The syntheses of the optically pure asymmetric hydroborating agents 1 (a, R = Ph; b, R = TMS) in both enantiomeric forms are reported. These reagents are effective for the hydroboration of cis-, trans- and trisubstituted alkenes. More significantly, they exhibit unprecedented levels of selectivity in the asymmetric hydroboration of 1,1-disubstituted alkenes (28-92% ee), a previously unanswered challenge in the nearly 50 year history of this reagent-controlled process. For example, the hydroboration of alpha-methylstyrene with 1a produces the corresponding alcohol 6f in 78% ee (cf., Ipc2BH, 5% ee). Suzuki coupling of the intermediate adducts 5 produces the nonracemic products 7 very effectively (50-84%) without loss of optical purity.

The synthesis of mixed borabicyclodecane (BBD)-derived 1,3-diborylpropenes (trans-1) is described. These new bimetallic reagents are effective for the selective asymmetric allylboration first of ketones (or ketimines) and second of aldehydes (or aldimines). Formed as a thermodynamic mixture of trans regioisomers from cis-1 through a series of 1,3-borotropic shifts, only trans-1 undergoes the monoallylation of ketones. After this single addition, this process is effectively shut down after the reaction of the 10-Ph-9-BBD portion in 1. Serving as a molecular gate, the rearranged 10-TMS-9-BBD trans-allylborane intermediate 11 reacts only after an aldehyde (or aldimine) is added. This allylation fixes the last two stereogenic centers of the 2-vinyl-1,3-diol stereotriad, ultimately resulting in 16 (or 1,3-amino alcohols) in 50-72% yield (>98% ee) as single observable diastereomers. These reagents 1 uniquely function as the equivalent of 1,1-bimetallic allylic reagents, adding sequentially first to ketones and second to aldehydes.

Simple Grignard procedures provide methallylboranes 1a and 1b in enantiomerically pure form from air-stable precursors in 98% and 95% yields, respectively. These reagents add smoothly to aldehydes and methyl ketones, respectively, providing branched 2°-(6, 69-89%, 94-99% ee) and 3°-(10, 71-87%, 74-96% ee) homoallylic alcohols.The asymmetric allylboration of aldehydes remains as one of the most powerful processes for the preparation of nonracemic 2°-homoallylic alcohols. 1 In 1978, R. W. Hoffmann 1a,c reported the first enantioselective synthesis of branched 2°-homoallylic alcohols employing a methallyl derivative of his camphor-derived boronic esters. Unfortunately, low enantioselectivity is generally observed with these reagents (40-76% ee). Brown's diisopinocampheylborane reagents proved to be more selective (90-96% ee), but the preparation of these reagents from high-purity air-sensitive organoborane precursors through organolithium procedures presents operational difficulties. 1d,o Moreover, these reagents are ineffective for the allylation of ketones. 1e A variety of alternative processes are now available for these types of "allylation" processes, 2 but for ketone substrates, the only successful methallylation was recently reported employing tetrakis-(methallyl)tin and a (R)-H 8 -BINOL/ Ti catalyst. 3 This method uses six (6) equiv of the toxic methallyltin moiety, a large catalyst loading (30 mol %) and exhibits modest to good enantioselectivity (46-90% ee). Since asymmetric methallylation is an important synthetic process, 4 we felt that a better, more selective and user-friendly process would represent an important advance. We envisaged that the methallylation of both aldehydes and ketones could be markedly improved through the use of the 10-substituted-9-borabicyclo[3.3.2]decanes which are easy to handle, effectively recovered and recycled, and are available in both enantiomeric forms.Recently, we reported the synthesis of the B-allyl-10-TMS-and -10-Ph-BBD systems (2) and their highly selective additions to aldehydes 5 and ketones, 6 respectively. The corresponding B-methallyl reagents 1 were envisaged as very attractive alternatives for the methallylboration of either aldehydes or ketones, depending upon the choice of the 10-substituent employed.I This work is dedicated to Professor Alfred Hassner on the occasion of his 77 th birthday.jas@janice.uprr.pr. The air-stable crystalline pseudoephedrine (PE) complexes 4a serve as efficient precursors to 2a (98%) through simple Grignard procedures. 5 However, the analogous process with 4a and methallylmagnesium chloride (0.5 M in THF) proved to be both sluggish and inefficient. Fortunately, the more reactive B-OMe derivatives 3a, which are readily prepared from 2a (87%), 5a provide an efficient entry to 1a through this Grignard method (98%) (Scheme 1). NIH Public AccessReagents 1a react smoothly with aldehydes to yield pure 3-methyl homoallylic alcohols 6 efficiently (69-89%) with excellent selectivities (94-99% ee) (Scheme 2, Table 1). The product ee...

Hydroboration O 0277 9-Borabicyclo[3.3.2]decanes and the Asymmetric Hydroboration of 1,1-Disubstituted Alkenes. -Optically pure asymmetric hydroborating agents in both enantiomeric forms are prepared from the precursors (I) by addition of Tms-Cl. These reagents are effective for the hydroboration of cis-, trans-and trisubstituted alkenes. More significantly, they exhibit unprecedented levels of selectivity in the asymmetric hydroboration of 1,1-disubstituted alkenes. -(GONZALEZ, A. Z.; ROMAN, J. G.; GONZALEZ, E.; MARTINEZ, J.; MEDINA, J. R.; MATOS, K.; SODERQUIST*, J. A.; J. Am. Chem. Soc. 130 (2008) 29, 9418-9419; Dep. Chem., Univ. Puerto Rico, Rio Piedras 00931, P. R.; Eng.) -Bartels 49-037