homoallyl alcohols 69. Barrett et al. were able to further expand this methodology for the preparation of β-amino allylalcohol 70. This was accomplished by the treatment of intermediate imine 68 with triflic anhydride and acidic work up (Scheme 12).



Scheme 12. Reaction of (B)-(E)-γ-(Diphenylmethyleneamino)allyldiisopinocampheylborane with aldehydes.

(B)-(E)-γ-((N,N-Diisopropylamino)dimethylsilyl)allyldiisopino Campheylborane

Barrett reported an elegant method for the preparation of anti diols 74 via a similar deprotonation, borylation, allylboration, and oxidative desilylation protocol (Scheme 13) (72–75). The requisite allylborane 73 was synthesized starting from allylsilane 71.



Scheme 13. Reaction of (B)-(E)-γ-(N,N-Diisopropylamino)dimethylsilyl)allyldiisopinocampheylborane with aldehydes. (B)-γ-(Dimethylphenylsilyl)allyldiisopinocampheylborane Roush reported the synthesis of diisopinocampheyborane reagent 76 via the reaction of allyl dimethylphenylsilane 75 with Schlosser’s base, Ipc2BOMe 17 and BF3.Et2O. Allylboration of this reagent 76 with aldehydes and subsequent work up under mild pH 6 buffer conditions resulted in the formation of anti αdimethylphenylsilyl homoallylic alcohols 77 (Scheme 14) (76–79).

Scheme 14. Reaction of (B)-γ-(Dimethylphenylsilyl) allyldiisopinocampheylborane with aldehydes. (B)-γ-(Trimethylsilyl)propargyldiisopinocampheylborane The lithiation of trimethylsilylpropyne 78 with tbutyl lithium followed by the treatment of the resulting propargyllithium 79 with Ipc2BOMe 17 resulted in the formation of (γ-trimethylsilyl) propargylborane 80. This reagent upon treatment with aldehydes yielded the homoallenyl alcohols 81 in good yield and selectivity (Scheme 15) (80). 80 Coca; Boron Reagents in Synthesis ACS Symposium Series; American Chemical Society: Washington, DC, 2016.


Scheme 15. Reaction of (B)-(γ-trimethylsilyl)propargyl-diisopinocampheylborane with aldehydes.

(B)-β-(Alkyldimethylsilyl)allyldiisopinocampheylborane Barrett demonstrated the synthesis of γ-silylhomoallylic alcohols 85 using a double transmetalation protocol, first via lithiation of allylstannane 82 and latter via the treatment of allyl lithium 83 with Ipc2BCl 16. The allylborane 84 upon allylboration with aldehydes yielded the vinylsilanes 85 (Scheme 16) (81).

Scheme 16. Reaction of (B)-β-(Alkyldimethylsilyl)-allyldiisopinocampheylborane with aldehydes.

Preparation of Allylboranes via Hydroboration of Dienes/Allenes This section deals with the preparation of chiral allylboranes employing hydroboration of 1,3-dienes or allenes. 81 Coca; Boron Reagents in Synthesis ACS Symposium Series; American Chemical Society: Washington, DC, 2016.

(B)-2-Cyclohexen-1-yldiisopinocampheylborane


Brown reported the hydroboration of 1,3-cyclohexadiene 86 with Ipc2BH 15 to yield cyclohexenylborane 87, that upon reaction with aldehydes and alkaline peroxide work up produced the cyclohexenyl alcohols 88 (Scheme 17) (82).

Scheme 17. Cyclohexenylboration of aldehydes.

(B)-(E)-γ-(1,3,2-Dioxaborinanyl)allyldiisopinocampheylborane Brown and Narla reported the hydroboration of boronoallene 89 with Ipc2BH 15 to furnish the (E)-γ-borinanylallylborane 90, which upon reaction with aldehydes followed by alkaline work up yielded the vicinal anti diols 92 in high yield and stereoselectivity (Scheme 18) (83). It should be noted that the intermediate 91 (obtained from the reaction of allylborane 90 with aldehydes) is also an allylboronate, which could still undergo another allylation with a second aldehyde. Roush cleverly made use of the differential reactivity of the allylborane 90 (which readily reacts with aldehydes even at -100 °C) and the allylboronate 91 (which reacts slowly even at higher temperatures) for carrying out the double allylation of two different aldehydes (84–87). Roush noted that the steric bulk on the boronates 91a-b was able to impact the olefin stereochemistry in the product diols E-94 and Z-94. The sterically unencumbered 1,3,2-dioxaborinane 91a upon reaction with aldehydes yielded the (E)-alkene E-94 while the hindered dioxaborolane 91b produced the (Z)-olefin Z-94 upon reaction with aldehydes. They were able to explain the difference in stereochemistry by invoking different transitions states (93a-b) so as to minimize the 1,3-pseudodiaxial interactions (Scheme 18).



Scheme 18. Double allylboration of aldehydes with (B)-(E)-γ-(1,3,2Dioxaborinanyl)allyldiisopinocampheylborane.

Roush was able to further exploit the kinetic and thermodynamic differences in the hydroboration of 1-methyl-1-borinanylallene 95 with Ipc2BH 15, for the synthesis of (Z)- and (E)-pentenediols 97 employing the double allylboration protocol (Scheme 19) (88).



Scheme 19. Hydroboration of 1,1-disubstituted allenes.

Roush further expanded this protocol for the enantiodivergent (89, 90) and enantioconvergent (91, 92) hydroboration of racemic 1,3-disubstituted silyl allene 98a, and stannyl allene 98b respectively (Scheme 20). These racemic allenes upon hydroboration with Ipc2BH yielded the enantiomerically pure allylboranes 99 which upon allylboration with aldehydes furnished the (E)-anti homoallylic alcohols 100.

Scheme 20. Hydroboration of 1,3-disubstituted allenes.

The same group also prepared higher order allylboranes 102 via hydroboration of 1,1-disubstituted allenes 101 for the synthesis of homoallylic alcohols 103 containing quaternary chiral centers (Scheme 21) (93).

Scheme 21. Preparation of higher order allylboranes. 84 Coca; Boron Reagents in Synthesis ACS Symposium Series; American Chemical Society: Washington, DC, 2016.


(B)-(Z)-γ-(Trifluoromethyl)allyldiisopinocampheylborane

Ramachandran reported the preparation of “fluoro” allylboranes for the synthesis of fluorinated homoallylalcohol derivatives. As is evident from above, hydroboration of monosubstituted allenes with silyl (101), boryl (89), or alkyl (35) side chains typically yields the (E)-allylboranes as the thermodynamic product. However, the hydroboration of trifluromethylallene with Ipc2BH yielded the (Z)-allylborane 105 and the regioisomeric vinylborane 106 in ~3:1 ratio. A weak coordination of fluorine and boron atoms might be able to explain the different stereochemical outcome during the hydroboration of 104 with Ipc2BH, thereby producing the (Z)-allylborane 105. The separation of regioisomers 105 and 106 was not necessitated as the allylborane 105 preferentially reacts with aldehydes at -100 °C generating the homoallylic alcohols 107 upon diethanolamine workup (Scheme 22) (94).

Scheme 22. γ-(Trifluoromethyl)allylboration of aldehydes.

Masamune Borolane

Masamune reported the reaction of chiral borolanes and aldehydes to produce the homoallylic alcohols in high levels of enantioselectivity (90-97% ee). The requisite allylboranes were prepared via the hydroboration of 1-trimethylsilyl-1,3-butadiene 108 followed by methanolysis and kinetic resolution with N-methylpseudoephedrine. The allylborane 6 was obtained from the chiral oxazaborolane 112 upon treatment with allyl magnesium bromide (Scheme 23) (27).



Scheme 23. Allylboration of aldehydes with B-allylborolanes.

Preparation of Allylboranes via Homologation or Isomerization (B)-(γ,γ-Difluoroallyl)diisopinocampheylborane Ramachandran demonstrated the preparation of γ,γ-difluoroallylborane 118 via the hydroboration of difluoroallene 117. The allylboration with 118 furnished difluorohomoallyl alcohols 119 in high ee. They also noted that an analogous Hoffmann’s camphor based reagent 116 which was obtained via Matteson homologation, did not provide good ee, even with the rate acceleration using Sc(OTf)3 (Scheme 24) (95).

Scheme 24. γ,γ-Difluoroallylboration of aldehydes. 86 Coca; Boron Reagents in Synthesis ACS Symposium Series; American Chemical Society: Washington, DC, 2016.

(B)-Homoallenylboronate via Matteson Homologation


Brown reported the synthesis of homoallenylboronate 121 from tartrate ester derived allenylboronate 120 employing Matteson homologation (Scheme 25) (96). This reagent upon allylboration with aldehydes furnished α-methylenylhomoallylic alcohols 122 in 60-90% ee.

Scheme 25. Homoallenylboration of aldehydes.

Iridium Catalyzed Isomerization of Vinylboranes Miyaura and co-workers demonstrated the use of transition metal catalyzed isomerization of vinylboronates 124 for the preparation of allylboronates 125 (97). The requisite vinylboronates 124 were obtained via hydroboration of propargyl silyl ether 123 with Ipc2BH 15 followed by the conversion to the tartarate ester. These allylboronates provided good enantioselectivity for the product β-alkoxyalcohols 126 upon allylboration with aldehydes (Scheme 26).

Scheme 26. Preparation of (E)-γ-alkoxyallylboronates via Iridium catalyzed isomerization. 87 Coca; Boron Reagents in Synthesis ACS Symposium Series; American Chemical Society: Washington, DC, 2016.

Borabicyclo[3.3.2]decane Chiral Auxiliary


(B)-“Allyl”-borabicyclo[3.3.2]decane: While α-pinene and tartrate based chiral reagents are effective towards allylboration of aldehydes and aldimines, they fail to provide good ee for ketones and ketimines. Soderquist was able to demonstrate the robustness of 10-trimethylsilyl/phenyl-9-borabicyclo[3.3.2]decanes (BBD) 7 towards the enantioselective “allyl”boration of ketones and ketimines as well. The requisite BBDs are obtained via Matteson homologation/ring expansion of B-methoxy-9-borabicyclo[3.3.1]-nonane 127 with trimethylsilyl-diazomethane followed by kinetic resolution with pseudoephedrine. Further treatment of the resulting oxazaborole 130 with allyl Grignard furnishes B-AllylBBD (7) which upon reaction with aldehydes and ketones yields the homoallylic alcohols in exceptional levels of enantioselectivity (generally >96% ee) (Scheme 27) (29).

Scheme 27. Allylboration of aldehydes with B-allyl-9-borabicyclo[3.3.2]decane.

Soderquist’s borane provides very high enantioselectivities in the allyl and crotylboration (131a) of a wide range of aldehydes (29) (>95% ee), ketones (80-99% ee) (98) and ketimines (99). Even in the case of α-chiral aldehydes, consistently higher enantio- and diastereoselectivities have been reported for the matched as well as the mismatched examples using BBDs as chiral auxiliary (100). Excellent selectivity was also reported for the methallylboration (131b) (101), allenylboration (131c) (102, 103), and propargylboration (131d) (104, 105) of a variety of aldehydes, ketones and imines (Scheme 28). Several other higher order allylborations of aldehydes and ketones including cyclohexenylboration 88 Coca; Boron Reagents in Synthesis ACS Symposium Series; American Chemical Society: Washington, DC, 2016.


(106) α-methylene-γ-alkyl-allylboration (107, 108), bisallylboration (109) etc. have also been reported to proceed with very good selectivities.

Scheme 28. Preparation of higher order B-“Allyl”-9-borabicyclo[3.3.2]decanes.

(B)-γ-Alkoxyallyl-borabicyclo[3.3.2]decane The (Z)-γ-alkoxyallylborane Z-133 reacts with aldehydes and aldimines to provide excellent diastereoselectivity for the product alcohols 134 and amines 135. While Brown’s alkoxyallylborane 47 fails to provide higher ee for ketones and ketimines, Soderquist’s γ-alkoxyallylborane 133 readily reacts with these substrates to provide very high ee and de for the homoallylic alcohol products (110, 111). Further it was observed that, while the faster reacting substrates such as alkyl aryl ketones and alkyl vinyl ketones provided the expected syn diastereomer of the product 136, the slower reacting ketones such as pinacolone 89 Coca; Boron Reagents in Synthesis ACS Symposium Series; American Chemical Society: Washington, DC, 2016.


resulted in the formation of the anti diastereomer of the 137 presumably due to the rapid isomerization of (Z)- γ-alkoxyallylborabicyclo[3.3.2]-decane Z-133 to the corresponding (E)-diastereomer E-133 (Scheme 29).

Scheme 29. Allylboration of carbonyl derivatives with B-(γ-alkoxy)allylborabicyclo[3.3.2]decane.

Binaphthol Based Chiral Auxiliary Kaufmann reported the synthesis of B-allylbinaphtholboronate 8 via the reaction of triallylborane with binaphthol and this reagent upon allylboration furnished the homoallylic alcohol in 88% ee (30). Chong and co-workers were able to extend this protocol further by using 3,3′-disubstituted binaphthols for this reaction with dramatic improvement in enantioselectivities for aldehydes as well as several ketones (112). They were also able to carry out allylboration of cyclic imines 141 with this disubstituted binaphtol reagent and extend this methodology for the synthesis of alkaloids 142 (113). Significant enhancement of enantioselectivity was observed for these reactions especially by the modification of the 3,3′-side chains on binaphthol to include groups such as trifluoromethyl and 3,5-bis(trifluoromethyl)phenyl (Scheme 30).



Scheme 30. Reaction of binaphthol derived allylboranes with carbonyl derivatives.

Schaus et al. reported the use of 3,3′-dibromobinaphthol 138 as a chiral catalyst for the allylboration of ketones with B-allyl diisopropylboronate 143a furnishing the product homoallylic alcohols 144a in high enantioselectivity. The corresponding reaction with (Z)- and (E)-crotylboronate reagents 143b-c furnished syn and anti β-methyl homoallylic alcohols 144b-c in >95% de and ee (114). An analogous reaction of N-acyl imines 145 with B-allyl diisopropylboronate 143a in the presence of 3,3′-diphenylbinaphthol 138 provided the corresponding homoallylic amine derivatives in excellent enantioselectivities. The crotylboration of acyl imines 145 with (E)-crotylboronate 143b yielded the expected anti product 146 as the major diastereomer in high yields and stereoselectivities. Interestingly however, the reaction of (Z)-crotylboronate 143c with acyl imines did not furnish the expected syn product and even in this case, the anti product 146 was still the predominant product albeit in lower yield and enantioselectivity. This reactivity pattern was presumably due to the trans diaxial interactions in the chair transition state, which forces the reaction of acylimines 145 with (Z)-crotylboronate 143c to assume a boat transition state thereby leading to the formation of the anti diastereomer 146 (Scheme 31) (115).



Scheme 31. Binaphthol catalyzed allylboration of carbonyl derivatives.

Ferrocene Based Chiral Allylboranes Jaekle and co-workers reported the use of ferrocene based chiral reagents for the allylboration of ketones to provide the products 150 with varying degrees of enantiocontrol ranging between 40-80% ee (Scheme 32). It is surprising to note that these allylboranes failed to provide any enantioselectivity for aldehydes (

Allylboration - ACS Symposium Series (ACS Publications)

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